The small blue cell dilemma associated with tamoxifen therapy

Several endometrial diseases, such as endometrial hyperplasia, endometrial carcinoma, and endometrial polyps, have been reported to be associated with tamoxifen administration. We recently observed a high incidence of distinctive small blue cells in Papanicolaou tests of women who had received tamoxifen treatment for breast carcinoma.

To define the characteristics of these small blue cells, to identify the patient population in which they are found, and to determine the clinical significance and possible etiology of these findings.

A total of 154 Papanicolaou tests from 60 patients with a clinical history of tamoxifen therapy were reviewed retrospectively.

Small blue cells were found in 40% of Papanicolaou tests from patients who received tamoxifen therapy. Patients with small blue cells in their Papanicolaou tests were an average of 9 years older at the time tamoxifen therapy was initiated than those without. Among the available follow-up surgical biopsies, no malignant diagnoses were made.

We conclude that these distinctive small blue cells are found more frequently in older patients and most probably represent proliferative reserve cells of cervical/vaginal epithelium resulting from the estrogenic agonist effect of tamoxifen. More importantly, they are nonneoplastic in nature.