Should adequacy criteria in cervicovaginal cytology be modified after radiotherapy, chemotherapy, or hysterectomy?

Abstract

BACKGROUND. The general criterion of an unsatisfactory Papanicolaou (Pap) test in the 2001 version of the Bethesda system is not applicable to patients after treatment with radiotherapy, chemotherapy, or hysterectomy. The current study was performed to determine whether specimen adequacy criteria for Pap tests should be modified for these conditions. METHODS. Consecutive patients who underwent conventional Pap tests between March and August 2006 were reviewed. The original reports were done according to the 2001 Bethesda system, with cellularity criteria modified in patients with a history of radiotherapy, chemotherapy, or hysterectomy. The slides of these patients were reviewed again. The degrees of cellularity, obscuring red blood cells, and inflammation were recorded. RESULTS. The final analyses included 7033 patients for which there were complete data. The original interpretation was unsatisfactory in 4.4% of all samples. When the 1337 slides obtained from patients with a history of radiotherapy, chemotherapy, and/or hysterectomy were reviewed using the general satisfactory threshold of >8000 squamous cells/slide and <75% of the epithelium obscured, the incidence of unsatisfactory Pap tests increased from 4.3% to 13.2% (176 of 1337 slides). The odds ratios for unsatisfactory Pap tests for a history of radiotherapy, chemotherapy, and age >50 years were 2.70, 2.51, and 1.39, respectively. The majority of unsatisfactory Pap tests were because of low cellularity. The lower limits of adequate cellularity after radiotherapy or chemotherapy can be set at 2000 cells/slide, which can lower the unsatisfactory rate while at the same time resulting in no increase in the false‐negative rate. Hysterectomy alone was not found to be associated with unsatisfactory Pap tests. CONCLUSIONS. In patients who received pelvic radiotherapy or chemotherapy, the incidence of low‐cellularity Pap tests was unacceptably high. A lower cellularity (estimated 2000 cell/slide) could be used as a satisfactory threshold. Cancer (Cancer Cytopathol) 2010. © 2010 American Cancer Society.

Factors contributing to high ThinPrep® Pap test unsatisfactory rates in an academic medical center laboratory

“…In addition, cellular degeneration and debris, particularly in cases of atrophic vaginitis, adds to the difficulty. In their study, Lu et al reported that age greater than 50 years was associated with a statistically significant, but only slight increase in the unsatisfactory rate as compared to women under 50 years of age.…”

“…The survey also reported that 79% of the participating laboratories applied minimum squamous epithelial cell adequacy criteria to atrophic and/or post‐irradiation specimens; however, it was not possible to ascertain from the responses whether the laboratories modified the minimum squamous epithelial cellularity criteria for women falling into these clinical categories. Using the 2001 Bethesda System criteria for specimen adequacy, Lu et al reported a higher incidence of scant cellularity on conventional pap smears from patients who received radiation and/or chemotherapy. In this group of patients, the unsatisfactory rate was 13.2%.…”

Cytopathologic evaluation of patients submitted to radiotherapy for uterine cervix cancer

“…On the other hand, a cytopathologist with little experience in this area may underestimate the changes, missing the opportunity to detect early or recurrent cancer. 19,[29][30][31] Persistent or recurrent carcinoma is diagnosed in the cervicovaginal smear when malignant cells are identified in the course of radiotherapy or immediately after its completion. It indicates radioresistance of the neoplastic cells, being thus related to a poorer prognosis.…”

“…The most reliable criterion to establish the viability of neoplastic cells is the finding of mitoses. 26,27,34 Since radiotherapy is associated with characteristic cytological changes, including nuclear activation, increased cytoplasm (with preservation of the nuclear-cytoplasmic ratio), cytoplasmic vacuolization, eosinophilia, polychromasia, multinucleated giant cells, nuclear membrane blebbing and nuclear vacuolization, as well as repair cells, atypical stromal cells, endothelial cells and macrophages, 29,31,35 cytological samples should be collected a few months after radiotherapy. However, it is true that radiotherapy is associated with unsatisfactory samples.…”

“…Other studies using the SurePath method also corroborated these results. 29,31,[36][37][38][39][40][41] However, the method is still too expensive to be used applied on a large scale. 29 Cells with actinic effects may be confused with dyskaryotic atypia and produce false-positive results.…”