Contents

Hematology : Introduction to WBC Disorders and Leukemias  1

Hematology : Myeloid Disorders, Lymphomas and Miscellaneous  9

Hematology : RBC Disorders  18

Hematology : Haemostasis, Blood Banking and

Practical Hematology  31

General Pathology : Cell Adaptations and Cell Injury  37

General Pathology : Inflammation and Neoplasia  44

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General Pathology : Immunity  57

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General Pathology : Genetics  64
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Systemic Pathology : Blood Vessels and Heart  74

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Systemic Pathology : CNS and Dermapathology  84

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Systemic Pathology : Respiratory System  91

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Systemic Pathology : Genital System and Breast  101

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Systemic Pathology : Gastrointestinal, Endocrine and

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Musculoskeletal System  113

Systemic Pathology : Kidney and Liver  125

Annexure136
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 Hematology : Introduction to WBC Disorders and Leukemias 1

HEMATOLOGY : INTRODUCTION TO WBC ----- Active space -----

DISORDERS AND LEUKEMIAS

Introduction to Hematology  00:01:35

PERIPHERAL SMEAR (PS)

Only mature cells +
Platelets
RBC : Eosinophil :
Central 1/3rd pallor. Bilobed nucleus, brick red granules.

Lymphocyte (Smallest) : Neutrophil :

Round nucleus, no granules. 3-5 lobes in nucleus, bluish granules.

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Monocyte (Largest) : Basophil :

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Reniform/kidney-shaped nucleus. gm Dense purple granules obscuring cytoplasm.
Normal PS
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Types of WBCs :
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1. Agranulocytes : No granules in cytoplasm.

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2. Granulocytes : Granules + in cytoplasm.

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BONE MARROW EXAMINATION

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Position : L Lateral, back facing the doctor Side screw

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Sites :
• Adults : Iliac crest (PSIS > ASIS) > Sternum.
• Children : Tibia (Shin).
Types of needles :
• Salah’s.
• Klima. Salah’s needle
• Jamshidi : Can be used for BM biopsy & aspiration.

Bone Marrow Aspirate (BMA) :

Dry tap : Dry needle on attempted BMA Needs BM bx.
Causes :
• Aplastic anemia : Fat > Cells.
• Myelofibrosis.
• Hairy cell leukemia.
• AML-M7 : ↑Platelet derived growth factor Myelofibrosis.
• Space occupying lesions in BM : Granuloma, metastasis.
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 2 Pathology

----- Active space ----- Appearance : Both mature & immature cells +
Cells
Normal myeloid : erythroid (M:E) ratio 3:1 to 15:1

Fat
BMA
Bone Marrow Biopsy (BM bx) :

Cells (% cellularity = 100 - age)

Fat

RBC
Bony trabeculae
BM bx

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WBC Disorders 00:15:35

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N TLC : 4000–11,000/mm3. gm
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Infection : > 11,000/mm3.

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Non-Neoplastic Disorders :
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Neutrophilia (> 40-70%) : Eosinophilia (> 2-6%) :

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• Acute/bacterial infections. • Allergic reactions : A sthma, hay fever,

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• Tissue necrosis : Burns, MI. Type I hypersensitivity.

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Monocytosis (> 1-8%) : • Parasitic infections.

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• Chronic infections : TB. • Malignancy : Hodgkin's lymphoma.

• Rickettsia. • Tropical pulmonary eosinophilia.
• IBD. Basophilia (≥ 1%) : Myeloproliferative disorders (CML).
• Malaria. Lymphocytosis (> 15-40%) : Chronic/Viral infections.
Note :
1. Tuberculosis : Bacterial infection with lymphocytosis.
2. Splenomegaly + ↓Neutrophil alkaline phosphatase (NAP) score + Basophilia
Myeloproliferative disorder (CML)
Morphological Abnormalities :
1. Abnormal number of lobes in the nucleus :
Hyposegmented neutrophil/Pseudo-
Hypersegmented neutrophil
Pelger-Huet cell
No. of lobes > 5 lobes < 3 lobes
Megaloblastic anemia d/t :
Seen in Myelodysplastic syndrome
Vit B12 deficiency
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 Hematology : Introduction to WBC Disorders and Leukemias 3

Hyposegmented neutrophil/Pseudo- ----- Active space -----

Hypersegmented neutrophil
Pelger-Huet cell

Appearance on PS

2. Abnormalities d/t infection :

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Toxic granules Dohle bodies :

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Patches of dilated endoplasmic reticulum.

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Neoplastic Disorders : gm
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Neoplastic disorder of WBC

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Leukemia Lymphoma :
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Systemic tissue involved (Spleen, lymph nodes)

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Acute Chronic
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Hodgkin’s Non-Hodgkin’s
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ALL AML CLL CML

Acute Leukemias 00:27:42

Diagnostic criteria :
WHO :
• > 20% blasts (Immature precursors) in BM/PS OR
• < 20% blasts + t(15:17)/t(8:21)/Inversion-16 translocation.
FAB : > 30% blasts in BM/PS.

Types of blasts :
Lymphoblast Myeloblast
Size Small Large
Cytoplasm Scanty Moderate amount
Granules Absent Present
Auer rods Absent Present (Clusters Faggot cells)
Chromatin Coarse, dark blue, clumped Homogenous, opened up, pink
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 4 Pathology

----- Active space ----- Lymphoblast Myeloblast

Nucleoli Inconspicuous 2-5, prominent
Myeloperoxidase (MPO), Sudan black B (SBB),
Special stain PAS
Non specific esterase (NSE)
Auer rods

Appearance

↑(> 20%) in ALL AML

ALL 00:35:54

Age at presentation : 2-9 yrs (M/c leukemia in children).

Clinical features : ↓RBC Pallor, fatigue.

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• D/t ↑blasts ↓Mature cells

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↓WBC ↑Infections.
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↓Platelets Bleeding manifestation.
Hepatosplenomegaly
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• Involvement of CNS, testes & LN (Absent in AML).

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Classification :
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FAB classification (Based on morphology) :

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L1 L2 L3
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Blast

Small, round Pleomorphic, larger Large

Morphology
Cytoplasm Scant Moderate Moderate, basophilic, vacuolated
Nucleus Round Irregular Round/oval
Chromatin Homogenous Fine Stippled
Nucleoli Indistinct ≥ 1, large, distinct
Occurrence 75% (M/c) 20 % 5%
Prognosis Best - Worst

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 Hematology : Introduction to WBC Disorders and Leukemias 5

WHO classification (Based on flowcytometric markers) : ----- Active space -----

B-ALL T-ALL
Occurrence 85 % (M/c) 10-15 % (L/c)
Age group affected Usually children Usually adults & adolescent
Mediastinal involvement Absent Present
Associated mutation LOF in PAX5, E2A, RUNX1, EBF gene GOF in NOTCH-1 gene
Prognosis Better Poor

Investigations :
1. CBC :
• ↓Hb, Platelets.
• ↑/↓ WBC’s. Block/dot +ve
2 PS :
• > 20% lymphoblasts.

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• Special stain : PAS (Block/Dot) +ve. Hand mirror cells in PAS staining

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3. Flowcytometric markers : ALL
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• B-ALL : CD19, CD20, CD22, PAX5, TdT, CALLA. AML-M6 : PAS (Diffuse) +ve.
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• T-ALL : CD1, CD2, CD3, CD5, CD7, TdT, CALLA.

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Prognostic Factor : Treatment :

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VAPD regimen
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Good prognosis Bad Prognosis

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• Vincristine.
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Age 2-9 <1, >10

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• L-Asparaginase.
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Sex F M
• Prednisolone.
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Race Whites Blacks

FAB type L1 L2, L3 • Doxorubicin.
WHO type B-ALL T-ALL
Organ involvement
CNS - +
Testis - +
Lymph node - +
Hyperdiploidy Hypodiploidy
Cytogenetics
Trisomy 4, 7, 10, t(12;21) t(9;22)
Leucocyte count <1, 00, 000/mL >1, 00, 000/mL

Note : If t(9;22) present in CML Good prognosis.

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 6 Pathology

----- Active space ----- AML 00:47:55

Age at presentation : 15-39 yrs (Same as CML).

Clinical features : Similar to ALL.
Additionally :
• Gum hypertrophy/bleeding.
• DIC.
• Chloroma : Soft tissue involvement.
- MPO +ve.
- M/c site : Orbit. Chloroma/Granulocytic sarcoma
- Arbiskov cells : Monocytes in chloroma.
Classification :
FAB classification :

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Cell type + Degree of differentiation Special Features

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M0 Undifferentiated AML -

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M1 AML with minimum maturation -
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M2 (M/c) AML with maturation A/w : t(8;21) & chloroma

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• Best prognosis.
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• Maximum Auer rods + Faggot cells +

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• A/w :
M3 Acute promyelocytic leukemia
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- t(15;17) Run X1/RunX1T1

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- DIC
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• Rx : All-trans retinoic acid, Arsenic trioxide.

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M4 Acute myelomonocytic leukemia Inversion 16

M4 eos Acute myelomonocytic leukemia with eosinophilia -
M5 Monocytic leukemia (a & b variants) -
• AKA Di Guglielmo disease.
M6 Acute erythroid leukemia
• Diffusely PAS +ve
• A/w :
- Down's syndrome
M7 (L/c) Acute megakaryocytic leukemia
- Myelofibrosis Dry tap on BMA.
• Markers : CD41, CD61
Common features of M4, M5 :
• M/c a/w gum bleeding (M5 > M4).
• NSE +ve (D/t monoblasts).
• Leukemia cutis. Auer rods Faggot cell

MPO
positivity

Myeloblasts
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 Hematology : Introduction to WBC Disorders and Leukemias 7

CML 01:00:17 ----- Active space -----

Age at presentation : Middle age to elderly.

Pathogenesis :
t(9;22) Philadelphia chromosome Constant activation Myeloproliferation.
(In 95% cases) of tyrosine kinase (TK)
Clinical features : Massive splenomegaly Dragging sensation in the abdomen.
Investigations :
1. CBC : N Hb, ↑↑WBC, ↑↑Platelets.
2. PS : Looks like BM.
- Basophilia.
- All stages of myeloid maturation + .
PS in CML
3. BMA :

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- Sea blue histiocyte.

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- Pseudo Gaucher cell
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4. NAP score : ↓( N 40-100).
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5. Fluorescent in situ hybridization (FISH) : t(9;22).

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Treatment : Imatinib mesylate (Inhibits TK). BMA in CML

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WHO criteria for CML in accelerated phase :

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• Blasts 10-19% in blood and/or bone marrow.

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• Peripheral blood basophils > 20%.

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• Persistent thrombocytopenia (< 100 x 109/L)

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unrelated to therapy, (or)

thrombocytosis (>1000 x109/L) unresponsive to therapy.
• Increasing spleen size and increasing WBC
unresponsive to therapy. FISH analysis in CML
• Cytogenetic evidence of clonal evolution.

Note :
1. D/D for massive splenomegaly :
- Malaria - Polycythemia vera. - Myelofibrosis.
- Kala azar - MDS (CML). - Gaucher’s disease.
2. NAP score :
• ↓ Paroxysmal Nocturnal Hemoglobinuria (PNH), CML.
• ↑ Leukemoid reaction, pregnancy, stress, other myeloproliferative
disorders.

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 8 Pathology

----- Active space ----- CLL 01:09:07

Age at presentation : Elderly (60-70yrs). Mature

Pathogenesis : Deletion of 13q, 11q, 17p; Trisomy 12. lymphocyte
Clinical features :
• Painless lymphadenopathy.
• H/o Autoimmune Hemolytic Anemia (AIHA). Smudge cell
PS in CLL
Investigations :
1. CBC : Absolute lymphocytosis (> 5000/mm3).
2. PS :
- Mature lymphocytosis.
- ↑Smudge/Parachute/Basket cells.
3. Lymph node bx : Proliferation centers (Pathognomonic).
4. Markers : CD5, CD23, CD200.

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Note :

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• CLL : Convent girl appearance (Uniform appearance of cells).
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• CML : College girl appearance (No cell uniformity).
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Summary of Leukemia
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ALL AML CLL/SLL CML

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Age 2-9 yrs 15-39 yrs 6 or 7th decade

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Elderly
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• CNS • Gum bleeding

• AIHA Massive
Special C/f • Testis • Chloroma
• Lymphadenopathy splenomegaly
• Lymph node involvement • DIC
All stages of
↑Lymphocyte count,
P/S > 20% lymphoblasts > 20% myeloblasts myeloid maturation,
Smudge cells.
basophilia.
MPO,
Stain PAS + Sudan black B, - -
Oil red O
B ALL : CD 19, 10 ; PAX 5,
CD 13, 33, 117 CD 5+, CD23+,
Markers T ALL : CD 1, 2, 5, 7 -
MPO CD200+
Both : TdT +
t(8;21) M2
Trisomy 12
Cytogenetics - t(15;17) M3 t(9;22)
del 13q, 17p
inv(16) M4

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 Hematology : Myeloid Disorders, Lymphomas and Miscellaneous 9

HEMATOLOGY : MYELOID DISORDERS, ----- Active space -----

LYMPHOMAS AND MISCELLANEOUS

Myeloproliferative Neoplasms  00:00:10

Disorders : Features :
• CML : Tyrosine kinase pathway. • Panmyelosis : ↑Hb, ↑TLC, ↑platelet count.
• Polycythemia vera. • Mutation of growth signaling pathways.
• Essential thrombocytosis. JAK-stat
• Hepatosplenomegaly.
• Myelofibrosis. pathway.
• Development of myelofibrosis.
POLYCYTHEMIA VERA

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↑Hb.

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Diagnostic criteria (2014) : gm
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All 3 major or first 2 major + 1 minor.

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Major :
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1. Hb (g/dL) : >16.5 men, >16 women.

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2. BM trilineage myeloproliferation with pleomorphic megakaryocytes.

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3. Presence of JAK 2 mutation.

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Minor : Subnormal S. erythropoietin level.

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Note : Relative polycythemia (High altitude, smokers, COPD) : ↑S. erythropoietin.

Clinical features :
Cause
Headache, dizziness ↑Hb
Intense itching after bath ↑basophils & mast cells (↑TLC)
Erythromelalgia (Throbbing/burning sensation) ↑platelets Vaso-occlusion
Rx :
Symptomatic : Phlebotomy.

ESSENTIAL THROMBOCYTOSIS
Diagnostic Criteria :
All 4 criteria must be present :
1. Platelet count ≥ 450,000/mm3. 3. Not meeting WHO criteria for other
2. JAK2V617F (+) or no evidence of MPNs.
reactive thrombocytosis. 4. Megakaryocyte proliferation with
large and mature morphology.
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 10 Pathology

----- Active space ----- PRIMARY MYELOFIBROSIS

Diagnostic Criteria :
Major : Minor (2 out of 4) :
1. Atypical megakaryocytic hyperplasia 1. Leukoerythroblastosis.
with reticulin/collagen fibrosis (D/t PDGF). 2. Elevated S. LDH.
2. Exclusion of WHO criteria for other MPN’s. 3. Anemia (Myelophthisic).
3. JAK2V617F or other clonal marker, 4. Palpable splenomegaly.
if not rule out secondary fibrosis.
Investigations :
• CBC : ↓Hb, ↓TLC, ↓platelet count. • Bone marrow (BM) aspirate : Dry tap.
• Peripheral smear (PS) : - BM biopsy (IOC) :
- Dacrocytes/tear drop cells.
- Immature myeloid & erythroid
Reticulin fibres

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cells (Leukoerythroblasts). Bony trabeculae

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Reticulin stained BM biopsy

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BM dry tap is seen in :

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• Aplastic anemia. • AML-M7.

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• Myelophthisic anemia. • Hairy cell leukemia.

• Myelofibrosis.

Hodgkin’s vs Non-Hodgkin’s Lymphomas 00:18:46

Lymphomas : Lymph node or tissue or systemic involvement.

Hodgkin’s vs Non-Hodgkin’s Lymphoma :
Hodgkin Non-Hodgkin
Age Bimodal Elderly
• Mostly localized to a single • Mostly involve multiple
axial group of lymph nodes peripheral nodes
Lymph node involvement
• Cervical (M/C), mediastinal, • Axillary, mediastinal,
para-aortic LN inguinal LN
Pattern of spread Contiguous spread Non-contiguous spread
Mesenteric node & Waldeyer ring Rarely involved Commonly involved
Extranodal involvement Uncommon Common

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 Hematology : Myeloid Disorders, Lymphomas and Miscellaneous 11

Hodgkin’s Lymphoma (HL) 00:20:51 ----- Active space -----

Characteristics:
• B cell lymphoma.
• Reed Sternberg cells.
Clinical features :
• Systemic symptoms : • Rubbery lymph nodes.
Fever, night sweats. • Pel Ebstein fever (Waxing & waning).
• Cervical lymphadenopathy.
WHO Classification :
Classical Non-classical
• Nodular sclerosis
• Mixed cellularity Nodular lymphocyte
Subtypes
• Lymphocyte rich predominant (NLPHL)

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• Lymphocyte depleted

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• CD 20 + , CD 45 + , Epithelial
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Reed Sternberg
CD 15 + , CD 30 + membrane antigen (EMA) +
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(RS) cell markers

• CD 50 - , CD 30 -
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Reed Sternberg (RS) Cell :

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RS cell :
• Binucleate.
• Eosinophilic macro nucleoli. Note : Owl's eye appearance also seen
• Owl’s eye appearance. in CMV infection
RS cell variants :

Lacunar variant Popcorn cell/L-H

(Seen in Nodular sclerosis HL) (NLPHL)

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 12 Pathology

----- Active space ----- Types of HL :

Lymphocyte
Nodular Mixed Lymphocyte Lymphocyte
Predominant
Sclerosis Cellularity Rich Depleted
(Non-Classical HL)
Most common Most common HIV
- -
type of HL type in India associated
M:F M=F M>F M>F M>F M>F
Biphasic (Young
Adolescent and
Age adults as well Old age Old age Young males
young adult
as >55 years)
Has eosinophils Pleomorphic LH cells (Popcorn
Lacunar
and plasma necrobiotic cells) in the
variant having
cells. Mononuclear or background.
RS Cell a clear space
Has maximum variant of RS mummified Other cells are
surrounding
number of RS variant of scanty. B cells
the cell
cells RS cells are absent

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CD 15 - CD 30 -
CD 15 + ; CD 15 + ; CD 15 + ; CD 15 + ;
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Markers gm CD 20 +
CD 30 + CD 30 + CD 30 + CD 30 +
BCL 6 + EMA +
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Uncommon
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(Usually not Associated Associated Associated Not associated
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Barr Virus)
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Good to
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Prognosis Excellent Very good Poor Best

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Staging : Ann Arbor staging.

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• Adriamycin. • Vinblastin.
• Bleomycin. • Dacarbazine.

Non-Hodgkins Lymphoma (NHL) 00:33:27

Follicular Mantle cell Burkitt’s Diffuse Large Marginal zone

lymphoma lymphoma lymphoma B Cell lymphoma lymphoma
M/c indolent M/c NHL in India/
Incidence - - -
NHL in world world
• t (8; 14)
• t (14; 18) Dysregulation
Pathology t (11; 14) • t (2; 8) t (11; 18)
• MLL gene BCL 6
• t (8; 22)
Lymphoepithelial
• Follicular Small to
Large pleomorphic lesion
arrangement medium Starry sky
Histology cells in diffuse (Lymphocytes
• Centrocytes irregular appearance
pattern entering
• Centroblasts lymphocytes
epithelium)

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 Hematology : Myeloid Disorders, Lymphomas and Miscellaneous 13

----- Active space -----

Follicular Mantle cell Burkitt’s Diffuse Large Marginal zone

lymphoma lymphoma lymphoma B Cell lymphoma lymphoma
Cyclin D1 +
Markers BCL-2 + CD 5 + , CD 19 + , CD 20 + , BCL-6 + CD 43 +
CD 23 - , SOX 11
Paratrabecular • EBV association Site of
Lymphomatoid
Features lymphoid • Jaw/GIT chronic
polyposis
aggregates involvement inflammation
Burkitt’s Lymphoma :
Features : Note :
• t (8; 14) C-myc amplification. 3 myc gene (Proto-oncogene) :
• Starry sky appearance. • C-myc : Burkitt lymphoma.
• Ki67 high ↑Proliferation. • L-myc : Lung cancer.

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• Chemosensitive. • N-myc : Neuroblastoma.

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Types : gm
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African : Sporadic : HIV associated

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• A/w : EBV (Epstein Barr virus) Site : GIT (Peritoneal/

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• M/c site : Jaw/mandible Ileal involvement)

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Lymphoid cells (Sky)

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Histiocytes (Stars)
Jaw involvement Starry sky appearance
Hairy Cell Leukemia :
Features :
• B cell disorder.
• Hair-like projections (Best seen : Phase contrast microscope).
• Massive splenomegaly.
• Pathology : BRAF V 600 E mutation.

Note :
Massive splenomegaly causes :
• CML. • Hairy cell leukemia.
• Polycythemia vera. • Malaria.
India.
• Myelofibrosis. • Kala-azar.
• Gaucher’s disease.

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 14 Pathology

----- Active space ----- Ix Finding

CBC Pancytopenia (D/t myelofibrosis)
P/S Hairy cells
Bone marrow aspiration Dry tap
Bone marrow biopsy Fried egg, honey comb appearance
Special stain TRAP + (Tartrate resistant acid phosphatase)
Marker Annexin A1, CD 25, CD I1c, CD 103 +

Microscopy :

Hair-like
projections

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Phase contrast microscopy PS

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Electron microscopy

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T-cell NHL : gm
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Mycosis fungoides/ Anaplastic large

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Adult T-cell leukemia

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Sezary syndrome cell lymphoma

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Human T-lymphotropic Cutaneous T-cell ALK gene on

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virus (HTLV) 1 lymphoma chromosome 2p

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Flower cell/Clover leaf Sezary cells Hallmark

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Histology
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cells (Cerebriform nuclei) (Doughnut) cell

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Note :
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ALK gene mutation is a/w :

• ALL.
• Adenocarcinoma lung.
• Inflammatory myofibroblastic tumor.

Plasma Cell Disorders 00:47:46

Tumors of post germinal centre B cells.

Microscopy :

• Oval cell.
• Eccentric nuclei with perinuclear halo.
• Cart wheel/Clock face chromatin.

Plasma cell
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 Hematology : Myeloid Disorders, Lymphomas and Miscellaneous 15

MULTIPLE MYELOMA ----- Active space -----

Diagnostic Criteria :
Clonal bone marrow plasma cells ≥10% or biopsy proven bony/
extramedullary plasmacytoma.
+
Myeloma defining event

One or more biomarkers of malignancy : Evidence of end organ damage :

(SLIM criteria) • Hypercalcemia.
• Clonal bone marrow plasma cells ≥sixty percent. • Renal insufficiency.
CRAB
• Involved : Uninvolved free Light chain ratio >100. • Anemia. features
• > 1 focal lesion on MRI. • Bone lesions.
PS : RBC Rouleaux formation.
Bone Marrow Aspirate :

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D/t abnormal immunoglobulins.

