Practice questions IV answers, female genital tract

Practice questions IV answers, female genital tract

Pathology of Ovary B

© Jun Wang, MD, PhD

1. B. Tubular glands lined by benign columnar cells without mucin production in a background of endometrioid stroma is consistent with endometrioid tissue. It is endometriosis if found outside uterine cavity. Endometrioid adenocarcinoma has irregular complex endometrioid type glands lined by atypical columnar cells, and commonly has squamous metaplasia, as those in endometrioid endometrial adenocarcinoma. Clear cell carcinoma has either clear cytoplasm or hobnail tumor cells. Both are associated with endometriosis. Squamous carcinoma has irregular nests or cords of atypical cells with squamous differentiation, such as intercellular bridges and/or squamous pearls. Mucinous cystadenocarcinoma has markedly atypical cells with mucinous differentiation.

2. C. See discussion in question 1.

3. C. See discussion in question 1.

4. B. Ovarian endometrioid adenocarcinoma is commonly associated with abnormalities of PTEN and CTNNB1 (beta-catenin). BRCA and p53 are usually associated with high-grade serous carcinoma. High-grade endometrioid adenocarcinoma may have p53 mutation as well. KRAS and Her2 mutations are seen in mucinous cystadenocarcinoma and low-grade serous carcinoma.

5. B. It is not uncommon to have concurrent endometrioid endometrial adenocarcinoma with ovarian endometrioid adenocarcinoma. Endometrial atrophy usually has thin endometrium. Other entities are possible but less concerned.

6. A. Ovarian tumor with marked cytological atypia and clear cytoplasm or hobnail tumor cells is most likely a clear cell carcinoma. Endometrioid adenocarcinoma has irregular complex endometrioid type glands lined by atypical columnar cells, and commonly has squamous metaplasia, but not clear cells. Endometriosis does not have clear cytoplasm. Mucinous cystadenocarcinoma has markedly atypical cells with mucinous differentiation. Serous cystadenocarcinoma has cords and nests of markedly atypical cells without mucin production, some form papillary architecture. Neither has clear cytoplasm.

7. C. Mucinous cystadenoma is usually multilocular with thick fluid contents, and lined by columnar benign mucinous cells, characterized by basally located small nuclei and pale cytoplasm due to mucin production. Endometrioid adenocarcinoma has irregular complex endometrioid type glands lined by atypical columnar cells, and commonly has squamous metaplasia. Mucinous cystadenocarcinoma has markedly atypical mucinous cells with pleomorphic large nuclei. Serous cystadenocarcinoma has cords and nests of markedly atypical cells without mucin production, some form papillary architecture. Serous cystadenoma is commonly unilocular with thin clear fluid and lined by single layer of flat to cuboidal cells with cilia.

8. A. Ovarian growth with urothelial differentiation are Brenner (urothelial) tumors. They are associated with hyperestrinism and mucinous neoplasm. If no atypia or invasion  is noted (benign appearing), it is benign Brenner tumors. Inclusion cysts have single layer of flat, cuboidal or columnar cell ling. Mucinous cystadenocarcinoma has markedly atypical cells with mucinous differentiation. Serous cystadenocarcinoma has cords and nests of atypical cells without mucin production, some form papillary architecture. None of these has urothelial differentiation. Metastatic urothelial carcinoma has various degree of atypia.

9. C. Brenner (urothelial) tumors are associated with hyperestrinism and mucinous neoplasm. In this patient, the background cystic lesion is a mucinous cystadenoma, characterized by columnar benign mucinous cells with basally located small nuclei and pale cytoplasm due to mucin production. Endometrioid adenocarcinoma has irregular complex endometrioid type glands lined by atypical columnar cells, and commonly has squamous metaplasia. Mucinous cystadenocarcinoma has markedly atypical mucinous cells with pleomorphic large nuclei. Serous cystadenocarcinoma has cords and nests of markedly atypical cells without mucin production, some form papillary architecture. Sertoli-Leydig cell tumor has two components, tubular Sertoli components and nests of Leydig cells (granular eosinophilic cytoplasm).

10. B. Invasive ovarian tumor with urothelial differentiation is a malignant Brenner (urothelial) tumors. Also see discussion in question 9.

11. C. Cystic ovarian mass contains mature tissue such as skin and adnexa is a mature cystic teratoma. Ectopic pregnancy should not have tissues seen in late gestational age. In addition, placental tissue is seen in ectopic pregnancy, regardless of the location. Immature teratoma has immature tissue, commonly neuronal. Mucinous cystadenoma is usually multilocular with thick fluid contents, and lined by columnar benign mucinous cells. Serous cystadenoma is commonly unilocular with thin clear fluid and lined by single layer of flat to cuboidal cells with cilia.

12. E. This patient has thyrotoxicosis caused by functioning struma ovarii, a type of teratoma that rarely can be functional. Metastatic thyroid follicular carcinoma to ovary would be extremely rare. All ovarian mucinous neoplasms have mucin production, a pale material instead of eosinophilic in routine H.E. stain. Serous cystadenoma is commonly unilocular with thin clear fluid and lined by single layer of flat to cuboidal cells with cilia.

13. E. Tumor with necrosis and hemorrhage is most likely malignant. Immature tumor cells surrounding vessels, and forming a vague space from other tumor cells is likely a Schiller-Duval body, a feature of yolk sac tumor. Ovarian choriocarcinoma has atypical trophoblasts, some might be multinucleated, but not forming Schiller-Duval body. Endometrioid adenocarcinoma has irregular complex endometrioid type glands lined by atypical columnar cells, and commonly has squamous metaplasia. Mucinous cystadenocarcinoma has markedly atypical mucinous cells with pleomorphic large nuclei. Granulosa cell tumor has Call-Exner bodies (small follicle-like structures filled with acidophilic material), but not Schiller-Duval body.

