Immunohistochemical Analysis of Morules in Colonic Neoplasms: Morules Are Morphologically and Qualitatively Different from Squamous Metaplasia

Abstract

Morules develop in several neoplasms and have been considered as a type of squamous metaplasia despite the absence of keratinization and intercellular bridges. The objective of this study was to clarify the pathological significance of morules and to distinguish morules from squamous metaplasia in colonic neoplasms. Ten cases of morule-associated colonic neoplasms (4 adenocarcinomas, 1 adenoma with carcinoma in situ, and 5 adenomas), and 3 cases of squamous metaplasia in colonic adenocarcinoma were examined morphologically and immunohistochemically. Morules were well-defined structures composed of small, oval to short-spindled cells with bland nuclei, and frequently associated with intranuclear inclusions that were positive for biotin and biotin-binding enzymes (pyruvic acid carboxylase and propionyl CoA carboxylase). On immunohistochemical examination, morules characteristically showed nuclear overexpression of β-catenin, cyclin D1 and p63, low Ki-67 labeling index (<1%), cytoplasmic overexpression of CD10, and no expression of cytokeratin 20. These molecules were useful for the differentiation of morules. Furthermore, p63 and 34βE12 positivities in morules suggested that they have a basal/stem cell phenotype. Thus, morules were morphologically and qualitatively different from squamous metaplasia. We consider that morules in colonic neoplasms are cell clusters with a basal/stem cell phenotype, and have less proliferative and less invasive potential than other cancer cells.

An Immunohistochemical Study of Morules in Endometrioid Lesions of the Female Genital Tract: CD10 Is a Characteristic Marker of Morular Metaplasia

“…Only occasional strong CD10 positivity has been reported in glands of endometrioid adenocarcinoma (23). However, a previous report failed to show its positivity in endometrial morules (19), and only in one recent article (24) was CD10 positivity shown in morules of colonic neoplasms. We have been able to show identical CD10 strong positivity in morules of well-differentiated fetal adenocarcinoma of the lung.…”

Endometrial metaplasias and reactive changes: a spectrum of altered differentiation

“…They are highly specific in rare neoplasms such as low-grade adenocarcinoma of fetal lung type and the cribriform morular variant of papillary thyroid carcinoma 71. It has been proposed that tumours containing morules reflect a common pathway of carcinogenesis involving molecular alterations of the Wnt-signalling pathway with nuclear β-catenin accumulation 54 71 75 80 81. Also, all morules have in common nuclear expression of CDX258 76 77 and β-oestrogen receptor,75 which appear to be related to their pathogenesis.…”

A squamous metaplasia in a gastric ulcer scar of the antrum

“…It has been rarely described with other associated diseases, such as peptic ulcers [4] , tuberculosis [5] , syphilis [6] , corrosive gastritis [7] , extreme cachexia [8] , pernicious anemia [9] and aberrant pancreatic tissue [10] . It may coexist with neoplasms [11,12] . However, there has been no report of squamous metaplasia occurring at an old ulcer scar site in the distal antrum with none of the associated diseases described above.…”