Lecture 8: Fallopian Tubes and Ovaries Flashcards
1
Q
Most common etiologies underlying suppurative salpingitis?
A
- N. gonorrhea = 60% of cases
- C. trachomatis = remainder
- More than one organism can be involved; any pyogenic organism
2
Q
Tuberculosis salpingitis is an important cause of what in endemic countries; what are the main histo features of this disorder?
A
- Infertility
- Caseating granulomas + multinucleated giant cells + epitheliod macrophages
3
Q
What are the most common primary lesions of the fallopian tubes (excluding endometriosis)?
A
- 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.
4
Q
Which uncommon benign tumor may arise in the fallopian tube?
A
Adenomatoid tumor (mesotheliomas)
5
Q
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?
A
Primary Adenocarcinoma
6
Q
In terms of the fallopian tubes what are the most common disorders you must consider?
A
- Ectopic pregnancy
- Endometriosis
- Inflammatory disorders –> Salpingitis
7
Q
What stage do most primary adenocarcinomas of the fallopian tube present at; what is the prognosis of these tumors?
A
- 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
8
Q
New data has suggested that a subset of serous ovarian cancers actually arise from where?
A
Epithelium of the fallopian tube
9
Q
What is the most common cause of an ovarian mass in a reproductive age female?
A
Cystic follicle –> originating from unrutured graafian follicles
10
Q
What are the growth characteristics of cystic follicles and how does size dictate their classification?
A
- Usually multiple and discovered incidentally; BENIGN
- If >2/2.5 cm then called follicle cyst –> may be palpable or cause pelvic pain
11
Q
What are cystic follicles and the larger follicle cysts filled with; how do they appear morphologically?
A
- Filled with a clear, serous fluid
- Lined by gray, glistening membrane
12
Q
How common are luteal cysts and what is their gross appearance that distinguishes them from cystic follicles?
A
- Present in the normal ovaries of reproductive age females
- Lined w/ rim of bright yellow tissue containing luteinized granulosa cells
13
Q
Polycystic ovarian syndrome (PCOS) is a complex endocrine disorder characterized by what findings clinically?
A
- Hyperandrogenism - hirsutism, acne, deep voice, male pattern baldness
- Menstrual irregularities - amenorrhea
- Chronic anovulation
- ↓ fertility
14
Q
Due to increase in free estrone levels, women with PCOS are at an increased risk for what?
A
Endometrial hyperplasia and cancer
15
Q
What underlying metabolic disorders are common in women with PCOS?
A
- Obesity due to altered adipose tissue metabolism
- T2DM due to insulin resistance
- Premature atherosclerosis
16
Q
Majority of ovarian tumors are (benign/malignant) and how does age play a role in this?
A
- 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
17
Q
What are the risk factors associated with malignant serous carcinomas of the ovary?
A
- Nulliparity (low parity) = never given birth
- Family hx
- Heritable mutations: BRCA1 and BRCA2
18
Q
The distinction between low-grade (well-differentiated) and high-grade (moderate to poor differentiated) serous ovarian carcinoma is based on what and correlates with?
A
Degree of nuclear atypia; correlates with patient survival
19
Q
Ovarian and endometrial serous tumors have what characteristic morphologic finding?
A
Psammoma bodies (concentric calcifications)
20
Q
Which precursor lesion associated with sporadic high-grade serous ovarian cancer has been described as originating in the fallopian tube?
A
Serous tubal intraepithelial carcinoma (STIC)
21
Q
Which cystic lesions of the ovary may be the origin of a vast majority of serous ovarian carcinomas?
A
Cortical inclusion cysts
22
Q
How do the genetic mutations observed in low- vs. high-grade serous ovarian carcinomas differ?
A
- 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.
23
Q
What are the morphological features of benign serous ovarian tumors both grossly and microscopically?
A
- Smooth glistening cyst wall w/ NO epithelial thickening or have small papillary projections
- Abundant cilia are found in benign tumors
24
Q
What gross morphological features of serous ovarian carcinomas are features of malignany?
A
- Larger areas of solid or papillary tumor mass
- Tumor irregularity
- Fixation or nodularity of the capsule
25
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**"
26
Serous tubal intraepithelial carcinomas consist of cells morphologically identical to high-grade serous ovarian carcinomas, but are distinguished how?
**LACK** of **invasion**
27
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**
28
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)
29
What is the prognosis of serous ovarian carcinomas dependent on?
Pathologic **classification** of the tumor and **growth** pattern on the **peritoneum**
30
Which genetic mutation is a consistent alteration observed in all type of mucinous tumors of the ovary?
***KRAS* proto-oncogene**
31
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
32
How do mucinous tumors of the ovary appear grossly and what are they filled with?
**Multiloculated** tumors w/ **sticky**, **gelatinous fluid** rich in **glycoproteins**
33
What type of differentiation is observed with **benign** mucinous ovarian tumors?
- **Gastric** or **intestinal** differentiation = **common**
- **Endocervical** type = **uncommon**
34
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
35
What type of growth pattern is characteristic of malignant mucinous carcinomas?
**Confluent** glandular growth = **"expansile" invasion**
36
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**
37
Since mucinous ovarian carcinomas are uncommon, what must they be distinguished from especially with **bilateral** presentation?
**Metastatic mucinous adenocarcinomas**
38
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**)\*\*\*
39
What are the 3 classifications of endometrioid ovarian tumors?
