Cancer 1.

Definition, nomenclature and

characteristics
Professor Lenka Munoz
School of Medical Sciences

lenka.munoz@sydney.edu.au
 Cancer Module
• 6 lectures
• Cancer 1. Definition, nomenclature and characteristics
• Cancer 2. Metastasis and epidemiology of cancer
• Cancer 3. Etiology, clinical features and diagnosis
• Cancer 4. Hallmarks of cancer and oncogenic drivers
• Cancer 5. Tumour suppressors, apoptosis and DNA damage
• Cancer 6. Targeted cancer therapy

• 3 Pracs
• Microscopy Practical 1: Benign tumours (4 May 2022)
• Microscopy Practical 2: Malignant tumours (11 May 2022)
• Museum tutorial: Macrospecimens of tumours (18 May 2022)

• Glioblastoma Carcinogenesis Project (elective) 5 May & 26 May @ 3pm

 Learning Objectives
• Define tumours
• Understand general appearance and characteristics of tumours
• Understand naming system for tumours
• Understand differences between benign and malignant tumours
• Understand differences in the macroscopic appearance of benign versus
malignant tumours
• Understand differences in the microscopic appearance of benign versus
malignant tumours
• Understand differences in the specific cell function, differentiation
vascularity, and host response of benign versus malignant tumours
Pathologist’s definition of a “tumour” (Willis, 1973)
• An abnormal mass of tissue that takes up space in the body and can
fatally interfere with normal function of organs
• The growth of the abnormal tissue exceeds and is uncoordinated with
that of the adjacent normal tissue
• Mutations in the tumour DRIVE growth & PREVENT normal cell-cell
contact inhibition
• Growth persists in the same excessive manner, even after cessation of
the stimuli which evoked the change
• Mutations incorporated into genome of tumour cells & passed onto
daughter cells
 Origin of the name
• Galen 2nd century Greek “karkinos” for crab
• became ‘cancer’ in Latin
• cancers adhere to any part they seize in an
obstinate manner; similar to crab’s behaviour
and tumours also have multiple “legs”
• Cancer is not one disease but many disorders
that share a profound growth dysregulation
• Some cancer are highly curable e.g., Hodgkin
lymphoma; but some e.g., cancer of the
pancreas or glioblastoma are fatal
 Fundamental and Shared Characteristics
• Cancer is a genetic disorder
• caused by DNA mutations that are acquired spontaneously or induced by
environmental stimuli
• caused by epigenetic changes e.g.; increased DNA methylation, histone modification
• genetic and epigenetic changes alter expression and function of key genes that
regulate fundamental processes such as cell growth, survival and senescence

• Genetic alteration: heritable, passed to daughter cells upon cell division

• Accumulation of mutations gives rise to a set of characteristics called

Hallmarks of Cancer (because cancer cannot be explained in one sentence)
 Hallmarks of Cancer
2000 Perspective
2011 Perspective

Weinberg & Hanahan, Cell 2000, 100: 57 - 70 Weinberg & Hanahan, Cell 2011, 144: 646 - 674

Simple read => https://coolscienceforyou.wordpress.com/2014/01/18/cancer/

Sustained Proliferative Signalling
Evading Growth Suppressors
Activating Invasion and Metastasis
Resisting Cell Death
Inducing angiogenesis
Enabling Replicative Mortality
 Basics Components of Tumours

• Parenchyma
• made of transformed/neoplastic/cancer cells
• determines biological behaviour of the tumour
• name of the tumour derived from this components

• Stroma
• supporting host-derived non-neoplastic stroma
• made of connective tissue, blood vessels and host-derived inflammatory cells
 Nomenclature
• Neoplasia = new growth
• Neoplastic cells = transformed cells
• transformed because they continue to replicate and are oblivious to
regulatory influences that control normal cell growth
• Neoplasm = tumour
• Oncology = study of tumours
• oncos = tumour; logos = study of

Based on a tumour’s potential clinical behaviour:

