November 2021 – Gynecological Pathology Case 1

Mesonephric-like adenocarcinoma

Mesonephric-like adenocarcinoma (MLA) is a recently recognized aggressive adenocarcinoma variant of the uterine corpus and ovary. Patients often present at advanced stage. MLA has a propensity to metastasize to the lung.

Morphologically, MLA exhibits heterogeneous architectural growth, including a mixture of tubular, papillary and slit-like patterns. Tubules frequently contain intraluminal eosinophilic secretions. The nuclear features are low grade and can resemble papillary thyroid carcinoma by the presence of angulated nuclei and occasional nuclear grooves. 

The typical MLA immunophenotype consists of expression of TTF1 and GATA3 with limited to no expression of ER and PR. This immunoprofile assists in their distinction from endometrioid carcinoma. 

MLA of the uterine corpus has considerable morphologic and immunohistochemical overlap with mesonephric adenocarcinoma of the cervix, with a significant distinguishing feature being MLA lacks associated mesonephric remnants or hyperplasia (Wolffian structures located predominantly in the para-ovarian region and deep in the lateral aspect of the cervix).

MLA and mesonephric adenocarcinoma exhibit similar molecular aberrations consisting of KRAS mutations, gain of chromosome 1q, 10 and 12, and lack of PTEN alterations. PIK3CA mutations are also found in MLA, providing evidence of both mesonephric and Mullerian differentiation.

References

1. McFarland M et al. Hormone receptor-negative, thyroid transcription factor 1–positive uterine and ovarian adenocarcinomas: report of a series of mesonephric-like adenocarcinomas. Histopathology. 2016;68:1013-1020.
2. Mirkovic J et al. Targeted genomic profiling reveals recurrent KRAS mutations in mesonephric-like adenocarcinomas of the female genital tract. Am J Surg Pathol. 2018;42:227-233.
3. Mirkovic J et al. Targeted genomic profiling reveals recurrent KRAS mutations and gain of chromosome 1q in mesonephric carcinomas of the female genital tract. Mod Pathol. 2015;28:1504-1514.
4. Patel V et al. Corded and hyalinized mesonephric-like adenocarcinoma of the uterine corpus: report of a case mimicking endometrioid carcinoma. Hum Pathol. 2019;86: 243-248.