Answer: Low-grade fibromyxoid sarcoma

Histology: The lesion is composed of spindle cells and shows varying cellularity with more myxoid zones punctuating more cellular ones. In places if is similar to a fibromatosis but the lesion differs by displaying hyperchromatic nuclei [compare them to the ones in the fibromatosis, Case 3789]. The collagen is less “kinky” than that seen in neurofibromas. The nuclei are too hyperchromatic for a “fibroma”.

Discussion: Low-grade fibromyxoid Sarcoma (Evans) and Hyalinizing Spindle cell tumor with Giant Rosettes
Low-grade fibromyxoid sarcoma is a tumor composed of bland, fibroblast-like cells with a swirling, whorled, vaguely storiform pattern in a fibrous and focally myxoid stroma, occasionally with plexiform vasculature. These were first reported by Evans who noted their deceptive resemblance to fibromatoses. Evans later expanded his observations and included examples that had undergone dedifferentiation to higher-grade sarcomas. These tumors have little mitotic activity and minimal nuclear pleomorphism. This lesion recurs, but many cases also metastasize (e.g. to lung). This tumor is not quite equivalent to low-grade examples of myxofibrosarcoma, as originally defined, since the latter occur in older patients, are more pleomorphic and less fibrous, and seldom metastasize when superficial. Ultrastructural reports have shown fibroblastic differentiation and this tumor is regarded as a low grade variant of fibrosarcoma. The differential diagnosis of low grade fibromyxoid sarcoma includes fibromatosis which differs by having blander nuclei, no swirling architectural pattern, and a characteristic vascular pattern, and perineurioma, which displays epithelial membrane antigen reactivity and has classic ultrastructural features.

Hyalinizing spindle cell tumor with giant rosettes is an entity closely resembling low-grade fibromyxoid sarcoma. Nineteen examples were reported by Lane et al. in 1997, as occurring principally as a painless, slowly growing, deeply situated mass of the proximal extremities in young to middle-aged adults (age range 14-65 years, mean 38;). Thirteen of the cases (68%) were in males. Fourteen tumors were in skeletal muscle, and three in subcutis. Although grossly circumscribed, the tumors had infiltrative borders microscopically and were composed of bland spindled cells situated in a hyalinized to myxoid stroma, often with “cracking” artefact in the collagen. Characteristic were scattered large rosette-like structures that often merged with serpiginous areas of dense hyalinization. The rosettes consist of a central collagen core surrounded by a rim of rounded cells morphologically and immunophenotypically different from the cells of the spindled stroma. These cells express a number of antigens, including S-100 protein, neuron-specific enolase, and Leu 22, in contrast to the stroma, which usually lacks these antigens. Of the 12 patients with available follow-up information in the original series, one patient treated with simple excision clinically developed local recurrence of the tumor 20 months later. No other recurrences were reported during the limited follow-up period, and no patient developed metastatic disease. However, the authors thought that the favorable prognosis might relate to the limited follow-up period (approximately 3 years), as well as initial treatment by wide excision in nearly half of the patients. They regarded this entity as a distinctive type of low- grade fibroblastic tumor that with time may prove to behave similarly to low-grade fibromyxoid sarcoma and therefore represent a variant of it. Subsequently such a case was reported to metastasize by Woodruff and a further study showed that the Evans tumor and the hyalinizing spindle cell tumor with giant rosettes were indeed ends of a diagnostic spectrum. The final component of the story has been the observation that there is the identical characteristic translocation in both types of tumors with its own fusion gene product; t(7;16)(q33;p11) fuses the FUS gene to BBF2H7.

There are no prospective reports of diagnosis of low grade fibromyxoid sarcoma or hyalinizing spindle cell tumor by aspiration cytology, although given that these tumors can be subtle to diagnose on open biopsies, accurate diagnosis by aspiration cytology would seem unrealistic.

The differential diagnosis of both ends of this spectrum is primarily with fibromatosis, which, as above, differs by featuring sweeping fascicles of bland spindle cells rather than a swirled architecture punctuated by rosettes. Nuclei are pale staining and not prominent at scanning magnification. Schwannomas are not likely to have rosettes and the cells are typically not rounded as the ones in the current lesion. If S100 staining is performed, all cells are reactive rather than a subgroup. Fibroma of tendon sheath is a paucicellular lobulated lesion that lacks rosettes. In its cellular phase, it resembles nodular fasciitis and features bland hyprchromatic cells arranged in a loose storiform pattern.