• Benign tumours: microscopic and gross characteristics relatively innocent,
localised, amenable to surgical resection
• Malignant tumour: usually termed cancer, lessions that invade and destroy
adjacent structures and spread into distant sites (metastasize)
 Benign Tumours
• Designated by suffix -oma to the cell type from which the tumour arises
• Benign tumour of fibrous tissue => fibroma

• Nomenclature of benign epithelial tumours is complex

• Sometimes classified on their microscopic patterns, sometimes on their macroscopic
pattern, sometimes on the cell of origin
• Adenoma => benign epithelial neoplasm producing gland patters or neoplasms
derived from glands but not necessarily exhibiting glandular patterns
• Papillomas => benign epithelial neoplasms growing on any surface and
producing microscopic or macroscopic finger-like fronds
 Is this CANCER?
• NO: this is a benign neoplasm of the breast -
fibroadenoma - that has grown to form a large mass
• Histologically, it has a characteristic morphology:
• Differentiated epithelial cells arranged in distinctive
glandular patterns
• Embedded in a dense fibrous connective tissue
stroma
• It is demarcated from the surrounding tissues
 Is this CANCER?

• No. These are colonic polyps

• Histologically, these are benign
adenomatous papillomas
• But, they have a potential to
progress to malignancy and are
considered pre-malignant
 Malignant Tumours
• Nomenclature essentially follows that of benign tumours, with certain
additions and exceptions
• Neoplasms arising in solid mesenchymal tissues => sarcoma
• Sarcomas are designated by the cell of origin: cancer of fibrous tissue => fibrosarcoma
• Neoplasm arising from mesenchymal cells of the blood => leukemias or
lymphomas
• Neoplasm of epithelial cells => carcinomas, regardless of the tissue of origin
• Growing in glandular patterns => adenocarcinoma
• Producing squamous cells => squamous cell carcinoma
 Malignant Tumours
• Transformed cell in the neoplasm often resemble each other = consistent
with monoclonal origin of tumours
• Sometimes, tumour cell undergo divergent differentiation creating mixed
tumours
• Mixed tumour of salivary gland
• Oligoastrocytoma - mixed glioma tumour, which contains both abnormal
oligodendroglioma and astrocytoma cells

Oligoastrocytoma showing two distinct regional variations

in cellular morphology, with oligodendroglial cells on the
left and astrocytic cells on the right.
 Teratoma
• Special type of mixed tumour containing mature and immature cells/tissues
representing more than one germ cell layer
• Originates from totipotential germ cells normally present in the ovary or testis
• Germ cells have the capacity to differentiate into any type of cell found in the
human body and give rise to neoplasm that mimic in helter-skelter fashion bits
of bone, epithelium, muscle…

Teeth
Multiple cell types derived from
pluripotent stem cell in gonad

Hair Skin
 Hamartoma
• Mass of disorganized tissue indigenous to the particular site
• e.g.; disorganized hepatic cells, blood vessels within the liver
• Originally considered as developmental malformations, but genetic studies
showed presence of acquired translocations suggesting neoplastic origin

Example of hamartoma:
Microcapillary haemangioma (Port wine stain)
Tissue of origin Benign Malignant

Connective tissue and derivatives Fibroma Fibrosarcoma

Lipoma Liposarcoma
Chondroma Chondrosarcoma
Osteoma Osteogenic sarcoma
Endothelial and related tissues
Blood vessels Hemangioma Angiosarcoma
Lymph vessels Lymphangioma Lymphangiosarcoma
Mesothelium Mesothelioma
Brain coverings Meningioma Invasive meningioma
Muscle
Smooth Leiomyoma Leiomyosarcoma
Striated Rhabdomyoma Rhabdomyosarcoma
Blood cells and related cells
Hematopoietic cells Leukemias
Lymphoid tissue Lymphomas
Tumours of epithelial origin
Stratified squamous Squamous cell papilloma Squamous cell carcinoma
Basal cells of skin or adnexa Basal cell carcinoma
Epithelial lining of glands or ducts Adenoma, Papilloma, Cystadenoma Adenocarcinoma, Papillary carcinomas
Respiratory passages Bronchial adenoma Bronchogenic carcinoma
Renal epithelium Renal tubular adenoma Renal cell carcinoma
Liver cells Liver cell adenoma Hepatocellular carcinoma
Urinary tract epithelium Urothelial papilloma Urothelial carcinoma
Placental epithelium Hydatidiform mole Choriocarcinoma
Testicular epithelium Seminoma, Embryonal carcinoma
Tumours of melanocytes Nevus Malignant melanoma
 Benign vs Malignant Tumour
• Benign tumour
• genetically simple, harbouring fewer mutations
• genetically stable, changing little in genotype over time

