Superficial (early) endocervical adenocarcinoma in situ: A study of 12 cases and comparison to conventional AIS

Agnieszka Witkiewicz, Kenneth R. Lee, Gilbert Brodsky, Aida Cviko, Joshua Brodsky, Christopher P. Crum

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


Although established histologic criteria for the diagnosis of endocervical adenocarcinoma in situ (AIS) have been published, some lesions are not readily classified or present with more subtle degrees of epithelial atypia. Lesions confined to the surface mucosa may be particularly challenging, possibly because they represent early disease. Twelve cases of superficial AIS (SAIS) confined to the surface mucosa or crypt openings culled from the in-house and consultation practices were examined histologically, immunostained for MIB-1 and p16, and analyzed (when possible) for HPV nucleic acids by DNA-DNA in situ hybridization (INFORM). The mean age was 26.7 years for SAIS versus 37.0 years for 42 consecutive cases of conventional AIS from the same practice (P < 0.001). Seven and five were biopsies and conization specimens, respectively. Five coexisted with CIN, four arose in endocervical papillae, and two arose in endocervical polyps. Nuclear hyperchromasia was conspicuous in 10 and mitoses were present in all; however, apoptosis was rare or absent in four, and six exhibited only mild nuclear atypia. Mib-1 staining exceeded 40% in 5 of 7 cases tested, and all (8 of 8) were strongly positive for p16ink4. Five of five were positive for HPV by ISH with an "integrated" dot-like pattern. SAIS is an early variant of AIS that 1) occurs at a younger mean age, 2) exhibits variable atypia, and 3) arises adjacent to morphologically normal columnar epithelium. Diffuse p16 expression and integrated HPV pattern are identical to that seen in more extensive forms of the disease. Superficial AIS should be suspected in endocervical columnar epithelium with segmental nuclear hyperchromasia with mitotic activity, and confirmed by bio marker staining (p16 and Mib-1) if the pathologist is uncertain of the diagnosis.

Original languageEnglish (US)
Pages (from-to)1609-1614
Number of pages6
JournalAmerican Journal of Surgical Pathology
Issue number12
StatePublished - Dec 2005


  • Adenocarcinoma in situ
  • Cervical neoplasms
  • HPV
  • In-situ hybridization
  • Ki-67
  • p16ink4

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine


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