Journal
AMERICAN JOURNAL OF SURGICAL PATHOLOGY
Volume 46, Issue 7, Pages 921-932Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/PAS.0000000000001873
Keywords
endometrial carcinoma; mesonephric-like carcinoma; endometrioid carcinoma; serous carcinoma; endometrial cancer; KRAS mutations; TTF-1
Funding
- UVA Department of Obstetrics & Gynecologic Peyton Taylor Endowed Research Scholarship Fund
- UVA Department of Pathology
- Stanford Department of Pathology
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Mesonephric-like endometrial carcinoma is a rare and aggressive malignancy that can be misclassified. Immunohistochemical expression of TTF-1 and ER can be used as initial screening, but final diagnosis requires integration of morphologic and molecular features.
Mesonephric-like endometrial carcinoma is a rare but frequently misclassified and aggressive malignancy. KRAS mutations, limited estrogen receptor (ER) expression, and TTF-1, GATA3, and luminal CD10 expression are described in these tumors, but an immunohistochemistry-based screening approach has not been studied. We assessed 300 endometrial carcinomas/carcinosarcomas to ascertain the specificity of TTF-1/GATA3/luminal CD10 expression with or without ER staining for this diagnosis. Next-generation sequencing and morphologic review were performed on screen-positive cases. In all, 3% (9/300) were TTF-1(+); 2 coexpressed GATA3. No cases expressed luminal CD10 or GATA3 in isolation. Two TTF-1(+)/ER- cases, one of which was also GATA3(+), were reclassified as mesonephric-like based on morphology and molecular results (KRAS mutations without mismatch repair deficiency, TP53 mutations, or PTEN mutations): these represented 0.7% of all cases (2/300). The reclassified cases were originally diagnosed as grade 1 and 2 endometrioid carcinoma, and the latter had pulmonary metastases and pelvic recurrences. Six TTF-1(+) cases retained their original serous (3) and endometrioid (3) diagnoses; 1 was reclassified as dedifferentiated. All had negative or low ER. KRAS mutations were identified in 4 TTF-1(+) non-mesonephric-like cases, including 1 serous and 1 grade 3 endometrioid with p53 abnormalities, 1 mismatch repair-deficient endometrioid with a complex molecular profile, and 1 endometrioid with mucinous differentiation. These findings suggest that TTF-1 and ER are good first-line screens for mesonephric-like carcinoma, but caution that a TTF-1(+)/ER- immunoprofile is not specific, even in the setting of KRAS mutations. A final diagnosis of mesonephric-like carcinoma requires integration of morphologic and immunohistochemical features, with molecular support when relevant.
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