Difference in cytoplasmic localization pattern of neutral mucin among lobular endocervical glandular hyperplasia, adenoma malignum, and common adenocarcinoma of the uterine cervix

Abstract

To investigate whether the cytoplasmic localization pattern of neutral mucin differs between lobular endocervical glandular hyperplasia (LEGH) and cervical adenocarcinoma (CxAd), including minimal-deviation adenocarcinoma (MDA), or adenoma malignum, alcian blue (pH 2.5)/periodic acid-Schiff (AB-PAS) staining was performed to formalin-fixed paraffin-embedded tissue sections of 13 lesions of LEGH and 53 tumors of CxAd, including 6 tumors of MDA. The cytoplasmic localization of neutral mucin was classified as a "whole cytoplasmic pattern," in which neutral mucin filled the cytoplasm entirely, or as an "apical pattern," in which neutral mucin was localized in the subsurface area only. Cytoplasmic neutral mucin patterns were detected in all 13 cases of LEGH and in 19 cases (36%) of CxAd, including five cases of MDA. The localization of neutral mucin was always the whole cytoplasmic pattern in 13 cases of LEGH, but was the apical pattern in these 19 cases of CxAd. The other 34 cases of CxAd, including 1 case of MDA, corresponded to the acid mucin pattern stained purple or blue or no staining pattern by AB-PAS. Among the 53 cases of CxAd, the apical neutral mucin pattern was an indicator of poorer patient prognosis by univariate and multivariate analyses. The examination of cytoplasmic localization of neutral mucin might be applicable, not only to differential diagnosis between LEGH and CxAd, including MDA, but also to estimate clinical aggressiveness of CxAd.

Endocervical adenocarcinomas associated with lobular endocervical glandular hyperplasia: a report of four cases with histochemical and immunohistochemical analyses

“…Diffuse immunopositivities of HIK1083 and predominantly periodic acid-Schiff-positive neutral mucin expression were recognized in the glands of the lobular endocervical glandular hyperplasia, corresponding with the observations of previous investigators. 29,33,34 HIK1083-positive pyloric gland mucin was focally evident in three of four adenocarcinomas. This common expression of pyloric gland mucin in both lobular endocervical glandular hyperplasia and mucinous endocervical adenocarcinomas suggests the possibility that there is a histogenetical relationship between these two lesions.…”

“…27,29,30,[32][33][34]36 Because of the identical mucin expression in these lesions, several investigators have suggested that metaplastic or hyperplastic glandular lesions with pyloric gland mucin could be a precursor of minimal deviation adenocarcinoma. 32,34,37 Pyloric gland metaplasia also has been described in several other organs such as the pancreas, the gallbladder and the small and large intestine.…”

“…Gastric phenotype has been described in endocervical gastric metaplasia, lobular endocervical glandular hyperplasia and minimal deviation adenocarcinomas from the findings of histochemistry and immunohistochemistry using monoclonal antibody (HIK1083) against pyloric gland mucin. [27][28][29][30][31][32][33][34][35][36] There is also speculation that hyperplastic or metaplastic glandular lesions with gastric mucin are precursors of endocervical adenocarcinoma or in situ lesions of minimal deviation adenocarcinoma when the correspondent mucin phenotype of these lesions is considered. 32,34,37 However, this is still under discussion and, to our knowledge, there has been no direct evidence to support this hypothesis.…”

Intranuclear cytoplasmic inclusion is a significant diagnostic feature for the differentiation of lobular endocervical glandular hyperplasia from minimal deviation adenocarcinoma of the cervix

“…Diffuse and reddish cytoplasmic staining occurs with the PAS reaction, indicating that the cells produce neutral mucin, whereas normal glands and common endocervical adenocarcinoma have bluish acidic mucin on alcian blue staining. 2,11 Conversely, some investigators have reported immunoreactivity for HIK1083, which reacts with pyloric gland mucin of the stomach. Thus, HIK1083 is considered to be a useful tool for the differentiation of gastric metaplasia/ LEGH, MDA from common cervical AC and other benign cervical lesions.…”

Absence of Human Papillomavirus Infection in Minimal Deviation Adenocarcinoma and Lobular Endocervical Glandular Hyperplasia

“…Although most cases are found incidentally, some may exhibit clinical, radiologic, and pathologic features resembling those of MDA (27,28). Therefore, it is difficult to differentiate MDA from LEGH preoperatively or postoperatively by clinical, radiologic, and pathologic features (29). To the best of our knowledge, the HPV status in LEGH has not been reported.…”