P504S/alpha-methylacyl-CoA racemase, HNF1β and napsin A in morular metaplasia and clear cell carcinoma of the endometrium: An immunohistochemical analysis

Aims: Endometrial morular metaplasia (MorM) can show cytoplasm clarification, which may mimic clear cell carcinoma (CCC), especially on biopsy. We aimed to assess the expression of CCC markers in MorM. Methods: Twenty cases of MorM with areas of cytoplasmic clarification were assessed by immunohistochemistry for HNF1β, Napsin A, and P504S/alpha-Methylacyl-CoA racemase (AMACR); 60 tumors were selected as controls (20 classical MorM, 20 conventional squamous differentiation and 20 CCC). Results: Eighteen cases (90%) showed overt squamous/keratinizing areas within MorM, and 11 cases (55%) showed isolated ghost cells which might mimic the hyaline globules of CCC. All cases (100%) showed expression of AMACR, which was mostly diffuse and strong; in all cases, the expression was restricted to the prototypical MorM areas, while glandular areas and overtly squamous areas were negative. Twelve cases (60%) showed HNF1β expression, which was focal/multifocal and/or weak; the expression was found in all tumor components. No case showed Napsin A expression in any component. Classical MorM showed similar immunophenotype, while conventional squamous differentiation did not show AMACR expression. Most CCC expressed AMACR (70%), HNF1β (85%), and Napsin A (75%), mostly with diffuse and strong positivity. Conclusion: MorM may show features that mimic CCC and consistently expresses AMACR, which may be accompanied by HNF1β expression; Napsin A is consistently negative instead. These findings should be considered to avoid overdiagnosis.