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• Flame cells. gm
• Mott cell (Cytoplasm is grape like).
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• Russell bodies. RBC rouleaux formation

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• Dutcher bodies.
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Dutcher bodies
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(Intranuclear
immunoglobulin)
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Rusell bodies
(Intracytoplasmic
immunoglobulin)

Rusell bodies Mott cell Dutcher bodies

Clinical Features :
• Fatigue, pallor, bone pain, pathological fracture.
• M/C set of bones affected : Axial skeleton.
• M/C vertebrae affected : Lumbar vertebra.
• M/C cause of death : Renal failure.
Investigations :
Biochemical tests :
• ↑S. calcium (Metastatic calcifications).
• ↓Hb (Anemia of chronic disease).
• ↑ESR.
• ↑S. beta 2 microglobulin (Best prognostic factor).
• Renal function test : Abnormal.

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 16 Pathology

----- Active space ----- • S. Albumin/Globulin reversed.

• Bence Jones proteinuria.
- Precipitates (ppt) at 40-60°C.
- Ppt disappears at 100°C.
- Ppt reappears on cooling.
• Markers : CD 138 (Syndecan 1), CD 56.
X-Ray : Electrophoresis :
↑Immunoglobulin (Ig) : IgG > A > M > D > E.

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globulin

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Lytic/punched out lesions Normal MM : ↑Gamma globulin

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Smoldering/ Monoclonal gammopathy
Plasma cell
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leukemia
myeloma significance
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• BM plasma cell • ↑IgM (Hyper viscosity syndrome)

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• BM plasma cell <10%

>10%
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>20% • No myeloma defining Lymphoplasmacytic

• No CRAB lesions
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plasma cell events

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• S. monoclonal M lymphoma
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• S. IgG <3 g/dL

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protein > 3g/dL • A/w MYD 88 mutations

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Langerhans Cell Histiocytosis (LCH) 01:00:42

Features :
• Abnormal proliferation of immature dendritic cell (Antigen presenting cells).
• BRAF V 600 E mutation.
Note :
BRAF V600E is a/w :
• LCH. • Papillary Ca thyroid.
• Hairy cell leukemia. • Pilocytic astrocytoma.

Hand Schuller Christian Disease :

1. Diabetes insipidus.
2. Exophthalmos.
3. Bone defect.

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 Hematology : Myeloid Disorders, Lymphomas and Miscellaneous 17

Investigations : ----- Active space -----

Biopsy : Coffee bean nuclei Electron microscopy : Birbeck granules

(Longitudinal groove) (Tennis racquet)
Note :
Coffee bean nuclei :
• Papillary carcinoma thyroid. • Chondroblastoma.
• LCH. • Granulosa cell tumor ovary.

om
• Brenner’s tumor.

l.c
ai
gm
Bone Marrow Findings in Diseases 01:05:05
@
60
23

Disorder Bone marrow aspirate Bone marrow biopsy

ik
hv

ALL >20% lymphoblasts

rit

AML >20% myeloblasts

|
w
ro

CLL ↑Lymphoid cells

ar

• Pseudogaucher cells
M
©

CML • Sea blue histiocytes -

• M : E ratio
HCL Dry tap Fried egg appearance
LCH - Coffee bean nuclei

Myelofibrosis Dry tap

• ↑Fibrosis
• Reticulin stain : Black fibers
Multiple myeloma ↑Plasma cells -
Aplastic anemia Dry tap ↑Fat
Megaloblasts :
Megaloblastic
Erythroid precursors with -
anemia
sieve like chromatin

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 18

----- Active space ----- HEMATOLOGY : RBC DISORDERS

RBC 00:01:50

Normal peripheral smear Romanowsky stains :

• Giemsa
Neutrophil Platelets • Leishman

RBC : Central
1/3rd pallor
Lymphocyte
Basophil
Monocyte

om
l.c
RBC development
ai
gm
Hemopoietic stem cell
@
60
23
ik

Common myeloid progenitor (CMP)

hv
rit
|

Proerythroblast
w
ro

• Hb production starts
ar
M

(Only seen on electron microscopy)

©

Early/Basophilic normoblast (Blue) • Cell size : ↓

• Nuclear size : ↓
Intermediate/Polychromatic normoblast (Pink + blue) • Hb : ↑(∴↑Pink)
• Hb first appears

Late/Orthochromatic normoblast (Pale pink)

Reticulocyte
• First stage without nucleus
1-2 days
RBC.

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 Hematology : RBC Disorders 19

RETICULOCYTE : ----- Active space -----

Immediate precursors of RBC.

P/S : Retic count :

Normal : 0.5 - 1.5 %

↑ ↓
• Haemolytic anemia • Aplastic anemia
• Acute blood loss • Bone marrow
• Response to Fe/B12 Rx suppression

Corrected retic count :

Reticulocytes Mature RBC
(Bluish meshwork) (No meshwork) Patient Hb/HCT
Retic count x
d/t N Hb/HCT for that age

om
l.c
RNA/Histones Hb : 15
ai
gm Normally
HCT : 45
@

Stain :
60

Supravital stains : Stain living state if cell in vitro

23
ik

• Brilliant cresyl blue.

hv
rit

• New methylene blues.

|
w
ro

Note : Blue stains Supravital stain, Prussian blue.

ar
M
©

RBC P/S Findings 00:10:36

Finding P/S Conditions

Mnemonic : SITA
• Sideroblastic anemia, lead poisoning
Microcytic hypochromic
• Iron deficiency anemia
anemia
• Thalassemia
• Anemia of chronic disease
Mnemonic : Lady Hardinge Medical College
• Liver disease
Macrocytic anemia • Hypothyroidism
• Megaloblastic anemia (Vit B12/Folate)
• Cytotoxic drugs

Pencil cells - Iron deficiency anemia

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 20 Pathology

----- Active space ----- Finding P/S Conditions

Bite cells G6PD deficiency

• Hereditary spherocytosis
Spherocytes : • Autoimmune hemolytic anemia
• Smaller. (M/c)
• No central pallor • Blood transfusion reaction
• Burns

• Chronic renal failure

Burr cell/Echinocytes
• Uremia
(Blunt projections)
• Liver disease

om
l.c
ai
gm
@
60

Spur cell/Acanthocytes
23

Abetalipoproteinemia
(Pointed projections)
ik
hv
rit
|
w
ro
ar
M

Sickle cell Sickle cell anemia

©

• Thalassemia
Target cell/Codocytes • Liver disease
• Iron deficiency anemia

• Microangiopathic Hemolytic
Schistocytes/Helmet/ Anemia (MAHA),
Fragmented RBC HUS, TTP, DIC.
• Cardiac prosthetic valves

• Myelofibrosis
Tear drop cells/
• Myelo dysplastic syndrome
Dacrocytes
• Myelophthisic anemia

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 Hematology : RBC Disorders 21

Finding P/S Conditions ----- Active space -----

Heinz bodies
G6PD deficiency
(Supravital stain)

Howell Jolly bodies • Asplenia

(Nucleus remnant) • Megaloblastic anemia

Pappenheimer bodies - Sideroblastic anemia

Cabot ring (Figure

of 8 configuration • Megaloblastic anemia
composed of • Thalassemia

om
microtubules)

l.c
ai
gm
Rouleaux - Multiple myeloma
@
60

Polychromasia - Hemolytic anemia

23
ik

• Sideroblastic anemia
hv
rit

• Lead poisoning
Basophilic stippling
|

• Thalassemia
w
ro

• Megaloblastic anemia
ar
M

Stomatocyte - Hereditary stomatocytosis

©

Note : WBC P/S

• Hyper segmented neutrophil : Megaloblastic anemia.
• Bilobed neutrophil : MDS.
• Toxic granules : Sepsis.
• Döhle bodies (Dilated endoplasmic reticulum) : Sepsis.
• Giant granules in neutrophils : Chediak Higashi syndrome.

PARASITES FINDINGS

Microfilaria Gametocyte Ring form of BMA : Histiocytes with

of plasmodium plasmodium Leishmania donovan bodies
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 22 Pathology

----- Active space ----- RBC Indices 00:26:02

Definition Normal Significance

• Sideroblastic, lead poisoning
Micro- • IDA
cytic • Thalassemia
• Anemia of chronic disease
• Aplastic anemia
• Acute blood loss
Mean Corpuscular Average volume of red Normo-
82 - 96 fL • PNH
Volume (MCV) cells cytic
• Hemolytic anemia
• Anemia of chronic disease

• Liver disease
Macro- • Hypothyroidism
cytic • Vit B12/Folate deficiency

om
• Cytotoxic drugs

l.c
Mean Corpuscular Average mass of • Hypochromic (>1/3rd pallor)
ai
27 - 32 pg
gm
Hemoglobin (MCH) hemoglobin/RBC • Normochromic
@
60

Mean Corpuscular
Average Hb conc. in a
23

Hemoglobin 33 - 37 gm/dL ↑ in Hereditary spherocytosis

volume of packed RBC
ik

Concentration (MCHC)
hv
rit

Red cell Distribution Coefficient of variation of To differentiate b/w

|

11 - 14%
w

Width (RDW) red cell size/Anisocytosis thalassemia and IDA

ro
ar

• <13 : Thalassemia
M

Mentzer index MCV/RBC count 13

• >13 : IDA
©

Anaemia 00:32:30

↓Hb/↓RBC mass

Hypoproliferative Hemolytic Deficiency

Aplastic Pure red cell aplasia Myelophthisic anemia

anemia • Parvovirus B19 (Space occupying lesion
• ↓RBC of bone marrow)

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 Hematology : RBC Disorders 23

APLASTIC ANEMIA ----- Active space -----

Clinical : H/o : Cytotoxic drugs/viral infection
• Anemia (↓Hb, ↓Retic count) BM Aspiration : Dry tap
- Pallor. Bone marrow biopsy : IOC
- Fatigue.
- Breathlessness. Bony trabeculae
• Thrombocytopenia :
- Petechiae.
- Purpura. ↓Cellularity, ↑Fat
- Bleeding tendency.
• Leukopenia :
↑Risk of infections.

Hemolytic Anemias

om
00:37:20

l.c
• ↑Destruction of RBC
ai
gm
• ↑Risk of gallstones (Pigment)
@
60

• Triad :
23
ik

Pallor
hv
rit
|
w
ro
ar
M
©

Jaundice Splenomegaly
Intravascular Extravascular (Liver/Spleen)
Hepatosplenomegaly -+ ++
Hemoglobinuria + -
Hemosiderinuria + -
S. Haptoglobin ↓ ↓/ N
• Paroxysmal
Nocturnal
Hemoglobinuria
(PNH)
• Hereditary spherocytosis
• Paroxysmal cold
• Sickle cell anemia
Examples hemoglobinuria
• Thalassemia
• MAHA
• AIHA
• G6PD deficiency
• Infections
• Prosthetic cardiac
valves

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 24 Pathology

----- Active space ----- HEREDITARY SPHEROCYTOSIS, G6PD DEFICIENCY, SICKLE CELL ANEMIA
Hereditary spherocytosis G6PD deficiency Sickle cell anemia
Autosomal dominant X linked recessive Autosomal recessive
Inheritance
M=F M>F M=F
Protein deficiency Missense point mutation :
Pathology • M/c : Ankyrin Deficiency of G6PD Glu is replaced by Val at 6th
• Most severe : Spectrin position of β-chain of Hb
• Episodic hemolysis • Pallor, jaundice
• Pallor
• Hemoglobinuria • Autosplenectomy
Clinical • Jaundice
• No splenomegaly • Crisis like bone pain,
• Splenomegaly
• No gallstones fractures, chest pain
H/o chronic infection, Crisis like bone pain,
History - drugs, fava beans fracture, chest pain
Hemolysis Extravascular Both Extravascular

om
P/S Spherocytes Bite cells, Heinz bodies Sickle cells

l.c
ai
gm • Sickling test
Special test Osmotic fragility • Hb electrophoresis
@
60

Methaemoglobin • HPLC
23

Flow cytometric reduction test

ik

Best • HPLC
hv

analysis of membrane
rit

Investigation • Globin chain sequencing

proteins
|
w

• Hydroxyurea
ro

Avoid oxidative
ar

Rx Splenectomy (↑HbF ↓Sickling)

M

stress
• Stem cell transplant
©

Note : HS, thalassemia, G6PD deficiency, sickle cell anemia

• More common in African/Mediterranean population.
• Protection from Plasmodium falciparum.

INVESTIGATIONS
Osmotic fragility test : X-ray skull :

• Right shift : HS • Thalassemia/Sickle cell anemia

• Left shift : Thalassemia • Crew cut/hair on end
(D/t extramedullary hematopoiesis)
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 Hematology : RBC Disorders 25

Hb electrophoresis : High Performance Liquid ----- Active space -----

(Cathode) Chromatography (HPLC) :
- cellulose acetate, pH 8.4 (Anode)
+
Normal adult
Normal newborn
Sickle cell disease
Sickle cell trait
Hb SC disease
AFSC control
Hb F
Hb A
Hb H
Origin
Hb A2/C/E/O
Hb S/D/G

Mnemonic : HAFSA2
(Anode to cathode) • Best investigation for
hemoglobinopathies
A2 S F A H
• Gives % of different Hbs
Normal adult :
• HbA : α2 β2 (95-97%)
• HbF : α2 γ2 (< 1%)

om
• HbA2 : α2 δ2 (2-3.5%)

l.c
ai
Thalassemia gm 00:52:16
@
60
23

Beta Thalassemia : (M/c) Alpha Thalassemia :

ik
hv

• ↓Beta chain • ↓Alpha chain

rit
|

• Chromosome 11 • Chromosome 16
w
ro

• Mostly d/t mutations • D/t gene deletion

ar
M

BETA THALASSEMIA
©

Major Intermedia Minor/Trait

β chain synthesis Markedly↓ Moderately↓ Minor↓
• Severe pallor, jaundice
• Mild pallor
• Hepatosplenomegaly
• Pallor, jaundice • Asymptomatic
Clinical • H/o repeated blood
• Hepatosplenomegaly • No response to
transfusion
iron therapy
• Chipmunk facies
Hb 3-5 gm% 5-8 gm% >8 gm%
• Many target cells
P/S • Basophilic stippling Few target cells No target cells
• Cabot ring
• MCV, MCH, MCHC↓
RBC indices Not much
• RDW N
Iron profile Iron↑ N N
Hb electrophoresis ↑↑HbF Both↑ HbA2 : 3.5-9%
HPLC ↑HbF Both ↑HbA2

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 26 Pathology

----- Active space -----

Chipmunk facies Hb electrophoresis

Note :
M/c cause of death in β thalassemia major : Cardiotoxicity d/t iron overload.

om
ALPHA THALASSEMIA

l.c
ai
Pathogenesis : Gene deletion gm
@
60

Types :
23
ik

Disorder Genotype MCV Anemia Hb electrophoresis

hv
rit

αα/α- Normal,
|

Silent carrier NL None

w

(1 α gene deleted) <3% Hb Barts at birth

ro
ar

αα/-- or
M

α Thalassemia Normal,
Low Mild
©

α-/α-
Minor 3-8% Hb Barts at birth
(2 α gene deleted)
Hb H disease α-/-- 5-30% HbH present in adults,
Low Moderate
(Deletional) (3 α gene deleted) 20-40% Hb Barts at birth
Major (Fetal hydrops)/ --/-- Fatal (Incompatible Hb Barts & HbH present,
Low
Hb Barts (4 α gene deleted) with life) HbA, HbF, and HbA2 absent

P/S :

Golf ball inclusions

seen in HbH disease
(3α gene deletion)

Supravital stain

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 Hematology : RBC Disorders 27

INVESTIGATION FOR HAEMOGLOBINOPATHIES ----- Active space -----

• Screening : Hb electrophoresis.
• IOC : HPLC.
• Definitive diagnosis : Globin gene sequencing.
• Mass screening : Nestrof test.

Paroxysmal Nocturnal Haemoglobinuria 01:02:00

Pathogenesis :
• Only acquired intra-corpuscular defect.
• PIGA gene mutation.
• ↓Synthesis :
- CD55 : DAF.
- CD59 : MiRL (More imp).

om
• ↑Risk of leukemia.

l.c
ai
Clinical : Pancytopenia + hypercellular marrow gm
@
60
23
ik
hv

Nocturnal intravascular Thrombosis (M/c cause of death) :

rit
|

haemoglobinuria Budd-Chiari syndrome

w
ro
ar

Investigations :
M

• Ham’s test (Acidified serum lysis).

©

• Flow cytometry (CD55 and CD59) : Best test.

Microangiopathic Haemoglobinuria 01:04:02

Types :
• Haemolytic uremic syndrome : H/o E.coli O157/H7.
• Thrombotic Thrombocytopaenic Purpura (TTP) : Mutation ADAMTS-13.
• Disseminated intravascular coagulation.

Clinical pentad : Note : ADAM mutation

• Fever. • ADAM TS 13 : TTP.
• MAHA. • ADAM 33 : Bronchial asthma.
• Thrombocytopaenia.
• Renal abnormality (M/c in HUS).
• Neurological abnormality (M/c inTTP).

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 28 Pathology

----- Active space ----- Iron Deficiency Anemia 01:05:20

• M/c worm : Hookworm (Ancylostoma duodenale).

• Max absorption site : Duodenum.
• Factors ↑absorption : Ascorbic acid, citric acid.
• Factors ↓absorption : Alkalis like phytates/tannates.
• Storage form of iron : Hemosiderin, ferritin.
• Stain for iron : Prussian blue/Perl’s stain.
• Transport form : Transferrin.
• Master regulator of iron metabolism : Hepcidin.
• History : Elderly with GI malignancy, PICA (M/c in women).
• Plummer Vinson syndrome : Triad Atrophic glossitis, esophageal webs, IDA.
Clinical : P/S :

om
l.c
ai
gm
@
60
23
ik
hv
rit
|
w

Microcytic hypochromic
ro

• Cheilosis/koilonychia
ar
M

(Spoon-shaped nails).
©

• Palpitations.
• Pallor, fatigue, breathlessness,
headache, dizziness.

Sideroblastic Anemia 01:08:03

Causes : P/S :
• Genetic : X-linked • Pappenheimer bodies
• Acquired : (Prussian blue stain).
- Alcohol. • Ringed sideroblasts.
- Anti-TB drugs. • Coarse basophilic stippling.
- Vit B12 deficiency. P/S : Sideroblasts Lab :
- Lead poisoning. • ↑Fe, Ferritin
• ↓TIBC

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 Hematology : RBC Disorders 29

Anemia of Chronic Disease 01:09:24 ----- Active space -----

Cause : Chronic infection, neoplasms, autoimmune disorders, idiopathic.

Hepcidin :
• Most important molecule affected.
• Master regulator of iron metabolism (↑Hepcidin ↓Iron).

Summary of Microcytic Hypochromic Anaemias 01:10:18

s. Iron s. Ferritin s. TIBC P/S Extra

Iron deficiency • ↑RDW
↓ ↓ ↑ Pencil cells.
anemia • Mentzer index >13
• Ringed sideroblasts.
Sideroblastic (Bone marrow)
↑ ↑ ↓ -
anemia • Coarse basophilic

om
stippling.

l.c
Anemia of chronic
↑/ N
ai
↓ ↓ Microcytic hypochromic RBCs ↑ESR
disease gm
@

↑HbA2
60

Beta (> 3.5 Thalassemia

23

N N N N
Thalassemia trait trait).
ik
hv

Mentzer index < 13.

rit
|
w

Megaloblastic Anemia
ro

01:12:10
ar
M

Causes : P/S :
©

• Vegetarian diet. • Megaloblasts (↑MCV, MCH).

• Gastrectomized people/Ileal resection. • Hypersegmented neutrophils
• Tape worm (M/c worm). (>5 lobes).
• Howell-Jolly bodies.
Clinical :
• Anemia.
• Beefy tongue.
• Pigmented knuckles.
• Neurological complications :
Subacute combined degeneration of spinal cord.
• Pancytopenia (Diff nuclear cytoplasmic asynchrony).
• ↑Risk of thrombosis.

Treatment : B12, folate supplementation.

BM aspiration : Megaloblasts Erythroid precursors with sieve-like chromatin

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 30 Pathology

----- Active space -----

Pigmented knuckles Hypersegmented Howell-Jolly BMA : Megaloblasts

neutrophils bodies.

Note :
Vit B12 vs. Folate deficiency anemia Neurological manifestations not seen in
folate deficiency anemia.

Pernicious Anemia 01:16:40

• Autoimmunity against parietal cell/Intrinsic factor.

om
• Type 2 hypersensitivity.

l.c
ai
• Anti-parietal cell Ab + . gm
@
60
23
ik
hv
rit
|
w
ro
ar
M
©

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 Hematology : Haemostasis, Blood Banking and Practical Hematology 31

HEMATOLOGY : HAEMOSTASIS, BLOOD BANKING ----- Active space -----

AND PRACTICAL HEMATOLOGY

Hemostasis  00:00:34

Mediated by : Platelets, vascular endothelium & coagulation cascade.

Primary haemostasis : Formation of platelet plug.

Process Factor interaction
Platelet adhesion gp 1b IX (Platelet) - vWF (Endothelium)
Platelet aggregation gp IIb-IIIa (Platelets)

om
Secondary haemostasis :

l.c
ai
Coagulation cascade (Clotting factors) Activation of fibrin.
gm
@
60

Extrinsic pathway (PT)

23

Intrinsic (aPTT)
ik
hv

Coagulation pathway :
rit
|
w
ro
ar
M
©

Calcium

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 32 Pathology

----- Active space ----- Disorders of Hemostasis 00:07:05

Bleeding vs. Coagulation Disorders :

Bleeding disorder Coagulation disorder
Inheritance Mostly autosomal : M = F X linked : M > F
Minor bleeding :
• Petechiae Major bleeding :
Clinical • Purpura • Ecchymosis
• Mucosal bleeds • Haemarthrosis
• Prolonged bleeding after injury
Platelet count
Can be affected Normal
BT
PT
Normal Can be affected
aPTT
ITP Haemophilia

om
Eg.
vWD & DIC

l.c
ai
gm
Disorders of Coagulation & Bleeding :
@
60

Disorder Pathogenesis Platelet count BT PT aPTT Features

23
ik

• Ristocetin Induced Platelet

hv

Deficiency of gp Ib-IX
Aggregation (RIPA) is
rit

Bernard Soulier N ↑ N N
|

Defect in platelet abnormal.

w

adhesion. • Giant platelets.

ro
ar

Deficiency of gp IIb-IIIa
M

Glanzmann’s Platelet aggregation with ADP is

©

N ↑ N N
thrombasthenia Defect in platelet abnormal.
aggregation.
• Antiplatelet • Bone marrow aspiration :
Immune antibodies + ↑Megakaryocytes.
Thrombocytopaenic • Type 2 ↓ ↑ N N • Acute : <6 months,
Purpura (ITP) hypersensitivity h/o viral infection.
reaction • Chronic : >6 months.
• Schistocytes.
Hemolytic Uremic E. coli O157 : H7,
↓ ↑ N N • ↑Reticulocyte count.
Syndrome (HUS) shigella
• Renal defects.
Thrombotic
• Same.
Thrombocytopaenic Mutation of ADAMTS 13 ↓ ↑ N N
• Neurological defects.
Purpura (TTP)
• Factor VIII deficiency.
Haemophilia A Deficiency of factor VIII N N N ↑
• M > F.
Haemophilia B
Factor IX deficiency • Factor IX deficiency.
(Christmas N N N ↑
(Christmas factor) • M > F.
disease)

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 Hematology : Haemostasis, Blood Banking and Practical Hematology 33

----- Active space -----

Disorder Pathogenesis Platelet count BT PT aPTT Features

vWF deficiency • Factor VIII deficiency.
Von Willebrand • RIPA : Abnormal.
N ↑ N ↑
Disease (vWD) Secondary deficiency • Autosomal recessive &
of factor VIII Autosomal dominant
• FDP ↑.
Disseminated • Endothelial injury.
• D-dimer ↑.
Intravascular • Coagulation & ↓ ↑ ↑ ↑
• Cause : Obstetric complications (M/c),
Coagulation (DIC) fibrinolytic.
AML-M3.
Vitamin K Deficiency of
N N ↑ ↑ -
deficiency factor II, VII, IX, X
Vascular
- N N N N Eg : Telangiectasia, scurvy.
disorders
BT : Bleeding time. aPTT : Activated Partial Thromboplastin Time.

om
PT : Prothrombin time. FDP : Fibrin Degradation Products.

l.c
ai
Note : Mutation ADAMTS13 TTP gm
@

ADAM33 Bronchial asthma

60
23

Treatment :
ik
hv

• Haemophilia A : Factor VIII concentrate (Cryoprecipitate).

rit

• Haemophilia B : Factor IX concentrate (Absent in cryoprecipitate).

|
w
ro

Blood Banking
ar

00:25:54
M
©

Blood Bag :
Normal volume : 350 mL.
For component separation : 450 mL.
CPD (Citrate Phosphate Dextrose) : 21 days.
Determines
Anticoagulants used CPDA (CPD + Adenine) : 35 days.
expiry date
SAG-M (Sodium, Adenine, Glucose, Mannitol) : 42 days.

