Chemotherapy-induced endometrial pathology: mimicry of malignancy and viral endometritis

Chemotherapy is a common type of preoperative neoadjuvant treatment and postoperative adjuvant or palliative therapy for many different types of malignancies. Certain chemotherapeutic agents can induce bizarre epithelial atypia that mimics malignancy. Unfamiliarity with these changes could potentially cause confusion with a neoplastic or infectious process. The endometrium is one of the few sites where chemotherapy-induced epithelial atypia has not been appreciated. We identified four patients with marked cytologic atypia of the endometrial glandular epithelium from the surgical pathology files of Severance Hospital. The histopathologic features, immunostaining results and medical records of these patients were reviewed. All patients underwent hysteroscopic examination with endometrial curettage for investigation of vaginal bleeding. They had previously undergone chemotherapy for uterine cervical cancer (n=1), rectal cancer (n=2) and myelodysplastic syndrome (n=1). The chemotherapy regimens included alkylating agents (busulfan, cyclophosphamide, ifosfamide, cisplatin, and oxaliplatin), pyrimidine antagonists (capecitabine, decitabine, and 5-fluorouracil), taxanes (paclitaxel), and topoisomerase inhibitors (irinotecan and etoposide). On histopathological examination, the atypical epithelial changes included marked nuclear enlargement and pleomorphism, a degenerative-looking chromatin pattern, abundant microvacuolated cytoplasm, and preservation of the nuclear/cytoplasmic ratio. This study demonstrates that certain chemotherapeutic agents may cause bizarre, reactive atypia of the endometrial glandular epithelium. These changes should not be interpreted as neoplastic or infectious in nature. An awareness of prior exposure to cytotoxic agents and a familiarity with the nature and distribution of these bizarre alterations is essential to avoid misinterpretation of the morphologic features and prevent unnecessary treatment.