Lobular endocervical glandular hyperplasia as a presumed precursor of cervical adenocarcinoma independent of human papillomavirus infection

Gynecol Oncol. 2007 Aug;106(2):289-98. doi: 10.1016/j.ygyno.2007.03.044. Epub 2007 May 30.


Objectives: The aim of this study was to investigate differences in the process of carcinogenesis between adenocarcinoma coexistent with LEGH and conventional adenocarcinoma. And we intend to describe appropriate treatment plans for LEGH in this study.

Methods: Using the surgical pathology files of patients who visited the University of Yamanashi Hospital, Yamanashi Central Hospital and Kofu Municipal Hospital between 1996 and 2005, pathological diagnoses were reevaluated based on criteria for the diagnosis of LEGH by Nucci et al. As for the cases including adenocarcinoma with LEGH: (a) we created a map showing position of the LEGH component and adenocarcinoma component and squamo-columnar junction (SCJ) in HE-stained specimens, (b) immunohistochemical staining was performed using antibodies to CEA, HIK1083 and p53, and (c) detection of HPV DNA was performed using PCR and in situ hybridization (ISH).

Results: Endocervical adenocarcinoma was observed coexistent with LEGH in 5 cases (19.2%). (a) LEGH was located in a remote place from the SCJ. Sizes of lesions in the 5 cases ranged from 18 to 35 mm in width and 7 to 16 mm in depth. (b) HIK1083 was diffusely immunopositive in the cytoplasm of LEGH component and focal immunopositive in 4 cases with adenocarcinoma component. Immunopositivity for CEA was seen in the cytoplasm of adenocarcinoma component in 4 cases. Immunopositivity for p53 was seen in adenocarcinoma component nuclei in 2 cases. (c) HPV DNA was not detected using PCR and ISH in either LEGH or adenocarcinoma components.

Conclusions: The present study suggests that clear differences exist in the process of carcinogenesis between adenocarcinoma associated with LEGH and conventional adenocarcinoma. LEGH may represent a precursor of cervical adenocarcinoma independent of HPV infection. As LEGH displays characteristics of precancerous mucinous adenocarcinoma, surgical treatment should be considered for LEGH growing beyond a certain size.

MeSH terms

  • Adenocarcinoma / pathology*
  • Adenocarcinoma / virology
  • Adult
  • Aged
  • Alphapapillomavirus / genetics
  • Cervix Uteri / pathology*
  • Cervix Uteri / virology
  • DNA, Viral / isolation & purification
  • Female
  • Humans
  • Hyperplasia
  • Immunohistochemistry
  • Middle Aged
  • Neoplasms, Glandular and Epithelial / pathology*
  • Neoplasms, Glandular and Epithelial / virology
  • Papillomavirus Infections / complications
  • Papillomavirus Infections / pathology
  • Precancerous Conditions / pathology*
  • Precancerous Conditions / virology
  • Uterine Cervical Neoplasms / pathology*
  • Uterine Cervical Neoplasms / virology


  • DNA, Viral