Blood Components :
Storage temp
Blood product Volume Shelf life Use
(°C)
CPD : 21 d
Acute blood loss, severe anemia,
Whole blood 350 mL 2-6 CPDA : 35 d
1 unit ↑hemoglobin by 1 gm%.
SAGM : 42 d
Multiple coagulation factor
FFP 200 mL -30 or lower 1 year
deficiencies, DIC, liver disease.
Haemophilia A, hypofibrinogenemia,
Cryoprecipitate 10-20 mL -30 or lower 1 year
vWD, factor XIII deficiency.
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 34 Pathology

----- Active space ----- Storage temp

Blood product Volume Shelf life Use
(°C)
Random donor 50-70 20-24 with Thrombocytopenia,
5 days
platelets mL agitation 1 unit ↑platelets by 10,000/mm3
Single donor 200- 20-24 with Thrombocytopenia,
5 days
platelets 300 mL agitation 1 unit ↑platelets by 30-50,000/mm3

Note :
• Infection transmitted by all blood products : Malaria.
• Component most prone to bacterial contamination : Platelets.
• Lifespan of transfused RBCs : 50-60 days.

Transfusion Protocol :
Start : Within 30 mins of taking out of fridge.
End : Within 4 hrs.

om
Size of needle : 18-19 G.

l.c
Size of micropore filter : 170 microns.
ai
gm
@

Massive Blood Transfusion

60

00:41:38
23
ik

Replacement of patient’s whole blood volume within 24 hrs.

hv
rit
|

Complications :
w
ro

Mnemonic : CATCH.
ar
M

• Coagulation abnormalities (DIC : M/c cause of death).

©

• Acidosis, alkalosis.
• Hypothermia.
• Citrate toxicity C/f : Tingling, numbness.
• Hyperkalemia C/f : Arrhythmia, hypocalcemia.

Transfusion Related Acute Lung Injury (TRALI) :

• Respiratory symptoms <6 hrs of transfusion.
• X-ray : B/L pulmonary infiltrates, white out appearance.
• D/t anti-leucocyte antibodies.
• M/c with plasma products.

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 Hematology : Haemostasis, Blood Banking and Practical Hematology 35

TRALI vs Transfusion Associated Circulatory Overload (TACO) : ----- Active space -----

TRALI TACO
Antibodies against HLA II,
Etiology Volume overload
anti-neutrophilic antibodies
Hypoxemia, respiratory failure, Dyspnoea, cough,
Clinically
hypotension, fever hypertension, tachycardia
• O2 support
Treatment Supportive care • IV diuretics
• Phlebotomy

Practical Hematology 00:36:29

Sahli’s Haemoglobinometer :
Use : Estimation of Hb.

om
Principle : Hb + HCl Acid hematin S erial dilution to match

l.c
colors of comparator box.
ai
gm
Comparator box
@
60
23

Thoma Pipette :
ik
hv
rit

RBC pipette WBC pipette

|

Red bead White bead

w
ro

Markings : Markings
ar
M

0.5, 1, 101 Upto : 11

©

Wintrobe’s Tube : Improved Neubauer Chamber :

Identification : Use : For cell counts.
Diluting fluids :
• WBC : Turk’s fluid.
• RBC : Dacie, Hayem’s fluid.
Closed end • Platelets : Rees & Ecker diluting fluid.
Use : ESR determination.
Anticoagulant used : EDTA.

Westergren’s Tube :
Identification : Longer tube, open at both ends.
Use : ESR determination.
Anticoagulant used : Citrate.

Pathology Revision • v4.0 • Marrow 8.0 • 2024

 36 Pathology

----- Active space ----- Vacutainers :

Color Contains Uses

Purple EDTA • Routine blood test

(1.5-2 mg/mL) • ESR determination by Wintrobe’s method

• Coagulation tests
Blue Trisodium citrate • ESR determination by Westergren’s method
• Platelet function assay

Grey Sodium fluoride

Blood sugar estimation
( - Enolase)

• Chemistry
Red Clot activator
• Serology
(No gel)
• Immunohematology

om
l.c
Yellow Acid citrate dextrose Preserve RBC for blood banking & HLA typing
ai
gm
@
60

• Osmotic fragility test

23

Green Sodium heparin • Blood gas analysis

ik
hv

• Immunophenotyping
rit

Order of draw :
|
w
ro

Mnemonic : Be loving, respectful, gracious, light-hearted & gentle.

ar

• Blood culture.
M

• Green.
©

• Light blue. • Lavender.

• Red. • Grey.
Microscope :

Pathology Revision • v4.0 • Marrow 8.0 • 2024

 General Pathology : Cell Adaptations and Cell Injury 37

GENERAL PATHOLOGY : CELL ADAPTATIONS AND ----- Active space -----

CELL INJURY

Effects of injurious stimuli : Necrosis.

Persistent
Cell injury Adaptation Reversible Irreversible Cell death Via
stimulus cell injury cell injury
• M/c cause of cell injury : Hypoxia. Apoptosis.
• Cell most susceptible to injurious stimuli : Neurons.

Cell Adaptations 00:02:54

Definition Mechanism Example

1. Physiological :
• ↑in size of cell - Uterus during pregnancy

om
• No. of cells : Remain same ↑synthesis of - Breast during lactation
Hypertrophy

l.c
• Seen in : Permanent or proteins - Skeletal muscle in exercise
ai
non-dividing cells
gm 2. Pathological :
@

LVH in hypertension
60

1. Physiological :
23
ik

- Hormonal Breast in pregnancy/puberty

• ↑in number of cell
hv

Growth factor - Compensatory Liver (Post hepatectomy)

rit

Hyperplasia • Seen in : Dividing cells &

induced proliferation 2. Pathological :
|

non-dividing cells
w

- BPH
ro

- Endometrial hyperplasia
ar
M

• Senile : Alzheimer’s
©

• Pressure
• ↓cell size ↓protein synthesis/
Atrophy • Ischemic : ↓blood supply
• ↓cell number ↑degradation
• Nutritional : Kwashiorkor/Marasmus
• Disuse : Fracture
• Chronic smoker :
Pseudo stratified Stratified squamous
• Reversible change of one epithelium epithelium
Reprogramming of
Metaplasia differentiated cell type to • Barrett’s esophagus
stem cells
another • Myositis ossificans
(Connective tissue metaplasia)
• Vit A deficiency metaplasia

Stratified squamous
epithelium

Glandular epithelium :
Goblet cells +
Hyperplasia in endometrium Atrophy of brain Barrett’s esophagus
Pathology Revision • v4.0 • Marrow 8.0 • 2024
 38 Pathology

----- Active space ----- Barrett’s Esophagus :

Etiopathogenesis :
• Seen in GERD.
• Stratified squamous Pseudo stratified columnar.
• ↑risk of adenocarcinoma of esophagus.
HPE :
• Intestinal metaplasia (Glandular epithelium).
• Goblet cells (Mucin containing). Alcian blue stain
Special stain : Alcian blue (Mucin).

Cell Injury 00:14:52

Characteristic features
• Cellular swelling/hydropic change (M/c morphological feature)

om
Reversible cell injury • Myelin figures

l.c
• M/c organelle affected : Mitochondria

ai
•
gm
Amorphous densities in mitochondria (Electron microscopy)
@

• Nuclear changes (Light microscopy) :

60

- Pyknosis : Chromatin clumping

23

Irreversible cell injury

- Karyolysis : Dissolution
ik
hv

- Karyorrhexis : Fragmentation
rit

• Myelin figures (Irreversible > reversible injury)

|
w
ro

Myelin figures
ar
M
©

Lysis of
Nucleus endoplasmic
Pyknosis reticulum Reversible Normal cell Recovery
or
injury
karyolysis Cell membrane
defects Membrane bleb
Myelin figures
Or Swelling of
Mitochondrial swelling endoplasmic
reticulum and
Karyorrhexis
Irreversible cell injury mitochondria
Reversible cell injury

Cell death 00:18:40

Process :
• Necrosis. • Necroptosis. • Ferroptosis.
• Apoptosis. • Pyroptosis. • Autophagy.

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 General Pathology : Cell Adaptations and Cell Injury 39

Necrosis : ----- Active space -----

Features Example
• Denaturation of proteins • All solid organs except brain
Coagulative • Type of dry gangrene - Heart (M/c) : myocardial infarction
(M/c) • Architecture preserved • Zenker’s degeneration
• Cell outline preserved • Burns
• Enzymatic digestion of cells • Brain
Liquefactive • Wet gangrene • Fungal infection
• Cell outline not preserved • Abscess
• Cheese-like appearance • TB
Caseous • Coagulative necrosis + • Fungal infections like histoplasmosis,
liquefactive necrosis coccidioidomycosis
• Traumatic : Breast
Fat • Enzymatic or traumatic • Enzymatic : O mentum, pancreas,
mesentery
• Pink color deposition (Fibrin-like) • PAN (type 3)

om
Fibrinoid • Type 2/type 3 hypersensitivity • Malignant hypertension

l.c
ai
reaction • Aschoff nodule (Rheumatic fever)
gm
• Dry gangrene
@

Gangrenous Limbs
60

• Wet gangrene
23
ik
hv
rit
|
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ro
ar
M

Coagulative necrosis Liquefactive necrosis Caseous necrosis : TB

©

Chalky white deposits : Fibrinoid necrosis : Gangrene

Fat necrosis Blood vessel wall
Apoptosis :
Definition : Genetically programmed cell death.
M/C organism used for apoptotic studies : C. Elegans (Nematode).
Caspases (Casp) : Apoptotic factors :
• Initiator caspases : Casp 8, 9, 10. • Pro-apoptotic : bax, bak, bim, bid, bad, PUMA, NOXA.
• Execution caspases : Casp 3, 6, 7. • Anti-apoptotic : bcl-2, bcl-x1, mcl-1.
Most important organelle affected : Mitochondria. Note : Annexin A1 : Hairy cell
Marker : Annexin V, CD-95. leukemia marker.
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 40 Pathology

----- Active space ----- Necrosis vs Apoptosis :

Necrosis Apoptosis
• Enzymatic/ischemic process • Genetically programmed cell death
• Passive process • Active process
Definition
• Death of groups of cells • Single cell death
• Always pathological • Physiological/pathological
Cell size ↑ ↓
Cell membrane Affected Intact
Inflammation Present Absent
Marker - Annexin V, CD-95
PAGE pattern Smear Step ladder
PAGE : Polyacrylamide gel electrophoresis.

Necroptosis :
Aka programmed necrosis.

om
• Mechanism : Apoptosis (But mediated by RIP 1 & 3).

l.c
ai
• Morphology : Necrosis. gm
• Seen in :
@
60

- Mammalian growth plate.

23

PAGE : Stepladder pattern

ik

- Acute pancreatitis.
hv
rit

- Neurodegenerative diseases.
|
w
ro

Pyroptosis :
ar

• Pyrogen induced apoptosis.

M
©

• Caused by fever and infections.

Entosis :
• Non macrophage cells kill other cells.
• Seen in autoimmune hepatitis.

Efferocytosis :
• Phagocytosis of apoptotic cell.
• - of pro-inflammatory cytokines.

Ferroptosis : Activates
• ↑Fe2+ levels gluthathione Lipid Loss of membrane Cell
dependent peroxidation permeability death.
defences function
• Role in cancer, stroke, neurodegenerative disease.

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 General Pathology : Cell Adaptations and Cell Injury 41

Calcification 00:36:14 ----- Active space -----

Dystrophic : Metastatic :
• Dead tissues. • Living tissues.
• Serum Ca : N .
2+
• Serum Ca2+ : ↑.
• Eg : • Eg :
- Rheumatic vegetation. - Bone disease (Multiple myeloma).
- Atheromatous plaque. Mnemonic : - Vit D related disease.
- TB lymph node. RAT - Sarcoidosis.
- Psammoma bodies. - Milk alkali syndrome.
- Parathyroid disease.

om
l.c
ai
gm
@

Von kossa (Special stain for psammoma bodies)

60

Psammoma bodies
23
ik

Pigments & Stains

hv

00:41:20
rit
|

Pigments :
w
ro
ar

Condition/pigment Microscopy Characteristics

M
©

• Black carbon pigment

Anthracosis
• M/C seen in : Lung

• Perinuclear brown pigment

• Cause : Free radical injury, aging/wear & tear
Lipofuscin
• Brown atrophy of liver/heart
• Special stain : Oil red O

• H&E : Golden yellow, brown colour

Hemosiderin • Iron overload
• Special stain : Prussian blue/Perl’s stain
H&E Prussian blue
• Black colored pigment (Derived from tyrosine)
• Special stain : Masson - Fontana
Melanin Note : Malignant melanoma
- IHC markers : Melan-A, HMB-45, S-100
- DOPA reaction +
Pathology Revision • v4.0 • Marrow 8.0 • 2024
 42 Pathology

----- Active space ----- Stains :

Accumulation H&E Special stain
Glycogen Clear vacuoles PAS
Lipid Clear vacuoles Sudan black, Oil red O
Proteins Eosinophilic, granular -
Hyaline Eosinophilic, smooth -
Calcium Basophilic, gritty Von Kossa, Alizarin red S

Cell Aging 00:49:20

Werner syndrome : Premature aging due to DNA helicase defect.

Hayflick limit : No. of times a cell divides throughout its lifespan ( N : 60-70).
Telomerase :
• Inhibits cellular aging (Immortality gene).
• Produces more telomeres.

om
l.c
• High telomerase activity : Cancer cells, stem cells, germ cells.
ai
gm
• Poor/zero activity : Somatic cells.
@

Sirtuins :
60
23

• NAD dependent protein deacetylases.

ik
hv

• ↑longevity.
rit

• Role in : Diabetes mellitus, cancer, cellular aging.

|
w

• Calorie restriction ↑lifespan (D/t ↓cellular aging).

ro
ar
M

Stains Summary 00:52:30

©

Cell/condition Stain
M/C stain in histopathology Hematoxylin & eosin
M/C in hematology Romanowsky : Leishman & Giemsa
Reticulocyte Supravital
Lymphoblast PAS
Myeloblast NSE, SBB, Oil red O, MPO
Monoblast NSE
Hairy cell TRAP
Lipid Oil red O, Sudan black
Iron Prussian blue
Calcium Von Kossa, Alizarin red S
Glycogen PAS
Copper Rhodamine, Rubeanic acid
Mast cell Toluidine blue

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 General Pathology : Cell Adaptations and Cell Injury 43

Cell/condition Stain ----- Active space -----

Mucin Mucicarmine, Alcian blue

Reticulin fibres Silver
Elastin fibres Van Gieson (VG/VVG)
Collagen Masson trichrome
Melanin Masson Fontana
H. pylori Warthins starry silver
Cryptococcus India ink
Fungi Silver methenamine (GMS), PAS
Amyloid Congo red

PAS : Periodic acid-Schiff.

NSE : Non-specific esterase.
SBB : Sudan black B.

om
MPO : Myeloperoxidase.

l.c
ai
GMS : Gomori’s methenamine stain. gm
@
60
23
ik
hv
rit
|
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ar
M
©

Pathology Revision • v4.0 • Marrow 8.0 • 2024

 44

----- Active space -----

GENERAL PATHOLOGY : INFLAMMATION
AND NEOPLASIA

Inflammation 00:01:14

Response of vascularized connective tissue to injury.

Types :
• Acute : Short, sudden, prominently neutrophilic.
• Chronic : Longer, insidious, prominently macrophage/monocyte.
Cardinal signs :
• Rubor (Redness). • Tumor (Swelling).
• Calor (↑Temperature). • Functio laesa (Loss of function).

om
l.c
• Dolor (Pain).
ai
gm
MECHANISM
@
60

Vascular Events :
23

Early transient vasoconstriction Rolling

ik
hv

(Earliest event)
rit

Adhesion
|
w

Vasodilation
ro

Transmigration/Diapedesis
ar
M

↑Vascular permeability
©

Chemotaxis
(Most critical event)
Opsonisation
Stasis (Slowing of blood flow)
(Coating of microbes)
Margination/redistribution/ Phagocytosis.
pavementing of cells
Rolling :
• Constant attachment & detachment to endothelium.
• Mediated by selectins.
Distribution on Ligands
E-Selectin Endothelium
Sialyl Lewis X modified glycoprotein
• Platelets (On Weibel Palade bodies) (And related glycans) and leukocytes
P-Selectin
• Endothelium
• GlyCAM-1
L-Selectin Leukocytes • MadCAM-1 On endothelium
• CD34
Pathology Revision • v4.0 • Marrow 8.0 • 2024
 General Pathology : Inflammation and Neoplasia 45

Adhesion : Transmigration : ----- Active space -----

Mediated by integrins. • Movement across endothelium/BM.
• β1 integrin VCAM 1. • Mediator : PECAM 1/CD31.
• β2 integrin Combines with ICAM 1.

Chemotaxis :
Move leukocytes in direction of chemical stimulus to the site of inflammation.
Source Chemoattractants
Exogenous Site of injury Bacterial cell wall products like N-Formyl methionine
• Leukotriene : LTB4
Endogenous Secreted by cell • Interleukin : IL8
• Complement factor : C5a
Opsonins :
• C3b.

om
• Serum protein (CRP).

l.c
• Fc fragment of IgG (Most potent).
ai
gm
@

Phagocytosis :
60
23

Leukocyte membrane
ik
hv

Pseudopods
rit

Receptors
|

Bacterium
w
ro

Cup shaped
ar

vesicle
M

Phagosome Phagolysosome
©

Lysosome
Kill
ing

Soluble debris
Exocytosis
Phagocytosis by leukocytes

Oxygen dependent killing : (Most potent)

O2 NADPH O2- H2O2 Cl HOCl
-
Kills bacteria.
Oxidase

Pathology Revision • v4.0 • Marrow 8.0 • 2024

 46 Pathology

----- Active space ----- LEUKOCYTE FUNCTION DEFECTS

Condition Inheritance Pathogenesis Clinical
LAD-1
Autosomal
(Leukocyte Defect in b2 integrin
recessive • Recurrent infections
adhesion defect 1)
• Delayed separation of umbilical stump
Autosomal Mutation in Sialyl lewis X
LAD-2
recessive modified glycoprotein
Chronic X-linked NADPH oxidase deficiency • Recurrent infections
granulomatous recessive (↓Oxygen dependent (Catalase positive organisms)
disease (M > F) killing) • Nitroblue tetrazolium test (NBT)
Pentad of symptoms :
1. Fever, recurrent infections
2. Albinism
3. Thrombocytopenia
4. Deafness (SNHL)

om
Chediak-Higashi Autosomal LYST defect (Required for 5. PS : Giant granules in neutrophils

l.c
syndrome recessive phagolysosome fusion)

ai
gm
@
60
23
ik
hv
rit

Note : Sepsis
|
w
ro

• Toxic granules.
ar

• Dohle bodies : Patches of dilated endoplasmic reticulum.

M
©

NEUTROPHIL EXTRA CELLULAR TRAPS (NET)

• Extracellular fibrillar meshwork by neutrophils at site of infection.
• High concentration of antimicrobial substance Prevent spread of microbes.
• Arginine required for production.
Note : Arginine NO production also.

EMPERIPOLESIS
• Cell within cell appearance.
• Cell inside is viable : Can exit w/o structural or
functional change.
• Seen in : NHL, Rosai Dorfman syndrome,
hematolymphoid disorders.

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 General Pathology : Inflammation and Neoplasia 47

Mediators of Inflammation 00:28:06 ----- Active space -----

Cell derived : Plasma derived :

• Histamine. • Chemokines. • Coagulation.
• Serotonin. • Cytokines. • Kinin.
• PAF. • Prostaglandins. • Complement.
• NO. • Leukotrienes.
Mediator Produced from Function

Histamine • Vasodilation
Mast cell : Toluidine blue • ↑Permeability

om
(Metachromatic)

l.c
Serotonin Platelets

ai
gm
• Platelets • ↑Platelet aggregation.
Platelet activating
@

• Endothelial cells • Bronchoconstriction, Vasoconstriction.

60

factor (PAF)
• Leukocytes • ↑Permeability.
23
ik
hv

NO/EDRF Arginine • Vasodilation.

rit

(Endothelium derived NO synthase cGMP • Smooth muscle relaxation.

|

Pathway
w

relaxation factor) NO • - platelet aggregation.

ro
ar
M

CYTOKINES
©

Phospholipid bilayer

- Steroid drugs
Montelukast Phospholipase A2 - Synthesis
- Interaction
with receptor Arachidonic acid

-
Lipoxygenase (LOX) Cyclooxygenase (COX) Aspirin
- COX1, COX2 - synthesis

Leukotrienes : Lipoxins Prostaglandins Prostacyclins Thromboxane

• LTB4 Chemotaxis (LxA4/B4) : (PGD2/E2) : (PGI2) : (TXA2) :
• LTC4, D4 E4 - Inflammation • Vasodilation • Vasodilation • Vasoconstriction
- Bronchospasm • ↑ Vascular • - platelet • + platelet
- ↑ Vascular permeability aggregation aggregation
permeability • Pain, fever

Pathology Revision • v4.0 • Marrow 8.0 • 2024

 48 Pathology

----- Active space ----- Function Cytokine

Pro-inflammatory IL 1, 2, 4, 6, 8, IFN gamma, TNF alpha
Anti-inflammatory IL 4, 6, 10, TGF beta
Both pro & anti IL 4, 6
Cancer cachexia TNF alpha
Granuloma formation IFN gamma, IL-12
Fibrosis TGF beta, PDGF
Angiogenesis VEGF
Fever IL 1
Eosinophil activation IL 5

CHEMOKINES
CXC Chemokines CC Chemokines C Chemokines CX3C Chemokines

om
AKA α Chemokine β Chemokine γ Chemokine δ Chemokine

l.c
ai
gm
• Eotaxin : Eosinophils
Specific Lymphotaxin : Monocytes and
@

IL-8 : Neutrophils • MCP-1 : Monocytes

60

for Lymphocytes T-cells

• MIP-1α : Macrophages
23
ik
hv

COMPLEMENT
rit
|

• C3a, C5a : Anaphylotoxins/Type I HS/Allergic.

w
ro

• C3b : Opsonin.
ar
M

• C5a : Chemotaxis.
©

• C5b-9 : Membrane attack complex (MAC).

