Overview: GYN Pathology Flashcards by Federico Girardi

Vulva

Raised, wart-like growths
Infectious etiology or reactive conditions of unknown etiology
- Conditions with unknown etiology:
  - Fibroepithelial polyps (skin tags)
  - Vulvar squamous papillomas
- Conditions with sexual transmission:
  - Condyloma acuminatum (HPV)
  - Condyloma larum (syphilis)

Benign exophytic lesions

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Vulva

Benign genital warts caused by HPV infection
- Low oncogenic risk HPV –> types 6 & 11
Sexually transmitted
Occur in vulva, perineum, perianal region & anus, vagina, and cervix (less commonly)
- Penile, urethral, and perianal condylomata in men
Usually multiple lesions (may be solitary)

Condyloma acuminata (genital wart)

Benign exophytic lesion

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Vulva

Architecture: papillary, exophytic
- Tree-like FV cores of stroma covered by thickened squamous epithelium
Epithelium: koilocytic atypia
- Nuclear enlargement
- Nuclear hyperchromasia
- Multinucleation
- Perinuclear cytoplasmic vacuolization (halo)

Histology

Condylomata acuminata

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Rare malignant neoplasm: 3% of genital cancers in females
30% associated with high-risk HPV (type 16)
- Classic VIN
- Develops from in situ lesion
70% not related to HPV
- Differentiated VIN
- Develops from premalignant lesion

Epidemiology

VIN = vulvar intraepithelial neoplasia

Vulvar carcinoma

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Vulva

Younger age
Multifocal lesions
A/w CIN and/or VAIN
Hx: STD, smoking, immunodeficiency
Precursor to basaloid & warty carcinomas

Classic VIN

VIN, HPV positive (16) type

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Vulva

Older age
Unifocal lesions
A/w inflammation, lichen sclerosus por squamos cell hyperplasia
p53 mutation
Precursor to keratinized squamous carcinomas

Differentiated VIN (VIN simplex)

VIN, HPV negative type

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Vulva

In situ lesion
Epidermal thickening
Nuclear atypia & enlargement
Hyperchromasia
Increased mitoses & lack of cell maturation w/ small basaloid cells extending to surface
- Basaloid = blue cells with high N:C ratio
- Basaloid cells span entire epithelium

Histology

Classic VIN

VIN, HPV-pos

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Vulva

Invasive lesion
Nests & cords of small, immature basaloid cells
- Immature cells resembling basal layer of normal epithelium
Invasive tumor w/ central necrosis

Histology

Basaloid vulvar carcinoma

VIN, HPV-pos; basaloid & warty carcinoma

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Vulva

In situ lesion
Mature superficial layers & atypia of basal layer
- Basal cells at basal layer
- Differentiated cells towards surface
Hyperkeratosis

Histology

Differentiated VIN

VIN, HPV-neg

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Vulva

Invasive lesion
Nests & cords of malignant squamous epithelium with keratin pearls

Histology

Well-differentiated vulvar SCC

HPV-neg; keratinized squamous carcinoma

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Vulva

Pruritis
Pain
Discharge
Bleeding

Clinical Presentation

Vulvar SCC

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Vulva

Usually solitary lesion
Exophytic mass +/1 ulceration
Ulcerated tumors may mimic STD

Histology

Vulvar SCC

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Vulva

Spread: direct extension to adjacent structures
- Urethra, bladder, vagina, anus, rectum
Metastases: femoral & inguinal lymph nodes
- Distant metastases may occur (e.g., bone)
Recurrence: usually local

Vulvar SCC

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Vagina

Normal pre-menopausal vaginal mucosa

Histology

Stratified squamous epithelium
Non-keratinized
Rich in glycogen, driven by estrogen

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Vagina

Normal post-menopausal vaginal mucosa

Histology

Stratified squamous epithelium
Non-keratinized
Atrophic

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Vagina

Normal stratified squamous epithelium

Histology

Basal cells
- Small undifferentiated cells that resemble histiocytes
- Seldom seen in pap smear –> sometimes w/ atrophy
Parabasal cells
- 1st to acquire squamous features
  - Dense cytoplasm / cell borders
- Moderate cytoplasm & nuclei (50 um)
- Cytoplasm = abundant, thin, blue, transparent
Intermediate cells
- Key reference for nuclear size
  - Nucleus = RBC (35 um)
- Chromatin = fine texture; normochromatic
- Slightly larger than parabasal cells
Superficial cells
- Final surface cell type
- Similar to intermediate cells except pyknotic nuclei (India ink dot-like)