• Fundamental features to distinguish benign from

malignant tumours are:
• Differentiation and anaplasia
• Rate of growth
• Local invasion
• Metastasis
 Differentiation and Anaplasia
• Characteristics seen only in the parenchymal cells that constitute the
transformed elements of the neoplasm
• Differentiation => extent to which they resemble their normal forebears
morphologically and functionally
• Anaplasia => Greek for “backward formation” => lack of differentiation
• Dysplasia => Disorderly but non-neoplastic proliferation
• Encountered mostly in epithelial lessions
• Loss in the uniformity of individual cells and in their architectural orientation
 Differentiation
• Benign tumours: composed of well-differentiated cells that resemble
their normal counterparts
• Lipoma made of mature fat cells laden with lipid vacuoles
• Mitosis are rare and are of normal configuration

• Malignant tumours: composed of wide range of parenchymal cells

• from well differentiated to completely undifferentiated
• well-differentiated adenocarcinoma of the thyroid contains normal-appearing
follicles
 Anaplasia
• Malignant neoplasm composed of undifferentiated cells => anaplastic
• Cancers arising from stem cells = failure of differentiation rather than dedifferentiation
• Anaplastic cells display pleomorphism (variation in size and shape)
• Nuclei are extremely hyperchromatic (dark staining), with mitoses and distinctly atypical, tripolar or
quadripolar mitosis
• Giants cells
• Anaplastic cells loose polarity
 Anaplastic Sarcoma

Mitosis Abnormal mitotic figure

(“caterpillar-like”) Tripolar mitosis Multi-nucleated cell
 Rate of Growth
• Benign tumours grow slowly over months to years
• Malignant grow much faster, spreading locally and to distant sites - metastasis
• Exception: growth rate of leiomyomas (benign smooth muscle tumour) is influenced
by the circulating levels of estrogens – rapid growth in pregnancy, cease after
menopause
• Growth rate of malignant tumour correlates inversely with their level of
differentiation
• Poorly-differentiated tumours grow more rapidly than well-differentiated tumours
• All tumours enlarge over time: some slowly, some rapidly but they never “come
out of the blue”
 Cancer Stem Cells and Lineages
• Tissues containing short-lived cells e.g.; epithelial cells of the gastrointestinal
tract and skin have a resident population of tissue stem cells
• Stem cells divide asymmetrically and produce two types of daughter cells
• one with limited proliferative potential which will undergo terminal differentiation
• one that will retain stemness and self-renewal capacity
• Cancer stem cell hypothesis is based on the same principle – only a subset of
cells within a tumour has the capacity for self-renewal
• Thus, eliminating cancer stem cells should cure cancer….
• Cancer stem cells are highly resistant to therapy via numerous mechanism
• Low rate of cell division (dormancy) protects against conventional therapy that is
designed to target rapidly proliferating cells
• Over-expression of drug efflux pumps
• Ability to activate survival pathways
 Macroscopic Differences: Benign vs Malignant
1. Local invasion
• Benign tumours grow by expansion
• Malignant tumours both expand and invade surrounding tissue
Benign tumours (generally) are:
• Well-circumscribed, round, cohesive and well-demarcated masses
• often have a capsule (due to adjacent pressure atrophy & fibrosis; facilitates enucleation)
• their size varies enormously
• colour and texture: grey or white and uniform
Malignant tumours (generally) have:
• Finger-like projections
• irregular margins
• are usually not circumscribed
• fail to recognise normal anatomic boundaries (penetrate through organs e.g.; wall of colon)
• have variable texture and colour, often due to haemorrhage & necrosis
Comparison between tumour margins
Benign fibroadenoma of the breast Malignant carcinoma of the breast

