Lobular endocervical glandular hyperplasia is a metaplastic process with a pyloric gland phenotype

Mikami, Yoshiki; Hata, Sakae; Melamed, Jonathan; Fujiwara, Keiichi; Manabe, Toshiaki

doi:10.1046/j.1365-2559.2001.01239.x

Cited by 105 publications

(113 citation statements)

References 17 publications

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“…2,6,7 The current study has shed further light on this issue. A review of 20 cases of MDA demonstrated coexistence of LEGH/PGM with some atypical features or morphologically usual-type AIS.…”

Section: Discussionmentioning

confidence: 68%

“…2,3 This antibody has since then been regarded as a promising diagnostic tool for MDAs. 4,5 However, its usefulness has been in dispute and Mikami et al 6,7 have demonstrated HIK1083 reactivity in pyloric gland metaplasia (PGM) of the cervix, which was described as lobular endocervical glandular hyperplasia (LEGH) by Nucci et al 8,9 These facts have provoked controversy concerning a possible link between LEGH/ PGM and MDA, and whether gastric phenotype is specific for these two conditions. In the current study, we have examined cervical adenocarcinomas including MDAs, adenocarcinoma in situ (AIS), and LEGH/PGM as well as a variety of benign glandular lesions to determine the incidence of gastric phenotypes and to shed light on the issue of histogenesis of MDA, employing antibodies to apomucins encoded by the MUC gene family, CD10 and chromogranin A (CGA), and HIK1083 and anti-p16 INK4 , the last for showing any relationship to high-risk HPV.…”

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confidence: 99%

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Gastrointestinal immunophenotype in adenocarcinomas of the uterine cervix and related glandular lesions: a possible link between lobular endocervical glandular hyperplasia/pyloric gland metaplasia and ‘adenoma malignum‘

et al. 2004

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Gastrointestinal phenotype in cervical adenocarcinomas was examined by immunohistochemistry and correlated with morphologic features. Antibody panels included anti-MUC2, MUC6, CD10, chromogranin A (CGA) and HIK1083. In addition, expression of p16 INK4 , a cyclin-dependent kinase inhibitor which is expressed in a variety of high-risk HPV-related conditions, was studied. A total of 94 invasive adenocarcinomas including 20 minimal deviation adenocarcinomas (MDAs) and 72 adenocarcinomas in situ (AIS) were examined. MDAs were most frequently positive for HIK1083 and/or MUC6, two representative gastric markers, with a rate of 95%, followed by intestinal-type adenocarcinomas (IAs) with a rate of 85% whereas only 27% of 56 usual endocervical-type adenocarcinomas (UEAs) were positive. MUC2, a goblet cell marker, was positive in 85% and 25% of IAs and MDAs, respectively, while in only 14% of UEAs. CD10 was positive in 15% of IAs, indicating incomplete intestinal differentiation without a brush border in most of the cases. CGA-positive cells were frequently seen in MDAs and IAs with rates of 60% and 62%, respectively. Nuclear and cytoplasmic p16 INK4 positivity was identified in 93% of UEAs, whereas 30% of MDAs were positive for p16 INK4 . Results in AISs were comparable to their invasive counterparts, but morphologically usual-type AISs identified in eight cases of MDA were frequently positive for HIK1083 (75%) and MUC6 (63%), and p16 INK4 . Of note was the existence of lobular endocervical glandular hyperplasia (LEGH) with atypical features including cytologic abnormalities, and/or papillary projection, which were identified in this study in pure form (n ¼ 3) or in association with MDAs (n ¼ 6), but not in cases of other types of adenocarcinomas. These observations indicate that gastrointestinal phenotype is frequently expressed in MDAs and IAs, and there seems to be a possible link between MDA, and LEGH and morphologically usual-type AIS with gastric immunophenotype in histogenesis. Frequent absence of p16 INK4 expression in MDAs suggests a possibility that high-risk HPV does not play a crucial role in development of MDAs, in contrast to the majority of endocervical adenocarcinomas. p16 INK4 immunohisto-

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Section: Discussionmentioning

confidence: 68%

mentioning

confidence: 99%

Gastrointestinal immunophenotype in adenocarcinomas of the uterine cervix and related glandular lesions: a possible link between lobular endocervical glandular hyperplasia/pyloric gland metaplasia and ‘adenoma malignum‘

et al. 2004

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“…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.…”

Section: Endocervical Adenocarcinoma With Hyperplasiamentioning

confidence: 89%

“…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.…”

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confidence: 99%

“…[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. In the current study, we report on four cases of endocervical adenocarcinoma associated with lobular endocervical glandular hyperplasia, and discuss the histogenesis of adenocarcinoma with respect to the presence of lobular endocervical glandular hyperplasia.…”