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Vagina

HPV infection
VIN / CIN or vulvar / cervical SCC
Immunosuppression
Prior pelvic irradiation for benign or malignant disease

Risk Factors

Vaginal cancer

Both VAIN & vaginal SCC

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Tumor associated with in utero / prenatal exposure to diethylstilbestrol (DES)

Vaginal clear cell carcinoma

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Vagina

Most common primary malignant vaginal neoplasm in adults

Vaginal SCC

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Vagina

Rare tumor: 0.6/100,000 women/year
Secondary carcinoma more common than primary
- Direct extension or metastasis via lymphatics / blood vessels
- Especially from cervical SCC
Most patients are post-menopausal

Epidemiology

Vaginal SCC

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Vagina

Painless vaginal bleeding / discharge
Dysuria
Urinary frequency

Clinical Presentation

Vaginal SCC

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Vagina

Tumors range from microscopic to large
May be indurated, ulcerated, or exophytic

Gross Appearance

Vaginal SCC

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Vagina

Spread: direct extension to mucosa of bladder or rectum
Metastases: inguinal or pelvic lymph nodes
- Distant metastases may occur (e.g., pulmonary)
Recurrence: usually local

Vaginal SCC

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Vagina

Greatest risk factor for vaginal SCC

Risk Factors

Previous carcinoma of cervix / vulva

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# Cervix Ectocervix vs. Endocervix | Histology

* Ectocervix: mature stratified squamous epithelium; outside external os * Endocervix: columnar, mucus-secreting epithelium; between internal os & external os

# Cervix Region of cervix susceptible to HPV infections

Transformation zone | Columnar epithelium abuts squamous epithelium; immature squamous cells

* Approx. 90% of deaths occur in low- & middle-income countries * Highest incidence: Latin America, the Caribbean, Africa, and South & Southeast Asia | Epidemiology

Cervical cancer

# Infections * Common cause of STD in US & worldwide * Can progress to CIN & invasive SCC

HPV

# HPV HPV types 6 & 11 | Genotypes

* Low-risk oncogenes * Benign cervical changes * Progress to genital warts

# HPV HPV types 16 & 18 | Genotypes

* High-risk oncogenes * Premalignant cervical changes * Progress to cervical cancer, anal & other cancers

# HPV Natural history of HPV infection

* Within 1 year: initial HPV infection --> * Cleared HPV infection * CIN 1 --> cleared HPV infection * CIN 1 --> persistent infection * Persistent infection * 1-5 years: persistent infection --> * CIN 2/3 * CIN 2/3 --> cleared HPV infection * Decades: CIN 2/3 * Cervical cancer * HPV infection is cleared in 6-12 mos in 70% of women, <24 mos in 90% of women

# Cervix * Mild cervical dysplasia (CIN 1) * Clinical & morphological manifestation of productive HPV infection * Most common & benign form of CIN * Usually resolves spontaenously within 2 years * Low-risk of concurrent or future cancer | Bethesda System

LSIL | LSIL = low-grade squamous intraepithelial lesion

# Cervix * Moderate & severe dysplasia (CIN 2/3) * CIS (CIN 3) * Significant risk of progressing to invasive cancer if untreated | Categories of squamous cell abnormalities

HSIL | HSIL = high-grade squamous intraepithelial lesion

# Cervix | Squamous Intraepithelial Lesions

# Cervix * Proliferation of basal / parabasal cels with abnormal nuclear features * Little cytoplasmic maturation in lower third but maturation begins in middle third & is relatively normal in upper third * Mitotic figures limited to lower third of epithelium * Diagnostic HPV cytopathic effect = koilocytes: * Multinucleation * Nuclear enlargement & pleomorphism * Nuclear hyperchromasia * Nuclear membrane irregularities * Perinuclear halos | Histology

