Biomarker resolution of uterine smooth muscle tumor necrosis as benign vs malignant

Uterine leiomyosarcomas are rare malignant tumors with a poor prognosis while leiomyomas are common benign tumors unrelated to their malignant counterparts. Diagnostic features commonly present in leiomyosarcoma include cytologic atypia, high mitotic index, and a sarcoma-specific geographic cell death designated 'tumor cell necrosis (TCN)'. TCN has a sharp viable-nonviable boundary lacking inflammation, fibrosis or granulation tissue seen in nonspecific infarction. These characteristics are sometimes difficult to interpret on routine hematoxylin and eosin slides, and can lead to diagnostic errors. In this study, we used extracellular matrix stains to test the hypothesis that the host response which characterizes nonspecific infarction may degrade the matrix in infarcted tumor more than in TCN. A 'honeycomb' pattern of reticulin highlighted individual tumor cells in viable regions of all cases. Nonviable area of reticulin patterns differed significantly by diagnosis (P<0.001), with a honeycomb pattern maintained (91%, 20/22) in leiomyosarcoma and lost (61%, 11/18) in leiomyomas. Retention of honeycomb reticulin in nonviable areas of leiomyosarcoma occurred irrespective of the presence of inflammation, hemorrhage, fibrosis, or diffuse hyalinization. Fibrosis/hyalinization as evidenced by trichrome stain was significantly (P<0.001) more common in nonviable areas of benign leiomyomas (100%, 18/18) compared with leiomyosarcomas (36%, 8/22). In those occasions where viable tissues contained discernable polarization of mitotic activity, these decreased toward the nonviable interface in leiomyosarcoma, and had an opposite pattern in leiomyomas, increasing toward the interface. There is a significant difference in the reticulin and collagen networks of nonviable areas of leiomyosarcoma compared with leiomyoma. At the time of early injury, both retain reticulin; however, this is cleared over time in benign, but not malignant, areas of necrosis. We conclude that proliferative repair of leiomyomas at the viable-nonviable interface includes remodeling of the extracellular matrix, in contrast to the static preservation of extracellular matrix ('mummification') in nonviable areas of leiomyosarcomas.