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20 April 2023 - Case of the Month #526

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Thanks to Dr. Stephanie Skala, University of Michigan, Ann Arbor, Michigan, USA for contributing this case and discussion and to Dr. Gulisa Turashvili, Emory University School of Medicine, Atlanta, Georgia for reviewing the discussion.

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Case of the Month #526

Clinical history:
A 62 year old woman presented with post-menopausal bleeding. A subsequent biopsy was diagnosed as high grade endometrial carcinoma. She underwent a hysterectomy.

Histopathology images:

What is your diagnosis?

Click here for diagnosis, test question and discussion:

Diagnosis: Mesonephric-like endometrial carcinoma

Test question (answer at the end):
Which immunohistochemical stains are most helpful for diagnosis of mesonephric-like endometrial carcinoma?

A. CD10, ER
B. GATA3, CD10
C. TTF1, CD10





Mesonephric-like endometrial carcinoma is a rare type of endometrial carcinoma that may be misdiagnosed as low grade (FIGO grade 1 - 2) endometrioid carcinoma due to its relatively bland histologic features (Am J Surg Pathol 2022;46:921). Accurate classification is important due to the mismatch between tumor behavior and histologic appearance; mesonephric-like endometrial carcinoma frequently recurs and metastasizes, often to the lung (Am J Surg Pathol 2021;45:498, Adv Anat Pathol 2022;29:208, Am J Surg Pathol 2022;46:921).

Microscopically, mesonephric-like endometrial carcinoma typically shows variable architecture including tubular, ductal, papillary, sieve-like, corded, spindled and glomeruloid patterns. Monotonous oval vesicular nuclei reminiscent of papillary thyroid carcinoma may be seen (Adv Anat Pathol 2022;29:208, Am J Surg Pathol 2022;46:921).

The main entity in the differential diagnosis is endometrioid carcinoma (usually low grade). In contrast to most low grade endometrioid carcinomas, mesonephric-like endometrial carcinoma should show no squamous or mucinous differentiation and no (or at most minimal) expression of estrogen receptor and progesterone receptor. Mesonephric markers that may be positive in mesonephric-like endometrial carcinoma include TTF1, GATA3 and CD10 (luminal pattern) (Adv Anat Pathol 2022;29:208, Am J Surg Pathol 2022;46:921). TTF1 and ER are good first line screens, although not all TTF1 positive / ER negative endometrial carcinomas are mesonephric-like carcinomas (Am J Surg Pathol 2022;46:921). Classification of these tumors requires assessment of morphologic, immunohistochemical and sometimes molecular features. Mesonephric-like endometrial carcinomas often harbor KRAS mutations without mismatch repair deficiency, TP53 mutation or PTEN mutation; however, KRAS mutations are also often seen in endometrioid carcinoma with mucinous differentiation (Am J Surg Pathol 2022;46:921, Am J Surg Pathol 2019;43:389). Cervical origin should be excluded before a diagnosis of mesonephric-like endometrial carcinoma is made.

Test question answer:
D. TTF1, ER. The most helpful pair of screening immunohistochemical stains among those listed are TTF1 and ER. Mesonephric-like endometrial carcinomas are often positive for TTF1 and negative for ER. Luminal CD10 staining can be seen in mesonephric-like endometrial carcinoma but this is not the most helpful marker. The combination of negative / minimal hormone receptor expression and positivity for mesonephric marker(s) is supportive of this diagnosis.

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