LSIL | Previously CIN 1

# Cervix * Abnormal nuclear features: * Increased nuclear size & N:C ratios * Irregular nuclear membranes * Little / no cytoplasmic differentiation in middle & upper thirds of epithelium * Mitotic figures may be found in middle and/or upper thirds of epithelium | Histology

HSIL

# Cervix Spectrum of CIN | Classification

1. Normal: normal squamous epithelium 2. LSIL (CIN 1): koilocytic atypia 3. HSIL (CIN 2): progressive atypia & expansion of immature basal cells above lower 1/3 of epithelium 4. HSIL (CIN 3): diffuse atypia; loss of maturation & expansion of immature basal cells to epithelial surface

# Cervix 1. Average age: 40-50 yo 2. High-risk HPV exposure: early age at 1st intercourse, multiple sexual partneres 3. Smoking 4. Immunodeficiency | Risk Factors

Invasive cervical SCC

# Cervix * Vaginal bleeding (especially post-coital) * Cervical discharge * Dyspareunia (painful intercourse) * Dysuria | Clinical Presentation

Invasive cervical SCC

# Cervix Invasive cervical SCC | Treatment

Surgical * Small tumors: cone biopsy * Large tumors: hysterectomy & LN dissection

# Cervix * Endocervical glands lined by crowded, atypical epithelial cells * Hyperchromatic nuclei containing coarse or granular chromatin * Increased N/C ratio * Mitotic figures common | Histology

Cervical adenocarcinoma in situ (AIS)

# Cervix Most common histologic type of cervical adenocarcinoma

Usual type * Glands exhibit a hybrid of endocervical & endometrioid differentiatiom

# Cervix * Patients are usually asymptomatic * Symptomatic patients present with abnormal vaginal bleeding | Clinical Presentation

Cervical AIS

# Cervix Cervical AIS | Epidemiology

* Less common than CIN (SIL) * Associated with high-risk HPV (most frequently type 18)

# Cervix Cervical AIS | Approach to Diagnosis

* Incidental finding in cervical biopsy done for CIN * Abnormal glandular cells detected on Pap smear

# Menstrual Cycle Days 0 - 14

* LH & FSH: peak before ovulation * LH surge at ~Day 14 triggers ovulation * Estrogen: peaks before ovulation * Secreted by follicle * Progesterone: low * Ovary: follicular phase; ends with ovulation * Ovum is ejected from follicle * Remaining follicle becomes corpus lutem * Endometrium: proliferative phase * Driven by estrogen

# Menstrual Cycle * Tubular shaped glands * Pseudostratified nuclei * Mitotic figures present | Histology

Proliferative endometrium | Cycle day 1-15

# Menstrual Cycle Days 15 - 28

* LH & FSH: low * Estrogen: low * Progesterone: high * Secreted by corpus luteum in ovary * Ovary: luteal phase * Endometrium: secretory phase * Driven by progesterone

# Uterus Increased proliferation of the endometrial glands relative to the stroma, resulting in crowded glands * Tends to be diffuse but may occasionally be focal | Pathophysiology

Endometrial hyperplasia

# Uterus * Increased gland/stroma ratio compared to normal proliferative endometrium * Glands with abnormal shapes, irregular sizes | Histology

Endometrial hyperplasia

# Uterus Prolonged estrogen stimulation of endometrium | Etiology

Endometrial hyperplasia

# Uterus Endometrial hyperplasia | Potential complications

* Important cause of abnormal bleeding * Malignant potential: continued prolfieration of glandular lesions may culminate in carcinoma

# Uterus Associated with mutation in PTEN tumor suppressor gene | Etiology

Endometrial hyperplasia | PTEN is mutated in ~20% of endometrial hyperplasias ## Footnote `

# Uterus Associated with mutation in PTEN tumor suppressor gene | Etiology

Endometrial hyperplasia | PTEN is mutated in ~20% of endometrial hyperplasias ## Footnote `

# Uterus Types of endometrial hyperplasia | Histology

* Simple hyperplasia * Complex hyperplasia * Atypical hyperplasia

# Uterus * Mild crowding of glands * "Swiss cheese" appearance * No cytologic atypia * Nuclei are correctly polarized, with cell's long axis perpendicular to gland luminal plane * Absence of eosinophilic macronucleoli | Histology

