Tumor heterogeneity and histopathology in epithelial ovarian cancer

The histopathology of the original and the persistent or recurrent epithelial ovarian cancer in 34 patients was simultaneously reviewed by two pathologists. The time between removal of the primary tumor and removal of the persistent or recurrent tumor ranged from four to 132 months (median, 13 months; mean, 25 months). The initial operation was followed by multiagent chemotherapy in 23 patients, single-agent chemotherapy in seven, radiation and chemotherapy in two, radiation in one, and no therapy in one patient. In four of the 34 primary tumors, a mixed tumor composition was initially identified. In comparing the initial histopathology with that of persistent or recurrent tumors, a change was identified in nine patients. In four patients, the tumor changed from a mixed to an undifferentiated histologic type; in four patients there was a change from a lower to a higher tumor grade, and two of these patients also had a change in tumor cell type from serous to undifferentiated. In the ninth patient, the tumor changed from a large cell undifferentiated to a small cell undifferentiated carcinoma. The observed changes could be the result of 1) modification of the tumor by cytotoxic therapy, 2) spontaneous dedifferentiation of the initial tumor, 3) tumor cell heterogeneity with preferential growth of one cell type over the others, or 4) the development of a second primary tumor.