Chronic Inflammation 00:39:52

Cardinal cell : Macrophage/monocyte

Lymph node Liver Placenta

Kupffer cells
Sinus histiocyte
Osteoclast Tissue Hofbauer cell
Bone macrophages PS : Macrophage
Mesangial cells • Largest cell
Pulmonary alveolar • Horseshoe/reniform nuclei
macrophages/ Littoral cells Microglia Kidney
Lungs Dust cells
Brain
Spleen

EM : Monocyte
Pathology Revision • v4.0 • Marrow 8.0 • 2024
 General Pathology : Inflammation and Neoplasia 49

GRANULOMA ----- Active space -----

Components :
Collection of :
1. Epitheloid cells (Hallmark) : 2. Surrounded by collar of lymphocytes.
- Modified/activated 3. Giant cells : D/t fusion of epitheloid
macrophages. cells.
- Slipper shaped nucleus. 4. Caseous necrosis.

Slipper
Epitheloid cells shaped
nuclei
Caseous
necrosis Giant cells

om
Lymphocyte
cells

l.c
Granuloma Microscopy

ai
gm
Types of giant cells :
@
60

Morphology Clinical condition

23
ik

Horse shoe/peripheral arrangement

hv

Langhans giant cells Tuberculosis

rit

of nuclei
|

Foreign body giant cell Haphazard arrangement of nuclei Foreign body

w
ro

Tumor giant cell Haphazard arrangement of nuclei -

ar
M

Reed Sternberg (RS) cell Owl’s eye appearance Hodgkin’s lymphoma

©

Touton giant cell - Xanthoma (Lipid tumour)

Aschoff giant cell - Rheumatic heart disease
Intracytoplasmic/Intranuclear
Warthin Finkeldey cell Measles
inclusions

Langhan’s giant cell Tumor giant cell Reed sternberg cell Touton giant cell

Pathology Revision • v4.0 • Marrow 8.0 • 2024

 50 Pathology

----- Active space ----- GRANULOMATOUS DISEASES

• TB. • Syphilis. Key
• Fungal (Histoplasmosis/ • Cat scratch disease. : Caseating granuloma
Coccidiomycosis). • Wegener’s granulomatosis. : Non-caseating, naked
• Sarcoidosis. • Crohn’s disease. granuloma
• Lympho granuloma venerum. • Berylliosis.
• Leprosy. • Chronic granulomatous disease.
Tuberculosis : Sarcoidosis :
Granuloma
• Non-caseating.
• Naked granuloma
Giant cell
(No lymphocytic
Lymphocyte collar).
collar • Asteroid bodies.

om
Caseating necrosis Granuloma • Schaumann bodies.

l.c
ai
(Cheesy appearance) gm
@

Note : Granuloma.
60
23

• Important cytokine for formation : IFN gamma, IL-12.

ik

• Hypersensitivity : Type IV.

hv
rit
|

GRANULATION TISSUE
w
ro
ar
M

Neovascularisation
©

(Cardinal sign)

Wound Healing 00:49:34

TYPES
Healing by 1o intention/ Healing by 2o intention/
1o reunion 2o reunion

Appearance Clean Lacerated

Infection Uninfected Infected
Margins Apposed Irregular
Tissue loss Absent Present
Road traffic accident
Example Surgical incision
wounds Primary Secondary

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 General Pathology : Inflammation and Neoplasia 51

STEPS IN WOUND HEALING ----- Active space -----

Time Events
0 hours Incision filled with blood clot.
<24 hours Neutrophils from margins infiltrate clot.
• Dense neutrophil infiltrate.
24-48 hours
• Continuous, thin, shiny layer of epithelium formed below scab.
• Neutrophils replaced by macrophages.
Day 3 • Early granulation tissue.
• Collagen : At margin of incision.
• Abundant granulation tissue Maximum neovascularisation
Day 5
• Collagen : Bridge incision.
• Fibroblastic proliferation.
2nd week • Collagen accumulation.
• ↓Inflammation ↓Edema.
3rd week Scar formation.

om
A wound never regains its full tensile strength (70-80%).

l.c
ai
gm
Neoplasia 00:52:26
@
60
23

PROPERTIES
ik
hv

Property Benign Malignant

rit

- +
|

1. Anaplasia
w

Most definitive marker :

ro

2. Rate of growth Slow Rapid

ar

Metastasis >> Local invasion.

M

- +
3. Local invasion
©

(Encapsulated) (Non-encapsulated)
4. Metastasis
- +
(Distant spread)
ANAPLASIA
• Pleomorphism (Size & shape).
• High N:C ratio of 1:1 ( N is 1:4).
• Hyperchromatic nuclei.
• Prominent nucleoli.
• Loss of polarity.
• Abnormal mitosis.
Anaplasia
METASTASIS

Lymphatic Hematogenous Direct seeding

(Most carcinomas) (Most sarcomas) (Pseudo myxoma peritonei)

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 52 Pathology

----- Active space ----- Cell changes :

Metaplasia Dysplasia Anaplasia Desmoplasia
Change Reversible Partially reversible Irreversible -
• Disordered growth
One differentiated cell Lack of Dense fibrosis
Definition or proliferation
type Another type differentiation in a tumor
• Intact BM
Example Barrett's esophagus Ca in situ - -

HALLMARKS OF CARCINOGENESIS
• Self-sufficiency in growth signals. • Sustained angiogenesis.
• Insensitivity to growth inhibitory • Altered cellular metabolism.
signals. • Invasion and metastasis.
• Limitless replicative potential. • Escape of immune recognition.
• Evasion of apoptosis.

om
ONCOGENES TUMOR SUPRESSOR GENE

l.c
Gene Cancer Gene Chromosome Tumors
ai
gm
C kit GIST • Retinoblastoma
@

Rb 13q
60

RET • Medullary Ca thyroid • Osteosarcoma

23

(Chr 10) • MEN II p53 : M/c 17p Li Fraumeni syndrome

ik
hv

• ALCL • Neurofibromas
rit

• Adeno Ca lung NF-1 17

• Optic nerve gliomas
|

ALK
• Inflammatory
w

• Schwannoma
ro

myofibroblastic tumor NF-2 22

ar

• Meningioma
M

ABL CML • Breast Ca

©

K-RAS Colon Ca, pancreatic Ca BRCA-1 17

• Ovarian Ca
M/c H-RAS Bladder Ca • Male & female breast Ca
BRCA-2 13
N-RAS Melanoma • Prostate Ca
C-MYC Burkitt’s lymphoma WT-1
11 Wilm’s tumor
L-MYC Small cell lung Ca WT-2
N-MYC Neuroblastoma PTEN (Cowden • Endometrial Ca
syndrome) 10
NOTCH T-ALL • Prostate Ca
• Clear cell RCC
VHL 3
• Cerebellar hemangiobastoma
• FAP
APC 5
• Colorectal cancer
• Basal cell carcinoma
PTCH -
• Gorlin syndrome
• Gastric adenocarcinoma
CDH 1 - (Diffuse type)
• Invasive lobular carcinoma breast

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 General Pathology : Inflammation and Neoplasia 53

TUMOR MARKERS ----- Active space -----

Marker Condition
PSA
Prostate Ca
PAP
Note :
Calcitonin Medullary Ca thyroid
• PSA, PAP :
CEA Colon Ca, pancreatic Ca ↑ In other
- Organ specific.
hCG Choriocarcinoma - Not tumor specific. prostatic diseases
Hepatocellular Ca, • Medullary Ca thyroid
AFP NSGCT like yolk sac
tumour, hepatoblastoma
Amyloid (A-Cal)
Immunoglobulins Multiple myeloma
CA 19-9 Colon Ca, pancreatic Ca
• GIST : M/c mesenchymal tumor of stomach
CA 125 Ovarian Ca

om
CA 15-3 Breast Ca

l.c
Catecholamines Phaeochromocytoma
ai
gm
IHC MARKERS
@
60

Cell of origin/Tumour Marker

23
ik

Epithelial origin (Carcinoma) Cytokeratin (CK)

hv
rit

Mesenchymal origin (Sarcoma) Vimentin

|
w

Glial GFAP
ro
ar

Smooth muscle (Leiomyoma) SMA, Vimentin

M
©

Skeletal muscle (Rhabdomyoma) Desmin, myogenin, Myo D1 (More specific)

Vascular (Angiosarcoma) VwF, CD31, VEGF
Neuroendocrine NSE, chromogranin, synaptophysin
Hepatic Hep par 1, Arginase 3
GIST DOG1 (Most Specific) > c-kit/CD-117 > CD-34
Malignant melanoma Hmb 45, S 100, Melan A
Malignant mesothelioma Calretinin, CK 5/6
Ewing’s sarcoma CD99, MIC 2
Osteosarcoma Osteopontin, Osteonectin, Osteocalcin
Markers for unknown primary : CK 7, CK 20 profile.
CK 7 CK 20 Cancer
+ve +ve Bladder Ca, stomach Ca, pancreatic Ca
-ve -ve Hepatocellular Ca, renal cell Ca
+ve -ve Cancers of female genital tract, cervix, endometrium, breast, lung & thyroid
-ve +ve Colorectal Ca
Pathology Revision • v4.0 • Marrow 8.0 • 2024
 54 Pathology

----- Active space ----- Paraneoplastic syndromes 01:08:21

Symptom complexes in cancer patients that cannot be explained by local/

indigenous spread.
Syndrome Tumour Substance
• SCC lung. Parathyroid hormone
Hypercalcemia (M/c)
• Breast Ca. related peptide (PTHrP)
SIADH (Syndrome of
ADH
Inappropriate secretion of ADH) Small cell Ca of lung :
Hypertrophic pulmonary Causes maximum
-
osteoarthropathy paraneoplastic syndromes.
Cushing’s syndrome ACTH
Polycythemia RCC Erythropoietin
• Ca pancreas.
Migratory thrombophlebitis -
• Ca colon.

om
Acanthosis nigricans • Ca stomach Epidermal growth

l.c
ai
(Velvety thickening of skin folds) • Ca colon
gm factor
• Thymoma
@

Myasthenia gravis -
60

• Ca lung
23
ik

CHEMICAL CARCINOGENESIS
hv
rit

Chemical Cancer
|
w

Polycyclic aromatic hydrocarbons (PAH) Lung Ca

ro
ar

Arsenic Skin Ca, hepatic angiosarcoma

M
©

• Lung adenocarcinoma : M/C.

Asbestos
• Malignant mesothelioma : Most specific
Aflatoxin HCC
Beta naphthylamine/Azo dyes Bladder Ca
Benzene Leukemia, AML
Diethylstilbestrol (In mother) Clear cell Ca vagina
Polyvinylchloride (PVC) Hepatic angiosarcoma
Cadmium Prostate Ca

MICROBIAL CARCINOGENESIS
Microbe Protein Cancer
• Gastric adenocarcinoma (M/c)
H. pylori Cag A
• MALToma (More specific)
• Cervical Ca
E6 (+ p53)
HPV • Anogenital Ca
E7 (+ Rb)
• Laryngeal Ca
HTLV 1 Tax Adult T cell leukemia

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 General Pathology : Inflammation and Neoplasia 55

Microbe Protein Cancer ----- Active space -----

HBV HBx Hepatocellular Ca

• Kaposi’s sarcoma
HHV 8 - • Primary effusion lymphoma
• Multicentric Castleman’s disease
• HL
• NHL
LMP 1 • Burkitt’s lymphoma
EBV
EBNA 2 • Nasopharyngeal Ca
• Post transplantation
lymphoproliferative disease

Note : Hodgkin’s lymphoma not a/w EBV.

Nodular lymphocyte predominant HL > Nodular sclerosis.

IMAGES

om
Squamous cell cancer : Adenocarcinoma :

l.c
ai
gm
• Keratin pearls
@
60

• Desmosomes
23

• IHC CK
ik
hv
rit
|
w

Glands lined by
ro

pleomorphic cells
ar
M
©

Mucinous cancer :

Mucin
(Extracellular)

Signet ring cells

(Intracellular
mucin)

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 56 Pathology

----- Active space ----- Small round blue cell tumors :

Tumor cell in
rosettes (Flower)

• Neuroblastoma. • Retinoblastoma : Flexner Wintersteiner

• Hepatoblastoma. rosette.
• Nephroblastoma/Wilm’s tumor. • Medulloblastoma.
• Rhabdomyosarcoma. • Ewing’s sarcoma/PNET Homer Wright
• Lymphoma. Rosette.

om
Papillary lesion : Cribriform pattern :

l.c
ai
gm
• Finger like Swiss
@

cheese
60

projection
23

• Fibrovascular core like

ik
hv

• Psamomma bodies
rit

common
|
w
ro
ar
M

Eg : Breast, thyroid Eg : Adenoidcystic Ca salivary gland

©

Neuroendocrine pattern : Coffee bean nuclei :

Nuclei with
Salt & pepper longitudinal
chromatin groove

• Pheochromocytoma (Zell Ballen pattern). • Papillary Ca thyroid.

• Carotid body tumor. • LCH.
• Paraganglioma. • Brenner’s tumor.
• Neuroblastoma. • Chondroblastoma.
• Small cell lung Ca. • Granulosa cell tumor.
• Carcinoid tumor.
(EM : Dense core neurosecretory granules)
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 General Pathology : Immunity 57

GENERAL PATHOLOGY : IMMUNITY ----- Active space -----

Hypersensitivity Reactions 00:00:44

Types : Type I, Type II, Type III, and Type IV hypersensitivity (HS) reactions.

Examples
Type I/Anaphylactic Type II/Antibody-mediated
Mnemonic : ABCD Mnemonic : My Blood Group Is Rh Positive
• Allergy/Atopy
• Myasthenia gravis
• Bronchial asthma • Immune hemolytic anemia
• Blood transfusion reaction

om
• Casoni’s test • Rheumatic fever

l.c
• Graves’ disease
• •
ai
Drug reaction (Any) gm Hyperacute graft rejection
• Goodpasture syndrome
• Hay fever • Pernicious anemia
@

• Immune thrombocytopenic
60

• Food allergy • Pemphigus vulgaris

23

purpura
• PK reaction
ik
hv
rit
|

Important features
w
ro
ar

Type I HS Type II HS
M
©

• Earliest mediator released : Histamine

(Vasodilation, ↑vascular permeability)
• Fixed antibodies
• Most important :
• Type V HS :
- Cell in Type I HS : Mast cells
- Modification of Type 2 HS
(Stained using : Toluidine blue)
- Antibodies against receptors +
- Cell in late phase : Eosinophil
- Eg : Graves’ disease, myasthenia gravis
- Antibody : IgE
- Cytokine released : IL-4, IL-5

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 58 Pathology

----- Active space -----

Examples
Type III/Immune complex mediated Type IV/delayed/cell mediated
Circulating antibodies -
• Tuberculin test
• Lepromin test
Mnemonic : SHARP • Sarcoidosis
• Serum sickness • Granuloma
• SLE (Visceral lesions : Type 3 HS & • Acute and chronic graft rejection
Hematological lesions : Type 2 HS) • Contact dermatitis
• Shick test • Rheumatoid arthritis (Type 4 > Type 3)
• Henoch Schonlein Purpura (HSP)
• Arthus reaction (Localized immune

om
complex disorder)

l.c
• Reactive arthritis
ai
gm
• Post-streptococcal Glomerulonephritis
@

Epithelioid cells
60

(PSGN) (Slipper shaped

23

• Polyarteritis Nodosa (PAN)

ik

nucleus)
hv
rit

Granuloma : Type IV HS
|
w
ro
ar

Transplant Pathology
M

00:12:56
©

Types of grafts Transplantation

Autograft Within the same body ; no rejection
Syngeneic/Isograft B/w identical twins

Allograft B/w different individuals of same species

Xenograft B/w different species

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 General Pathology : Immunity 59

Major Histocompatibility Complex (MHC)/Human Leukocyte Antigen (HLA) : ----- Active space -----
• Gene located on : Chromosome 6p (Short arm).
• HLA matching done prior to transplantation.

MHC 1/HLA 1 MHC 11/HLA 11

All nucleated cells of Only on antigen presenting cells
Location
body and platelets (APC)
DP, DQ, DR (Most important loci
Encoded by (Loci) A, B, C
for matching)
Structure a1, a2, a3, b2-microglobulin a1, b1, a2, b2

Antigen (Ag) binding cleft B/w a1 and a2 B/w a1 and b1

Presents Ag to CD 8 lymphocytes CD 4 lymphocytes

om
Graft-versus-host disease
Role Graft rejection

l.c
(GVHD)
ai
gm
@

Transplant Rejections :
60
23

Type Onset Mechanism + vessel histology Types of HS

ik
hv
rit

• Preformed antibodies
|
w

(Previous Rh/ABO blood

ro
ar

Hyperacute Immediate or < 48 hrs group incompatibility) II

M

• Thrombosis + Occlusion of
©

graft vessels
• T cell mediated response
Host vs. graft

Acute (M/c) :
• Inflammation + Leucocyte Humoral : II
• Humoral Weeks - months
infiltration of graft vessels Cellular : IV
• Cellular
• Tubulitis, endotheliitis
• T cell mediated (Foreign
MHC ‘looks like' self MHC
Chronic Months - years carrying Ag) III & IV
• Intimal thickening + Fibrosis
of graft vessels

GVHD : Organs affected Skin, GIT, Liver.

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 60 Pathology

----- Active space ----- Important Autoantibodies 00:22:57

Disease Antibody
Most specific for SLE Anti ds-DNA, Anti-Smith
Most sensitive for SLE Anti nuclear (ANA)
Drug induced Lupus Anti-histone
Neonatal lupus Anti Ro
Diffuse scleroderma Anti scl-1
Limited scleroderma (CREST Syndrome) Anti centromere antibodies
Inflammatory myopathies Anti-Jo 1
Sjogren Syndrome Anti Ro (SS-A), Anti La (SS-B)

om
l.c
ANA pattern on
ai
Antibodygm Associated disease
immunofuoroscence(IF)
@
60

• Anti ds-DNA • SLE

Homogenous
23

• Anti histone • Drug induced lupus

ik
hv
rit

• Anti Smith
• SLE
|
w

Speckled (Nuclear dense) • Anti SS-A

ro

• Sjogren’s syndrome
ar

• Anti SS-B
M
©

Diffuse Systemic sclerosis/

Nucleolar (Clumpy) Anti-RNAP
scleroderma
• SLE
Centromeric Anti ds-DNA • Limited systemic sclerosis/
scleroderma

Homogenous Speckled Nucleolar Centromeric

pattern pattern pattern pattern

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 General Pathology : Immunity 61

Immunodeficiency Disorders 00:27:45 ----- Active space -----

Disorder Defect Clinically

• BTK (Bruton Tyrosine
Kinase) gene defect
Bruton’s agammaglobulinemia :
• B cell defect : • Recurrent sinopulmonary
• Boys >> Girls
- Defective humoral infections
• X-linked recessive
immunity
- Germinal centres -

• Defect in TBX 1 gene

DiGeorge Syndrome • Mnemonic : CATCH 22
• T cell defect

• X-linked recessive : Mutation

om
Severe Combined in common gamma chain of
• Diaper rash

l.c
Immunodeficiency disorder cytokine receptors
ai
gm • Oral candidiasis
(SCID) • Autosomal recessive : ADA
@

deficiency
60
23
ik
hv

Common variable • BAFF gene : B cell defect

• Recurrent sinopulmonary
rit

Immunodeficiency disorder • ICOS gene : T cell defect

|

infections
w

(CVID) • Hypogammaglobulinemia
ro
ar
M
©

Hyper IgM Syndrome : • CD40L / CD40 defect

• Recurrent bacterial infections
• X linked recessive • Defect in class switching
• ↑risk of pneumocystis carinii
• M>>F • ↑IgM without IgG, IgA, IgE

• Mucosal immunity affected

Isolated IgA deficiency ↓ IgA production • ↑Sinopulmonary infections
• Give washed RBCs always
Wiskott Aldrich Syndrome : • Mnemonic : TIE
• X linked recessive WASP gene defect on Xp 11.23 (Thrombocytopenia,
• M>>F Infections, Eczema)
• Ataxia
• ATM gene defect on
Ataxia telangiectasia : • Telangiectasia
chromosome 11
Autosomal recessive • Neurological problems
• B + T cell defect
• Tumors

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 62 Pathology

----- Active space -----

DiGeorge Syndrome Wiskott Aldrich Syndrome

Mnemonic : CATCH 22 Mnemonic : WAITER
• Cleft lip/cleft palate • Wiskott / WASP gene
• Abnormal facies • Aldrich
• Thymic hypoplasia • Immunodeficiency disorder
• Cardiac defects : • Thrombocytopenia
Fallot's tetralogy • Eczema
• Hypocalcemia : • Recurrent infections
Parathyroid hypoplasia
• del 22q11

om
l.c
ai
gm
@
60
23
ik
hv
rit
|
w
ro

Cleft lip Cleft palate del 22q 11

ar
M
©

Amyloidosis 00:37:20

Proteinaceous, extra-cellular, homogenous pink deposition.

Physical Nature :
a) Electron microscopy : b) X-ray crystallography

Cross beta pleated

sheet

Non-branching fibrils : 7.5-10 nm

Apple green
birefringence on
polarizing lens
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 General Pathology : Immunity 63

Disease/condition Types of amyloid ----- Active space -----

Primary amyloidosis (Light chain disorders : Multiple myeloma) AL

Secondary amyloidosis
AA (From liver)
(Chronic inflammatory disorders : Rheumatoid arthritis)
Familial Mediterranean fever AA/Apyrin
Familial amyloidotic polyneuropathy ATTR
Senile/Cardiac amyloidosis (TTR : Transthyretin)
Chronic Renal failure/long term dialysis Ab2 microglobulin
Prion disease Apr
Diabetes mellitus AIAPP
Medullary carcinoma thyroid ACal (Calcitonin)
Alzheimer's disease Ab
Effect on Organs :
• M/c organ affected : Kidney.

om
• Part of liver affected : Space of Disse.

l.c
ai
• Clinical condition developed in heart : Restrictive cardiomyopathy.
gm
@

Spleen :
60

• Sago Spleen : Splenic follicles affected

23
ik

(Looks like white sago grains in spleen).

hv
rit

• Lardaceous spleen : Splenic sinuses affected

|
w

(Large geographical map-like areas + ).

ro
ar

Staining : Sago spleen

M
©

Gross staining : Lugol’s iodine.

