Lecture 8: Fallopian Tubes and Ovaries Flashcards
Most common etiologies underlying suppurative salpingitis?
- N. gonorrhea = 60% of cases
- C. trachomatis = remainder
- More than one organism can be involved; any pyogenic organism
Tuberculosis salpingitis is an important cause of what in endemic countries; what are the main histo features of this disorder?
- Infertility
- Caseating granulomas + multinucleated giant cells + epitheliod macrophages
What are the most common primary lesions of the fallopian tubes (excluding endometriosis)?
- Paratubal Cysts = small translucent cysts filled w/ clear, serous fluid
- Hydatids of Morgagni = larger cysts found near the fimbriated end of the tube or in the broad ligaments; remnants of müllerian duct.
Which uncommon benign tumor may arise in the fallopian tube?
Adenomatoid tumor (mesotheliomas)
Which rare tumor of the fallopian tube may present as dominant tubal mass on pelvic examination or due to abnormal discharge, bleeding, and occasionally abnormal cells on Pap smear?
Primary Adenocarcinoma
In terms of the fallopian tubes what are the most common disorders you must consider?
- Ectopic pregnancy
- Endometriosis
- Inflammatory disorders –> Salpingitis
What stage do most primary adenocarcinomas of the fallopian tube present at; what is the prognosis of these tumors?
- 50% of the tumors are stage I at diagnosis
- But nearly 40% of pt’s are dead within 5-years
- Higher stage tumors pursue an even more aggressive course
New data has suggested that a subset of serous ovarian cancers actually arise from where?
Epithelium of the fallopian tube
What is the most common cause of an ovarian mass in a reproductive age female?
Cystic follicle –> originating from unrutured graafian follicles
What are the growth characteristics of cystic follicles and how does size dictate their classification?
- Usually multiple and discovered incidentally; BENIGN
- If >2/2.5 cm then called follicle cyst –> may be palpable or cause pelvic pain
What are cystic follicles and the larger follicle cysts filled with; how do they appear morphologically?
- Filled with a clear, serous fluid
- Lined by gray, glistening membrane
How common are luteal cysts and what is their gross appearance that distinguishes them from cystic follicles?
- Present in the normal ovaries of reproductive age females
- Lined w/ rim of bright yellow tissue containing luteinized granulosa cells
Polycystic ovarian syndrome (PCOS) is a complex endocrine disorder characterized by what findings clinically?
- Hyperandrogenism - hirsutism, acne, deep voice, male pattern baldness
- Menstrual irregularities - amenorrhea
- Chronic anovulation
- ↓ fertility
Due to increase in free estrone levels, women with PCOS are at an increased risk for what?
Endometrial hyperplasia and cancer
What underlying metabolic disorders are common in women with PCOS?
- Obesity due to altered adipose tissue metabolism
- T2DM due to insulin resistance
- Premature atherosclerosis
Majority of ovarian tumors are (benign/malignant) and how does age play a role in this?
- 80% are benign, typically occur in younger women btw 20-45 y/o
- Malignant tumors often older women btw ages of 45-65 y/o
What are the risk factors associated with malignant serous carcinomas of the ovary?
- Nulliparity (low parity) = never given birth
- Family hx
- Heritable mutations: BRCA1 and BRCA2
The distinction between low-grade (well-differentiated) and high-grade (moderate to poor differentiated) serous ovarian carcinoma is based on what and correlates with?
Degree of nuclear atypia; correlates with patient survival
Ovarian and endometrial serous tumors have what characteristic morphologic finding?
Psammoma bodies (concentric calcifications)
Which precursor lesion associated with sporadic high-grade serous ovarian cancer has been described as originating in the fallopian tube?
Serous tubal intraepithelial carcinoma (STIC)
Which cystic lesions of the ovary may be the origin of a vast majority of serous ovarian carcinomas?
Cortical inclusion cysts
How do the genetic mutations observed in low- vs. high-grade serous ovarian carcinomas differ?
- Low-grade = mutations in KRAS, BRAF, or ERBB2;* withwild-type*TP53
- High-grade = high frequency of TP53 mutations and lack mutations in either KRAS or BRAF.
What are the morphological features of benign serous ovarian tumors both grossly and microscopically?
- Smooth glistening cyst wall w/ NO epithelial thickening or have small papillary projections
- Abundant cilia are found in benign tumors
What gross morphological features of serous ovarian carcinomas are features of malignany?
