Fallopian tube Disorders

- Inflammatory conditions
o Gonococcus (60%) followed by Chlamydiae
o Tuberculous salpingitis rate in the United States
- Ectopic (tubal) pregnancy
o Implantation of a fetus outside the normal uterine location
o Risk factors
 Scarring from previous PID (most common cause)
 Endometriosis, altered tubal motility, SIN, Progestin-only pill, previous tubal ligation
o Sites of implantation
 Mostly within tubes, broad ampullary portion below the fimbriae
 Ovaries, abdominal cavity
o Clinical findings
 Sudden onset of lower abdominal pain and tenderness (95% of cases)
 Usually ~6 weeks after a previous normal menstrual period
 Classic triad - “Vaginal Bleeding, Pelvic Pain, Adnexal Mass”
o Diagnosis β-hCG is the best screening test (Urine/Serum)
 Vaginal ultrasound is the confirmatory test
 Laparoscopy is used in equivocal cases
- Endometriosis
- Tumors and cysts
o Hydatids of Morgagni (from Mullerian duct remnants)
o Adenomatoid tumors (mesotheliomas)
o Adenocarcinomas (rare)
- Salpingitis isthmica nodosa (SIN) “Tubal Diverticulosis”
o invagination of the mucosa into the muscle  Produces nodules in the tube that narrow the lumen
o Probably a post-infectious reaction (previous C. trachomatis infection)
o Complications Infertility, Ectopic Pregnancy
o Diagnosis with hysterosalpingography Beading appearance in areas of constriction

Ovarian Disorders
- Oophorits Complication of mumps or PID
- Stromal hyperthecosis Causes bilateral ovarian enlargement
o Primarily in obese postmenopausal women
o Hypercellular ovarian stroma
• Vacuolated (luteinized) stromal hilar cells are present
• Synthesize excess androgens
• May cause hirsutism or virilization
o Association with acanthosis nigricans, insulin resistance, PCOS, Hypertension
Non-neoplastic and Functional Cysts
- Cystic follicles – very common, 1 to 2 cm in diameter, arise from
o Unruptured Graafian follicles
o Follicles that have ruptured and immediately sealed
- Follicular cyst (if >2 cm in diameter)
o Most common ovarian mass Can cause pelvic pain
o Granulosa cells may be absent, may be lined by theca cells
o Ex. A 19-year-old woman has the sudden onset of abdominal pain. On physical examination, there is pelvic pain on palpation. Her stool is negative
for occult blood. The serum and urine pregnancy tests are negative. Transvaginal ultrasound shows no intrauterine gestational sac, and uterus
and adnexa are normal in size. Culdocentesis yields a small amount of blood-tinged fluid. Which of the following has most likely led to these
findings? Follicle cyst
 Follicle cysts and lutein cysts of the ovary are so common that they are virtually normal findings and incidentalomas in diagnostic
studies. Though most of them are less than 2 cm and asymptomatic, occasionally they can be larger (4 to 5 cm) and even enlarge a
little more in response to midcycle hormones, occasionally rupturing to produce pain and bleeding.
- Luteal cyst
o Most common ovarian mass in pregnancy
o Lined by a rim of bright yellow tissue containing luteinized granulosa cells

