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Benign Ovarian Pathology

Microscope

  • Grossly will appear as ovoid, smooth or nodular surface with a dense, white fibrotic cut surface +/- small simple cysts

  • Should see ovarian follicles & dense spindled stroma

  • Often will see corpus luteum or corpora albicantia (left over from previous menstrual cycles)

INTRODUCTION

Normal Ovarian  Histology

Endometriosis.png

  • The ovary is the most common site of EM. Breakdown of the hemorrhagic material results in the "chocolate cyst" appearance on gross examination

  • Typical histology

    • Endometrial glands​

    • Dense stroma surrounding glands

    • Extravasated RBCs

    • +/- hemosiderin

​

View Virtual Slide

Endometriosis/ Endometrioma

Ovarian torsion_edited.jpg

  • Twisting of the ovary (especially large, cystic ovaries) can disrupt the blood supply

  • Doppler will show decreased/no blood flow to the ovary

  • Medical emergency! Must operate immediately & untwist the ovary to reduce ischemia. May require removal (oophorectomy)

  • Grossly, the ovary will be dark & dusky with hemorrhagic

Gross Examination

Ovarian Torsion

Streak ovary.jpg

  • Small, atrophic, not properly developed ovaries --> DEC estrogen

  • Associated with Turner Syndrome (45 XO)

    • Streak ovaries (seen left)

    • Cystic Hygroma​ (web neck)

    • Lymphangiectasia

    • Coarctation of the aorta

  • Delayed puberty & Premature menopause​

  • Histology: Lack of follicle development - will not see ova (eggs/follicles) in the ovarian stroma

Gross Examination

Streak Ovaries

PCOS

  • Multiple cysts (often, but not required for clinical diagnosis)

  • Clinical= Obesity, Hirsutism, Diabetes/Insulin resistance, secondary amenorrhea

    • Infertility from anovulatory cycles

  • Histology: Thick capsule, multiple follicular cysts +/- luteinization ​

  • Stein Leventhal syndrome

Learn More...

Polycystic Ovaries

ChorioCA of uterus with bilateral theca

  • Bilateral theca lutein cysts are seen in patients with choriocarcinoma of the uterus

Large

cysts -->

Theca Lutein Cysts

Ectopic tubal gestation.png

  • Most often in fallopian tube, but could occur in ovary

  • Clinical pic= +/- hx of PID, Amenorrhea, Vaginal bleeding, Pain

  • Diagnosis =  elevated/abnormal HCG levels & ultrasound

  • D&C (of endometrium) would NOT have fetal parts

  • Requires emergency surgery 

​​

<-- Click to examine this slide demonstrating an ectopic tubal gestation. Notice the chorionic villi present and abundant hemorrhage from rupture of the tube.

View Virtual Slide

Ectopic Pregnancy

Ovarian Neoplasms

  • Ovarian tumors can be either primary (arising from the ovary) or metastatic.

  • Primarily discovered late after disease has already spread to the pelvic surfaces

  • 25,000 women annually; Kills 3/5 of those affected

  • Risk factors:

    •   ​# of lifetime ovulations

  • Protective factors (decrease the risk of ovarian cancer)​

    • Birth control​

    • Tubal ligation

    • Low dose aspirin

Primary Ovarian Tumors: An Overview

Microscope Slide

  • Most common type (65-70%)

  • Avg patient = OLDER (>20 years old)

  • Types:

    • Serous​

    • Mucinous

    • Endometrioid

    • Clear Cell

    • Brenner

​​

- See Section Below - 

Surface Epithelial Tumors

Microscope

  • 2nd most common (15-20%)

  • Avg patient age = YOUNGER (0-25) 

  • Types:

    • Cystic Teratoma

    • Small cell carcinoma

    • Dysgerminoma

    • Yolk Sac Tumor
    • Embryonal Carcinoma
    • Polyembryoma
    • Choriocarcinoma
    • Gonadoblastoma
    • Gynandroblastoma

Germ Cell

Tumors

Microscope

  • Least common primary tumor (10%)

  • Affects ALL ages

  • Types:

    • Granulosa Cell Tumor​

    • Juvenile Granulosa Cell Tumor

    • Fibroma/Thecoma​

    • Sertoli Cell Tumor

    • Leydig Cell Tumor

    • Carcinosarcoma

Sex Cord-

Stromal Tumors

#1-    Surface Epithelial Tumors

  • TYPICAL CHARACTERISTICS

    • ​LOWER GRADE Tumors

    • Relatively benign course

    • Often arise from precursor lesion

    • Large cystic masses, often unilateral

  • CLASSIFICATION

    • Benign​

    • Borderline

    • Invasive

  • TYPES

    • LOW GRADE serous or endometrioid CA,

    • Mucinous CA

    • Clear cell CA (some)

  • MOLECULAR

    • KRAS, BRAF, ARIDIA​

    • Rarely BRCA1, BRCA2 or TP53

Type 1  Surface Epithelial Tumors

  • TYPICAL CHARACTERISTICS

    • HIGH GRADE​ Tumors

    • More aggressive

    • Typically present in advanced stages

    • Can be from tubal origin

  • TYPES

    • HIGH GRADE Serous

      • Primary ovary= HG Serous CA ovary​

      • Fallopian tube CA or 

      • Primary peritoneal/ Pelvic

    • HIGH GRADE Endometrioid CA

    • Carcinosarcoma (MMMT)

