Atypical immature metaplasia (AIM) of the cervix: Is it related to high-grade squamous intraepithelial lesion (HSIL)?

Atypical immature metaplasia (AIM) is a poorly characterized cervical lesio n with uncertain biological and clinical significance. AIM shares some, but not all, morphological features of squamous intraepithelial lesions (SILs) . SILs are characterized by human papillomavirus (HPV) positivity and incre ased cellular proliferation, but these features have not been fully evaluat ed in AIM. Genomic DNA was extracted from 27 microdissectcd cervical biopsy specimens diagnosed as AIM. HPV DNA tvas detected by polymerase chain reac tion (PCR), using two different sets of LI gene consensus primers. HPV type s were identified by sequence analysis of PCR products and comparison with published HPV sequences. The cell proliferation index was assessed by immun ohistochemical staining for Ki-67 (MIB-1) antigen and expressed as the perc entage of Ki-67-positive cells. Comparison groups included normal cervix (n = 10) and low-grade (LSILs, n = 19) and high-grade squamous intraepithelia l lesions (HSILs, n = 11). Intermediate- or high-risk HPV DNA was detected in 67% (18 of 27) of AIM cases. Low-risk HPV DNA was not detected in any of the specimens. The Ki-67 index in AIM (mean, 33.0 +/- 20.3; median, 29) wa s comparable to that of LSILs (mean, 21.4 +/- 4.6; median, 21) and was sign ificantly higher than that of normal cervix (mean, 11.0 +/- 2.1; median, 11 ) (P < .01) and lower than that of HSILs (mean, 60.4 +/- 13.2; median, 60) (P < .01). Of the cases with available follow-up, HPV-positive AIMs were si gnificantly more likely to have a concurrent or subsequent diagnosis of typ ical HSIL (12 of 15, 80%) than HPV-negative AIMs (one of six, 45%) (P = .01 4). The wide range of Ki-67 indices and variable HPV status in AIM suggest that AIM represents a heterogeneous group of lesions including bona fide HS ILs (high-risk HPV-positive, high Ki-67 index), antecedents (precursors?) o f HSILs (highrisk HPV-positive, low to moderate Ki-67 index), and benign re active conditions (HPV-negative, variable Ki-67 index). HPV testing may be useful in the assessment of atypical epithelial proliferations of the cervi x for which a diagnosis of AIM is considered. HUM PATHOL 30:345-351. Copyri ght (C) 1999 by W.B. Saunders Company.