Poly Cystic Ovarian Syndrome (PCOS), Stein Leventhal syndrome

- Hyperandrogenism, menstrual abnormalities, polycystic ovaries, chronic anovulation, and decreased fertility
- Associated with obesity, type 2 diabetes, and premature atherosclerosis
o Insulin resistance and altered adipose tissue metabolism
- Numerous cystic follicles or follicle cysts that enlarge the ovaries
- Risk for endometrial hyperplasia and carcinoma
- Usually young women of reproductive age who present with oligomenorrhea or secondary amenorrhea, hirsutism (testosterone), infertility (estrogen), or
obesity
- Lab studies: elevated luteinizing hormone (LH), low follicle-stimulating hormone (FSH), and elevated testosterone
- Ex. A 21-year-old woman experienced menarche at age 14 years and had regular menstrual cycles for the next 3 years. For the past year, she has had
oligomenorrhea and has developed hirsutism. She has noticed a 10-kg weight gain in the past 4 months. On pelvic examination, there are no vaginal or
cervical lesions, the uterus is normal in size, and the adnexa are prominent. A pelvic ultrasound scan shows that each ovary is twice normal size, whereas the
uterus is normal in size. Magnetic resonance imaging is shown in the figure. Which of the following conditions is most likely to be present in this woman?
Poly Cystic Ovarian Syndrome
Tumors of the ovary
Grouped according to origin from each of the 3 main ovarian cell types
- Müllerian Epithelium
- Germ Cells
- Sex Cord-stromal Cells

Epithelial tumors Arise from Müllerian epithelium

- 3 major histologic types
o Serous
o Mucinous
o Endometrioid
- Classified as Benign, Borderline, and Malignant
- Benign tumors
o Cystadenomas (cystic areas)
o Cystadenofibromas (cystic and fibrous areas)
o Adenofibromas (predominantly fibrous areas)
- Malignant tumors with cystic component
o Cystadenocarcinomas
o Ex. A 35-year-old woman has had increasing abdominal enlargement for the past 6 months. She states that she feels like she is pregnant, but
results of a pregnancy test are negative. On physical examination, there is abdominal distention with a fluid wave. A pelvic ultrasound scan shows
bilateral cystic ovarian masses, 10 cm on the right and 7 cm on the left. The masses are surgically removed. On gross examination, the excised
masses are unilocular cysts filled with clear fluid, and papillary projections extend into the central lumen of the cyst. Microscopic examination
shows that the papillae are covered with atypical cuboidal cells that invade underlying stroma. Psammoma bodies are present. What is the most
likely diagnosis? Cystadenocarcinoma
o Ex. A 40-year-old woman has noticed progressive enlargement of the abdomen over the past 5 months, although her diet has not changed, and
she has been exercising more. Physical examination shows no palpable masses, but a fluid wave is present. Paracentesis yields 500 mL of slightly
cloudy fluid. Cytologic examination of the fluid shows malignant cells. An abdominal ultrasound scan shows a 15-cm multilobular mass that
involves the right adnexal region. The uterus is normal in size. The mass is surgically removed; the figure shows the gross features of a section of
the excised mass. What is the most likely diagnosis? Mucinous cystadenocarcinoma
 Mucinous tumors of the ovary are of epithelial origin, are less common than serous tumors, and tend to be multiloculated. The
appearance of ascites suggests metastases, which is most common with surface epithelial neoplasms of the ovary.