Other stains : Salmon pink appearance Apple green birefringence

Glomerulus

Amyloid :
Homogenous, pink
material
H & E staining of kidney Congo red staining Polarizing lens
Best stain : Congo red under polarizing lens.
M/c biopsy site :
• Abdominal fat pad aspirate. • Tongue
• Rectum. (In macroglossia).
M/c Cause of Death :
• 10 amyloidosis Cardiac failure.
• 20 amyloidosis Renal failure. Acal deposition in thyroid
Pathology Revision • v4.0 • Marrow 8.0 • 2024
 64

----- Active space ----- GENERAL PATHOLOGY : GENETICS

Mendelian models of inheritance :

Autosomal dominant Autosomal recessive X linked recessive X linked dominant

Autosomal Dominant 00:01:27

• M = F : Autosomes affected.
• Can be expressed in heterozygous state.
(Homozygous dominant is incompatible with life).

Pathology : Defect in structural proteins. (Collagen, elastin, fibrillin).

om
l.c
ai
gm
@
60
23
ik
hv
rit
|
w
ro

Pedigree chart : Autosomal dominant

ar
M
©

Properties :
• Incomplete penetrance : Genetic defect not manifested clinically each time
d/t heterozygotic state (Aa).
• Variable expressivity : Clinical features are variably expressed.

Examples :
Mnemonic : He Has A Very DOMINANT Father.
• Huntington’s disease. • Intermittent porphyria.
• Hereditary spherocytosis : Defect in • Neurofibromatosis-1 .
ankyrin/spectrin of RBC membrane. • Autosomal Dominant Polycystic
• Achondroplasia. kidney Disease.
• Von Willebrand disease. • Neurofibromatosis-2 .
• Von Hippel Lindau syndrome. • Tuberous sclerosis.
• Dystrophia myotonica. • Familial Adenomatous Polyposis (FAP).
• Osteogenesis Imperfecta. • Familial hypercholesterolemia.
• Marfan’s syndrome.
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 General Pathology : Genetics 65

MARFAN’S SYNDROME ----- Active space -----

Defect in Fibrillin-1 gene on chromosome 15.
Tall stature.
Clinical Presentation : Dolichocephalic head.
Skeletal defects
Hyperextensible joints
Long fingers.

Ocular defects : CVS defects :

Ectopia lentis : Superotemporal • Mitral valve prolapse : M/c CVS defect.
dislocation of lens • Aortic dissection : M/c cause of death.

Autosomal Recessive :  00:08:15

om
• M=F : Autosomes affected.

l.c
ai
• Only expressed in homozygous state (Heterozygous state : Carrier).
gm
@
60

Examples : Mnemonic ABCDEFGHI

23
ik
hv
rit

• Ataxia. • Emphysema.
|
w

• Alpha-1 antitrypsin • Friedreich’s ataxia.

ro
ar

deficiency. • Gaucher’s disease.

M

• Alkaptonuria. • Glycogen storage

©

• β-Thalassemia. disorders.
• Congenital adrenal • Hemochromatosis.
PKU heterozygote (Carrier) hyperplasia. • Homocystinuria.
PKU homozygote • Cystic fibrosis. • Inborn errors of
Pedigree chart of autosomal recessive • Deafness. metabolism.

Note :
Enzyme deficiencies which are not AR :
• G6PD deficiency.
X-linked recessive
• Fabry’s disease.

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 66 Pathology

----- Active space ----- Autosomal dominant vs autosomal recessive :

AD AR
Expressed in Homozygous & heterozygous Homozygous
Age of onset Adult Childhood
Penetrance Incomplete Complete
Skip generations Absent Present
Pathology Structural protein defects Enzyme deficiencies

Tay Sach’s Disease :

Mnemonic : TAYSACHS
• Autosomal recessive.
• Young adults affected.
• Cherry red spot in macula.
• Ashkenazi Jews.

om
• CNS abnormalities.

l.c
• Hexosaminidase A
ai
gm
deficiency.
@
60

• Onion skin appearance. Onion skin appearance on electron microscopy Ballooned neurons on brain biopsy
23
ik

Note : Onion skin appearance

hv
rit

a. Malignant hypertension
|

Biopsy
w

b. 1˚ Sclerosing cholangitis
ro
ar

c. Chronic Inflammatory Demyelinating

M

Polyneuropathy (CIDP) : Nerve biopsy.

©

d. Spleen in SLE : Gross appearance.

e. Ewing’s sarcoma : X-ray.
f. Tay-Sachs disease : EM.

Gaucher’s Disease :

Gaucher’s cells Stains : PAS, oil red O +ve.

Crumpled tissue paper appearance
of cytoplasm.
Note : Pseudo-Gaucher’s cells (Seen in CML).
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 General Pathology : Genetics 67

Neimann Pick Disease : ----- Active space -----

Electron microscopy : Zebra bodies

X-Linked Recessive 00:16:44

• M >> F.
• Females are usually carriers.

Examples :

om
Mnemonic : Lady Hardinge College Girls Dont Care About Foolish Words.

l.c
ai
gm • Lesch Nyhan syndrome.
@

• Hemophilia A & B.
60
23

• Hunter’s disease.
ik

•
hv

Colour blindness.
rit

• G6PD deficiency.
|
w

• Duchenne muscular dystrophy.

ro
ar

• Chronic granulomatous disease.

M
©

• Agammaglobulinemia (Bruton’s).
Pedigree chart of XLR • Fabry’s disease.
• Fragile X syndrome.
• Wiskott Aldrich syndrome.

X Linked Dominant 00:18:53

• Extremely rare.
• Mother affects both sons and daughters.
• Father affects only daughters (Not sons).
Examples :
Mnemonic : RAVI.
• Rett’s syndrome. • Vitamin D resistant rickets.
• Alport syndrome : Follows all modes of • Incontinentia pigmenti.
inheritance (M/c is XLD).

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 68 Pathology

----- Active space ----- Barr Body :

Female genotype
XX
Active Inactive
Barr body
• Drum stick appearance.
• Sample : Buccal mucosa.

Indications for barr body examination :

Turner’s syndrome (XO) : NO barr body.
klinefelter syndrome (XXY) : ↑barr body. Barr body

Non-Mendelian Modes of Inheritance 00:23:30

om
MITOCHONDRIAL INHERITANCE

l.c
ai
• Exclusive maternal inheritance. gm
• M/c affected organs : Brain, eye, skeletal muscle (D/t ↑no. of mitochondria).
@
60

• Heteroplasmy : mutation of mitochondrial DNA.

23
ik
hv
rit
|
w
ro
ar
M
©

Pedigree chart

Examples :
• Mitochondrial encephalopathy, lactic acidosis, stroke-like episodes (MELAS).
• Leigh syndrome.
• Leber’s hereditary optic neuropathy.
• NARP syndrome (Neurogenic ataxia & retinitis pigmentosa).
• Chronic progressive external ophthalmoplegia (CPEO).

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 General Pathology : Genetics 69

TRINUCLEOTIDE REPEAT MUTATIONS ----- Active space -----

Codon :
• Sequence of 3 nucleotides.
• Normal individuals : Repeats are fixed in number.
• Mutations : Exponentially ↑ number of repeats.

Examples :
Diseases Repeats
Huntington’s chorea CAG
Myotonic dystrophy CTG
Friedreich’s ataxia GAA
Fragile X syndrome CGG

Anticipation : ↑Disease severity in successive generations.

Fragile X Syndrome :

om
X-linked recessive (M >> F).

l.c
ai
Pathogenesis : Mutation of FMR-1 (Familial Mental Retardation) gene
gm ↑CGG
@

repeats.
60
23

P
ik

Seen in Number of CGG repeats

hv
rit

Normal individuals 40-50

|

q
w

Pre - mutation (Carrier) 50-200

ro

Fragile
ar

Full mutation (Clinical manifestations present) 200-4000 site

M

Normal X chromosome Fragile X chromosome

©

Cells cultured in folate deficiency media Develop C onstriction in long arm of

X-chromosome “Fragile” X.
Clinical features :
• Large head.
• Large everted ears.
• Large mandible.
• Large testes (Macro orchidism).
• Mental retardation (2nd most common genetic cause).
Note : Down syndrome (M/c genetic cause of mental retardation).
Fragile X associated 1˚ ovarian failure :
Permutation in CGG + Fragile X tremor/ataxia.

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 70 Pathology

----- Active space ----- GENOMIC IMPRINTING

Gene silencing/imprinting 1 functioning allele + 1 non-functioning allele.

Examples :
Prader Willi syndrome Angelman syndrome
Chromosome 15
Gene
SNORP UBE3A
Silencing Maternal Paternal
Deletion Paternal Maternal
Pathology
Disomy Maternal Paternal
Small, fat kid : AKA Happy puppet syndrome :
• Small bird like head • Seizures
• Hyperphagia Obesity • Ataxia
Clinical features
• Mentally retarded • Mental Retardation
• Respiratory problems • Inappropriate laughter

om
• Short life span • Microcephaly

l.c
ai
gm
@
60
23
ik
hv
rit
|
w
ro
ar
M
©

Phenotype Karyotype : Deletion in chr. 15

Prader - Villi syndrome Angelman syndrome

Pedigree Analysis 00:35:00

1. Rule out mitochondrial inheritance/gonadal mosaicism/Y-linked.

2. Rule out dominant/recessive : Skip generation.

Present Absent

Recessive Dominant

M=F M >> F Father to son transmission

Autosomal X-linked Present Absent

+
Autosomal 100% daughters affected

X-linked
Pathology Revision • v4.0 • Marrow 8.0 • 2024
 General Pathology : Genetics 71

X-linked recessive : Skip generation + ----- Active space -----

M >>> F

Mitochondrial inheritance :

Maternal Paternal

om
transmission transmission

l.c
ai
gm
@

All affected None affected

60
23

Chromosomal Disorders 00:37:47

ik
hv

Down’s Syndrome :
rit
|

Trisomy 21 (M/c : Meiotic non-dysjunction).

w
ro
ar

Clinical feature :
M
©

Mental retardation
(M/c genetic cause) Broad flat face
Growth failure Slanting eyes
Epicanthic eyefold
Flat back of head Short nose Down’s syndrome
Abnormal ears
Oblique palpebral fissures
Single palm crease Complications :
Short and broad hands
(Simian crease) 1. Cardiac :
Small and - M/c cardiovascular defect :
Unilateral or bilateral
arched palate Endocardial cushion defect
absence of one rib
Big, wrinkled tongue - VSD
Intestinal blockage Dental anomalies 2. GIT :
Umbilical hernia Congenital heart disease - Hirschsprung disease
Enlarged colon - Duodenal atresia
Abnormal pelvis (D/t Hirschsprung disease) - Intestinal obstruction
Diminished muscle tone 3. ↑Risk :
Big toes widely spaced
- Pre-mature Alzheimer’s
(Sandal gap)
- Acute leukemia (AML : M7)
Note : 2nd m/c genetic cause (Mental retardation) Fragile X syndrome.

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 72 Pathology

----- Active space ----- Edward Syndrome : Patau Syndrome :

Trisomy 18 Trisomy 13
Micrognathia Prominent occiput
Mental retardation Microcephaly
Low set ears
Short neck Microphthalmia
Overlapping Cleft lip and
fingers palate

CVS defects
Patent ducts arteriosus (M/C) Polydactyly
Renal
malformations Umblical hernia
Renal defects
Limited hip
abduction
Rocker bottom
feet

om
l.c
ai
Turner’s Syndrome vs. Klinefelter’s Syndrome : gm
@

Turner's Syndrome Klinefelter’s Syndrome

60
23

Definition Loss of one X chromosome Extra X chromosome

ik
hv

Phenotype Female Male

rit

Karyotype 45 XO 47 XXY, 47 XXXY

|
w

Barr bodies - Extra +

ro
ar

Mnemonic : CLOWNS
M

• Tall stature
©

• Cardiac defects • Small Webbed neck. • Poor muscle tone

Clinical (Co-arctation of aorta) • Nipples widely • ↓ 2° sexual characteristics
features • Cystic hygroma. spaced. • Gynaecomastia
• Lymphedema. • Short stature. • Small testis/infertility
• Ovary streaked/small. • Short 4th metacarpal.

Turner’s syndrome (45 XO) Klinefelter’s Syndrome

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 General Pathology : Genetics 73

Karyotyping 00:48:21 ----- Active space -----

Karyogram : Clinical application : Chromosomal disorders.

Arrangement of chromosomes in descending Banding/Stain : Giemsa/G-banding (m/c).
order of length F/b Sex chromosomes. Stage in which cell arrested : Metaphase.
Karyograms of Chromosomal Disorders :
Normal karyotype Trisomy 13/Patau syndrome Trisomy 21/Down’s syndrome

om
l.c
ai
gm
@

Trisomy 18/Edward’s syndrome Turner syndrome Klinefelter Syndrome

60
23
ik
hv
rit
|
w
ro
ar
M
©

Cri-du-chat Syndrome : Deletion of Chromosome 5. (Cat-like cry)

DiGeorge Syndrome : Deletion of Chromosome 22q11.

Fluorescence In Situ Hybridisation (FISH) 00:52:07

Chromosomes tagged with red and green dyes.

Normal FISH Trisomy Monosomy Translocation

(2 green + 2 red signals) Amplification (1 green signal - ) Red + green signal fusion

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 74

----- Active space -----

SYSTEMIC PATHOLOGY :
BLOOD VESSELS AND HEART

Blood Vessels 00:02:46

Anatomy :
AKA adventitia
Thickest : Smooth muscle cells
Single layer of endothelial cells

Stain : VVG (Verhoeff-von Gieson), VG

om
l.c
Sclerosis
ai
gm 00:04:36

Thickening/hardening of arteries
@
60
23

Monckeberg’s medial Arteriosclerosis Atherosclerosis

ik
hv

calcific sclerosis
rit
|
w

Monckeberg’s Medial Calcific Sclerosis :

ro
ar

• Elderly.
M

RBC
• Asymptomatic.
©

• Stains for Ca : Von kossa/Alizarin red S.

Ca in T.media : Densely basophilic & gritty on H/E
Arteriosclerosis :
Hyaline Hyperplastic
• Benign hypertension
Seen in Malignant hypertension
• Diabetes mellitus

Microscopy

Pink, homogenous thickening of • Concentric laminated thickening of

vessel wall Luminal narrowing vessel wall (Onion skin appearance)
• Fibrinoid necrosis
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 Systemic Pathology : Blood Vessels and Heart 75

Note : Onion skin appearance. ----- Active space -----

• Malignant hypertension
• Primary sclerosing cholangitis Biopsy.
• Chronic inflammatory demyelinating polyneuropathy (CIPD)
• Ewings sarcoma : X-ray.
• Tay sach’s disease : EM.
• Spleen in SLE : Gross.

Atherosclerosis :
• Deposition of atherosclerotic plaque in vessel wall.
• Earliest leison : Fatty streak.
• M/c vessel : Abdominal aorta.
• Infections ↑ risk : CMV, chlamydia, herpes.
• ↑ S. Homocysteine ↑ Risk of plaque.

om
Plaque :

l.c
ai
gm
Fibrous cap : Smooth muscle cells, macrophages,
@

collagen, lymphocytes, elastin.

60
23

Cholesterol clefts
ik
hv

Foam cells (Lipid laden macrophages)

rit
|

Necrotic core : Cell debris, foam cells,

w

cholesterol crystals, Ca.

ro
ar
M

Vasculitides
©

00:16:43

Modified Chapel Hill Classification : Size of vessel

Large vessel : Medium vessel : Small vessel Variable vessel :

• Giant cell. • Polyarteritis nodosa (PAN). Behcet’s disease.
• Takayasu. • Kawasaki disease.
• Buergers disease.

ANCA associated : Immune complex associated :

• Wegeners granulomatosis. • Henoch-schonlein purpura.
• Microscopic polyangiitis. • Good Pasteur syndrome.
• Churg strauss syndrome. • SLE.

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 76 Pathology

----- Active space ----- Antineutrophilic cytoplasmic antibody (ANCA):

p - ANCA c - ANCA
Staining
Perinuclear Cytoplasmic
IF
AKA Anti-MPO ANCA Anti-proteinase-3 ANCA
• Microscopic polyangitis Wegener’s
Seen in
• Churg strauss syndrome granulamatosis

Note : p-ANCA is not specific to vasculitis (Seen in other autoimmune conditions).

Age Artery affected Clinically Biopsy Other associations
• Giant cells.
• Superficial • Headache
• > 50 yrs. • Granuloma • A/w
temporal : • Jaw pain
Giant cell/ • M/c • Fragmentation polymyalgia
M/c • Jaw claudication
Temporal arteritis vasculitis of internal rheumatica

om
• Ophthalmic A. (Most specific)
in eldery elastic lamina • ↑ ESR
• Vertebral A. • Blindness

l.c
(IEL)
ai
gm
Takayasu / • Loss of pulse in
@

Pulseless disease/ upper extremity • Giant cells

60

< 40 yrs Subclavian A -

Aortic arch • Pulse difference in • Granuloma
23
ik

syndrome upper & lower limb

hv

Renal A. : M/c. • Transmural • 30% HbsAg

rit
|

• GIT • Hematuria necrotizing positive

w

PAN (Type III

- • Heart • Malena inflammation • A/w
ro

hypersensitivity)
ar

Note : Never in • Abdominal pain • Fibrinoid mononeuritis

M

Pulmonary A. necrosis multiplex

©

• Fever
• < 5 yrs
• Cervical LN (U/L)
Kawasaki / • Most
• Strawberry tongue
Mucocutaneous specific Anti endothelial Ab
Coronary m/c • Conjuctival Non-specific
Lymph node arteritis positive
involvement
syndrome in children
• Cardiac complication
(Asia)
(MI)
• Granulomatous
• Middle • Intermittent
Buerger’s disease/ inflammation.
age Arteries, veins, claudication &
Thromboangiitis • Neutrophilic A/w HLA B5, A9
• Male nerves rest pain
obliterans micro-abscess
• Smokers • Gangrene
in vessel wall
• Upper respiratory
Granulamatosis
tract : Sinusitis.
with polyangiitis / c-ANCA positive
Any Any • Lower tract : Lung • Granulomas
Wegeners (95 %)
granuloma
granulomatosis
• Kidney : FPGN, RPGN

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 Systemic Pathology : Blood Vessels and Heart 77

----- Active space -----

Age Artery affected Clinically Biopsy Other associations

Microscopic
• Lung
polyangiitis / Fragmented
- - • Kidney p - ANCA positive
Leucocytoclastic neutrophils
• GIT
vosculitis
• Bronchial
Churg strauss Necrotizing
- - asthma p - ANCA positive
syndrome granulomas
• Eosinophilia
• B/L uveitis
Behçet’s
- - • Oral ulcers - HLA B-51
disease
• Genital ulcers
Note : Granulomatous vasculitis.
• Wegeners granulamatosis. • Buergers disease.
• Takayasu arteritis. • Giant cell arteritis.

om
• Churg strauss syndrome.

l.c
ai
gm
Clinical Findings :
@
60

Kawasaki disease :
23

Mnemonic : KAWASAKI.
ik
hv

K : Conjuctival redness.
rit
|

A : Age <5 yrs.

w
ro

W : Vasculitis.
ar
M

A : Adenopathy (Cervical).
©

S : Strawberry tongue, skin rash.

A : Anti-endothelial Ab.
K : Coronary artery involved.
I : Increased platelets.

Granulamatosis with polyangiitis/

Wegener’s granulomatosis :

Polyarteritis nodosa :

RBC

Fibrinoid necrosis
Granulomas & patchy (Pinkish material)
necrosis in arteries & veins
Pathology Revision • v4.0 • Marrow 8.0 • 2024
 78 Pathology

----- Active space ----- Giant cell arteritis :

VVG stain : Temporal artery Giant cells

Fragmentation of IEL

Vascular Tumours 00:41:56

Capillary hemangiomas : Cavernous hemangioma :

• More common. • Less common.
• Benign tumours, self resolving. • Deeper tissues (Liver).

om
• Superficial/subcutaneous. • A/w Von Hippel Lindau syndrome.

l.c
• Microscopy : Proliferation of • Microscopy : Large dilated vascular
ai
gm
large no. of small blood vessels. spaces.
@
60
23
ik
hv
rit
|
w
ro
ar
M
©

Kaposi’s Sarcoma :
• Borderline vascular tumour. Spindle shaped cells.
• Causative organism : HHV-8.
Slit like vascular spaces.
• H/o HIV positive.
• Lesion : Patch, plaque or nodule.
Angiosarcoma :
• Highly malignant. - Factor VIII
• Risk factors : - VEGF
- Polyvinyl chloride (PVC). - CD31
- Arsenic
- Thorotrast
• Commonly affects liver.
• IHC markers :
- VWF
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 Systemic Pathology : Blood Vessels and Heart 79

CVS : Myocardial Infarction 00:47:24 ----- Active space -----

• Area of coagulative necrosis in the heart. < 12hrs of MI :

Transmural. Paint the crossection with TTC
• Types
Subendocardial (Least perfused).
• M/c vessel : LAD > RCA > LCX. Normal area Infarct :
(Left anterior descending > Brick red Pale yellow (Loss
Right coronary > Left circumflex). of dehydrogenase
• Best biomarker : Troponin I. enzyme)
• Stain : Triphenyltetrazolium chloride (TTC).

om
l.c
ai
gm
Post MI gross and microscopic changes :
@
60
23

Gross Light microscopy

ik
hv

0-1/2 hr Normal (Reversible changes)

rit

Normal
|

1/2-4 hr Waviness of fibres

w
ro
ar

4-12 hr Coagulative necrosis

M
©

Dark mottling Coagulative necrosis, pyknosis of nuclei,

12-24 hr
contraction band necrosis, neutrophilic infiltrate
Coagulative necrosis, interstitial infiltrate of
1-3 days Yellow central infarct
neutrophils
Hyperemic border to
3-7 days Neutrophils replaced by macrophages
central infarct
Depressed red-tan
7-10 days Granulation tissue
margins to infarct
Well established granulation tissue, new blood
10-14 days -
vessels, collagen deposition
2-8 wks - Increased collagenous deposition
> 2 months - Dense collagenous scar

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 80 Pathology

----- Active space ----- Post MI biopsies :

• Neutrophilic infiltrate. • New blood vessel Granulation tissue.

• Age < 3 days. • Age : > 7 days.

CVS : Rheumatic Heart Disease 00:56:35

• 5 - 15 years.
• H/o URTI/streptococcal infection 2-3 weeks ago.
• JONES criteria :

om
- J : Migratory polyarthritis.

l.c
ai
- : Carditis. gm
- N : Nodules.
@
60

- E : Erythema marginatum.
23
ik

- S : Sydenhams chorea.
hv
rit

• Pathology : Type II hypersensitivity (Antibody mediated).

|

• M/c valve : Mitral. • Acute RHD Mitral regurgitation.

w
ro

• L/c Valve : Pulmonary. • Chronic RHD Mitral stenosis.

ar
M
©

Morphology :

1. Aschoff bodies (Pathognomonic) : 2. Fish mouth/button 3. Small, warty,verrucous

- Plasma cells, lymphocytes, hole stenosis (Chronic) vegetations along line
fibrinoid necrosis area. of closure of valves.
- Anitshkow cell/caterpillar cells :
Slender wavy ribbon like nuclei
(In Aschoff bodies).
4. Bread & butter pericarditis : Heart surface + yellow exudate.
5. Subendocardial jets / McAllum plaques : Acute regurgitation.

