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

Abstract

Purpose:To analyze immunohistochemically morules in endometrioid lesions to show that CD10 is a sensitive marker for morular metaplasia. Experimental Design: Immunohistochemical analysis of 53 instances of morular metaplasia comprising 1 cyclic endometrium and 52 endometrioid lesions associated with focal glandular complexity corresponding to 9 polyps, 4 atypical polypoid adenomyomas, 24 complex endometrial hyperplasias (18 with and 6 without atypia), 12 grade 1 endometrioid adenocarcinomas in early clinical stages of both uterus and ovary, and three ovarian adenofibromas. Immunohistochemistry in paraffin sections was done for CD10, h-catenin, estrogen and progesterone receptors, and cytokeratins 5-6, 7, 8, 13, 18, 19, 20, and 34h-E12. Results: Morules were negative for estrogen and progesterone receptors and had h-cateninp ositive nuclei. Cytokeratins 8, 18, 19 were positive; cytokeratins 7 and 20 were negative; and cytokeratins 5-6, 13, and 34h-E12 were weakly positive. All cases revealed strongly positive membranous CD10 staining in morules, which was absent in glands. CD10 positivity allowed easy identification of morules at low power in various types of surgical specimens and in curettings. CD10 also highlighted early morular metaplasia in glandular epithelium. In cases associated with squamous, keratinizing metaplasia, CD10 discriminated between both types of metaplasia. Conclusions: CD10 staining represents a useful marker of morules in endometrioid neoplasms of the female genital tract, permitting identification of lesions usually associated with an attenuated malignancy. Considering the immunohistochemical and genetic similarities of morules in tumors of different organs, it is likely that this marker may be also useful to diagnose morular metaplasia in similar neoplasms of extragenital locations.Morules (1) are nodular structures found in endometrial-type glands formed by a peculiar metaplastic non-keratinizing squamoid epithelium (2). Morphologically similar structures have also been described in neoplastic lesions in other anatomic sites, such as thyroid (3), lung (4, 5), stomach (6), pancreas (7), and colon (8).In both eutopic and ectopic endometrioid tissues, morules are almost invariably associated with the glandular architectural complexity of premalignant and low-grade glandular malignant lesions but are absent in high-grade ones. Thus, it can be said that the presence of morules in the endometrium relates well with an attenuated malignancy.This study deals with the immunohistochemical findings in a series of 53 cases of morular metaplasia from both uterus and ovary, showing for the first time that CD10 staining is a marker of morules, allowing its easy identification in various endometrioid lesions. Materials and MethodsA total of 53 cases of endometrioid morular metaplasia were collected from the files of the

CD10 Immunostaining distinguishes atypical polypoid adenomyofibroma (atypical polypoid adenomyoma) from endometrial carcinoma invading the myometrium

“…The morular component of APA is strongly positive for CD10 as previously described in the literature [17], and this finding acts as an internal positive control for CD10 immunostaining. Strong CD10 immunoreactivity within the morular component with a complete lack of CD10 staining within the myofibromatous stromal component of the same specimen excludes a false-negative finding.…”

Endometrial metaplasias and reactive changes: a spectrum of altered differentiation

“…Although ESM originates de novo from neoplastic glands, in a fifth of cases it coexists with morules (see below), where transitions between the distinct two types of metaplasia occur 1 23 53 58. This does not mean that neither all ESMs are necessarily neoplastic nor that all ESMs necessarily originate from morules.…”

Thyroid transcription factor-1 expression in endometrioid tumors: a note of caution

“…For these reasons, we think that caution should be applied in the interpretation of the article by Fujiwara et al [1] and in others [5] that reported TTF1 immunoreactivity in tumors other than those originating in the lung or thyroid and that used both antigen retrieval and/or avidin-biotin peroxidase complex methods. Chiarelli et al [3] have demonstrated that CD10 is a useful immunomarker of morules in endometrioid lesions of the female genital tract, and most recently, our group [4] evidenced that CD10 can also be useful in identifying morules in the BROCN-family tumors, all sharing alterations in the APC/β-catenin pathway. In fact, we believe the lesion depicted in Fig.…”

“…The biotin is sometimes located in the nuclei, as can be seen in pregnancy-related endometria (Fig. 1A, B), in some morule-lacking adenocarcinomas of the gallbladder, in morules in cyclic endometrium and endometrial hyperplastic lesions [3], and in a group of tumors containing morules with cells displaying biotin-rich optically clear nuclei (BROCN; BROCN-family tumors), which includes endometrioid endometrial adenocarcinomas (Figs. 1C-E), ovarian endometrioid tumors, and others [4].…”