Serous Tumor
- Risk factors
o Nulliparity Higher frequency of carcinoma
o Family history
o Heritable mutations Inherited germline mutations in BRCA1 & BRCA2 (20 to 60% risk by 70 years )
 Low-grade tumors arising in serous borderline tumors - mutations in KRAS, BRAF, or ERBB2 oncogenes, PIK3CA, RB.
 High-grade familial tumors - BRCA -1/2, TP53
 High-grade sporadic – No BRCA ½
o Women 40 to 59 years of age who have taken oral contraceptives or undergone tubal ligation have a lower risk of developing ovarian cancer
- Origin of tumors
o High-grade serous carcinomas arise from the fallopian tube
o Arise from cortical inclusion cysts (invagination of the surface epithelium, followed by serous metaplasia)
o Arise from implantation of detached fallopian tube epithelium at sites where ovulation has disrupted the surface of the ovary
- Women at high-risk for ovarian carcinoma (BRCA mutation carriers and women with strong family history of breast/ ovarian cancer), now undergo
salpingo-oophorectomy, instead of simple oophorectomy
- Gross Morphology
o Multicystic lesion or mass projecting from the ovarian surface
o Benign tumors Smooth glistening cyst wall, no epithelial thickening/papillary projections
o Borderline tumors Increases papillary projections
o Malignant tumors Larger areas of solid or papillary tumor mass, tumor irregularity, and fixation or nodularity of the capsule
o Bilateral 20% of benign, 30% of borderline and 66% of serous carcinomas
- Microscopic features
o Benign Columnar epithelium with abundant cilia
o Borderline tumors Increased complexity of the stromal papillae, stratification of the epithelium and mild nuclear atypia, but No invasion
o High-grade serous carcinomas  More complex growth patterns, infiltration of the underlying stroma
 Tumor cells display marked nuclear atypia (pleomorphism, atypical mitotic figures, and multi-nucleation)
 Concentric calcifications (Psammoma bodies)
- Serous tumors of ovary
o Both low- and high-grade, spread to the peritoneal surfaces and omentum and are commonly associated with ascites
o Extent of the spread outside the ovary determines the stage of the disease
o 5-year survival rate for borderline and malignant tumors
 Confined to ovary : 100% and 70%
 Involving the peritoneum : 90% and 25%
o 5-year survival is not synonymous with cure
- Ex. A 56-year-old woman has had weight loss accompanied by abdominal enlargement for the past 5 months. There is a family history of breast and ovarian
carcinoma. On physical examination, there are no lesions of the cervix, and the uterus is normal in size, but there is a left adnexal mass. An abdominal
ultrasound scan shows a 10-cm cystic mass in the left adnexal region, with scattered 1-cm peritoneal nodules, and ascites. Cytologic studies of peritoneal
fluid show malignant cells. Which of the following mutated genes is most likely a factor in the development of this neoplasm? BRCA1
o Some familial cases of ovarian carcinoma (usually serous cystadenocarcinoma) are associated with the homozygous loss of the BRCA1 gene. This
tumor-suppressor gene also plays a role in the development of familial breast cancers
Mucinous Tumors
• 20% to 25% of all ovarian neoplasms, 3% of all ovarian cancers
• Mainly in middle adult life
• Mutation of the KRAS proto-oncogene
• Surface of ovary is rarely involved
• Only 5% of tumors are bilateral
• Larger cystic masses up to 25 kg
• Multiloculated tumors filled with sticky, gelatinous fluid rich in glycoproteins
• Epithelial lining - tall, columnar epithelial cells with apical mucin that lack cilia
• Gastric or intestinal type differentiation (more common)
• Endocervical type
• Borderline tumors
• Epithelial stratification, tufting, and/or papillary intraglandular growth
• Carcinomas
• Confluent glandular growth - “expansile” invasion
• 10-year survival rates
• Stage I, noninvasive “intraepithelial carcinomas” >95%
• Frankly invasive malignant tumors 90%
• Mucinous carcinomas rarely spread beyond the ovary
• must be distinguished from metastatic mucinous adenocarcinomas

Pseudomyxoma peritonei
- Extensive mucinous ascites
- Cystic epithelial implants on the peritoneal surfaces
- Adhesions
- Frequent involvement of the ovaries
- If extensive, may result in intestinal obstruction and death
- Source In almost all cases, extraovarian (usually appendiceal)
- Ex. A 42-year-old woman has noted dull lower abdominal pain for the past year. She reports no abnormal bleeding. On physical examination there is a large
left adnexal mass. The pregnancy test is negative. Transvaginal ultrasound shows a right adnexal 10-cm cystic mass filled with fluid. The mass is removed and
has the microscopic appearance shown in the figure. Which of the following is most likely to be associated with this lesion? Peritoneal implants
o This is a borderline serous tumor of the ovary, and the figure shows a complex papillary projection into the cyst lumen. This is the most common
serous ovarian tumor, and though most act in a benign fashion even when peritoneal implants are present, some tend to recur, particularly when
KRAS or BRAF mutations are present, and the implants are invasive.

