Florid Endocervical Glandular Hyperplasia with Intestinal and Pyloric Gland Metaplasia: Worrisome Benign Mimic of “Adenoma Malignum”

Mikami, Yoshiki; Hata, Sakae; Fujiwara, Keiichi; Imajo, Yóshinari; Kohno, Ichiro; Manabe, Toshiaki

doi:10.1006/gyno.1999.5462

Cited by 98 publications

(99 citation statements)

References 11 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 contrast, LEGH/PGM frequently involves the portion of internal os away from the transformation zone. 6 Therefore, it seems reasonable for MDAs derived from LEGH not to express p16 INK4 , possibly due to a lack of high-risk HPV being involved in the tumorigenesis. On the other hand, morphologically usual-type AISs related to MDA more frequently expressed p16 INK4 The final issues to be discussed are the concept of MDA, and whether ''mucinous adenocarcinoma of gastric-type'' is a distinct entity and acceptable term as a substitute for MDA.…”

Section: Discussionmentioning

confidence: 99%

“…LEGH/PGM, which was defined as proliferation of small glands arranged in a lobular fashion surrounding dilated endocervical glands, 6,8 were identified in one patient with IA, 10 with MDA, and nine who underwent hysterectomy for benign diseases. In the process of the review, nine cases of LEGH/PGMs with atypical features, including nuclear atypia, loss of polarity, mitotic figures, and papillary architecture in a variety of combinations, were identified in pure form or in association with MDA, and were also examined.…”

Section: Methodsmentioning

confidence: 99%

“…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.…”

mentioning

confidence: 99%

“…17 This protein is overexpressed as a consequence of incorporation of E7 derived from high-risk HPV, and it has been shown to be positive in invasive and in situ adenocarcinomas of the cervix, most of which are also considered to be HPV related. 18,19 The frequent location of LEGH/PGM, a putative precursor of MDA, in the portion of internal os away from the transformation zone, 6 prompted the authors to assume that a subset of cervical adenocarcinomas with gastric phenotype may have tumorigenesis distinct from high-risk HPV-related ordinary cervical adenocarcinomas.…”

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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%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

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

Hashi

Yuminamochi

et al. 2008

Diagnostic Cytopathology

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Lobular endocervical glandular hyperplasia (LEGH) is a cervical lesion with pyloric gland metaplasia. Minimal deviation adenocarcinoma (MDA) is an extremely well differentiated form of endocervical adenocarcinoma (AC). To date, it is difficult to differentiate LEGH from MDA because they share similar clinical, radiological, and immunohistochemical features. Furthermore, the cytological features of LEGH and MDA have not been well defined. In the present study, we describe the cytological features of LEGH and MDA. We reviewed 24 cases of LEGH (18 pure and six mixed forms) and four MDA cases of the cervix. A total of 40 cytologic smears from 28 patients were reviewed. Abundant yellow mucin was frequently present in both LEGH and MDA; however, an INCI was found in 22 of the 24 LEGH cases and it was not found in either MDA or adenocarcinoma cells associated with LEGH. Neither cell atypia nor architectural distortion was observed in LEGH. In MDA, slight cellular atypia, three dimensional, irregular cell clustering, and prominent nucleoli were observed. The presence of an INCI is a good parameter for the diagnosis of LEGH. Cytology is an effective aid in the differentiation of LEGH from MDA.

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Florid Endocervical Glandular Hyperplasia with Intestinal and Pyloric Gland Metaplasia: Worrisome Benign Mimic of “Adenoma Malignum”

Cited by 98 publications

References 11 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‘

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

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

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