ORIGINAL ARTICLE

Morules and morule-like features associated with carcinomas in various organs: report with immunohistochemical and molecular studies

S Makishi¹, T Kinjo¹, S Sawada¹, K Chinen¹, T Hirayasu², T Hamada³, K Saito⁴, T Iwamasa¹

¹ Division of Pathology and Cell Biology, Graduate School and Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan
² Department of Surgery, National Okinawa Hospital, 867 Ganeko, Ginowan, Okinawa 901-2214, Japan
³ Division of Pathology, Kyushu Rosai Hospital, Kokuraminami, Kitakyushu 800-0296, Japan
⁴ Division of Pathology and Laboratory Medicine, Toyama City Hospital, Imaizumihokubu, Toyama 939-8511, Japan

Correspondence to:
Correspondence to:
Dr S Makishi
Division of Pathology and Cell Biology, Graduate School and Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan; k048718{at}eve.u-ryukyu.ac.jp

Background: Morules have been reported in pulmonary blastoma (PB), well differentiated fetal adenocarcinoma of the lung (WDFA), and uterine endometrioid carcinoma (EC), and rarely in other carcinomas. ß Catenin gene mutation has been associated with morule formation.

Aims: To compare and clarify the cellular characteristics of morules in carcinomas in various organs and show that morules are distinct from epithelial cellular nodules.

Methods: Twenty tumours were studied: two PBs, three WDFAs, three papillary lung adenocarcinomas, 11 ECs, and one papillary thyroid carcinoma. Numerous epithelial cell, oncofetal, and neuropeptide antibodies were used for immunohistochemistry. ß Catenin gene mutation was investigated.

Results: Morules in PBs and ECs were uniform cell clusters distinct from squamous differentiation. All were immunonegative for epithelial cell and oncofetal antigens, but those in ECs were positive for neurone specific enolase (NSE). Synaptophysin, encephalin, and somatostatin were sporadically immunopositive in PB morules. Morules were not seen in the other carcinomas and WDFAs, although morule-like features closely resembling morules histopathologically were seen. These were positive for epithelial cell and oncofetal antigens, and showed squamous differentiation. Their nuclei were more atypical and slightly larger than those in morules. Morule-like features were seen in WDFAs. ß Catenin gene mutation was demonstrated in one EC and PB, and in two WDFAs.

Conclusion: Morules were non-epithelial cell clusters showing neuronal differentiation. There were two types: endometrioid type, expressing NSE, and blastoma type, expressing neuropeptides. In contrast, similar morule-like features were epithelial nodules. Although the number of cases was small, the presence of morules showed no clear prognostic correlations.

Abbreviations: EC, endometrioid carcinoma; HPV, human papillomavirus; NSE, neurone specific enolase ; PB, pulmonary blastoma, PCR, polymerase chain reaction; WDFA, well differentiated fetal adenocarcinoma

Keywords: morules; morule-like features; squamous differentiation; ß catenin gene

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