- **Benign** = **endometrioid adenofibromas**
- **Borderline**
- **Malignant**
40
How are endometrioid ovarian tumors distinguished from serous and mucinous tumors?
Presence of **tubular glands** resembling **benign** or **malignant** endometrium
41
Endometrioid ovarian tumors commonly arise in what settings?
- In association w/ **endometriosis** and **borderline** tumors
- 10-30% are accompanied by **carcinoma** of the **endometrium**
42
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
43
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**
44
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
45
How common are bilateral endometrioid ovarian carcinoma and what does bilaterality imply?
- **40% are bilateral**
- Usually implies **extension** of neoplasm beyond **genital tract**
46
What is 5-year survival for pt's with stage I endometrioid ovarian carcinoma?
**75%**
47
What are the 3 **B's** for remembering **B**renner tumors?
- Resemble **b**ladder epithelium (transitional cell tumor)
- "Coffee **b**ean" nuclei on H&E stain
- Usually **b**enign
48
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**
49
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)
50
Common sites of metastasis for ovarian carcinomas?
- **Regional LN's**
- **Lungs**
- **Liver**
- **GI**
- **Opposite ovary** (**50% of cases**)
51
Which serum marker is used in patients w/ known ovarian carcinoma to monitor disease recurrence and progression?
**CA-125** and **HE4** (new)
52
What are the 3 categories of teratomas?
1. **Mature** (benign)
2. **Immature** (malignant)
3. **Monodermal** or **highly specialized**
53
What are the majority of **benign** teratomas are **cystic** referred to as?
**Dermoid cysts**, due to almost always being lined by **skin-like** structures
54
Mature benign (aka cystic teratomas) are most often seen in whom?
**Young women** during **active** reproductive years
55
Occasionally benign teratomas are associated with what paraneoplastic syndrome?
Inflammatory limbic encephalitis
56
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**
57
About 1% of dermoid cysts (benign teratomas) undergo malignant transformation, most often to what?
**Squamous cell carcinoma**
58
What is the karyotype of almost all benign ovarian teratomas?
**46, XX**
59
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**
60
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**
61
What is the ovarian counterpart of testicular seminoma?
Dysgerminoma
62
Which tumor accounts for 50% of malignant ovarian germ cell tumors?
Dysgerminoma
63
Dysgerminomas are most commonly seen in what age group?
**10-30 y/o**; may also be seen in **children**
64
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**
65
Dysgerminomas that produce ↑ levels of hCG correlates with the presence of what cell type?
**Syncytiotrophoblastic GIANT cells**
66
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**
67
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%**
68
Treatment options for dysgerminoma?
- **Salpingo-oophorectomy** for **low-grade**
- These neoplasms **ARE** responsive to **chemotherapy**
69
What is the 2nd most common **malignant** germ-cell tumor of the ovary?
**Yolk Sac Tumor** (aka **endodermal sinus tumor**)
70
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)**
71
What tumor marker is elaborated by yolk sac tumors?
α-fetoprotein (AFP)
72
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**
73
What is the prognosis of yolk sac tumors?
**80% survival** w/ **combination chemotherapy**
74
What do choriocarcinomas of the ovary elaborate which may be useful for diagnosis and detecting recurrences?
↑↑↑ **chorionic gonadotropins** (**hCG**)
75
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
76
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**
77
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**
78
For what 2 reasons are granulosa cells tumors of clinical importance?
1. May elaborate large amounts of **estrogen**
2. May behave like **low-grade malignancies**
79
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**
80
How would an adult present with a granulosa cell tumor?
- **Proliferative breast disease**
- **Endometrial hyperplasia**
- **Endometrial carcinoma**
- Dysfunctional uterine bleeding
81
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**
82
Almost all adult granulosa cell tumors have mutations of what gene?
***FOXL2***
83
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%**
84
How is the course of granulosa tumors composed predominantly of theca cells different?
Almost **never** malignant
85
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
86
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 **inactiv****e**
87
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**
88
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**
89
What is the triad of Meigs Syndrome?
- **Ovarian tumor** (majority are fibromas)
- **Ascites**
- **Pleural effusion** (**hydrothorax**) on the **right**
90
Fibromas, thecomas, and fibrothecomas are benign or malignant?
**Benign**
91
What is the peak incidence for Sertoli-Leydig cell tumors in women?
**10-30 y/o**; can occur at **all** ages
92
Mutation of which gene is common to Sertoli-Leydig cell tumors?
***DICER1***, gene encoding **endonucleases** needed for **micro-RNA** processing
93
Sertoli-Leydig cell tumors arise (unilaterally or bilaterally) and may appear like what other tumor?
**Unilateral** and may resemble **granulosa cell tumors**
94
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**
95
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**
96
What is the predominant hormone elaborated by Hilus cell tumors (pure Leydig cell tumors)?
**Testosterone** --\> hirsutism, voice changes, and clitoralmegaly
97
Which uncommon tumor is composed of germ cells and sex cord-stroma derivatives resembling immature Sertoli and granulosa cells?
Gonadoblastoma
98
In 50% of Gonadoblastoma cases there is co-existence of what other tumor?
**Dysgerminoma**
99
What is the prognosis of Gonadoblastomas?
**Excellent** if completely excised
100
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
101
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