- Larger areas of solid or papillary tumor mass
- Tumor irregularity
- Fixation or nodularity of the capsule
What epithelial proliferation pattern is thought to be the precursor to low-grade serous carcinomas?
Growth in a delicate, papillary pattern known as “micropapillary carcinoma”
Serous tubal intraepithelial carcinomas consist of cells morphologically identical to high-grade serous ovarian carcinomas, but are distinguished how?
LACK of invasion
Both low- and high-grade serous ovarian tumors have a propensity to spread where; assoc. w/ what common presenting sign?
- Spread to peritoneal surfaces and omentum
- Commonly assoc. w/ presence of ascites
What is the 5-year survival rate for borderline and malignant serous ovarian carcinomas confined to the ovaries; what is prognosis for same tumor involving the peritoneum?
- Confined to ovary = 100% (borderline) and 70% (malignant)
- Peritoneum = 90% (borderline) and 25% (malignant)
What is the prognosis of serous ovarian carcinomas dependent on?
Pathologic classification of the tumor and growth pattern on the peritoneum
Which genetic mutation is a consistent alteration observed in all type of mucinous tumors of the ovary?
KRAS proto-oncogene
What are some of the major difference between mucinous and serous ovarian tumors in terms of growth patterns?
- Mucinous RARELY involve the surface of the ovary (unlike serous)
- Mucinous are RARELY bilateral
- Mucinous produce larger cystic masses
How do mucinous tumors of the ovary appear grossly and what are they filled with?
Multiloculated tumors w/ sticky, gelatinous fluid rich in glycoproteins
What type of differentiation is observed with benign mucinous ovarian tumors?
- Gastric or intestinal differentiation = common
- Endocervical type = uncommon
How are mucinous borderline tumors distinguished from benign mucinous (cystadenomas) based on morphology?
- Epithelial stratification + tufting; and/or papillary intraglandular growth
- Often appear similar to tubular adenomas or villous adenomas of the intestine
What type of growth pattern is characteristic of malignant mucinous carcinomas?
Confluent glandular growth = “expansile” invasion
What is the 10-year survival for stage I (noninvasive) mucinous carcinoma vs. invasive mucinous carcinoma?
- Stage I = 95%
- Invasive = 90%
- Spread beyond ovary is usually fatal
Since mucinous ovarian carcinomas are uncommon, what must they be distinguished from especially with bilateral presentation?
Metastatic mucinous adenocarcinomas
What does pseudomyxoma peritonei refer to and what is it related to?
- Extensive mucinous ascites + cystic epithelial implants on peritoneal surface + adhesions + frequently involves ovaries
- Almost all cases due to extraovarian source (usually APPENDICEAL)***
What are the 3 classifications of endometrioid ovarian tumors?
- Benign = endometrioid adenofibromas
- Borderline
- Malignant
How are endometrioid ovarian tumors distinguished from serous and mucinous tumors?
Presence of tubular glands resembling benign or malignant endometrium
Endometrioid ovarian tumors commonly arise in what settings?
- In association w/ endometriosis and borderline tumors
- 10-30% are accompanied by carcinoma of the endometrium
How does the age of pt with endometrioid ovarian tumor in setting of ovarian endometriosis differ?
Occur earlier, on average pt’s 10 years younger than normal
Is ovarian endometrioid carcinoma in the setting of carcinoma of the endometrium due to metastasis?
- No, relatively good prognosis suggests the 2 arise independently
- Synchronous primaries
Which mutations are commonly associated with endometrioid ovarian carcinomas?
- Alterations that ↑ PI3K/AKT signaling = PTEN, PIK3CA, ARID1A, and KRAS
- -* Mutations in DNA mismatch repair and CTNNB1
- TP53 mutations common in poorly differentiated tumors
How common are bilateral endometrioid ovarian carcinoma and what does bilaterality imply?
- 40% are bilateral
- Usually implies extension of neoplasm beyond genital tract
What is 5-year survival for pt’s with stage I endometrioid ovarian carcinoma?
75%
What are the 3 B’s for remembering Brenner tumors?
- Resemble bladder epithelium (transitional cell tumor)
- “Coffee bean” nuclei on H&E stain
- Usually benign
What is the gross morphology, growth pattern and characteristics of Brenner tumors of the ovary?