Endometrioid Ovarian Tumors

- 10 to 15% of all ovarian cancers, 40% are bilateral
- Tubular glands resembling endometrium
- Benign (endometrioid adenofibromas) and borderline are uncommon
- Endometrioid carcinomas
o May arise in the setting of endometriosis (15 to 20% cases)
o TP53 and PTEN mutations

Transitional Cell Tumors

- 10% of ovarian epithelial tumors mostly unilateral (90%)
- Neoplastic cells resembling urothelium
- Usually benign (Brenner tumor)
- Fibrous stroma + Nests of Transitional cell epithelium
- If some malignant cells are present - Malignant Brenner tumor
- If >50% malignant transitional epithelium - Transitional cell carcinoma
- Lower abdominal pain and abdominal enlargement
- Gastrointestinal complaints, urinary frequency, dysuria
- Benign lesions are easily resected and cured
- Malignant tumors
o Most women present with high stage disease
o Progressive weakness, weight loss, and cachexia
o Massive ascites with exfoliated tumor cells
o Peritoneal pattern of spread
o CA-125 : to monitor disease recurrence/progression

Germ cell tumors

- Teratomas
o Mature (benign), Immature (malignant), Monodermal or highly specialized
o Unilocular cysts containing hair and sebaceous material
o Cut surface: thin wall lined by an opaque, gray-white, wrinkled epidermis, with hair shafts, tooth structures and areas of calcification
o Microscopically
 Cyst wall composed of stratified squamous epithelium with underlying sebaceous glands, hair shafts, other skin adnexal structures
 Tissues from other germ layers - cartilage, bone, thyroid, and neural tissue
 Sometimes associated with other tumors
o Mature benign teratomas (Dermoid cysts)
 Mostly cystic, lined by skin-like structures may be bilateral
 Young women during the active reproductive years
 May be associated with paraneoplastic ‘Inflammatory Limbic Encephalitis’
 1% undergo malignant transformation, mostly to squamous cell carcinoma
  Ex. A 33-year-old woman has had dull, constant abdominal pain for 6 months. On physical examination, the only finding is a right
adnexal mass. CT scan of the pelvis shows a 7-cm circumscribed cystic mass on the right ovary, and it contains irregular calcifications.
The right fallopian tube and ovary are surgically excised. The gross appearance of the ovary, which has been opened, is shown in the
figure. Microscopic examination of this lesion is most likely to show which of the following? Mature squamous epithelium
 A cystic tumor with a mass of hair in the lumen is the typical appearance of a mature cystic teratoma. This tumor also is
known as a dermoid cyst because it is cystic and filled with hair and sebum derived from well-differentiated ectodermal
structures. Teratomas with mature tissue elements are benign tumors of germ cell origin, and they can contain various
ectodermally, endodermally, and mesodermally derived tissues.
o Monodermal or Specialized Teratomas
 Rare tumors, always unilateral
 Struma ovarii Composed entirely of mature thyroid tissue
 May be functional and cause hyperthyroidism
 Ovarian carcinoid Arises from intestinal tissue found in teratomas
 Can cause carcinoid syndrome even without hepatic metastases
 Must be distinguished from metastatic intestinal carcinoid (usually bilateral)
