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

Abstract

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

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

“…To avoid misdiagnosis, it must be kept in mind that LEGH is sometimes mixed with malignant cervical lesions; several previous studies have reported some LEGH cases mixed with MDA, 7,11 and we reported previously four LEGH cases coexisting with adenocarcinoma. 18 It has been well demonstrated that an INCI is an invagination of the cytoplasm into the nucleus; however, the underlying mechanism is unclear.…”

“…We previously reported four cases of endocervical adenocarcinoma associated with LEGH. 18 We included 10 control cases each of normal endocervical glandular lesions and common mucinous AC of the cervix. All patients underwent a hysterectomy and gave written, informed consent.…”

A Pyloric Gland-Phenotype Ovarian Mucinous Tumor Resembling Lobular Endocervical Glandular Hyperplasia in a Patient with Peutz-Jeghers Syndrome

“…LEGH in the uterine cervix is thought to be a precursor lesion of gastric-type cervical adenocarcinoma [5], which is often identified in patients with PJS. Therefore, the premalignant potential of an ovarian mucinous tumor resembling LEGH should be closely monitored.…”

Usefulness of a management protocol for patients with cervical multicystic lesions: A retrospective analysis of 94 cases and the significance of GNAS mutation

“…Therefore, a differential diagnosis between LEGH and MDA is challenging. Although LEGH was first reported as a benign disease, it has been reported as a precursor of MDA, because of frequent association between LEGH and MDA as well as its genetic characteristics 6, 7, 8, 9, 10, 11. We previously reported that some LEGH lesions were a precancerous form of MDA due to the pattern of X chromosome inactivation using the human androgen receptor (HUMARA) method 12.…”