- May be solid or cystic, and 90% are unilateral
- Can be small or massive
- Fibrous stroma resembling normal ovary w/ sharply demarcated nests of epithelium resembling that or urinary tract often w/ mucinous glands in center
What stage do the majority of ovarian carcinoma present in and what are the signs and sx’s?
- Majority present w/ high stage disease; primary reason for relatively poor prognosis of these tumors
- Weakness, weight loss —-> cachexia
- Peritoneal disease –> massive ascites (positive cytology part of staging)
Common sites of metastasis for ovarian carcinomas?
- Regional LN’s
- Lungs
- Liver
- GI
- Opposite ovary (50% of cases)
Which serum marker is used in patients w/ known ovarian carcinoma to monitor disease recurrence and progression?
CA-125 and HE4 (new)
What are the 3 categories of teratomas?
- Mature (benign)
- Immature (malignant)
- Monodermal or highly specialized
What are the majority of benign teratomas are cystic referred to as?
Dermoid cysts, due to almost always being lined by skin-like structures
Mature benign (aka cystic teratomas) are most often seen in whom?
Young women during active reproductive years
Occasionally benign teratomas are associated with what paraneoplastic syndrome?
Inflammatory limbic encephalitis
What is the characteristic gross and microscopic morphology of mature (benign) teratomas?
- Unilocular cysts containing hair + sebaceous material
- Teeth and calcification frequently found within wall
- May contain cartilage, bone, thyroid and neural tissue
About 1% of dermoid cysts (benign teratomas) undergo malignant transformation, most often to what?
Squamous cell carcinoma
What is the karyotype of almost all benign ovarian teratomas?
46, XX
What are struma ovarii composed of and are the bilateral or unilateral teratomas?
- Composed of mature thyroid tissue, may be functional, causing hyperthyroidisim
- ALWAYS unilateral
How do immature malignant teratomas differ from benign teratomas based on their components; who is most often affected?
- Component tissues resemble embryonal and immature fetal tissue; most often primitive neuroepithelium
- Prepubertal adolescents and young women, mean age = 18 y/o
What is the ovarian counterpart of testicular seminoma?
Dysgerminoma
Which tumor accounts for 50% of malignant ovarian germ cell tumors?
Dysgerminoma
Dysgerminomas are most commonly seen in what age group?
10-30 y/o; may also be seen in children
Which proteins expressed by dysgerminomas are useful diagnostic markers and which may serve as therapeutic target?
- OCT-3, OCT-4, and NANOG = maintain pluripotency
- KIT may serve as therapeutic target
Dysgerminomas that produce ↑ levels of hCG correlates with the presence of what cell type?
Syncytiotrophoblastic GIANT cells
What are the characteristic morphological features of dysgerminomas and are they typically bilateral or unilateral?
- Majority are UNILATERAL; may be small or fill entire abdomen
- Large vesicular cells w/ clear cytoplasm + well-defined borders + central nuclei growing in sheets or cords
What is the prognosis of dysgerminomas?
- ALL are malignant, but only 1/3 are aggressive
- Unilateral tumor that has not broken capsule or spread outside ovary has excellent prognosis
- Overall survival >80%
Treatment options for dysgerminoma?
- Salpingo-oophorectomy for low-grade
- These neoplasms ARE responsive to chemotherapy
What is the 2nd most common malignant germ-cell tumor of the ovary?
Yolk Sac Tumor (aka endodermal sinus tumor)
What is the characteristic histologic feature of yolk sac tumors (aka endodermal sinus tumor)?
Glomerulus-like structure composed of central blood vessel enveloped by tumor cells within a space also lined by tumor cells (Schiller-Duval body)
What tumor marker is elaborated by yolk sac tumors?
α-fetoprotein (AFP)
Who are yolk-sac tumors most commonly seen in and what is the most common presentation?
- Child or young woman presenting w/ abdominal pain + rapidly growing pelvic mass
- Typically involving single ovary
What is the prognosis of yolk sac tumors?
80% survival w/ combination chemotherapy
What do choriocarcinomas of the ovary elaborate which may be useful for diagnosis and detecting recurrences?
↑↑↑ chorionic gonadotropins (hCG)
How do choriocarcinomas of the ovary differ from those found in the placenta?
- Generally unresponsive to chemotherapy
- More aggressive and often fatal due to hematogenous metastases at time of dx
Granulosa cell tumors of the ovary are divided into adult and juvenile forms, which is more common and peak age range?
