Enlarged Squamous Cell Nuclei in Cervical Cytologic Specimens From Perimenopausal Women (“PM Cells”)

Abstract

We studied the appropriateness of interpreting squamous cells with enlarged, smooth, bland nuclei in perimenopausal women ("PM cells") as atypical squamous cells (ASCs). Papanicolaou smears (Paps) from 100 women (40-55 years old) with a cytologic interpretation of ASC of undetermined significance (ASCUS) and human papillomavirus (HPV) testing or a biopsy within 6 months were reviewed by 2 observers without knowledge of the biopsy diagnosis or HPV results. Cases in which both reviewers agreed that the Paps were diagnosed more properly as "negative for intraepithelial lesion or malignancy" were compared with cases of "true ASCUS," using histologic squamous intraepithelial lesion and/or a positive high-risk HPV test as a positive outcome (abnormal follow-up). Of 100 cases, 28 were reclassified as benign by both observers. In 15 of these, the original ASCUS interpretation was based on cells with bland nuclear enlargement (2-3 times the area of intermediate cell nuclei), smooth nuclear membranes, and fine chromatin. Abnormal follow-up was identified in 1 (7%) of 15 benign cases but in 30 (42%) of 72 true ASCUS cases (P = .023). PM cells are a significant cause of ASC overdiagnosis in women 40 to 55 years old. Cervical Paps with cells no more atypical than these can be interpreted safely as negative for intraepithelial lesion or malignancy.

Is visual inspection with acetic acid better than cervical cytology to screen women ≥40 years of age for carcinoma cervix? A cross-sectional study on proportion of screen-positive women (by VIA and cervical cytology) having CIN II/III lesion on cervical biopsy: difference between two age groups and among screening methods

“…Recent studies suggest that, cervical cytology has a lower sensitivity in predicting preinvasive cervical lesions especially in women ¸40 year age as it has been shown that hormonal changes in this age group brings forth changes in the cells of transformation zone which may mimic cellular atypia [22]. These cells with bland nuclear enlargement are termed as perimenopausal cells or PM cells [23]. Keating and Wang report in perimenopausal women a signiWcantly higher ASC-US: LSIL ratio and a lower positive predictive value of ASC-US in predicting a diagnosis of SIL on subsequent pap smears or biopsies.…”

Significance of High-Risk Human Papillomavirus DNA–Positive Atypical Squamous Cells of Undetermined Significance Pap Smears in Perimenopausal and Postmenopausal Women

“…This overall low positive rate for high risk HPV DNA in these perimenopausal and postmenopausal women has been explained as resulting from overdiagnosis of atrophy-related epithelial changes as ASCUS. 3,4 In addition, lower incidence of HPV infection or a lower viral load in infected individuals may also be contributing factors. Although a second spike of HPV positivity has been reported in women ≥ 55 years, 7 an obvious second spike of HPV positivity in these women was not observed in our study.…”

“…1,2 It has been speculated that atrophyassociated epithelial change and reactive metaplasia may cause overdiagnosis of ASCUS in these women. 3,4 Reflex testing for high-risk human papillomavirus (HPV) DNA in patients with ASCUS has been demonstrated to be highly sensitive for detecting cervical intraepithelial neoplasia (CIN) grade 3 (CIN 3), the precursor of cervical cancer, resulting in fewer women, both younger and older, being referred for colposcopy. 5,6 The overall sensitivity of HPV DNA testing at the 1.0 pg/mL level for detecting CIN 3 or cancer was reported to be 96.1% and varied minimally from 93.9% to 97.8% among women of different ages with an ASCUS interpretation.…”

Cervical and Vaginal Cytology

“…126 The cause of nuclear enlargement in squamous cells from perimenopausal women is not known. 126 The cause of nuclear enlargement in squamous cells from perimenopausal women is not known.…”