14. A. AFP is elevated in yolk sac tumor and hepatocellular carcinoma. Elevated CEA may be associated with various malignancies, such as ovarian mucinous adenocarcinoma. HE4 may be elevated in ovarian serous cystadenocarcinoma and endometrioid adenocarcinoma. Trophoblast diseases, including complete mole, partial mole and choriocarcinoma, or germ cell tumor trophoblast components, may have elevated hCG.  Elevation of inhibin is seen in ovarian sex cord-stroma tumors and dysgerminoma. Elevated PLAP may be seen in dysgerminoma. 

15. A. Ovarian tumor with hemorrhagic changes and multinucleated cells (trophoblast) expressing hCG is a choriocarcinoma. Endometrioid adenocarcinoma has irregular complex endometrioid type glands lined by atypical columnar cells, and commonly has squamous metaplasia. Endometriosis has benign endometrial glands and stroma, as well as hemorrhagic changes. Mucinous cystadenocarcinoma has markedly atypical mucinous cells with pleomorphic large nuclei. Yolk sac tumor has Schiller-Duval body.

16. B. Dysgerminoma has large vesicular cells with well-defined cell borders, cleared cytoplasm containing glycogen and central nuclei. Ovarian choriocarcinoma has hemorrhagic changes and multinucleated cells (trophoblast) expressing hCG.  Fibroma has benign spindle cells with collagen in the background. Thecoma has spindle cells with moderate pale cytoplasm containing lipid droplets. Yolk sac tumor has Schiller-Duval body.

17. E. Dysgerminoma may have elevated serum hCG, AFP, LDH, PLAP and inhibin. CA125 and HE4 elevations are seen in ovarian serous cystadenocarcinoma and endometrioid adenocarcinoma. Elevated CEA and CA19.9 may be associated with various malignancies, such as ovarian mucinous adenocarcinoma.

18. B. Thyroid follicle-like structure (Call-Exner bodies) is seen in granulosa cell tumor. Ovarian Brenner (urothelial) tumors has urothelial differentiation. Mucinous cystadenoma is usually multilocular with thick fluid contents and lined by columnar benign mucinous cells.  Struma ovarii is a type of teratoma with normal appearing thyroid follicles. Yolk sac tumor has Schiller-Duval body.

19. D. FOXL2 mutation is seen granulosa cell tumor. BRCA1 mutation is seen in various malignancies, including high grade serous carcinoma, fallopian tube carcinoma, and certain type of breast cancers, such as medullary carcinoma. CTNNB1 and PTEN mutation is seen in various neoplasms, including ovarian endometrioid adenocarcinoma and pancreas solid-pseudopapillary neoplasm. DICER mutation is seen in Sertoli-Leydig cell tumor.

20. B. Ovarian granulosa cell tumor is associated with hyperestrinism.

21. E. Elevation of inhibin is seen in ovarian sex cord-stroma tumors and dysgerminoma. CA125 and HE4 elevations are seen in ovarian serous cystadenocarcinoma and endometrioid adenocarcinoma. Elevated CEA and CA19.9 may be associated with various malignancies, such as ovarian mucinous adenocarcinoma.

22. D. Virilization is a sign of elevated androgen. The elevated androgen could be cause by either abnormal hormone metabolism as seen in polycystic ovary disease and stromal hyperthecosis, or androgen producing tumors, such as Sertoli-Leydig cell tumor. Sertoli-Leydig cell tumor has two components, tubular Sertoli components and nests of Leydig cells (granular eosinophilic cytoplasm). Polycystic ovary disease have multiple ovarian follicular cysts. These two are usually seen in young women. Stromal hyperthecosis has uniform ovarian enlargement, and is commonly seen in older women in age 60 to 70. Brenner (urothelial) tumors have urothelial differentiation and are associated with hyperestrinism and mucinous neoplasm. Endometriosis has benign endometrial glands and stroma, as well as hemorrhagic changes. Mucinous cystadenoma is usually multilocular with thick fluid contents, and lined by columnar benign mucinous cells. Yolk sac tumorhas Schiller-Duval body and usually do not have endocrine manifestations.

23. B. Benign ovarian spindle cell proliferation with collagen production is a fibroma. Leiomyoma is positive for desmin. Peritoneal carcinomatosis usually has similar morphology as serous carcinoma. Thecoma has spindle cells with moderate pale cytoplasm containing lipid droplets. Serous cystadenocarcinoma has cords and nests of atypical cells, some form papillary architecture. Combination of pleural effusion, ascites and ovarian fibroma is likely Meigs syndrome. Pleural effusion and ascites may recess after removal of ovarian fibroma.

24. E. Ovarian spindle cell tumor with pale cytoplasm and lipid droplets is most likely thecoma. Stromal hyperthecosis has uniform ovarian enlargement, not discrete mass. Leiomyoma is a smooth muscle neoplasm, usually has eosinophilic cytoplasm without vacuoles. Metastatic adenocarcinoma has the morphology of original tumor, such as irregular glands lined by atypical cells, forming an invasive pattern. Sertoli-Leydig cell tumor has two components, tubular Sertoli components and nests of Leydig cells (granular eosinophilic cytoplasm).

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