3
Macroscopic differences: Benign vs Malignant

2. Ulceration: ulcers may form on mucosal surfaces or on skin

• Benign ulcers: rarely occur; tend to have very sharp edges, are shallow and the
floor is usually not indurated
• Malignant ulcers: tend to have rolled edges and tend to feel hard; are irregular in
shape and may be irregularly indurated

3. Polyps: tumour tissue protruding from the skin or from a mucosal surface
• Benign polyps: usually pedunculated (have a stalk) and with a uniform texture
• Malignant polyps: usually sessile (flat); may ulcerate and bleed; often have an
indurated base
Macroscopic differences: Benign vs Malignant
Benign Transitional cell “carcinoma” bladder Malignant squamous cell carcinoma bladder

Pedunculated with uniform texture Sessile, ulcerated, bleeding with indurated base
 Microscopic Differences: Benign vs Malignant
1. Organisation of tumour cells
• Tumour cells may be organised into structures that resemble their tissue of
origin, e.g.; glandular tumours often form glandular (acinar) tumour structures
• The more regular and ordered these structures, the less likely that they are
malignant
• Glands that are haphazard/chaotic in size and organisation suggest malignancy
• Malignant glands may become substantially more anaplastic in more malignant
tumours and lose all glandular organisation
Junction between benign colonic polyp and normal mucosa

Crypts of normal colonic Fern-like structure of benign

mucosa colonic polyp
Adenocarcinoma of the colon
Normal
colonic
mucosa

• Pleomorphic cells
• ­nuclear/cytopl ratio
• Cells “heaped up”
• Necrosis
 Microscopic Differences: Benign vs Malignant
2. Altered cell function and differentiation: Benign and well differentiated malignant
tumours often retain function; anaplastic malignant tumours are more likely to lose all
function or express bizarre functions:
• Synthesis of mucin: occurs in well differentiated adenocarcinomas but not in anaplastic
adenocarcinomas

• Synthesis of keratin: may occur in abnormal locations (keratin pearls) or not at all in anaplastic tumours
• Synthesis of melanin: a primary melanoma usually is pigmented but occasionally a metastasis from a
primary lesion may lose its pigmentation, suggesting more anaplastic change in that subclone of
metastatic cells

• Synthesis of normal or abnormal hormones: the tumour may produce large amounts of normal or
abnormal hormones, e.g.; phaeochromocytoma produces excess normal catecholamines (adrenalin &
noradrenaline); many tumours may produce abnormal "hormones"
 Microscopic Differences: Benign vs Malignant
3. Rate of growth
• Benign: slow, low mitotic rate, well demarcated (encapsulated) expansion
• Malignant: rapid, high mitotic rate & abnormal mitoses; irregular border; not
encapsulated
Note: After surgery benign tumours are unlikely to recur, while malignant tumours are

4. Secondary changes
• Vascularity: benign tumours not very vascular (except a haemangioma!);
malignant tumours are very vascular
• Necrosis/ulceration: not common in benign tumours; common in malignant
Microscopic Differences: Benign vs Malignant
5. Host responses
•Inflammatory response is common around a malignant tumour - tumour seen
as "foreign" by immune system
• May correlate with prognosis e.g. the greater the lymphocyte infiltration in a
melanoma, the better the prognosis
• Malignant tumours may excite a strong fibrous (collagenous) response -
referred to as desmoplasia
 What do I need to know?
• Fundamental and shared characteristics of cancers
• Nomenclature: neoplasia, neoplastic/transformed cells, benign vs malignant tumour
• Naming the cancer hallmarks
• Components of tumours, basic nomenclature of tumours, hamartoma, teratoma
• Features of benign and malignant tumours
• Definition of differentiation, anaplasia and dysplasia
• Macroscopic differences between benign and malignant tumours
• Microscopic differences between benign and malignant tumours