    • Undifferentiated CA

    • Clear cell CA (some)

  • MOLECULAR​

    • BRCA1 OR BRCA2​

    • TP53

Type 2 Surface Epithelial Tumors

Cystadenofibroma with Brenner tumor.png

Cystadenofibroma

Brenner Tumor.png

​

  • Over 95% are benign

  • Histology

    • Transitional epithelium

    • Moderate cellularity

    • Sheets of cells

    • Can see "coffee-bean" nuclear grooves

      • POP QUI​Z- What other GYN tumor has nuclear grooves??Granulosa Cell Tumor​​

  • Differential Diagnosis​​

    • Metastatic Renal Cell Carcinoma​

  • View the virtual slide that contains both endometrioid adenocarcinoma & clear cell adenocarcinoma!

Brenner Tumor

Serous Cystadenoma/borderline.png

  • Most common type (25-50%)

  • Unicystic or Multilocular Cysts filled with serous fluid

    • Look for/sample any solid areas

    • Look for any papillary projections

    • Is there surface involvement?

      • Higher chance of LN or spread​

  • Clues on Histology:

    • Psammoma bodies​

  • Spectrum of Disease (click to open virtual slide):

    • Serous cystadenoma​ (70%)

      • Benign, simple cyst​

      • Low grade, single cell layer, no atypia

    • Borderline/ Low malignant potential (5-10%)

      • Overgrowth, Branching, Tufting​

      • Microinvasion= <5mm2

    • Micropapillary Serous CA​

      • Low grade nuclei

      • Bilateral​ ovaries involved

      • Surface involvement + omental spread common

      • Invasive vs desmoplastic type

    • Cystadenocarcinoma (20-25%)

      • Low vs. High grade

      • Clue on low power= clearing around the invasive component​

Serous Tumors

Endometrioid adenocarcinoma of ovary.png

  • Looks just like endometrial carcinoma of the uterus (or colon ADC too)

  • Histology

    • Tall columnar cells, "pencil" nuclei

    • Microacini​/Glandular

    • Mitosis & apoptosis

    • ​Squamous differentiation

      • CLUE: Seeing squamous portions helps DDx endometrial from colon CA​

      • Colon CA also has "dirty necrosis"

Endometrioid Carcinoma

Mucinous Cystadenoma.png

Mucinous Tumors

Clear Cell Adenocarcinoma of Ovary.png

  • Associated with endometriosis

  • Histology

    • Clear, vacuolated cytoplasm

    • Papillary structures have thicker, wider fibrous core lined by "hobnailing" cells

    • Can have hyaline (dense pink) cytoplasmic inclusions 

    • Pleomorphic macronucleoli​

  • Differential Diagnosis​​

    • Metastatic Renal Cell Carcinoma​

  • View the virtual slide that contains both endometrioid adenocarcinoma & clear cell adenocarcinoma!

Clear Cell Carcinoma

#2-   Germ Cell Tumors

Microscope

  • 2nd most common (15-20%)

  • Avg patient age = YOUNGER (0-25) 

  • Types:

    • Cystic Teratoma

    • Small cell carcinoma

    • Dysgerminoma

    • Yolk Sac Tumor

    • Embryonal Carcinoma

    • Polyembryoma

    • Choriocarcinoma

    • Gonadoblastoma

    • Gynandroblastoma

Germ Cell

Tumors

#3- Sex Cord- Stromal    Tumors

Microscope

  • Least common primary tumor (10%)

  • Affects ALL ages

  • Types:

    • Granulosa Cell Tumor​

    • Juvenile Granulosa Cell Tumor

    • Fibroma/Thecoma​

    • Sertoli Cell Tumor

    • Leydig Cell Tumor

    • Carcinosarcoma

Sex Cord-

Stromal Tumors

Practice Questions

                   QUESTION                                                                                           ANSWER

​

What is the most common form of hereditary colorectal cancer syndromes?

A. Familial Adenomatous Polyposis (FAP)

B. Lynch Syndrome (HNPCC)

C. Juvenile polyposis

D. Cowden syndrome

E. Gardner syndrome

​

ANS: B

​

What is the most common extra-colonic malignancy in Lynch syndrome?

A. Endometrial cancer

B. Gastric cancer

C. Pancreatic cancer

D. Ovarian cancer

E. Biliary cancer

​

ANS: A

​

What germline mutation is present in Lynch Syndrome?

​

ANS: DNA mismatch repair genes (MMR)

​

Female patients with Peutz-Jeghers syndrome are also at inc risk of which GYN tumor?

A. Dysgerminoma

B. Clear cell carcinoma of ovary

C. Leydig cell tumor

D. Germ cell tumors of the ovary

E. Cervical adenoma malignum

​

ANS: E

​

What is the manner of inheritance for Peutz-Jeghers syndrome?

​

ANS: Autosomal dominant

​

What is the hallmark finding of a Peutz-Jeghers intestinal polyp?

A. Absence of lamina propria around glands

B. Desmoplasia

C. Arborizing smooth muscle in lamina propria

D. Monomorphic cells

E. Mucus retention cysts

​

ANS: C

​

​

REFERENCE:

Dr. Anwar. Online lecture. Osler.org. AP Pathology Review.  Female Reproductive Tract.

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