Simple endometrial hyperplasia | Cystic dilation of glands: lumens resembles holes in swiss cheese

# Uterus * Moderate-to-severe glandular crowding * Irregular / branched glands * No cytologic atypia: no loss of polarity; no macronucleoli | Histology

Complex endometrial hyperplasia

# Uterus * Severe glandular crowding * Irregular / round glands * Nuclear atypia * Stratification & loss of polarity * Vesicualr chromatin & nucleoli | Histology

Atypical endometrial hyperplasia

# Uterus Most common invasive cancer of the female genital tract

Endometrial carcinoma | Accounts for 7% of all invasive cancers in women

# Uterus * Increased life expectancy * Tamoxifen use * Obesity | Risk Factors

Endometrial carcinoma

# Uterus Types of endometrial carcinoma | Histology

* Type 1: estrogen-dependent adenocarcioma w/ endometroid morphology * Type 2: non-estrogen dependent adenocarcinoma

# Uterus Age: 55-65 yrs | Characteristics of Endometrial Carcinoma

Endometrial carcinoma, type 1

# Uterus Clinical setting * Unopposed estrogen * Obesity * Hypertension * Diabetes | Characteristics of Endometrial Carcinoma

Endometrial carcinoma, type 1

# Uterus Morphology: endometrioid | Characteristics of Endometrial Carcinoma

Endometrial carcinoma, type 1

# Uterus Precursor: atypical endometrial hyperplasia | Characteristics of Endometrial Carcinoma

Endometrial carcinoma, type 1

# Uterus Genetic abnormalities * Mutations in MMR genes * Mutations in PTEN tumor suppressor gene | Characteristics of Endometrial Carcinoma

Endometrial carcinoma, type 1

# Uterus Behavior: indolent; spreads via lymphatics | Characteristics of Endometrial Carcinoma

Endometrial carcinoma, type 1

# Uterus Most common type of endometrial carcinoma

Endometrial carcinoma, type 1

# Uterus Age: 65-75 yrs | Characteristics of Endometrial Carcinoma

Endometrial carcinoma, type 2

# Uterus Clinical setting: * Endometrial atrophy * Thin physique | Characteristics of Endometrial Carcinoma

Endometrial carcinoma, type 2

# Uterus Morphology: serous; clear cell; mixed mullerian tumor | Characteristics of Endometrial Carcinoma

Endometrial carcinoma, type 2

# Uterus Precursor: serous endometrial intraepithelial carcinoma | Characteristics of Endometrial Carcinoma

Endometrial carcinoma, type 2

# Uterus Genetic abnormalities: * Mutations in TP53 TSG | Characteristics of Endometrial Carcinoma

Endometrial carcinoma, type 2 | Mutations in DNA MMR genes & PTEN are rare

# Uterus Behavior: aggressive; intraperitoneal & lymphatic spread | Characteristics of Endometrial Carcinoma

Endometrial carcinoma, type 2

# Uterus Presents as a fungating mass in the uterus | Gross Appearance

Endometrial carcinoma, type 1

# Uterus Endometrioid adenocarcinoma w/ preserved glandular architecture but lack of intervening stroma * Less than 5% solid growth | Histology

Well-differentiated (grade 1) endometrial carcinoma, type 1 | Lack of intervening stroma distinguishes carcinoma from hyperplasia

# Uterus Endometrioid adenocarcinoma w/ glandular architecture admixed with solid areas * Less than 50% solid growth | Histology

Moderately differentiated (grade 2) endometrial carcinoma, type 1

# Uterus Endometrioid carcinoma w/ predominantly solid growth * Greater than 50% solid growth | Histology

Poorly differentiated (grade 3) endometrial carcinoma, type 1

# Uterus Subtypes of type 2 endometrial carcinoma | Histology

1. Serous endometrial carcinoma 2. Clear cell endometrial carcinoma

# Uterus Most common subtype of endometrial carcinoma, type 2

Serous endometrial carcinoma

# Uterus Nuclei are oval, mildly enlarged, and have evenly dispersed chromatin | Endometrial Carcinoma: Nuclear Grading

Grade 1

# Uterus Nuclei are markedly enlarged & pleomorphic, with irregular coarse chromatin, and prominent eosinophilic nucleoli | Endometrial Carcinoma: Nuclear Grading

