Premalignant / preinvasive lesions
Atypical immature metaplasia

Author: Seema Khutti, M.D. (see Authors page)

Revised: 10 April 2017, last major update October 2013

Copyright: (c) 2003-2017, PathologyOutlines.com, Inc.

PubMed Search: Atypical immature metaplasia [title]
Cite this page: Atypical immature metaplasia . PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/cervixatypicalimmaturemetaplasia.html. Accessed April 23rd, 2017.
Definition / General
  • First described by Crum et al (Cancer 1983;51:2214) as a low grade lesion, but now often includes both high grade and low grade lesions
  • Currently is a poorly reproducible diagnosis which lacks a uniform definition; spans a morphologic spectrum and includes many diagnostically challenging cases with an immature appearance
  • HPV+ cases are associated with future diagnosis of HSIL
  • Squamous proliferation of transformation zone and endocervical glands associated with abnormal Pap smears and a colposcopically visible abnormality
  • Based on size and distribution of lesion
Micro Description
  • More cellular than usual immature squamous metaplasia
  • Nonpapillary, metaplastic squamous epithelium with nuclear atypic
  • Basal layer of uniform cells with a uniform chromatin pattern and variable hyperchromasia
  • Overlying squamous cells are monomorphic with prominent chromocenters and regular nuclear membranes
  • Normal cell polarity, rare/no cell crowding
  • Mitoses are < 1 per 10 HPF, normal (not atypical) and confined to lower third of epithelium
  • Occasionally higher mitotic rates, multinucleation, nuclear enlargement and perinuclear halos
Micro Images

Atypical immature metaplasia

Atypical immature metaplasia


Use of immunostains to reclassify atypical immature metaplasia

Cytoplasmic CK17



Positive Stains
  • p16 and Ki-67 can classify these lesions further (see Table)
  • HSIL: diffusely positive for both (19%)
  • Reactive atypia / benign: p16-
  • Atypical immature metaplasia: p16+ and Ki-67- (may represent HSIL precursor or regressing HGSIL)
  • CK17 can be used in conjunction with p16 based on reciprocal immunoreactivity (Histopathology 2007;50:629 , Pathol Oncol Res 2013;19:707)
Reporting method
  • Atypical immature metaplasia is not commonly used as a diagnostic term in surgical pathology reports
  • Soslow et al. currently use diagnosis of HSIL if diffusely p16+ and hyperproliferative based on Ki-67 (Arch Pathol Lab Med 2009;133:729)
  • HPV+, p16+ hypoproliferative lesions with Ki-67+ may be early or regressing lesions
  • If immunostains do not support a proliferative, HPV associated lesion, diagnosis often includes explanatory note
Molecular / Cytogenetics Description
Differential Diagnosis
  • HSIL: marked nuclear pleomorphism, atypical mitosis
  • Papillary immature metaplasia: papillary architecture