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 Systemic Pathology : Blood Vessels and Heart 81

Vegetations on Heart Valves : ----- Active space -----

RHD Infective Non-bacterial Libman-Sacks

• Small, warty, endocarditis thombotic endocarditis endocarditis
verrucous. • Destructive • Bland vegetations. • Vegelations on both
• Along line of • Unsterile • Along line of closure. sides of leaflets
closure. • Along line • Seen in malignancy. • Seen in SLE.
of closure.

om
CVS : Cardiomyopathies

l.c
01:05:01

ai
gm
Dilated Cardiomyopathy :
@
60

• M/c.
23

• Causes :
ik
hv

- Idiopathic.
rit
|

- Alcohol.
w
ro

- Post partum. Ventricular dilation

ar
M

- Cardiotoxic drugs (Adriamycin, doxorubicin). (Muscle fibres have stretched)

©

- Haemochromatosis (Dilated > restrictive).

- Genetic.
- Titin gene mutation (On biopsy : Ninja star nuclei).

Takotsubo Cardiomyopathy :
A type of DCM.

↑ Catecholamines
(Stress)

Takotsubo
(Octopus trap)
Normal LV Dilated LV

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 82 Pathology

----- Active space ----- Hypertrophic Cardiomyopathy :

• Cause : Mutation in sarcolemmal

proteins like
- Beta myosin heavy chain.
- Myosin binding protein c.
• M/c cause of sudden cardiac
death in young athletes.
Excessive wall Banana split
• Helter-Skelter (Haphazard) thickening of configuration
arrangement of muscle fibres. cardiac muscle

Restrictive Cardiomyopathy :
Causes :
• Radiation induced.

om
• Metastatic cancer.

l.c
• Idiopathic
ai
gm
• Haemochromatosis.
@

• Amylodosis (ATTr).
60
23
ik
hv

CVS : Tumours 01:10:55

rit
|

• M/c tumour of heart : Secondaries.

w
ro

• M/c primary tumour of heart in adults : Myxoma.

ar
M

• M/c primary tumour of heart in children : Rhabdomyoma.

©

Rhabdomyoma :
• A/w tuberous sclerosis.
• Spider cells on biopsy.
• Desmin, myogenin, myo D1 (IHC).

Myxoma :
• Young adult.
• Left atrium.
• Ball like Ball valve obstruction.
Stellate cells

Mucopolysaccharide
background

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 Systemic Pathology : Blood Vessels and Heart 83

Miscellaneous 01:13:04 ----- Active space -----

Heart failure cells

(Haemosiderin laden
macrophages)

Liver biopsy : Hemochromatosis

Stain : Prussian blue/Perl’s stain
Lung in CHF
Iron/hemosiderin

om
Contraction band necrosis
(Pinkish band)

l.c
ai
gm
@
60

Ischemia reperfusion injury Nutmeg liver

23

(Chronic venous congestion)

ik
hv
rit
|
w
ro
ar
M
©

Pathology Revision • v4.0 • Marrow 8.0 • 2024

 84

----- Active space -----

SYSTEMIC PATHOLOGY : CNS AND
DERMAPATHOLOGY

CNS Non-Neoplastic Conditions 00:00:30

PRIONS
Proteinaceous infectious particle (No DNA, no RNA).
Pathology : Misfolded protein disease Amyloid APr.
Diseases : Transmissable spongiform encephalopathy (TSE).
• CreutzfeldtJakob encephalopathy.
disease (CJD). • Mad cow disease.

om
• Kuru. • Scrapie.

l.c
• Bovine spongiform
ai
gm HPE : Spongiform change
(Vacuolations)
ALZHEIMER’S
@
60

Cause of dementia in elderly.

23
ik

Pathology :
hv
rit

• Amyloid : Aβ.
|

• Lobes : Parietal, frontal, temporal.

w
ro

Gross changes :
ar
M
©

Normal • Atrophy of brain.

• Widening of sulci.

Microscopy :

a. Neuritic plaques : b. Neurofibrillary tangles : c. Hirano bodies: (Composed of actin.)

(Aβ 40, Aβ 42) (Hyperphosphorylated tau proteins)
(Bielschowsky silver stain)
d. Cerebral amyloid angiopathy.
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 Systemic Pathology : CNS and Dermapathology 85

Other CNS Findings 00:06:34 ----- Active space -----

Negri bodies : Liquefactive necrosis :

• Rabies. Seen in
• Intracytoplasmic eosinophilic bodies. • Brain necrosis.
• Seen in hippocampus & purkinje cells. • Fungal infection.

om
Owl’s eye inclusion : Lewy body :

l.c
ai
gm
@
60
23
ik
hv
rit
|
w

• Basophilic inclusions. • Contain α - synuclein.

ro
ar

• Coinfection of HIV + CMV. • Parkinson’s disease.

M
©

CNS Tumours 00:10:08

Glial : Undifferentiated : Meningial : Neuronal : Others :

• Astrocytoma Medulloblastoma Meningioma • Neurocytoma • Lymphoma
• Ependymoma • Ganglioglioma • Germ cell tumour
• Oligodendroglioma • Ganglioneuroma

M/c overall :
• CNS tumour : Secondaries.
• Primary brain tumour : Glioma.
M/c in children :
• Brain tumour : Pilocytic astrocytoma.
• Malignancy of CNS : Medulloblastoma.

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 86 Pathology

----- Active space ----- PILOCYTIC ASTROCYTOMA

• Children. Gross : Microscopy :
• Cerebellum.
• Cystic nodules.
• WHO grade I tumour.
• Excellent prognosis.

Cystic/Mural nodule Rosenthal fibres

GLIOBLASTOMA
• Elderly.
• WHO grade IV (Highly malignant).
Gross : Microscopy :
• Geographical/Serpentine necrosis
(Tumour cells surrounding necrotic

om
area).

l.c
ai
gm
@
60

• Glomeruloid bodies (Endothelial

Butterfly tumour, crosses midline.
23

vascular proliferation).
ik
hv
rit
|

Note : Glomeruloid bodies - Yolk sac (Schiller - Duval bodies).

w
ro

OLIGODENDROGLIOMA
ar

• WHO grade II.

M
©

• Cerebral hemispheres.
• Gene : IDH1, IDH2.
Microscopy :
• Fried egg appearance
(Central nuclei & peripheral clearing).
• Calcification.
• Chicken-wire blood vessels
(Anastomosing vasculature).
Note : Fried egg appearance also in bone marrow Bx of hairy cell leukemia.

EPENDYMOMA
Involves spinal cord/Ependymal lining.
Microscopy : Perivascular pseudorosette
(Tumour cells surrounding blood vessel).

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 Systemic Pathology : CNS and Dermapathology 87

MEDULLOBLASTOMA ----- Active space -----

• M/c CNS malignancy in children.
• Posterior fossa.
• Microscopy :
- Blastemal cells : Small, round, blue.
- Homer Wright rosettes : Cells surrounding pink lumen.
Note : Small round blue tumour cells with rosettes.

om
• Neuroblastoma. • Rhabdomyosarcoma.

l.c
ai
• Medulloblastoma. • Ewing’s sarcoma (PNET).
gm
•
@

Hepatoblastoma. • Lymphoma.
60

• Retinoblastoma (Flexner-Wintersteiner). • Nephroblastoma.

23
ik
hv

MENINGIOMA
rit
|

• Arise from meninges.

w
ro

• Female > males.

ar
M

• Hormone dependent.
©

Microscopy : Psammoma bodies

(Foci of dystrophic calcification).

Note : Psammoma bodies.

• Papillary Ca thyroid. • Meningioma.
• Papillary RCC. • Prolactinoma.
• Serous cystadenocarcinoma of
ovary.

SCHWANNOMA
• NF-2 gene of chromosome 22.
• Involves vestibulocochlear nerve.
• Microscopy :
- Verrocay bodies.
- Hypercellular area (Antoni A).
- Hypocellular area (Antoni B).
Pathology Revision • v4.0 • Marrow 8.0 • 2024
 88 Pathology

----- Active space -----

Tumour Histological feature Tumour Histological feature

Pilocytic astrocytoma Rosenthal fibres, microcysts Ependymoma Perivascular pseudorosette
Serpentine necrosis, Small round blue cells,
GBM Medulloblastoma
glomeruloid bodies Homer Wright rosettes
Fried egg, chicken wire Meningioma Psammoma bodies
Oligodendroglioma
blood vessel calcification Antoni A, Antoni B, Verrocay
Schwannoma
bodies
Syndromes associated with brain tumours :
1. Li Fraumeni syndrome : p53
2. Turcot syndrome : APC Medulloblastoma.
3. Gorlin syndrome : PTCH

om
4. Cowden syndrome : PTEN Dysplastic gangliocytoma.

l.c
ai
gm
Dermapathology 00:26:50
@
60

LAYERS OF SKIN
23
ik

Histologically :
hv
rit
|
w
ro
ar
M
©

Mnemonic : Come Let’s Get Sun Burnt.

Stratum Corneum
Stratum Lucidum
Stratum Granulosum

Stratum Spinosum

Stratum Basale

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 Systemic Pathology : CNS and Dermapathology 89

MOLLUSCUM CONTAGIOSUM ----- Active space -----

Caused by pox virus.
Gross : Microscopy :
Dome shaped, pearly Henderson Paterson/Molluscum bodies (Intracytoplasmic
umbilicated lesion. eosinophilic bodies) in stratum corneum.

SKIN MALIGNANCIES
Squamous Cell Ca :

om
• Broder’s classification : • Microscopy :

l.c
ai
Differentiation gm
- Keratin pearls.
@

- Desmosomes
60

Well Moderately Poorly

23

(High power).
ik

• IHC markers :
hv
rit

- Cytokeratin (Epithelial Ca).

|
w

- p63.
ro
ar

Basal cell Ca :
M

• AKA Rodent ulcer (No metastasis).

©

• Clinically : Purplish nodule with telangiectasia.

• A/w Gorlin syndrome (PTCH gene).
• Microscopy :
- Nest of basaloid cells (Small blue cells with
hyperchromatic nuclei & scanty cytoplasm).
- Peripheral palisading.
- Retraction/Separation artifact.

Malignant melanoma :
• Highly aggressive
• Biopsy :
- Black pigment : Melanin (Derived from tyrosine).
- Stain : Mason Fontanna, DOPA reaction.

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 90 Pathology

----- Active space ----- • Marker : HMB-45, Melan-A, S-100.

• Indicators of malignancy (ABCDE) :
- Asymmetry.
- Border irregular.
- Color variation.
- Diameter > 6mm.
- Elevated margins.

BULLOUS DISORDERS
Diseases Microscopy/Immunofluorescence
Subcorneal bullae :

Pemphigus folliaceus

om
Fishnet/Reticular IF

l.c
ai
Suprabasal bullae gm
Pemphigus vulgaris
@

• Type 2 hypersensitivity.
60
23

• Row of tombstone
ik

appearance.
hv

• Ab to Dsg 1 & 3 : IgG.

rit

Subrabasal blister
|
w
ro
ar
M

Bullous pemphigoid :
©

Ab to Hemidesmosomes
(IgG).
Subepidermal bullae
Eosinophils at DEJ Linear/Ribbon candy IF

Dermatitis herpatiformis
• A/w coeliac disease
• Ab : IgA Subepidermal bullae : Granular IF
Neutrophils abscesses
at the tip of dermal
papillae.

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 Systemic Pathology : Respiratory System 91

SYSTEMIC PATHOLOGY : RESPIRATORY SYSTEM ----- Active space -----

Respiratory tract :
Trachea

Lungs
1° bronchus
2° bronchus
Bronchiole

Terminal bronchiole
Resp. bronchiole

om
Acinus

l.c
Alveolar ducts

ai
gm
Alveolar sacs
@
60
23
ik

Histology
hv

00:00:46
rit
|

Layers of Respiratory Tract :

w
ro
ar
M

Mucosa : Submucosa Muscularis Cartilage

©

• Epithelium. Submucosal glands :

• Lamina propria. Secrete mucus.
• Muscularis mucosa. Pseudostratified ciliated
columnar epithelium
Note :
Lining of vocal cords :
Stratified squamous epithelium.

Respiratory tract histology

Alveoli :
Lined by : Alveoli
1. Type I pneumocytes (95%)
2. Type II pneumocytes (5%) Produce
surfactant.

Alveolar biopsy
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 92 Pathology

----- Active space ----- Emphysema 00:02:20

Definition : Irreversible enlargement of air spaces distal to terminal bronchioles

(Acinus) with destruction of walls.
Note :
Obstructive lung diseases

COPD : Asthma. Bronchiectasis.

• Emphysema.
• Chronic bronchitis.

C/f : Pink puffers. • TB : Terminal bronchiole

• RB : Respiratory bronchiole
Types : • A : Alveoli.
1. Centrilobular/Centriacinar :
• M/c type.

om
l.c
• Central acini affected, distal acini spared.
ai
gm
• Associated with smoking.
@

• Usually affects upper lobes of lung.

60
23
ik

2. Panacinar :
hv

• Dilatation of the entire acinus.

rit
|

• Associated with α1 antitrypsin deficiency.

w
ro

• Usually affects lower lobes of lung.

ar
M
©

3. Paraseptal/Distal acinar :
• Distal acini affected, central acini spared.
• Associated with spontaneous pneumothorax.
4. Irregular :
• M/c clinical type.
• Can affect any part of the lung.
Note :
α1 antitrypsin deficiency
Organs affected :
1. Lungs
2. Liver Inclusion bodies :
Genetics : PAS +ve, diastase
• Chromosome 14 : Gene for α1 antitrypsin (α1 AT). resistant.
• Genotype :
- Normal : PiMM.
Liver biopsy
- Diseased : PiZZ.

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 Systemic Pathology : Respiratory System 93

Histology : Gross : ----- Active space -----

Distal airspace
Broken alveoli/
floating septae

Normal airspace

Centriacinar emphysema

Chronic Bronchitis 00:08:06

Definition :
Persistent productive cough for at least 3 consecutive months for 2 consecutive
years in the absence of any identifiable cause (D/d : Tuberculosis).

om
C/f :

l.c
ai
Blue bloaters (Cyanosis + ), 90% patients Smokers.
gm
Epithelium
@

Reid index (RI) :

60

a Basement
23

Thickness of submucous gland layer membrane

ik

RI = b
hv

Thickness of wall b/w epithelium & cartilage Submucous

rit

gland
|

bc
w

RI = c
ro

ad
ar

d
M

Cartilage
©

• Normal : 0.4
• ↑ed in chronic bronchitis : D/t submucosal gland hyperplasia.

Bronchial Asthma 00:09:45

Pathogenesis :
Reaction : Type 1 hypersensitivity reaction (Allergic).
Antibody : IgE.
Mediator : Histamine (Stain : Toluidine blue).
Cells : Mast cells, eosinophils.

Genetics :
Gene for atopy : Chr. 5.
Association : ADAM 33 (Matrix metalloproteinases).

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 94 Pathology

----- Active space ----- Sputum Examination :

Mnemonic : 3C.

Curschmann's spirals : Charcot Leyden crystals :

Whorled mucus plugs. Made of eosinophil
membrane protein.
(Galectin 10)

Creola bodies :
Sloughed mucus epithelium.

om
l.c
ai
gm
@
60
23
ik
hv

Bronchiectasis
rit

00:12:50
|
w

Defnition : Abnormal permanent dilatation of bronchi & bronchioles.

ro
ar
M

Kartagener syndrome
©

AKA Immotile cilia syndrome/Primary ciliary dyskinesia.

Defect : Dynein arm of cilia.
C/f :
Situs inversus (Inversion of organs)

Bronchiectasis Sinusitis

Complications : Recurrent infections,

Bronchiectatic lung
abscess, amyloidosis.

Pneumoconiosis 00:15:49

• Restrictive lung disease.

• Occupational lung disorders.

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 Systemic Pathology : Respiratory System 95

Types : ----- Active space -----

Coal worker’s pneumoconiosis Silicosis (M/c) Asbestosis

Lung lobe affected Upper lobe Upper lobe Lower lobe
Occupation Coal mining Sand mining/grinding Construction, shipping
• Lung adenocarcinoma (M/c)
• TB
↑Risk of - • Malignant mesothelioma (Most
• Lung adenocarcinoma
specific)

Asbestos/ferruginous body
• Asbestos fiber coated with iron

om
• Dumbbell shaped, fusiform,

l.c
Histology beaded, rod-like structure

ai
gm
@
60

Anthracotic pigmentation Whorled collagen bundles

23

Stain : Masson’s trichrome

ik
hv
rit
|
w

Prussian blue staining

ro

of asbestos body
ar
M
©

• Polarised microscopy : • Asbestos fibers:

Birefringent silica particles - Amphibole (↑Carcinogenic)
• CXR : Egg shell calcification - Serpentine
• Pleural plaque : M/c & earliest
Types : lesion.
• Simple
Other features • Complicated
• Progressive massive
fibrosis

Note :
1. Caplan syndrome : CWP + Rheumatoid arthritis.
2. Calretinin : Tumor marker for malignant mesothelioma.

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 96 Pathology

----- Active space ----- 3. Malignant mesothelioma vs. adenocarcinoma :

Malignant mesothelioma Adenocarcinoma
Long, slender microvilli/tonofilaments

Electron
Short, stubby villi
microscopy

Cryptogenic Organising Pneumonia 00:26:18

• AKA Bronchiolitis Obliterans Organising Pneumonia (BOOP).

• Restrictive lung disease.

om
l.c
ai
gm
@

Inflammation
60
23

Masson bodies (Loose fibrous plugs)

ik
hv
rit

Hemorrhage
|

Histology of BOOP
w
ro
ar
M

Sarcoidosis 00:27:29
©

• Multisystem disorder.
• M/c seen in middle aged women.

Pathogenesis :
Type IV hypersensitivity reaction (Delayed/cell-mediated) Granuloma formation.

Clinical features :
• Skin involvement.
• Keratoconjunctivitis sicca.
• Salivary gland enlargement.
• Lung involvement : Hilar lymph node enlargement.
• Hypercalcemia.

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 Systemic Pathology : Respiratory System 97

Histology : ----- Active space -----

Non-caseating/naked granuloma
(Absent lymphocytic collar)

Note :
Granulomas : Epithelioid cells surrounded by lymphocytes & giant cells.
Giant cells
Star shaped
inclusion body

om
Basophilic calcium concretions :

l.c
D/t hypercalcemia

ai
gm
@
60

Asteroid bodies Schauman bodies

23

Biochemical tests :
ik
hv

1. Hypercalcemia (Causes metastatic calcification).

rit
|

2. ↑Angiotensin converting enzyme.

w
ro
ar

Tuberculosis 00:32:22
M
©

Microscopy :

Acid-fast bacilli

Langhan’s giant cell

(Horseshoe/necklace
pattern of nuclei)

H & E : Caseating granuloma Ziehl-Neelson staining of sputum

Miliary TB :
• D/t disseminated disease.
• Poor prognosis.

Note :
TB can also have a non-caseating granuloma.
Miliary TB

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 98 Pathology

----- Active space ----- Miscellaneous 00:33:52

COVID 19 Infection :

Histopathology :
• Diffuse alveolar damage +
inflammation + mononuclear cells
• Hyaline membrane deposition.

CMV Pneumonia :
Association : HIV/immunosuppression.

om
l.c
ai
gm Owl’s eye appearance
(Intranuclear
@

basophilic inclusions).
60
23
ik
hv
rit
|

Chronic Venous Congestion (CVC) Lung :

w
ro
ar
M
©

Heart failure cells

• Hemosiderin laden macrophages
• Stain : Perl’s/Prussian blue stain

Lung Tumors 00:33:52

• M/c lung tumor : 2° tumors/metastases (M/c : Breast).

• M/c 1° lung cancer : Adenocarcinoma.

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 Systemic Pathology : Respiratory System 99

----- Active space -----

SCC Adenocarcinoma Small cell Ca Large cell Ca

Incidence M>F F>M M>F M>F
Location Central Peripheral Central Peripheral
Smoking Both smokers &
Yes No Strongest
association non-smokers
(Highest PNS association)
Paraneoplastic Hypercalcemia d/t Migratory• Cushing syndrome
Syndromes Parathyroid Hormone- • SIADH
thrombophlebitis/ Gynecomastia
(PNS) related Peptide (PTHrP) • Hypertrophic pulmonary
Trousseau syndrome
osteoarthropathy
Loss of chromosome 3p, K-RAS, EGFR 1, ALK Loss of chromosome 3p,
Pathogenesis -
p53 mutation (Chr 17) mutations L-myc amplification
Adenocarcinoma in situ, DIPNEH (Diffuse Idiopathic
Precursor
Carcinoma In Situ (CIS) Atypical Adenomatous Pulmonary Neuroendocrine -
lesion

om
Hyperplasia (AAH) Hyperplasia)

l.c
• Small cells
ai
Keratin pearls Glands lined by gm
• Salt & pepper chromatin Large,
H&E
• Nuclear moulding
@

Desmosomes pleomorphic cells pleomorphic cells

60

• Azzopardi effect
23

• Synaptophysin
ik

• CK
hv

• TTF 1 • Chromogranin
rit

IHC • p63 -
• NAPSIN A • Bombesin
|

• p40
w

• NSE (Neuron Specific Enolase)

ro
ar
M

Microscopy :
©

Keratin pearl

SCC Large cell Ca Rare

Filigree/lepidic/butterflies
Glands lined by on a fence pattern :
pleomorphic cells Tumor cells grow along
bronchoalveolar lining.

Adenocarcinoma Adenocarcinoma in situ/Bronchoalveolar Ca

Precursor for adenocarcinoma
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 100 Pathology

----- Active space -----

Small cell Ca
• Worst prognosis
• Chemosensitive
• Azzopardi effect : Basophilic staining of blood vessel walls
(D/t broken DNA).
Note :
1. ‘Lepidic’s in pathology :

om
Lepidic

l.c
cells

ai
gm
@
60
23
ik
hv

a. Bronchoalveolar carcinoma b. Cardiac myxoma

rit

• M/c 1° cardiac tumor

|

• M/c affects Lt. atrium Ball-valve obstruction.

w
ro
ar

2. Rhabdomyoma :
M

• M/c 1° tumor in children.

©

• Markers : Myogenin, myo-D1, desmin.

Carcinoid Tumor 00:48:30

Origin : Kulchitsky cells. Gross :

Clinical features : Diarhhoea, sweating, flushing.
IHC markers : NSE, bombesin, chromogranin,
synaptophysin.
Microscopy :
Coat button lesions

Salt & pepper

chromatin

Histology
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 Systemic Pathology : Genital System and Breast 101

SYSTEMIC PATHOLOGY : GENITAL SYSTEM ----- Active space -----

AND BREAST

Infective Lesions 00:00:55

Molluscum Contagiosum :
Molluscum/Henderson-
Umbilicated Paterson bodies :
dome-shaped lesions
Intracytoplasmic eosinophilic
inclusion bodies

om
l.c
Gross appearance Histology
ai
gm
@

Condyloma Acuminata/Genital Warts :

60

Low risk HPV Genital warts.

