Lynch syndrome is an autosomal dominant cancer predisposition syndrome caused by germline mutations in mismatch repair (MMR) genes, conferring an increased risk of endometrial and colorectal malignancies. While classic MMR mutations are well characterised, combined EPCAM–MSH2 deletions are rare and clinically significant. We present a case of a 52-year-old multiparous woman with secondary amenorrhea and recurrent uterine bleeding. Family history was notable for colorectal carcinoma in her father and sister (diagnosed at 48 years). Imaging revealed a thickened endometrium, and biopsy confirmed well differentiated endometrial adenocarcinoma. Total laparoscopic hysterectomy with bilateral salpingo-oophorectomy and lymphadenectomy was performed. Histopathology confirmed FIGO grade 1, stage pT1a endometrial adenocarcinoma. Immunohistochemistry demonstrated loss of MSH2 and MSH6 expression, prompting advanced molecular evaluation. A hereditary cancer NGS panel identified a heterozygous large deletion of MSH2 exons 1–7, which was confirmed by digital MLPA, revealing a concurrent large deletion encompassing the downstream region of EPCAM . No POLE mutation was detected, and p53 expression was normal. This rare combined EPCAM–MSH2 deletion confirms Lynch syndrome and highlights the utility of integrated molecular diagnostics, as combined deletions confer a higher risk of endometrial cancer than single-gene variations. Moreover, early identification enables cascade testing and prophylactic interventions in relatives.
Sebastian et al. (Sun,) studied this question.