 2% of carcinoids in teratomas metastasize
o Immature Malignant Teratomas
 Rare tumors
 Component tissues resemble embryonal and immature fetal tissue
 Prepubertal adolescents and young women (mean age 18 years)
 Immature neuroepithelium, cartilage, bone, muscle, and other elements along with areas of necrosis and hemorrhage
 Risk for extraovarian spread depends on histologic grade of tumor (I to III), which is based on the proportion of immature
neuroepithelium
 Ex. A 23-year-old woman has had pelvic discomfort for 4 months. On pelvic examination, there is a large, nontender, right adnexal
mass. An abdominal CT scan shows the 11-cm mass to be solid and circumscribed. On surgical removal, the mass is solid and white,
with small areas of necrosis. Microscopically, it contains mostly primitive mesenchymal cells along with some cartilage, muscle, and
foci of neuroepithelial differentiation. What is the most likely diagnosis? Immature teratoma
 Immature teratomas are not cystic like mature teratomas. Tissues derived from multiple germ cell layers are present, as in
all teratomas, but at least one immature tissue element is present. Often that immature element is neuroectodermal tissue.
The less differentiated and more numerous the neuroepithelial elements, the higher the grade and the worse the
prognosis. Adjuvant chemotherapy and radiotherapy yield a high response rate.
- Dysgerminoma
o Ovarian counterpart of testicular seminoma
o 2% of ovarian cancers, 50% of malignant ovarian germ cell tumors
o Mostly 2nd and 3rd decades, some in patients with gonadal dysgenesis
o Most tumors have no endocrine function, few may have elevated levels of HCG that correlates with the presence of syncytiotrophoblastic giant
cells
o Express OCT-3, OCT4, NANOG (transcription factors implicated in maintenance of pluripotency) and the receptor tyrosine kinase KIT
o Cut surface: solid yellow-white to gray-pink, soft and fleshy
o Microscopic:
 Sheets/cords of tumor cells separated by scant fibrous stroma, infiltrated by mature lymphocytes
 Large vesicular cells with clear cytoplasm, well-defined cell boundaries, and centrally placed regular nuclei
o A unilateral tumor without capsular infiltration or confined to ovary up to 96% cure rate after simple salpingo-oophorectomy
o Responsive to chemotherapy
- Yolk Sac Tumor, “Endodermal sinus tumor”
o 2nd most common malignant germ cell tumor, arise from germ cells differentiating along extraembryonic yolk sac lineage, elaborate AFP
o Schiller-Duval body glomerulus-like structure with central blood vessel enveloped by tumor cells within a space that is also lined by tumor cells
o Intracellular and extracellular hyaline droplets (stain for α-fetoprotein)
o Children/young women with abdominal pain and rapidly growing pelvic mass
- Choriocarcinoma
o Extraembryonic differentiation of malignant germ cells
o Mostly in combination with other germ cell tumors, pure form is rare
o Histologically identical to placental lesions
o Aggressive and have usually metastasized hematogenously to the lungs, liver, bone, and other sites by the time of diagnosis
o High levels of chorionic gonadotropins (HCG)
o Unresponsive to chemotherapy and often fatal (unlike placental tumors)