23
ik

High risk HPV Cervical/Anogenital/Laryngeal cancer.

hv
rit
|
w
ro
ar
M

Warty, red Koilocytes :

©

cauliflower-like • Large polyhedral cells.

lesions. • Resinoid nucleus.
• Perinuclear clearing/halo.
Gross appearance Histology

Ovaries & Ovarian Tumor Classification 00:05:31

Gross and Microscopic Features :

Surface epithelium
Ovary Fallopian tube

Stroma

Anterior Posterior

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 102 Pathology

----- Active space ----- Classification of Ovarian Tumors :

Surface epithelial Germ cell tumors : Sex cord stromal tumors : Metastatic tumors :
tumors : • Dysgerminoma. • Granulosa cell tumor. krukenberg’s
• Serous. • Teratoma. • Leydig cell tumor. tumor.
• Mucinous. • Choriocarcinoma. • Fibroma.
• Brenner’s. • Yolk sac tumor. • Thecoma.
• Clear cell. • Embryonal Ca.
• Endometroid.
Note : Seminoma Male counterpart of dysgerminoma.

Surface Epithelial Tumors 00:07:38

Serous epithelial tumor vs mucinous tumors :

om
l.c
Serous epithelial tumors Mucinous tumors
ai
gm
Incidence More common Less common
@
60

Laterality Bilateral Unilateral

23

• Family history
ik

Risk factor Smoking

hv

• Nulliparity
rit
|

Genetics BRCA1, BRCA2 K RAS

w
ro

Psammoma bodies Present Absent

ar
M
©

Gross

Uniloculated, serous fluid Multiloculated, Mucinous fluid

HPE

Ciliated columnar epithelial Tall, columnar cells with

cells mucin

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 Systemic Pathology : Genital System and Breast 103

----- Active space -----

Psammoma bodies
Papillae Dense basophilic inclusion
Psammoma bodies seen in :
bodies • Papillary Ca of thyroid
• Serous cystadenoma
of ovary
Psammoma bodies in serous
ovarian tumors • Meningioma
Brenner’s Tumor : • Prolactinoma
Benign, solid, U/L tumor.

Bladder-like epithelium
(Nests of cells)

om
l.c
ai
gm
Coffee bean nuclei
(Longitudinal groove + )
@
60
23
ik
hv
rit
|

Germ Cell Tumors 00:14:05

w
ro
ar

Dysgerminoma :
M
©

• 20-30 yrs.
• Radiosensitive (Good prognosis).
• Large tumor.

Fibrous septa (Infiltrated by

lymphocytes + Plasma cells)

Large polygonal cells with

central nuclei & perinuclear
halo (Arranged in sheets)

Gross : Cut potato appearance Histology

IHC markers :
• PLAP +ve. • OCT 3/4 +ve.
• Nanog +ve. • AFP -ve (Always).
• hCG +ve.

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 104 Pathology

----- Active space ----- Choriocarcinoma :

• Usually elderly population (>60 yrs). Large areas of
• Aggressive tumor (Poor prognosis). hemorrhage &
necrosis
• Cannonball mets in lung.
• Chemosensitive.

Histology : Gross appearance

1. Cytotrophoblast (Large, polyhedral cells).
2. Syncitiotrophoblast (Giant cells)

IHC markers : β HCG.

Blood

om
Yolk Sac/Endodermal Sinus Tumor : Glomeruloid bodies

l.c
ai
Children <5 yrs. gm 1. Yolk sac tumor
@

2. Glioblastoma multiforme
60
23

(Grade IV)
ik
hv

Microscopy : .
rit
|
w
ro
ar
M
©

Schiller-Duval/Glomeruloid body Eosinophilic hyaline globules

IHC markers :
• a fetoproteins (AFP). Note : Hepatocellular carcinoma is also
• a1 antitrypsin (a1 AT). AFP +ve.

Embryonal Carcinoma :
• Large, polyhedral cells arranged in
papillaroid configuration.
• Marker : CD30+.

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 Systemic Pathology : Genital System and Breast 105

Teratoma : ----- Active space -----

Derivatives of all 3 germ layers.

Teeth

Hair

Cyst
Rokitansky protruberance

Teratoma Dermoid cyst/Mature cystic teratoma

Histological types : Hair follicle
Immature & mature teratoma.
Epithelium

Has immature fetal/neural elements Fat

om
Glands

l.c
Poor prognosis. Bone
ai
gm
Histology
@
60

Sex Cord Stromal Tumors

23

00:26:50
ik
hv

Granulosa Cell Tumor :

rit
|

Coffee bean nuclei

w

Coffee bean nuclei

ro

(Longitudinal groove + ) • Papillary Ca of thyroid

ar
M

• Brenner’s tumor
©

Call-Exner bodies • Chondroblastoma

(Tumor cells surrounding • Granulosa cell tumor
a pinkish material)
• Langerhans cell
histiocytosis
Leydig Cell Tumor :

Reinke’s crystals
(↑ in tumor cells)

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 106 Pathology

----- Active space ----- Metastatic Tumors 00:29:40

KRUKENBERG TUMOR
Diffuse gastric adenocarcinoma Metastasis Ovary.
• B/L.
• Symmetric enlargement of both ovaries.

Signet ring cells

Microscopy Gross appearance

om
l.c
SUMMARY OF OVARIAN TUMORS
ai
gm
Tumor Histopathology Marker
@

Serous epithelial tumor Cells with cilia, Psammoma bodies CA 125

60
23

Yolk sac tumor

ik

Schiller duval bodies, hyaline globules AFP, a1 AT

hv

(<5 years)
rit
|

Teratoma Skin, bone, cartilage, teeth, hair -

w
ro

Choriocarcinoma Cytotrophoblast, syncytiotrophoblast,

ar

β HCG
M

(>60 years) no villi

©

Embryonal carcinoma Primitive cells, no villi CD30+, CK+

• Call Exner bodies
Granulosa cell tumor -
• Coffee bean nuclei
Sertoli cell tumor - Inhibin
Leydig cell tumor Reinke’s crystal -
PLAP, LDH,
Cells in nodules with fibrous septa
Dysgerminoma HCG, Oct 3/4,
containing lymphocytes
Nanog; AFP -
Brenner’s tumor Transitional epithelium, bean nuclei -
Krukenberg’s tumor Signet ring cells -

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 Systemic Pathology : Genital System and Breast 107

Gestational Trophoblastic Disease 00:36:18 ----- Active space -----

Partial Mole Complete Mole

Empty ova + sperm (XY+23)
≥2 sperms (XY+23) + 1 Ova
Genetics (Duplicates genetic
(XX+23) Triploid (69)
material) Diploid (46)
Fetal parts Present Absent
Mucosal edema ++ +
Villi Some villi normal All edematous
Trophoblastic proliferation Patchy Diffuse
Risk of choriocarcinoma Minimal 2-3% risk

Prostatic Adenocarcinoma 00:38:17

Gleason’s Score :

om
• Primary dominant pattern + Secondary dominant pattern.

l.c
ai
• In case only one type of pattern present : Double the number.
gm
@
60

Gleason’s patterns :
23
ik
hv
rit
|
w
ro
ar
M
©

5. Only occasional
gland formation
Prostatic adenocarcinoma

Gleason scoring :
Traditional gleason score New grading system group 1
GLEASON 3 + 3 = 6 GRADE 1
Only individual discrete well formed glands.
GLEASON 3 + 4 = 7 GRADE 2
Predominantly well formed glands + Lesser poorly formed glands.
GLEASON 4 + 3 = 7 GRADE 3
Predominantly poorly formed glands + Lesser well formed glands.
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 108 Pathology

----- Active space -----

Traditional gleason score New grading system group 1

GLEASON 4 + 4 = 8
Only poorly formed/fused/cribriform glands
or
Predominantly well formed glands with a lesser component GRADE 4
lacking
or
Predominantly lacking glands with a lesser component of well
formed glands.
GLEASON 9 - 10
Lacks gland formation (Or with necrosis) GRADE 5
with or without poorly formed/fused/cribriform glands.
Gleason (3+4) has better prognosis than Gleason (4+3) d/t predominant well

om
formed pattern.

l.c
ai
gm
Breast Histology & Paget’s Disease 00:42:44
@
60
23

Histology of Breast :
ik
hv

Duct Note :
rit

• Invasive lesion : BM + myoepithelium lost.

|

Interlobular stroma
w

• In-situ lesion : BM + myoepithelium intact.

ro

Lobule
ar
M
©

Intralobular stroma

Basement membrane
Myoepithelial cells
Luminal epithelial cells
Acinus

Lumen

Paget’s Disease :
U/L erythematous eruptions over the nipple (D/d : Eczema).

Paget’s cells : Large cell, central

nuclei with perinuclear clearing

Stains : PAS +ve, Oil Red o +ve,

diastase resistant

IHC marker : HER2 neu overexpression.

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 Systemic Pathology : Genital System and Breast 109

Benign Tumors of Breast 00:46:07 ----- Active space -----

Types :

Epithelial Stromal

Ductal : Lobular : Fibroadenoma Phyllodes tumor

DCIS, IDC. LCIS, ILC.
Ductal Carcinoma In-Situ (DCIS) :
Types :

om
l.c
ai
gm
@

1. Comedo : 2. Cribriform : 3. Solid :

60
23

• Central necrotic area. Sieve/Cookie cutter Entire duct filled with cells.
ik
hv

• Poor prognosis. appearance.

rit
|
w
ro
ar
M
©

4. Micropapillary : 5. Papillary : 6. Mixed

Small papillae inside Large papillae inside
the duct. the duct.

Fibroadenoma :
Presentation : Staghorn appearance
Small, mobile mass with of ductal epithelial cells
smooth margins.

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 110 Pathology

----- Active space ----- Phyllodes Tumor/Cystosarcoma Phyllodes :

Leaf-like pattern

Stromal hyperplasia

Slit like spaces

(Compressed ducts)

Breast Carcinoma 00:51:12

Genetics :
BRCA1 BRCA2 P53 CHEK2

om
Chromosome 17 13 17q 22

l.c
ai
• Breast Ca gm
• Male breast cancer Li Fraumeni • Breast Ca
Association • Ovarian Ca : Serous
@

• Prostate cancer syndrome • Thyroid Ca

60

cystadenocarcinoma
23
ik
hv

Note :
rit

NF2 Location : Chr. 22.

|
w
ro

Mutation : B/L acoustic neuroma/schwannoma.

ar
M

Invasive Ductal Carcinoma (IDC) :

©

M/c type.

Histological features :
1. Cells in ducts/tubules
2. Pleomorphism.
3. Mitosis.

Bloom Richardson (BR) score :

• Criteria % of tubule formation.
No. of mitosis.
Degree of pleomorphism.
• Grading Well differentiated.
Moderately differentiated.
Poorly differentiated.

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 Systemic Pathology : Genital System and Breast 111

Invasive Lobular Carcinoma (ILC) : ----- Active space -----

• B/L, multicentric lesion.
• Indian file/Single file pattern :
Single, monomorphic cells arranged serially.

Genetics : CDH1 mutation Loss of E-cadherin.

Note :
CDH1 mutation & Loss of E-cadherin seen in :
• Invasive lobular carcinoma.
• Diffuse gastric adenocarcinoma.

Mucinous Carcinoma :
Excellent prognosis.

om
l.c
ai
gm
Signet ring cell
@

Tumor cells floating (Intracellular mucin pushes

60

in pools of mucin
23

nucleus to periphery)
ik
hv
rit
|
w
ro
ar

Medullary Carcinoma :
M
©

Poor prognosis.

Histological features :
• Sheets of pleomorphic cells.
• ↑No. of mitosis.
• Lymphoplasmacytic infiltrate
(Unique to medullary ca in breast).
• Pushing borders.

Association : BRCA1 +ve.

IHC Markers :
ER PR HER2 neu
Receptor type Nuclear receptors Membranous receptor
when +ve :
a. Prognosis Good Poor
b. Responsive to Tamoxifen Trastuzumab

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 112 Pathology

----- Active space -----

Not cancer +ve stain (Brown) -ve stain

ER

PR

Nuclear staining : ER/PR +ve cells Strong HER2 neu positivity

(Stains the cell membrane)

Molecular Classification of Ca Breast 01:00:44

Based on ER, PR, HER2 neu.

om
l.c
Luminal A (M/C type) Luminal B Her 2 neu positive Triple negative

ai
ER, PR +ve, gm
ER, PR +ve, ER, PR -ve,
Hormonal status HER2 neu +ve. ER,PR, HER2 neu -ve.
@

HER2 neu -ve. HER2 neu +ve.

60

(Triple Positive Ca.)

23

Age Elderly Elderly Middle to elderly Perimenopausal women

ik
hv

Differentiation Well differentiated Well differentiated Poorly differentiated -

rit
|

Prognosis Best prognosis Good prognosis Poor prognosis Worst prognosis

w
ro

Proliferation
ar

Low Low Low-High High

index : Ki 67
M
©

H&E

IHC

ER

PR

HER2

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 Systemic Pathology : Gastrointestinal, Endocrine and Musculoskeletal System 113

SYSTEMIC PATHOLOGY : GASTROINTESTINAL, ----- Active space -----

ENDOCRINE AND MUSCULOSKELETAL SYSTEM

H. Pylori 00:00:54

Present in 95% Indian population.

H. Pylori
Causes :
• Chronic type B gastritis.
• Gastric adenocarcinoma (M/c malignancy by H. Pylori).
• MALToma/Marginal zone lymphoma : Most specific malignancy by H. Pylori. Biopsy

Biopsy :
• Site : Pyloric antrum. • Organism over mucosa.

om
• Intraepithelial neutrophils, subepithelial plasma cells s/o H.pylori.

l.c
ai
• Stain : Warthin starry silver stain (Black color). gm
@
60

Note : Silver stains

23

• Warthin starry silver. • Reticulin stain (Fibrosis).

ik

Warthin starry silver stain

hv
rit

Gastric Tumors
|

00:05:00
w
ro
ar

Most commons :
M

• Malignant gastric tumor : Gastric adenocarcinoma.

©

• Malignant mesenchymal gastric tumor : Gastrointestinal stromal tumor (GIST).

• Site of adenocarcinoma : Antrum.
• Site of adenocarcinoma in patient of pernicious anemia : Fundus/Body.

GASTRIC ADENOCARCINOMA
Laurens Classification :
Intestinal Diffuse
Etiology Environmental Familial
Mutation APC gene microsatellite instability CDH 1 gene ↓E-cadherin (Adhesion molecule)
Gender M>F F>M
Age ↑Incidence with age Younger age group
Microscopy Malignant glands (Adenocarcinoma) • Dyscohesive cells (poorly differentiated) :
D/t loss of E-Cadherin
• Signet ring cells : Mucin
Prognosis - Poorer
Spread Hematogenous Transmural/Lymphatic
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 114 Pathology

----- Active space -----

Extracellular Leather bottle
mucin appearance

Signet ring cells (Black arrows) : Linitis plastica :

Intracellular mucin pushes aside the nucleus End stage disease ; Very poor prognosis

Note : Tumors with E-cadherin loss.

• Diffuse gastric Ca
• Invasive lobular Ca
GIST
• Origin : Interstitial cells of Cajal.

om
• M/c mesenchymal gastric tumor.

l.c
ai
Mutations : gm
@

• c-KIT mutation (M/c)

60

• PDGF-RA
23
ik

• SDH-B
hv
rit

Spindle cells in palisading arrangement

|

Markers :
w
ro

• DOG-1 (Most specific)

ar
M

• CD117/c-KIT (95%)
©

• CD-34
KRUKENBERG’S TUMOR
• Diffuse gastric adenocarcinoma
Metastasis to ovaries.
• Gross : B/L symmetrical enlargement +
intact capsule.
• Microscopy : Signet ring cells. Krukenberg’s tumor

Inflammatory bowel disease 00:15:10

• F > M.
• Bimodal age distribution.
Note : Bimodal age distribution
• IBD
• Hodgkin’s lymphoma.
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CROHN’S DISEASE ----- Active space -----

Mnemonic : SISTER MACC
• Skip lesions; Skin nodules. • Microscopy : Non-caseating
• Ileum (M/c). granuloma.
• String sign of Kantor • Aphthous ulcers, anti-saccharomyces
(Radiology). cerevisiae Ab +
• Transmural (Entire thickness). • Creeping fat.
• Rectum spared. • Cobble stone appearance of mucosa.

ULCERATIVE COLITIS
Mnemonic : COLITIS.
• Continuous lesions (Surgery possible). • Immunity : p-ANCA.
• Often rectum involved (Retrograde • Toxic megacolon.
spread). • ↑Risk of cancer.

om
• Lead pipe appearance (Radiology). • Submucosal involvement.

l.c
ai
Note : p-ANCA also in gm
@

• Microscopic polyangiitis.
60

• Churg-Strauss syndrome.
23
ik
hv

Crohn’s vs. Ulcerative Colitis :

rit
|
w

Crohn's Disease Ulcerative Colitis

ro
ar

Site Ileum, Cecum Rectum, Colon

M
©

HLA Association HLA-DR1 HLA-DR2

Smoking Risk factor Protective
Cell CD4-TH1 cells CD4-TH2 cells
Lesions Skip lesions Continuous lesions
Cobblestone appearance Present Absent
Ulcers Deep knife-like Superficial, broad based
Gross Pseudopolyps
Absent Present
Mucosal bridges
Wall feature Thick rubbery Distension (Toxic Megacolon)
Depth of inflammation Transmural Submucosal
Granuloma Present Absent
Cryptitis
Microscopy Less common More common
Crypt abscess
Ulcers Less prominent More prominent

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 116 Pathology

----- Active space -----

Crohn's Disease Ulcerative Colitis

Stricture/Fissure/
More common Less common
Fistula/Sinuses
Complications
Colitis Associated
Less prominent More prominent
Neoplasia (CAN)
Radiological appearance String sign of Kantor Lead pipe/Hose pipe
Antibody Anti-saccharomyces cerevisiae p-ANCA

Giant cell

Granuloma

Collar of
lymphocytes

om
Crohn’s : Cobblestone appearance
Crohn’s : Granuloma

l.c
ai
gm
Modified macrophages (Epitheloid cells) surrounded by a collar of lymphocytes
@
60

±
23

Giant cells
ik
hv

Update :
rit
|

Early onset IBD

w
ro

• Seen in infants & children.

ar
M

UC : Crypt abscess • Mutation in genes for epithelial transport or immunity.

©

Neutrophilic infiltration into crypts • Mutation in IL-1 or IL-10 receptor.

Malabsorption Diseases 00:24:26

Condition Clinical & pathological features Gross & microscopy

• Gluten sensitive enteropathy
• Site : Duodenum 1. Villous
• Dietary restriction to BROW atrophy
Barley, Rye, Oats, Wheat
• Antibodies 2. Crypt
- Anti-gliadin hyperplasia
Celiac - Antiendomysial (Most specific)
disease - Anti-tissue transglutaminase (TTG)
• HLA associated 3. ↑Intraepithelial lymphocytes
- HLA DQ2
- HLA DQ8
MARSH score : Above histological features quantified
• A/w ↑risk of :
to check extent of disease.
- Enteropathy associated T-cell lymphoma
- Dermatitis herpetiformis
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 Systemic Pathology : Gastrointestinal, Endocrine and Musculoskeletal System 117

----- Active space -----

Condition Clinical & pathological features Gross & microscopy

• Organism : Tropheryma whipplei

• Clinical Mnemonic : CAN
Whipple’s disease - CNS involvement
- Arthralgias
- LN involvement
Foamy histiocytes PAS + Diastase resistant
in lamina propria Organism filling the
foamy histiocytes

om
l.c
ai
• Organism : Clostridium difficile gm
Pseudomembranous
• Cause : Long term antibiotic Rx
@

colitis
(E.g : Cephalosporin)
60
23

Gross : Microscopy :
ik
hv

Thick, dirty Volcano-like appearance

rit

yellow membrane of neutrophilic exudate

|
w
ro
ar
M
©

Giardia :
Giardiasis - • Pear/oval shaped
• Flagellate

• AKA Davidson disease

• Autosomal recessive
• D/t MYO5B gene mutation
Microvillous • Defect in protein helping in
inclusion disease vesicular transport (Ion & water
absorption)
• Clinical : Diarrhea
• Markers : Villin, CD 10 Microscopy : Electron microscopy :
Tiny eosinophilic Inclusion with microvilli
inclusion at the apex

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 118 Pathology

----- Active space ----- Intestinal polyps 00:34:16

True protrusions of mucosa.

Non-neoplastic : Neoplastic : Adenomatous

Hyperplastic Inflammatory Hamartomatous :

(Solitary rectal ulcer) • Peutz Jeghers
• Cowden’s
• Juvenile polyposis
• Cronkhite-Canada syndrome

om
Condition Pathology Clinical Microscopy

l.c
ai
gm
@
60
23

• Elderly (60-70yrs)
Hyperplastic
ik

• Site : Left colon -

hv

Polyp
• Pathology : No of cells ↑
rit
|
w
ro

Upper 1/3rd : Serration

ar

Lower 2/3rd : Normal

M
©

• Age : 20-30yrs
• Autosomal dominant
Peutz Jeghers
LKB 1/STK 11 gene
Syndrome
mutation • Perioral melanosis
• Site : Jejunum • Multiple polyps
• Hyperpigmentation : M/c
• ↑Risk of cancer
(Thyroid, breast, colon) Arborising pattern of smooth muscle
(Christmas tree appearance)

Mnemonic : PTEN
• Polyp
Cowden’s Mutation :
• Trichilemmoma -
Syndrome PTEN gene on Chr. 10
• Thyroid cancer
• Endometrial cancer

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 Systemic Pathology : Gastrointestinal, Endocrine and Musculoskeletal System 119

Adenomatous Polyps : ----- Active space -----

Tubular Tubulovillous Villous

Tubular Villous Highest malignant

component component potential

Adenocarcinoma Colon 00:41:16

• Microscopy : Glands lined by malignant cells.

om
• Markers : CA-19-9, CEA.

l.c
ai
Familial adenomatous polyposis : gm
@

• Mutation : APC gene on • Autosomal dominant

60

• >100 polyps +
23

chromosome 5.
ik
hv

Pathogenesis :
rit
|

Adenoma-Carcinoma sequence (M/c) : In polypoid cancer.

w
ro

Mnemonic : AK53.
ar
M

Carcinoma
©

Normal colon Mucosa at risk Adenomas

First hit : At APC Second hit : APC Protooncogene Tumor suppression

(Tumor suppressor gene) Beta catenin mutation : K-RAS gene mutation :
on Chr 5q21 pathway on Chr 12p12 p53 on Chr 17p13
Mismatch repair pathway : In HNPCC.

Normal colon

Mutation of mismatch repair genes : Sessile serrated adenoma Carcinoma

MLH1, MSH2, MSH6, PMS1, PMS2

Pathology Revision • v4.0 • Marrow 8.0 • 2024

 120 Pathology

----- Active space ----- Pheochromocytoma 00:45:00

Adrenal medullary tumor.

