Adenocarcinoma of the rete testis: clinicopathological study of 18 cases with emphasis on MET amplification and a review of the literature.

Background: Knowledge regarding adenocarcinoma of the rete testis (ACRT) is extremely limited due to its scarcity.

Methods and results: This study enrolled 18 patients with ACRT from multiple institutions. Clinicopathological and immunohistochemical features were investigated, together with a comprehensive review of 95 previously reported cases. One case was assessed using next-generation sequencing (NGS). The median age of the patient cohort was 54 years (range = 20-69 years), with the majority presenting with a testicular mass (13 of 18); predominantly right-sided (11 of 18). Six patients died within the second year following diagnosis. The morphology of ACRT spans a wide spectrum, including newly identified mucinous carcinoid-like features, with mucous cells floating in mucus and signet-ring cells. Notably, transition from a benign to a malignant rete epithelium was noted in 38.9% of cases (seven of 18). Immunohistochemically, tumour cells most frequently showed strong positivity for CK7 (12 of 16) and CK20 (10 of 17), with occasionally positivity for calretinin (three of 16), WT-1 (two of 17) and PAX-8 (two of 15). According to NGS in a single case, MET was amplified, leading to the patient benefiting from mesenchymal-epidermal transition factor (MET) inhibitors. Furthermore, MET amplification was assessed in 13 cases using fluorescence in-situ hybridisation and detected in two cases (15.4%). No significant correlation between MET amplification and mesenchymal-epidermal transition factor (MET) levels was observed in the cases studied.

Conclusions: Primary ACRT is a rare malignant tumour which poses a diagnostic challenge, and is associated with poor prognosis. Cases of ACRT with MET amplification might represent promising candidates for the treatment with MET inhibitors.