Cytologic changes of ovarian epithelial cancer induced by neoadjuvant chemotherapy

Objective: Neoadjuvant chemotherapy (NACT) followed by cytoreduction has now become a part of standard care for patients with advanced ovarian cancer. Cytologic changes of the cancer cells induced by NACT, however, sometimes may cause confusion in terms of pathologic diagnosis and therefore inappropriate management. The objective of this study was to characterize the histologic or cytologic features of the ovarian cancers from those patients who received NACT in order to improve the diagnostic accuracy and reduce unnecessary clinical workup. Methods: Specimens from 120 patients with advanced ovarian cancer who received NACT were studied. All 120 cases had either cytologic samples from ascites (n=108) or fine needle aspiration (n=12) and the diagnosis of consistent with cancers of ovarian origin was made prior to NACT. There were 70 (58.3%) patients received subsequent tumor debulking surgery after NACT. The time frame between NACT and debulking surgery ranged from 28 to 65 with an average of 45 days. Among the 70 cases with cytoreductive surgery, 48 cases containing both pre-NACT cytology/histology and subsequent debulking specimens were suitable for the study. All 48 post-NACT ovarian cancers were reviewed and the characteristic pathologic features in gross were summarized. Microscopic evaluation and immunohistochemical stainings with antibodies against ER, PR, p53, WT1, PAX8, CK7, CK20, and CDX2 were performed to confirm the primary site and histologic type of the cancers. Results: Grossly, tumor size within the ovaries from those debulking specimens ranged from 2.3 to 6.5 cm in greatest dimension. The cancers were mainly solid (average of 65%) and cystic areas had more or less hemorrhagic appearance. Extensive tumor necrosis and some with fibrosis were present. Microscopically, the non-necrotic cancer cells were arranged in cords, islands and sometimes as scattered single large cells with large amount of eosinophilic cytoplasm with vacuoles. The viable cancer cells contained more or less vacuolated cytoplasm in almost all post chemotherapy cases. Multinucleated tumor giant cells were noted in close to half of the cases. The cancer cells commonly had large hyperchromatic bizarre nuclei with coarse chromatin clumping and sometimes prominent nucleoli. Due to the unusual cytologic changes after NACT, there was a concern of non-ovarian origin or the different histologic type of the cancers. Therefore, immunohistochemical (IHC) staining with the antibodies against ER, PR, PAX8, WT1, CK7, CK20, and CDX2 was performed in all 48 pairs of the cases. The 48 paired samples showed identical immunophenotype in pre- and post-NACT cancers, confirming there was no metastatic or new primary cancer involved in the study. Conclusions NACT can apparently induce significant cytologic/histologic changes in ovarian cancer. Aware of such NACT induced changes will be useful to make correct diagnosis for those patients who have received NACT. IHC with appropriate panels of the antibodies will be helpful to aid the diagnosis, particularly when nuclear change is dramatic and the clinical history of ovarian cancer is not available.