Does endometrial morular metaplasia represent odontogenic differentiation?

Antonio Travaglino,Sara Pignatiello,Marialaura Del Basso De Caro,Massimo Mascolo,Luigi Insabato,Elia Guadagno,Fulvio Zullo,Daniela Russo,Paola Moretta,Antonio Raffone

doi:10.1007/s00428-021-03060-2

Antonio Travaglino, Sara Pignatiello + Show 8 more

Open Access

https://doi.org/10.1007/s00428-021-03060-2

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Abstract

The nature of endometrial morular metaplasia (MorM) is still unknown. The nuclear β-catenin accumulation and the not rare ghost cell keratinization suggest a similarity with hard keratin-producing odontogenic and hair matrix tumors rather than with squamous differentiation. We aimed to compare MorM to hard keratin-producing tumors. Forty-one hard keratin-producing tumors, including 26 hair matrix tumors (20 pilomatrixomas and 6 pilomatrix carcinomas) and 15 odontogenic tumors (adamantinomatous craniopharyngiomas), were compared to 15 endometrioid carcinomas with MorM with or without squamous/keratinizing features. Immunohistochemistry for β-catenin, CD10, CDX2, ki67, p63, CK5/6, CK7, CK8/18, CK19, and pan-hard keratin was performed; 10 cases of endometrioid carcinomas with conventional squamous differentiation were used as controls. In adamantinomatous craniopharyngiomas, the β-catenin-accumulating cell clusters (whorl-like structures) were morphologically similar to MorM (round syncytial aggregates of bland cells with round-to-spindled nuclei and profuse cytoplasm), with overlapping squamous/keratinizing features (clear cells with prominent membrane, rounded squamous formations, ghost cells). Both MorM and whorl-like structures consistently showed positivity for CD10 and CDX2, with low ki67; cytokeratins pattern was also overlapping, although more variable. Hard keratin was focally/multifocally positive in 8 MorM cases and focally in one conventional squamous differentiation case. Hair matrix tumors showed no morphological or immunophenotypical overlap with MorM. MorM shows wide morphological and immunophenotypical overlap with the whorl-like structures of adamantinomatous craniopharyngiomas, which are analogous to enamel knots of tooth development. This suggests that MorM might be an aberrant mimic of odontogenic differentiation.

Highlights

Morular metaplasia (MorM) is a common type of altered differentiation found in endometrioid lesions [1]
Unlike squamous differentiation (SqD), MorM typically shows decreased CK7 expression compared to the background endometrium; CK8/18 expression, typically strong in both MorM and conventional SqD, may be lost in squamous cells originating from MorM [5, 6, 8, 9, 12,13,14,15]
This study showed a wide morphological and immunophenotypical overlap between MorM and the whorl-like structures (WS) of adamantinomatous craniopharyngioma (ACP); no morphological or immunophenotypical analogies were found between MorM and hair matrix tumors

Summary

Introduction

Morular metaplasia (MorM) is a common type of altered differentiation found in endometrioid lesions [1]. The nature of MorM has not yet been defined: several authors support that it is an immature form of squamous differentiation (SqD), while others consider it a completely different entity [1,2,3,4,5,6,7,8]. The lack of overt squamous features, such as prominent cell membranes and keratinization, has been used to distinguish MorM from conventional SqD [8]. We and others highlighted that MorM not uncommonly displays overt squamous features and a characteristic ghost cell keratinization [9,10,11]. Squamous cell markers, such as p40, p63, and cytokeratin (CK) 5/6, can be expressed in MorM, less commonly and intensely than conventional SqD. Unlike SqD, MorM typically shows decreased CK7 expression compared to the background endometrium; CK8/18 expression, typically strong in both MorM and conventional SqD, may be lost in squamous cells originating from MorM [5, 6, 8, 9, 12,13,14,15]

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