Rule of 10 : Microscopy :
• 10% are B/L.
• 10% are malignant.
• 10% occur in children.
• 10% are extraadrenal. • Zellballen pattern.
• 10% do not present with • Salt & pepper
headache & hypertension. chromatin
containing cells.
Presentation :
• Young male.
• Persistant tachycardia/Hypertension.
• Excretion of VMA in urine.

om
l.c
IHC markers : NSE, Synaptophysin, Chromogranin.
ai
gm
Electron microscopy : Dense, core, neurosecretary granules.
@
60
23

Associated Familial Syndromes :

ik
hv
rit

Syndrome Gene Associated Lesion Other Features

|

Multiple endocrine neoplasia, Medullary thyroid carcinoma,

w

RET Pheochromocytoma
ro

Type 2A (MEN-2A) Parathyroid hyperplasia

ar
M

Medullary thyroid carcinoma,

Multiple endocrine neoplasia,
©

RET Pheochromocytoma Marfanoid habitus,

Type 2B (MEN-2B)
Mucocutaneous Ganglioneuroma
Neurofibromatosis,
Neurofibromatosis, type 1
NF 1 Pheochromocytoma Café-au-lait spots,
(NF 1)
Optic nerve glioma
Pheochromocytoma, Renal cell carcinoma (Clear cell),
Von Hippel-Lindau VHL
paraganglioma Hemangioblastoma,
(VHL) (Chr 3)
(Uncommon) Pancreatic endocrine neoplasm
Pheochromocytoma,
Familial paraganglioma 1 SDHD -
paraganglioma
Familial paraganglioma 3 SDHC Paraganglioma -
Pheochromocytoma,
Familial paraganglioma 4 SDHB -
paraganglioma
NF 1 : Neurofibromin Update : Polycythemia paraganglioma syndrome
SDH B : Succinate Dehydrogenase Complex, subunit B
• Defect : EPAS-1, ↑ HIF 2 alpha
SDH C : Succinate Dehydrogenase Complex, subunit C
SDH D : Succinate Dehydrogenase Complex, subunit D • Can lead to pheochromocytoma,
paraganglioma & polycythemia

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 Systemic Pathology : Gastrointestinal, Endocrine and Musculoskeletal System 121

Neuroblastoma 00:49:12 ----- Active space -----

• Abdominal mass in infant/child. (D/d : Nephroblastoma.)

• Mutation : N-myc.

Microscopy : Note :
c-myc : Burkitt lymphoma.
l-myc : Lung cancer.

• Small, round, blue cells with scanty cytoplasm.

• Rosette arrangement (Homer Wright).

om
l.c
ai
gm
Hashimoto’s Thyroiditis/Struma Lymphomatosum 00:52:10
@
60

• F > M.
23
ik

• Autoimmune.
hv

Thyroid Normal
rit

follicles thyroid
|

Genes :
w

follicles
ro

• CTLA 4. PAS +ve

ar
M

• PTPN 22. pinkish

©

• HLA DR3. colloid

Normal thyroid histology Microscopy : Lymphoid follicle aggregates.
• HLA DR5

Antibodies :
• Anti-TPO.
• Anti-thyroglobulin.
• Anti-microsomal Ab. Lymphocytic
infiltrate
Gross : Symmetric enlargement Hurthle cell/Oncocytic change :
↑Risk for : Cells with abundant eosinophilic granular
cytoplasm d/t increased mitochondria.
• Papillary Ca thyroid (Primary).
• Non-Hodgkin lymphoma (MALToma).
• Other autoimmune diseases.

Pathology Revision • v4.0 • Marrow 8.0 • 2024

 122 Pathology

----- Active space ----- Criteria for adequacy in thyroid FNAC :

A specimen should display at least :
• 6 groups of follicular cells, with each group composed of
10 cells preferably on a single slide.
Exceptions :
• Thyroiditis : Abundant inflammatory cells + .
• Benign colloid nodule : Abundant thick colloid + .
• Atypical malignancy : Malignant/atypical cells + .

Thyroid Malignancies 00:56:20

Papillary Follicular Medullary Anaplastic

Incidence M/c 2nd M/c L/c
• Radiation • Iodine deficiency

om
Risk • Thyroglossal cyst • MNG
- -

l.c
factors • Hashimoto's • Long standing

ai
thyroiditis gm
goitre
@

Parafollicular Follicular
60

Origin Follicular cells Follicular cells

cells/C cells cells
23
ik

Metastasis Lymphatic Hematogenous Both Both

hv
rit

• BRAF • K–RAS • RET

Genetics P53
|

• RET-PTC • PI3K • MEN II

w
ro

Prognosis Best - - Worst

ar
M

• Orphan Annie eye

©

nuclei
H&E Follicles Amyloid -
• Psammoma
bodies

PAPILLARY THYROID CANCER

Cells in papillae

Nuclear
pseudoinclusion
Coffee bean nuclei
(Longitudinal groove)
Optically clear nuclei Psammoma bodies
(Orphan annie eye) • Dystrophic calcification
Note : Special stain for calcium • Densly basophilic
• Von kossa.
• Alizarin red S.
Pathology Revision • v4.0 • Marrow 8.0 • 2024
 Systemic Pathology : Gastrointestinal, Endocrine and Musculoskeletal System 123

----- Active space -----

Follicular variant of Papillary cancer

• Follicular arrangement of cells.

• Orphan annie eye nuclei + .
• Nuclear features similar to follicular variant.

FOLLICULAR CARCINOMA MEDULLARY CARCINOMA

FNAC not useful for diagnosis : • Origin : Parafollicular cell/C-cells of thyroid.
Need vascular & capsular invasion. • IHC marker :
- Calcitonin.
- CEA (In calcitonin -ve tumors).
Invasion of

om
tumor cells • Gene : RET gene on Chr 10.

l.c
• Syndrome : MEN 2.
ai
Capsule gm
@
60
23
ik
hv
rit

Capsular invasion
|
w
ro

• Amyloid : A. Cal Best stain :

ar

• Spindle shaped cells Congo red under polarizing lens

M
©

Apple green birefringence.

Bone & soft tissues 01:06:00

Tumors Age Location Genetics X ray Microscopy Gross

Metaphysis of • Codman's
New bone Large, tan,
Bimodal age, long bones triangle
Osteosarcoma Rb gene formation, lace white gritty
10-20 yrs (M/c site : • Sunburst
like pattern masses
Distal femur) appearance

Mushroom
Osteochondroma Metaphysis of EXT1, EXT2
- - - shaped
(Exostosis) long bones gene defect
protrusions

Multinucleated
Giant cell tumor F > M, Lower end of
- - osteoclast type
(Osteoclastoma) 20-50 yrs femur
giant cells

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 124 Pathology

----- Active space -----

Tumors Age Location Genetics X ray Microscopy Gross

Axial skeleton, Malignant hyaline,
M>F Chr 1p
Chondrosarcoma pelvis, ribs, - myxoid cartilage, -
40 years rearrangement
sternum pleomorphic cells
Ewings sarcoma
Markers :
Diaphysis of Onion skin Small, round, blue
• CD99 <20 yrs t (11;22) -
long bones appearance cells with rosettes
• MIC2
• PAS +ve

om
l.c
ai
gm
@
60
23

Osteosarcoma Giant cell tumor Chondrosarcoma

ik

Lace like pattern of new bone formation

hv

Multinucleated giant cells Shiny appearance (Cartilage)

rit
|
w

Ewing’s sarcoma :
ro
ar
M
©

• Small round blue cells. • PAS +ve (Glycogen).

• Rosettes. • CD-99 +ve.
• mic-22 +ve.

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 Systemic pathology : Kidney and Liver 125

SYSTEMIC PATHOLOGY : KIDNEY AND LIVER ----- Active space -----

Urine Microscopy  00:00:24

1. Cells
2. Casts : All composed of Tamm Horsfall protein.
Casts Causes
Hyaline cast Normal individuals, pregnancy, fever, stress
RBC casts Glomerulonephritis
WBC casts Pyelonephritis
Broad/waxy casts Chronic renal disease

om
Muddy brown granular casts Acute tubular necrosis (ATN)

l.c
ai
Lipid/fatty casts Nephrotic syndrome
gm
@

3. Crystals :
60
23
ik
hv
rit
|
w
ro
ar
M
©

Struvite : Uric acid : Ammonium urate :

Rectangular/coffin lid Varying shapes Associated with
appearance (Rhomboids/parallelograms). laxative abuse.

Forms staghorn calculi

Cystine : Calcium oxalate (M/C)

• Hexagonal.
• Acidic urine.
Monohydrate Dihydrate

Dumbbell shaped Envelope shaped

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 126 Pathology

----- Active space ----- Note : 3Cs of bronchial asthma in sputum

• Curschmann spirals. • Charcot laden crystals. • Creola bodies.

Kidney Biopsy  00:03:56

Investigations :

Light Electron Immuno

microscopy microscopy fluorescence

• H & E. Bowman's space

(Space b/w parietal

• PAS : Basement membrane. 2.

& visceral layer)

• Silver stain.
• Congo red : Amyloid (Apple green). Layers of glomerular

om
epithelium

l.c
1.

ai
gm (Contains podocytes/
foot processes)
@
60
23
ik
hv

Glomerulus
rit

LIGHT MICROSCOPY :
|
w

Interpreting a kidney biopsy :

ro
ar

• Count the number of glomeruli (10-15) :

M

- <50% glomeruli affected : Focal.

©

- >50% glomeruli affected : Diffuse.

- Portion of a glomerulus affected :
Segmental.
- Entire glomeruli affected : Global.
- ↑cellularity : Proliferative.

1-2 cells/
capillary tuft

Open capillary Neutrophils +

loops

Normal glomeruli Proliferative : ↑cellularity

Pathology Revision • v4.0 • Marrow 8.0 • 2024

 Systemic pathology : Kidney and Liver 127

----- Active space -----

ELECTRON MICROSCOPY :
Deposits :

Subepithelial : Subendothelial : Intramembranous : Mesangial :

• PSGN • MPGN I • MPGN II • HSP
• RPGN • Lupus • IgA nephropathy
• Membranous GN nephritis

IMMUNOFLUORESCENCE :
Linear pattern Granular pattern
Immune complex/
Cause GBM disease
complement deposition

om
Good pasture syndrome PSGN

l.c
(Anti-GBM antibodies) (Lumpy-bumpy appearance)
ai
gm
@
60
23
ik
hv

Examples
rit
|
w
ro
ar
M
©

Note : Starry sky pattern (Biopsy)

• Burkitts lymphoma.

Nephritic Syndromes 00:12:44

Syndrome Pathology & Clinical Findings

• Type III hypersensitivity • LM : Enlarged hyper cellular
(Immune complex) glomerulus
Post
• Age : 5-15 yrs • EM : Subepithelial humps
streptococcal
• 2-4 weeks after (Immune complex)
GN
streptococcal sore throat • IF : : Lumpy bumpy/granular/
• Cola colored urine (Hematuria) starry sky appearance

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 128 Pathology

----- Active space -----

Syndrome Pathology & Clinical Findings

• Type 1 : Anti GBM associated Crescenteric glomeruli

Rapid Progressive (Good pasture’s syndrome) (>50%)
GN • Type 2 : Antibody mediated Formed by
(AKA crescenteric (SLE, PAN) Proliferation of parietal
GN) • Type 3 : Pauci immune cells, fibrin, neutrophils
(Wegener’s granulomatosis)

• Type 1 RPGN
• Type 2 Hypersensitivity • Antibody : Anti-GBM
Good pasture
• Alpha 3 chain affected • LM : Crescents
Syndrome
• Type 4 collagen affected • EM : Linear

om
• Clinical : Hemoptysis + hematuria

l.c
ai
(Lung) (Renal) gm
• EM : Basket weave pattern (Diagnostic)
@

• a-5 chain of collagen type 4

60

• All 4 modes of inheritance • LM

23

Inconclusive
• X linked dominant (M/c) • IM
ik
hv

• Clinical :
rit

- Anterior lenticonus
|

- Sensorineural deafness
w
ro

- Hematuria
ar
M

Alport Syndrome
©

Note :
Wegeners granulomatosis : URT + LRT + Kidney (c-ANCA positive).

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 Systemic pathology : Kidney and Liver 129

Nephrotic Syndromes 00:22:02  ----- Active space -----

M/c causes in :
• Children : Minimal Change Disease (MCD).
• Adults : Focal Segmental Glomerulosclerosis (FSGS).
• Elderly : Membranous nephropathy.

Disease Pathology & Clinical features Findings

• Age : 2-4 yrs • EM : Podocyte foot processes effacement
Minimal change • Unknown pathogenesis (Diagnostic)
disease • Clinical : Selective proteinuria • LM : No change
• Rx : Steroids • IF : No deposits (Nil deposit ds)

• Primary : Idiopathic
• Secondary : Segmental sclerosis
- HIV, heroin abuse, hypertension (<50% of the
Focal segmental

om
- Renal ablation surgery glomerulus)
GS

l.c
- Reflux nephropathy

ai
- IgA nephropathy gm
- Sickle cell anemia
@
60
23
ik
hv
rit
|
w
ro

• Primary : Defect in Phospholipase

ar
M

A2 gene
©

• Secondary :
Membranous - Autoimmune : SLE H&E PAS
nephropathy - Bacterial : Malaria, syphilis, Diffuse thickening of GBM
hepatitis B & C
- Cancer : Lung, colon, pancreas
- Drugs : Gold, penicillamine Silver stain :
Spike & dome
appearance

Silver stain :
Membrano • MPGN I : Primary & secondary Tramtrack
Proliferative GN • MPGN 11 appearance

Pathology Revision • v4.0 • Marrow 8.0 • 2024

 130 Pathology

----- Active space ----- Diabetic Nephropathy  00:31:50

Thickened wall of glomerular Diffuse sclerosis Pink PAs +ve nodules :

capillary/ GBM (Earliest) M/c finding Kimmelstiel wilson lesion
Nodular glomerulosclerosis : Most specific

Vacuoles
filled with

om
glycogen :

l.c
PAS +ve
ai
gm
@
60
23
ik

Fibrin caps Capsular drops Armanni-Ebstein lesions

hv
rit

Lupus Nephritis 
|

00:35:04
w
ro
ar

Renal involvement in SLE.

M
©

Grades Disease
Grade 1 Minimal mesangial
Grade 11 Mesangio-proliferative
Grade 111 Focal proliferative
Grade 1V Diffuse proliferative :
(M/c type) Wire loop lesion (Maximum)
Grade V Membranous LN
Grade V1 Dense sclerosing

IF : Fullhouse effect

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 Systemic pathology : Kidney and Liver 131

Malakoplakia 00:36:54 ----- Active space -----

Gross : Microscopy :
Yellowish Basophilic concretions :
white plaques Michaelis Guttman bodies

Kidney Tumors 00:38:12

RCC Type Pathology & Prognosis Gross Microscopy

om
l.c
Cells with clear
ai
gm
• M/c cytoplasm
• Solitary
@

• From PCT
60

Clear Cell RCC • U/l

• VHL gene mutation on
23

• Yellowish
ik

chromosome 3p
hv
rit

PAS, oil red O : Stain (Glycogen)

|
w
ro

• Papillae filled
ar

• 2 m/c
nd
with foamy
M

• Multicentric
©

Papillary RCC • A/w dialysis histiocytes

• B/l
• Trisomy 7, 17 & loss of Y • Psammoma
bodies

• From intercalated cells

of collecting ducts • Plant like
• A/w : cells (Well
Chromophobe - Birt-Hogg-Dube defined)
- +
RCC syndrome
- Loss of chromosomes • Perinuclear
- Hypodiploidy halo
• Best prognosis Hale’s colloidal iron stain
• L/c
• From collecting ducts in • Hobnail cells
Bellini duct RCC -
medulla • Desmoplasia
• Worst prognosis

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 132 Pathology

----- Active space ----- WILMS TUMOR/NEPHROBLASTOMA :

• 2-5 yrs. Note : Abdominal mass in child
• Abdominal mass. • Neuroblastoma : n-MYC.
• WT1, WT2 gene mutation. • Nephroblastoma : WT1, WT2.

Epithelial component :
• Small, round, blue cells
• Rosettes

Blastemal component
Mesenchymal
component

om
Liver Pathology

l.c
00:44:24

ai
gm
Liver biopsy :
@
60

Vim Silverman needle.

23
ik
hv
rit
|
w

Portal vein
ro

Portal triad Hepatic artery

ar
M

Central vein Bile duct

©

Zone 1 Zone 2 Zone 3

(Centrilobular) (Midzonal) (Perioportal)

Portal triad
Hepatocytes
Central vein
Space of Disse
Hepatocytes
Sinusoid
Sinusoids
Kupffer cells
Space of Disse : Ito cells
(Amyloid deposition in
liver first occurs here)
Hexagonal plate High power view
Pathology Revision • v4.0 • Marrow 8.0 • 2024
 Systemic pathology : Kidney and Liver 133

Liver cirrhosis 00:47:10 ----- Active space -----

End stage liver disease.

Causes :
• Alcoholic liver disease (ALD). • Enzyme deficiency : a 1 antitrypsin
• Biliary disease (PBC, PSC) deficiency.
• Cryptogenic cirrhosis. • Hepatitis.
• Drug induced. • Hemochromatosis.
• Wilson’s disease.
Types :
<3 mm : Micronodular >3 mm : Macronodular
Causes : Causes :
• Early ALD. • Late stage ALD.
• Hemochromatosis. • Wilson’s.

om
• PBC. • Viral hepatitis.

l.c
ai
• Indian childhood gm
@

cirrhosis
60
23

Histology :
ik
hv
rit

Fibrous septa
|
w

Collagen type I & 3

ro

(Stain blue with

ar
M

Masson's trichrome)
©

Cords of
hepatocytes
Nodules

Masson’s trichrome staining

Alcoholic Liver Disease 00:50:30

Microscopically : Steatosis (Fatty change) Hepatitis Cirrhosis.

Can be microvesicular/macrovesicular
Pathology Revision • v4.0 • Marrow 8.0 • 2024
 134 Pathology

----- Active space ----- MALLORY HYALINE BODIES :

• Composed of intermediate filaments CK8 & CK18.
• Seen in : Mnemonic New Indian WATCH.
- Non alcoholic - Tumor (Hepatocellular
steatohepatitis (NASH). carcinoma).
- Indian childhood cirrhosis. - Cirrhosis (10 biliary
- Wilson’s disease. cirrhosis).
- ALD (M/c). - Focal nodular Hyperplasia.
ALD VS. NASH :
Alcoholic steatohepatitis/ASH NASH
H/o alcohol intake Present Absent
Obesity, DM,
Risk factors May or may not be present
hypercholesterolemia present

om
Mallory hyaline bodies More prominent Less prominent

l.c
Prominent cells Neutrophils Monocytes

ai
AST/ALT ratio >2
gm <1
@
60

Reye’s Syndrome 00:54:10

23
ik
hv
rit

• Children with fever + aspirin intake.

|
w

• Nausea, vomiting.
ro
ar

• Microscopy : Microvesicular steatosis.

M
©

Metabolic Liver Disease 00:55:06

Prussian
Haemosiderin blue
(Brown)

Hemochromatosis

PAS +ve,
Diastase resistant
KF ring inclusion bodies in
hepatocytes.

Wilsons disease a1 AT deficiency

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 Systemic pathology : Kidney and Liver 135

Wilsons disease ----- Active space -----

Hemochromatosis Alpha-1 AT deficiency
(Hepatolenticular disease)
Genetic HFE gene mutation on ATP7B gene mutation on Def of alpha-1 AT,
defect vCh 6p Ch 13 gene on Ch 14
Impaired incorporation
Metabolic ↑ neutrophil elastase
Excessive iron deposition of Cu into bile, excess
defect activity
copper deposition
• Bronze pigmentation of
skin (D/t melanin) • KF ring
• Pan acinar
Clinical • DM • Liver disease
emphysema,
features • Cirrhosis • Neuropsychiatric
• Liver disease
• Arthritis symptoms
• Hypogonadism.

• ↑ iron
Biochemical • ↓ ceruloplasmin
• ↑ ferritin -
tests • ↑ Urinary exc of Cu
• ↓ TIBC

om
l.c
ai
PAS positive, diastase
Hemosiderin Steatosis, hepatitis,
gm
Liver biopsy resistant globules in
(Prussian blue/Perl’s stain) (Rhodamine, orcein stain)
@

hepatocytes
60
23
ik

Hepatitis
hv

01:00:12
rit
|
w
ro

Acute : Chronic :
ar

• Ballooning degeneration. • Ground glass hepatocytes (Hepatitis B).

M
©

• Apoptosis (Councilman bodies). • Bridging necrosis.

• Scant mononuclear infiltrate. • Bridging fibrosis.
Ballooning
degeneration

Ground glass
hepatocytes

Note : Nutmeg liver

Chronic venous congestion of liver

Pathology Revision • v4.0 • Marrow 8.0 • 2024
 136

----- Active space ----- ANNEXURE

Psammoma bodies (Foci of dystrophic calcification)

• Papillary thyroid Ca.

• Serous cystadenoma of ovary.
Special stain : Von Kossa
• Meningioma. (Other : Alizarin red S)
• Prolactinoma.
• Malignant mesothelioma.

om
l.c
ai
gm
‘Masson’s in pathology
@
60
23
ik
hv

• Masson bodies.
rit
|

• Masson Fontana stain Melanin.

w
ro

• Masson Trichrome stain Collagen.

ar
M
©

Masson’s trichrome
Owl’s eye appearance

• CMV inclusion bodies.

• Reed Sternberg cells
(Hodgkin’s lymphoma).

Pathology Revision • v4.0 • Marrow 8.0 • 2024

 Annexure 137

----- Active space -----

Onion skin appearance

• Malignant HTN.
• 1° sclerosing cholangitis. Biopsy
• Chronic Inflammatory
Demyelinating Polyneuropathy (CIDP).
• Spleen in SLE : Gross appearance.
• Ewing’s sarcoma : X-ray.
• Tay Sach’s disease : Electron microscopy.

Dry tap on bone marrow aspiration

• Aplastic anemia.
• Myelofibrosis.
• Hairy cell leukemia.

om
• AML-M7.

l.c
• Myelophthisic anemia.
ai
gm Dry tap N BM
@

Myc genes (Proto-oncogenes) ADAM gene mutations

60
23

• C-myc Burkitt’s lymphoma, Breast cancer.

• Thrombotic Thrombocytopenic Purpura (TTP) : ADAMTS13.
ik

• L-myc Lung cancer.

hv

• Bronchial asthma : ADAM33.

• N-myc Neuroblastoma.
rit
|

BRAF V600E mutations

w
ro
ar

• Pilocytic astrocytoma. • Hairy cell leukemia.

M

• Papillary Ca of thyroid. • Langerhan cell histiocytosis.

©

• Malignant melanoma.

Massive splenomegaly
• CML. • Gaucher’s disease.
• Polycythemia vera. • Hairy cell leukemia.
• Myelofibrosis. • Malaria & Kala-Azar in India.

Pathology Revision • v4.0 • Marrow 8.0 • 2024

©
M
ar
ro
w
|
rit
hv
ik
23
60
@
gm
ai
l.c
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