- Adult tumors account for 95% of all granulosa cell tumors
- Majority (2/3’s) occur in postmenopausal women
What small, distinctive, glandlike structures filled with acidophilic material are sometimes seen in granulosa cell tumors and make the diagnosis straight forward?
Call-Exner bodies
For what 2 reasons are granulosa cells tumors of clinical importance?
- May elaborate large amounts of estrogen
- May behave like low-grade malignancies
How would a juvenile granulosa cell tumor commonly present in a child and what age?
- Early breast development
- Early menarche
- Pubic or underarm hair
*ALL before the age of 8
How would an adult present with a granulosa cell tumor?
- Proliferative breast disease
- Endometrial hyperplasia
- Endometrial carcinoma
- Dysfunctional uterine bleeding
Elevated tissue and serum levels of what product of granulosa cells can be useful for identifying granulosa and other sex cord-stromal tumors + monitoring treatment?
Inhibin
Almost all adult granulosa cell tumors have mutations of what gene?
FOXL2
What is the prognosis, chance of malignancy and recurrence like for granulosa cell tumors?
- All are potentially malignant; but histology does NOT predict behavior
- Malignant tumors = generally indolent course and local recurrences may be amendable to surgery
- Recurrences may appear 10-20 years after removal
- 10-year survival = 85%
How is the course of granulosa tumors composed predominantly of theca cells different?
Almost never malignant
What’s an ovarian fibroma, thecoma, and fibrothecoma?
- Fibroma = composed of fibroblasts
- Thecoma = composed of plump spindle cells w/ lipid droplet
- Fibrothecoma = mixture of the cells
How does the hormonal activity of thecomas and fibromas differ?
- Pure thecomas = RARE; but if predominant cell type of fibrothecoma may be hormonally active
- Fibromas as a rule are hormonally inactive
Fibromas of the ovary are typically (bilateral or unilateral) and how do they appear grossly?
- 90% are unilateral
- Usually solid, spherical or slightly lobulated, encapsulated, hard, gray-white masses covered by glistening, intact ovarian serosa
Most ovarian fibromas come to attention how?
- Pelvic mass, sometimes w/ pain
- Large tumors (>6 cm) assoc. w/ ascites and uncommonly hydrothorax, usually only on right side = Meigs Syndrome
- Also assoc. w/ basal cell nevus syndrome
What is the triad of Meigs Syndrome?
- Ovarian tumor (majority are fibromas)
- Ascites
- Pleural effusion (hydrothorax) on the right
Fibromas, thecomas, and fibrothecomas are benign or malignant?
Benign
What is the peak incidence for Sertoli-Leydig cell tumors in women?
10-30 y/o; can occur at all ages
Mutation of which gene is common to Sertoli-Leydig cell tumors?
DICER1, gene encoding endonucleases needed for micro-RNA processing
Sertoli-Leydig cell tumors arise (unilaterally or bilaterally) and may appear like what other tumor?
Unilateral and may resemble granulosa cell tumors
Sertoli-Leydig cell tumors are functional and commonly lead to what signs/sx’s in children and adults?
- Block normal female sexual development in children
- Defeminization –> atrophic breasts, amenorrhea, sterility, and loss of hair
- May progress to striking virilization (hirsutism) assoc. w/ male pattern baldness, hypertophy of clitoris and voice changes
Pure Leydig cell tumors are also known as what; what distinguishing cell type is seen?
- Hilus cell tumor
- UNILATERAL tumor w/ large lipid-laden Leydig cells w/ distinct borders and characteristic cytoplasmic structures called Reinke crystalloids
What is the predominant hormone elaborated by Hilus cell tumors (pure Leydig cell tumors)?
Testosterone –> hirsutism, voice changes, and clitoralmegaly
Which uncommon tumor is composed of germ cells and sex cord-stroma derivatives resembling immature Sertoli and granulosa cells?
Gonadoblastoma
In 50% of Gonadoblastoma cases there is co-existence of what other tumor?
Dysgerminoma
What is the prognosis of Gonadoblastomas?
Excellent if completely excised
The most common metastatic tumors of the ovary are derived from tumors of which origin?
Müllerian origin = uterus, fallopian tubes, contralateral ovary, or pelvic peritoneum
What is a Krukenberg tumor and what is it characterized by?
- Bilateral tumor of the ovaries from a mestastic GI carcinoma (diffuse-type)
- Composed of mucin-producing, signet-ring cancer cells