Sex Cord-Stroma Tumors

- Granulosa Cell Tumor
o Produce large amount of estrogen
o Adult and juvenile granulosa cell tumors
o 5% of all ovarian tumors (95% are adult GCTs – mostly postmenopausal)
o Mostly unilateral, hormonally active tumors – yellow on cut surface
o Histology:
 Small, cuboidal to polygonal cells
 Anastomosing cords, sheets, or strands
 Call-Exner bodies: small, distinctive, gland-like structures filled with an acidophilic material resembling immature follicles
 Luteinized granulosa-theca cell tumors
o Clinical Features
 May elaborate large amounts of estrogen
 In pre-pubertal girls: precocious sexual development
 In adult women: can lead to proliferative breast disease, endometrial hyperplasia and carcinoma
 May produce androgens, masculinizing the patient
  May behave like low-grade malignancies
 Potentially malignant (5 to 25%)
 10-year survival rate is approximately 85%
 Elevated tissue and serum levels of inhibin
 Mutations of the FOXL2 gene in 97% of adult granulosa cell tumors
o Ex. A 42-year-old woman has had menometrorrhagia for the past 2 months. She has no history of prior irregular menstrual bleeding,
and she has not yet reached menopause. On physical examination, there are no vaginal or cervical lesions, and the uterus appears
normal in size, but there is a right adnexal mass. An abdominal ultrasound scan shows the presence of a 7-cm solid right adnexal
mass. Endometrial biopsy shows hyperplastic endometrium, but no cellular atypia. What is the most likely lesion that underlies her
menstrual abnormalities? Granulosa-theca cell tumor
 The mass is probably producing estrogen, which has led to endometrial hyperplasia. Estrogen-producing tumors of the
ovary are typically sex cord tumors, such as a granulosa-theca cell tumor or a thecoma-fibroma, the former more often
being functional.
- Fibromas, Thecomas, and Fibrothecomas
o Tumors arising in the ovarian stroma, 4% of all ovarian tumors
o Pure Fibromas
 Composed of fibroblasts (hormonally inactive)
o Pure thecomas
 Plump spindle cells with lipid droplets (hormonally active)
o Mostly fibrothecomas
 Unilateral in 90% of cases
 Solid, encapsulated, hard, gray-white masses covered by glistening, intact ovarian serosa
 Well-differentiated fibroblasts and a scant interspersed collagenous stroma
 Focal areas of thecal differentiation
o Ex. A 52-year-old woman has had dull pain in the lower abdomen for the past 6 months and minimal vaginal bleeding on three occasions. Her last
menstrual period was 2 years ago. Pelvic examination shows a right adnexal mass, and the uterus appears normal in size. An abdominal
ultrasound scan shows an 8-cm solid mass, a small amount of ascites, and a right pleural effusion. A total abdominal hysterectomy is performed,
and the mass is determined to be an ovarian fibrothecoma. Which of the following additional lesions is most likely to be found in the excised
specimen? Endometrial hyperplasia
 Fibromas and thecomas are sex cord–stromal tumors that may be hormonally active and secrete estrogens that can lead to
endometrial hyperplasia or even carcinoma
- Fibro-thecomas associations
o Meigs syndrome
 Ovarian tumor > 6 cm in diameter
 Ascites
 Hydrothorax, usually only on the right side
o Basal cell nevus syndrome
- Sertoli-Leydig Cell Tumors
o Functional tumors, produce masculinization or defeminization
o Peak incidence in 2nd and 3rd decades, DICER1 mutations in >50% cases
o Unilateral and may resemble granulosa cell tumors grossly
o Cut surface - solid and gray to golden brown
o Well-differentiated tumors show tubules composed of Sertoli cells or Leydig cells interspersed with stroma
o Ex. A clinical study of women diagnosed with ovarian neoplasms reveals that 1 in 200 develop masculinizing signs and symptoms, including
hirsutism, acne, breast atrophy, and amenorrhea. These women are found to have well-circumscribed, lobulated, firm, yellow mass lesions
averaging 5 cm. Microscopically they have plump pink cells that show positive immunohistochemical staining for inhibin. Which of the following
neoplasms are most likely to have these features? Sertoli-Leydig Cell Tumors
 The Sertoli cell group of ovarian neoplasms mimics testicular differentiation and may produce androgens. These neoplasms tend to be
better differentiated and act in a more benign fashion.
- Hilus cell tumors (pure Leydig cell tumors)
o Rare, unilateral tumors
o Large lipid-laden Leydig cells with distinct borders and characteristic cytoplasmic structures called Reinke crystalloids
o Hirsutism, voice changes, and clitoral enlargement
o The tumors produce predominantly testosterone
o Treatment is surgical excision
- Other tumors
o Pregnancy luteoma
 Resembles corpus luteum of pregnancy
 May produce virilization in pregnant patients and their female infants
o Gonadoblastoma
 Germ cells + sex cord-stroma derivatives (immature Sertoli and granulosa cells)
 In individuals with abnormal sexual development
 In gonads of indeterminate nature
 80% are phenotypic females
 20% are phenotypic males (undescended testicles, female internal secondary organs)
 Co-existent dysgerminoma in 50% of the cases
 Excellent prognosis with complete excision
- Metastatic Tumors
o Most common metastatic tumors
 derived from tumors of müllerian origin: the uterus, fallopian tube, contralateral ovary, or pelvic peritoneum
o Most common extra-müllerian tumors metastatic to ovary
 Carcinomas of the breast and gastrointestinal tract, including colon, stomach, biliary tract, and pancreas
 Pseudomyxoma peritonei - derived from appendiceal tumors
 Krukenberg tumor- bilateral metastases composed of mucin-producing, signet-ring cancer cells, most often of gastric origin