Grade 3

# Uterus Nuclei have features intermediate to grades 1 & 3 | Endometrial Carcinoma: Nuclear Grading

Grade 2

# Uterus <5% of tumor composed of solid masses | Endometrial Carcinoma: Architectural Grading

Grade 1

# Uterus <50% of tumor composed of solid masses | Endometrial Carcinoma: Architectural Grading

Grade 2

# Uterus >50% of tumor composed of solid masses | Endometrial Carcinoma: Architectural Grading

Grade 3

# Endometrial Carcinoma: Architectural Grading Carcinoma confined to corpus uteri itself | Endometrial Carcinoma: Staging

Stage I

# Uterus Carcinoma involves corpus & cervix | Endometrial Carcinoma: Staging

Stage II

# Uterus Carcinoma extends outside uterus but not outside pelvis | Endometrial Carcinoma: Staging

Stage III

# Uterus Carcinoma extends outside pelvis or involves mucosa of bladder or rectum | Endometrial Carcinoma: Staging

Stage IV

# Ovary Originate from unruptured graafian follicles or from follicles that rupture & seal * Develop subadjacent to ovarian serosa | Pathology

Follicular & luteal cysts

# Ovary * Typically small (1-1.5 cm) lesions * Filled with clear serous fluid * Lined by granulosa cells (as fluid accumulates pressure leads to atrophy of these cells) | Presentation

Follicular & luteal cysts

# Ovary * Occassionally become large (4-5 cm) & produces palpable masses & pelvic pain * Can rupture causing intraperitoneal bleeding & peritoneal symptoms (acute abdomen) | Potential Complications

Follicular & luteal cysts

# Ovary Types of ovarian tumors | Histology

Classification of tumors is based on origin 1. Surface epithelial tumors: 65-70% 3. Germ cell tumors: 15-20% 4. Sex cord-stromal tumors: 5-10% 5. Metastasis

# Ovary Most common type of ovarian tumor

Surface epithelial tumor | 65-70% of cases

# Ovary 2nd most common type of ovarian tumor

GCT | 15-20% of cases

# Ovary Types of superficial epithelial tumors | Histology

1. Serous tumors 2. Mucinous tumors 3. Endometrioid tumors 4. Brenner tumors

# Ovary Types of GCT | Histology

1. Teratoma 2. Dysgerminoma 3. Endodermal sinus tumor 4. Choriocarcinoma 5. Embryonal carcinoma

# Ovary Most common GCT in females

Teratoma

# Ovary Most common malignant GCT in females

Dysgerminoma

# Ovary Most common GCT in children

Endodermal sinus tumor

# Ovary Types of sex-cord stromal tumors | Histology

1. Fibroma 2. Granulosa-theca cell tumor 3. Sertoli-Leydig cell tumor

# Ovary * 25% of gynecologic malignancies * 90% of cases are sporadic; 10% inherited * Highest mortality due to a pelvic malignancy * General population lifetime risk: 1.5% * 80% diagnosed in Stages III/IV; dismal survival * 92% survival if diagnosed in Stage I | Epidemiology

Ovarian carcinoma

# Ovary * Increased risk: * Age * Nulliparity * Late menopause * Incessant ovulation * Decreased risk: * Pregnancy * Lactation * Oral contraception | Risk Factors

Ovarian carcinoma

# Ovary Progression from benign tumors through borderline tumors that may give rise to low-grade carcinoma * Slow growth; rarely progress to high-grade carcinomas | Pathogenesis

Type I ovarian carcinoma

# Ovary Type I ovarian carcinoma | Precursor

Cystadenoma

# Ovary Type I ovarian carcinoma | Prototype

Low-grade serous carcinoma * Also mucinous and endometrioid carcinomas

# Ovary Associated with mutations in KRAS, BRAF | Etiology

Type I ovarian carcinoma

# Ovary Arise from inclusion cysts / fallopian tube epithlelium via intraepithial precursors that are often not identified * Often demonstrate high-grade features and are most commonly of serous histology * Highly aggressive; rapid progression | Pathogenesis