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confidence: 99%

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

et al. 2005

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We report on four cases of endocervical adenocarcinoma associated with lobular endocervical glandular hyperplasia using histochemical and immunohistochemical analyses. The patients ranged in age from 59 to 67 years (mean 62 years). Chief complaints were watery vaginal discharge in two cases, genital bleeding in one and no subjective symptoms in one. Cytological examinations of the cervical smears revealed adenocarcinoma cells and benign-looking glandular cells with intracytoplasmic golden-yellow mucin in all cases. Radical hysterectomy was performed in three patients, and simple total hysterectomy was performed in one. From surgical specimens, three tumors were diagnosed as mucinous adenocarcinoma and one was adenocarcinoma in situ. All adenocarcinomas were located proximally on the cervix, and did not involve the transformation zone. Adjacent to carcinoma tissues in the cervix, lobular endocervical glandular hyperplasia was detected. The cells of lobular endocervical glandular hyperplasia were dominantly positive with neutral mucin, and immunohistochemistry revealed that these cells had prominent pyloric gland mucin (HIK1083). Focal immunopositivity for pyloric mucin was also observed in three adenocarcinomas. Either CEA or p53 were immunopositive in all adenocarcinomas and negative in the tissues of lobular endocervical glandular hyperplasia. Histopathological features of the present cases suggest that some endocervical adenocarcinomas may originate from lobular endocervical glandular hyperplasia. Keywords: endocervical adenocarcinoma; lobular endocervical glandular hyperplasia; gastric mucin; HIK1082; immunohistochemistry; histochemistry Endocervical adenocarcinomas account for 10-15% of all cervical cancers and have been increasing in relative and absolute numbers.1-4 Therefore, understanding the precursor lesions of endocervical adenocarcinoma has become more important for gynecologists and pathologists. Endocervical glandular dysplasia and atypical tubal metaplasia are recognized premalignant lesions, and a considerable number of studies on these lesions have been conducted so far. [5][6][7][8][9][10][11][12][13] Consequently, the question arises whether other precursors exist. Microglandular hyperplasia, 14-17 mesonephric hyperplasia, 18,19 tunnel clusters, 20-22 diffuse laminar endocervical glandular hyperplasia 23 and lobular endocervical glandular hyperplasia are currently considered benign hyperplastic glandular lesions in the uterine cervix, 24 but little is really known about their relationship with endocervical carcinomas. 25,26 Recently, several studies have focused on gastric mucin (or pyloric gland mucin) in glandular lesions of the cervix and its connection with endocervical glands' carcinogenesis. Gastric phenotype has been described in endocervical gastric metaplasia, lobular endocervical

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Diagnostic significance of endocervical glandular cells with “golden‐yellow” mucin on pap smear

Hata

Mikami

Manabe

2002

Diagnostic Cytopathology

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Endocervical glandular cells rarely show "golden-yellow" mucin staining using the Papanicolaou technique, whereas the cells of adenoma malignum (minimal deviation adenocarcinoma) do. To further evaluate the significance of this finding, we reviewed the Pap smears of six cases in which atypical glandular cells containing golden-yellow mucin was identified. Microscopic examination of the hysterectomy specimens confirmed one case of adenoma malignum, whereas the other five cases were diagnosed as endocervical glandular hyperplasia with pyloric gland metaplasia. Glandular cells observed in all six cases were filled with golden-yellow mucin. In the case of adenoma malignum the nuclei were somewhat more enlarged and the chromatin texture was coarsely granular, although a distinction between adenoma malignum and the five benign lesions was difficult. Special staining performed on tissue sections in all cases demonstrated that the intracytoplasmic mucin of the glandular cells in portion of both pyloric gland metaplasia and adenoma malignum was predominantly PAS-positive and showed immunoreactivity for M-GGMC-1 (HIK1083), which reacts with pyloric gland mucin of the stomach. A review of 1,165 consecutive Pap smears failed to identify cells with golden-yellow mucin. These observations indicate that golden-yellow mucin on Papanicolaou smear seems to represent a gastric phenotype of endocervical glandular cells, which is a unique characteristic shared by adenoma malignum and pyloric gland metaplasia. This finding should therefore be regarded as a warning sign, raising the possibility of adenoma malignum and requiring prompt histopathologic assessment, although not of itself diagnostic of malignancy.

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Lobular endocervical glandular hyperplasia is a metaplastic process with a pyloric gland phenotype

Cited by 105 publications

References 17 publications

Gastrointestinal immunophenotype in adenocarcinomas of the uterine cervix and related glandular lesions: a possible link between lobular endocervical glandular hyperplasia/pyloric gland metaplasia and ‘adenoma malignum‘

Gastrointestinal immunophenotype in adenocarcinomas of the uterine cervix and related glandular lesions: a possible link between lobular endocervical glandular hyperplasia/pyloric gland metaplasia and ‘adenoma malignum‘

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

Diagnostic significance of endocervical glandular cells with “golden‐yellow” mucin on pap smear

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