A new view of the so-called adenoma malignum of the uterine cervix

Ishii, Keiko; Hosaka, Noriko; Toki, Toshihiko; Momose, Masanobu; Hidaka, Eiko; Tsuchiya, Satoshi; Katsuyama, Tsutomu

doi:10.1007/s004280050172

Cited by 126 publications

(96 citation statements)

References 18 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: 67%

“…In 1997, it was shown to have a gastric phenotype by mucin histochemistry and immunohistochemistry using HIK1083, an antibody recognizing pyloric gland mucin of the stomach. 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.…”

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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: 67%

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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“…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. [49][50][51][52] Pathogenesis of this metaplastic change in most organs is still under discussion; however, its relationship to carcinogenesis in the pancreas has received particular attention.…”

Section: Endocervical Adenocarcinoma With Hyperplasiamentioning

confidence: 99%

“…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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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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