Type II ovarian carcinoma

# Ovary Type II ovarian carcinoma | Precursor

Serous tubal intraepithelial carcinoma (STIC) | Same p53 mutation

# Ovary Type II ovarian carcinoma | Prototype

High-grade serous carcinoma

# Ovary Associated with p53 mutation | Etiology

Type II ovarian carcinoma

# Ovary * 30% of all ovarian tumors * 50% of ovarian epithelial tumors * 70% are benign or borderline; 30% are malignant * Benign & borderline tumors are most common between ages 20-45 | Epidemiology

Ovarian serous tumors

# Ovary Cystic neoplasms lined by tall, columnar, ciliated & non-ciliated epithelial cells and filled with clear watery fluid | Histology

Ovarian serous tumors

# Ovary Types of ovarian serous tumors | Histology

* Benign: serous cystadenoma * Borderline: serous borderline tumor * Malignant: serous cystadenocarcinoma

# Ovary * Most common malignant ovarian tumor * Most common ovarian epithelial tumor * ~75% of cases are detected in Stage III * More common in postmenopausal women * Earlier onset in familial cases (BRCA1) * Mostly bilateral (70% of cases) * Widespread peritoneal involvement | Epidemiology

Ovarian serous carcinoma

# Ovary * Papillary structures * Psamomma bodies | Histology

Ovarian serous carcinoma

# Ovary * Architecture: micropapillae * Nuclear features: * Mostly uniform round/oval shape * Evenly distributed chromatin * +/- conspicuous nucleoli | Histology

Low-grade ovarian serous carcinoma

# Ovary * Architecture: * Large, complex papillae/glands/solid areas * Nuclear features: * Variation in size, shape * Irregular chromatin * +/- macronucleoli * Multinucleated tumor giant cells | Histology

High-grade ovarian serous carcinoma

# Ovary * Mainly occur in middle adult life * Rare before puberty / after menopause * 30% of all ovarian tumors * 80% are benign or borderline; 15% are malignant | Epidemiology

Ovarian mucinous tumors | Primary ovarian mucinous carcinomas are rare (<5% of ovarian cancers)

# Ovary * Variable size cysts: large cystic masses (up to 25 kg) * Smooth external surface * Multilobulated * Filled w/ sticky, gelatinous fluid: glycoprotein rich | Gross Appearance

# Ovary Types of ovarian mucinous tumors | Histology

* Benign: mucinous cystadenoma * Borderline: mucinous borderline tumor * Malignant: mucinous cystadenocarcinoma

# Ovary * Uncommon primary ovarian tumor * Typically metastatic from appendiceal tumor * Associated w/ pseudomyxoma peritonei * Unilateral, stage I, infiltrative stromal invasion | Presentation

Ovarian mucinous cystadenocarcinoma

# Ovary Implantation of mucinous tumor in the peritoneum with excessive mucin production | Pathology

Pseudomyxoma peritonei

# Ovary Ovarian mucinous cystadenocarcinoma | Approach to Diagnosis

IHC: CK7+/CK20-

# Ovary * Represents 10-15% of ovarian carcinomas * Typically unilateral (13% bilateral) * Associated endometrial carcionoma: 15% of cases * Associated endometriosis: 10-20% of cases * More common in younger patients | Epidemiology

Ovarian endometrioid carcinoma

# Ovary * Nuclei are cleared out & pleomorphic * Distinct glandular spaces * Occassional "gland-in-gland" organization * Central necrosis within some glands | Histology

Ovarian endometrioid carcinoma | Resembles uterine endometrioid carcinoma

# Ovary * 6% of ovarian carcinomas * Often associated with endometrioid carcinoma & endometriotic cysts * Highest association with ovarian & pelvic endometriosis and paraendocrine hypercalcemia * Often unilateral & low-grade malignancy | Epidemiology

Ovarian clear cell carcinoma

# Ovary * Polyhedral cells with abundant clear and/or eosinophilic granular cytoplasm * Hobnail cells w/ scant cytoplasm & enlarged, bulbous nuclei protruding into cystic lumens * Glycogen-rich & PAS-pos cytoplasm | Histology

