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

Pathol Res Pract. 2022 Aug:236:153953. doi: 10.1016/j.prp.2022.153953. Epub 2022 May 27.

Abstract

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.

Keywords: Clear cell; Diagnosis; Endometrial; Immunohistochemical; Morula; Squamous.

MeSH terms

  • Adenocarcinoma, Clear Cell* / genetics
  • Adenocarcinoma, Clear Cell* / pathology
  • Aspartic Acid Endopeptidases* / genetics
  • Biomarkers, Tumor / genetics
  • Carcinoma, Squamous Cell* / genetics
  • Carcinoma, Squamous Cell* / pathology
  • Endometrium / pathology
  • Female
  • Hepatocyte Nuclear Factor 1-beta* / genetics
  • Humans
  • Metaplasia
  • Racemases and Epimerases* / genetics

Substances

  • Biomarkers, Tumor
  • HNF1B protein, human
  • Hepatocyte Nuclear Factor 1-beta
  • Aspartic Acid Endopeptidases
  • NAPSA protein, human
  • Racemases and Epimerases
  • alpha-methylacyl-CoA racemase