Case 1

An 80-year-old female presented with abnormal uterine bleeding who was found to have an large endometrium mass, and she underwent hysterectomy. She does not have any other history of malignancy.

1. What is your big category of this lesion?

   A: Primary carcinoma

   B: Neuroendocrine tumor/carcinoma

   C: Sex-cord stromal tumor in uterus (Uterine tumor resembling ovarian sex cord tumor)

   D: Metastasis (endocervical, GI, etc)

   E: Atypical endometrial hyperplasia

   F: Weird sarcoma

Answer

The correct answer is A. However, B, C, D are all valid thoughts at this point.

2. What is your panel of stains to work-up?

   
   

IHC

• ER, PR
• PAX8
• WT1
• Inhibin

See All Options

You can vote for more than one answer.

Answer

Honestly, there is not a perfect panel. The above stains are all reasonable. However, a panel of first round would be appropriate with this morphology: PAX8, ER, PR, Inhibin, WT1, p16, P53, MMR, GATA3, TTF-1.

3. A selective panel of stains showed that both ER and PR (-); MMR normal; P53 wild-type of staining pattern. What are the possible considerations of ER, PR negative carcinomas in uterine pathology?

   A: Clear cell carcinoma

   B: Endometrioid carcinoma, FIGO1-2

   C: Endometrioid carcinoma, FIGO 3

   D: Serous carcinoma

   E: Endocervical adenocarcinoma

   F: CHEC (Corded and Hyalinized Endometrial Carcinoma)

   G: Carcinosarcoma

   H: Mucinous carcinoma of gastrointestinal type

   I: Mesonephric-like adenocarcinoma

Answer

• Clear cell carcinoma: ER and PR are usually negative or only focally positive

• Endometrioid carcinoma: Low-grade EEC showed diffuse strong immunoreactivity for ER/PR; However, FIGO3 endometroid carcinoma can show negative ER and PR (28% and 35% respectively)

• Serous carcinoma showed variable ER and PR stains.

• Endocervical adenocarcinoma are negative for ER and PR.

• CHEC are still typically positive for ER, PR and B-catenin.

• Carcinosarcoma are diagnosed by morphology, ER PR can be positive.

• Mucinous carcinoma of gastrointestinal type are ER, PR negative.

• Mesonephric-like adenocarcinoma are ER, PR negative tumors.

4. Addtional panels showed that the tumor is diffusely positive for TTF-1 and negative for GATA3. What's your final diagnosis?

   A: Endocervical adenocarcinoma

   B: Endometrioid carcinoma, FIGO 3

   C: Mesonephric-like adenocarcinoma

   D: Mucinous carcinoma of gastrointestinal type

Answer

The correct answer is D. Mesonephric-like adenocarcinomas typically show a variety of histological patterns and a classic presentation is a low grade well differentiated endometrial carcinoma with some intra-luminal eosinophilic colloid-like material, much basaloid appearance, and the mixed patterns of papillary, cribriform, tubular, or spindled cells. Typically ER, PR negative, wild type P53, and GATA3 and TTF1 can show an inverse staining pattern, meaning diffuse GATA3 with negative TTF-1 or verse vesa. It can also show luminal CD10 positivity. MLA are clinically aggresive tumors.

5. What is the molecular alterations of mesonephric-like adenocarcinoma?

   A: PTEN loss

   B: P53

   C: CTNNB1

   D: KRAS

Answer

The correct answer is D. MLA or MA can have KRAS mutations with gain of 1q, and a lower proportion have ARID1A mutations.

Bonus homework: Why there is mesonephric adenocarcinoma and mesonephric-like adenocarcinoma? What is the difference?

References:

https://tumourclassification.iarc.who.int/chaptercontent/34/12

https://www.pathologyoutlines.com/topic/uterusendometrioid.html

Shen F, Gao Y, Ding J, Chen Q. Is the positivity of estrogen receptor or progesterone receptor different between type 1 and type 2 endometrial cancer? Oncotarget. 2017 Jan 3;8(1):506-511. doi: 10.18632/oncotarget.13471. PMID: 27888807; PMCID: PMC5352172.

Case credit: UCSD Pathology

Author: Wangpan Jackson Shi, MD