Ovarian clear cell carcinoma

# Ovary Ovarian clear cell carcinoma | Approach to Diagnosis

* Histology: hobnail cells (hallmark) * IHC: cytokeratin+, EMA+ * Most exhibit CK7+/CK20- profile

# Ovary Types of Ovarian GCT | Histogenesis

* Undifferntiated --> dysgerminoma (oocytes) * Differentiated * Embryonal * Embryonal carcinoma (fetal tissue) * Teratoma (fetal tissue) * Extraembryonal * Endodermal sinus tumor (yolk sac) * Choriocarcinoma (placental tissue)

# Ovary * Most common malignant GCT in females * Most often seen in patients age < 30 * Seen in pregnant patients (age-related) * Associated with gonadal anomaly: 5-10% of cases * Analogous to seminoma of testis * Can be pure form or associated with other GCT | Epidemiology

Dysgerminoma

# Ovary Unilateral, solid, gray, soft encapsulated tumors; rapid destructive growth | Presentation

Ovarian dysgerminoma

# Ovary * Large tumor cells of undifferentiated germ cell origin arranged in sheets, nests, trabeculae * Clear cytoplasm * Central nuclei * Fibrous septae infiltrated by lymphocytes & plasma cells; often granulomas with giant cells | Histology

Ovarian dysgerminoma

# Ovary Ovarian dysgerminoma | Approach to Therapy

Radiotherapy, CTX

# Ovary * 15-20% of ovarian tumors * 90% benign; rare malignant variant | Epidemiology

Teratomas

# Ovary Most common type of teratoma

Benign mature cystic teratoma | >90% of teratomas; immature, malignant variant is rare

# Ovary Most common type of teratoma

Benign mature cystic teratoma | >90% of teratomas; immature, malignant variant is rare

# Ovary * Size: ~10 cm * May contain sebaceous secretions, hair, teeth, etc. | Gross Appearance

Teratoma

# Ovary * 90% are unilateral; R. side more common * Most discovered in young women as ovarian masses or found incidentally on abdominal scans * Malignant transformation: usually SCC; rare (1%) | Epidemiology

Mature cystic teratoma (dermoid cyst)

# Ovary Rare tumors composed of tissues that resemble embryona & immature fetal tissue * Typically occur in prepubertal / young women * Rapid growth; frequent invasion of capsule * Local or distant spread * Stage I tumors: excellent prognosis * Most recurrences within first 2 yrs * Absence after 2 yrs: great chance of cure | Pathology

Immature malignant teratomas

# Ovary * Bulky & smooth external surface * Solid / predominantly solid structure * +/- hair, sebaceous material, cartilage, bone, Ca2+ | Gross Appearance

Immature malignant teratomas

# Ovary * Islands of immature tissue: usually neuroepithelium * Can be cartilage, muscle, bone, etc. * Invasion of capsule | Histology

Immature malignant teratomas

# Ovary Immature malignant teratomas | Approach to Therapy

Prophylactic CTX

# Ovary Specialized ovarian teratomas | Histology

Monodermal teratomas * Only thyroid elements (follicles & colloid): struma ovari * Pts present w/ hyperthyroidism * Only carcinoid elements: neuroendocrine tumor * Pts present w/ unilateral mass / carcinoid syndrome * Thyroid & carcinoid elements: strumal carcinoid

# Ovary * Most common between 20s-30s * Origin: primitive embryonal cell * Can be pure form or component of mixed GCT * Sometimes contralateral to dermoid cyst | Epidemiology

Ovarian embryonal carcinoma

# Ovary Rapidly growing, large, soft, necrotic & hemorrhagic tumor mass | Gross Appearance

Ovarian embryonal carcinoma

# Ovary Ovarian embryonal carcinoma | Approach to Diagnosis

Labs: elevated AFP IHC: Cytokeratin+, CD30+, OCT3/4+, NANOG+, SALL4+, SOX2+

# Ovary * Histological patterns resemble yolk salk development * Reticular, myxoid, glandular, polyvesicualr patterns * Schiller-Duval bodies: papillations w/ central blood vessels | Histology

Endodermal sinus tumor | Schiller-Duval bodies = histological hallmark

# Ovary Endodermal sinus tumor | Approach to Diagnosis

Histology: Schiller-Duval bodies; eosinophilic hyalin globules IHC: AFP+, glypican3+, SALL4+, cytokeratin+

