Hemosiderotic Fibrolipomatous Tumor, Pleomorphic Hyalinizing Angiectatic Tumor, and Myxoinflammatory Fibroblastic Sarcoma: Related or Not?

Hemosiderotic fibrolipomatous tumor is an unusual, distinctive soft tissue neoplasm with locally recurring potential, which most commonly occurs in the ankle and foot. Morphologic evidence strongly suggests that hemosiderotic fibrolipomatous tumor is related to another rare, locally aggressive tumor of the distal extremities, pleomorphic hyalinizing angiectatic tumor, with areas identical to hemosiderotic fibrolipomatous tumor seen at the periphery in most if not all pleomorphic hyalinizing angiectatic tumor. This morphologic evidence is further supported by molecular genetic data, showing recurrent TGFBR3 and/or MGEA5 rearrangements in both hemosiderotic fibrolipomatous tumor and pleomorphic hyalinizing angiectatic tumor. A possible link between hemosiderotic fibrolipomatous tumor and yet another low-grade sarcoma of the distal extremities, myxoinflammatory fibroblastic sarcoma, has also been suggested based on the occurrence of unusual examples of hemosiderotic fibrolipomatous tumor showing progression to myxoid sarcoma, demonstrating some but not all features of myxoinflammatory fibroblastic sarcoma. These "hybrid hemosiderotic fibrolipomatous tumor-myxoinflammatory fibroblastic sarcoma" also commonly show TGFBR3 and/or MGEA5 rearrangements. However, classic myxoinflammatory fibroblastic sarcoma lacks areas resembling hemosiderotic fibrolipomatous tumor, and shows a very low frequency of TGFBR3 and/or MGEA5 rearrangements in prospectively diagnosed cases. This suggests that so-called "hybrid hemosiderotic fibrolipomatous tumor-myxoinflammatory fibroblastic sarcoma" represents a form of malignant progression within hemosiderotic fibrolipomatous tumor, rather than a lesion strictly related to classic myxoinflammatory fibroblastic sarcoma. This article will review the morphologic features, genetic features, and differential diagnosis of these rare neoplasms, and discuss their interrelation, or lack thereof.