# Ovary Uncommon tumors with potential hormonal activity composed of stroma & sex cord elements | Pathology

Sex cord-stromal tumors

# Ovary Types of sex cord-stromal tumors | Histology

1. Fibroma, fibrothecoma 2. Granulosa cell tumor 3. Sertoli & Sertoli-Leydig cell tumors 4. Steroid (lipid) cell tumors

# Ovary Benign fibroblast tumor * A/w nevoid BCC (Gorlin's syndrome) | Pathology

Ovarian fibroma

# Ovary Firm, well-circumscribed white whorled masses with smooth surface | Gross Appearance

Ovarian fibroma

# Ovary Short fascicles of closely packed bland spindle cells with a storiform arrangement | Histology

Ovarian fibroma | "Storiform": fascicles intertwine in pattern resembling cartwheel

# Ovary Ovarian fibroma | Potential Complications

Meig's syndrome: ascites, right hydrothorax * Syndrome resolves with removal of tumor

# Ovary Benign theca cell tumor * Estrogenic | Pathology

Thecoma

# Ovary Yellow, lipid-rich masses | Gross Appearance

Thecoma

# Ovary Fascicles of spindle cells w/ central nuclei & moderate pale cytoplasm * IHC: inhibin+ | Histology

Thecoma

# Ovary Thecoma | Potential Complications

Estrogenic - may cause endometrial hyperplasia / carcinoma

# Ovary * Only 2% of all ovarian tumors * 2 types: * Adult: 95% * Juvenile: 5% * Hormonally active: mostly estrogenic * Rarely androgenic * Most are unilateral & diagnoed in early stages | Epidemiology

Granulosa cell tumor

# Ovary Solid, cystic, soft, hemorrhagic masses | Gross Appearance

Granulosa cell tumor

# Ovary * Uniform cells w/ grooved nuclei, C-Ex bodies * Patterns: microfollicular, macrofollicular, insular, trabecular, diffuse | Histology

Granulosa | Carl-Exner (C-Ex) bodies = histological hallmark

# Ovary * Uniform cells w/ grooved nuclei, C-Ex bodies * Patterns: microfollicular, macrofollicular, insular, trabecular, diffuse | Histology

Granulosa | Carl-Exner (C-Ex) bodies = histological hallmark

# Ovary * Prepubertal: precocious puberty * Post-menopausal: endometrial hyperplasia | Clinical Presentation

Granulosa cell tumor

# Ovary Granulosa cell tumor | Potential Complications

Estrogenic - may result in endometrial carcinoma or fibrocystic change in breast

# Ovary Granulosa cell tumor | Approach to Diagnosis

Elevated inhibit: tissue & serum levels * Used to identify & monitor granulosa cell tumors | Strong IHC positivity with anti-inhibin AB = characteristic

# Ovary * Average age: 30 yrs * Unilateral * Mostly diagnosed in Stage 1: good prognosis | Epidemiology

Ovarian Sertoli cell tumors

# Ovary Firm, solid, yellow-brown masses | Gross Appearance

Ovarian Sertoli cell tumors

# Ovary Hollow or solid tubules lined by cuboidal cells with vacuolated cytoplasm | Histology

Ovarian Sertoli cell tumors

# Ovary * Rare; average age: 25 yrs * Androgenic tumors | Epidemiology

Sertoli-Leydig cell tumors

# Ovary Solid, cystic yellow masses with necrosis & hemorrhage | Gross Appearance

Sertoli-Leydig cell tumors

# Ovary Tubules lined by Sertoli-like cells separated by variable numbers of round, eosinophilic Leydig-like cells | Histology

Sertoli-Leydig cell tumors

# Ovary * About 70% bilateral * Presence of multiple nodules or tumors on surface * Solid & cystic | Presentation

Metastatic ovarian cancer | Consider mets when tumor is bilateral & multifocal on exterior

# Ovary Origins of metastatic ovarian cancer | Pathology

* Gastric origin: Krukenberg tumors * Intestinal origin: mostly colonic * Breast carcinoma * Other origins: endometrial, tubal, lymphoma etc.