Myxoinflammatory Fibroblastic Sarcoma

Not clinically relevant

Tumors showing histological overlap with MIFS and haemosiderotic fibrolipomatous tumor (HFLT) have been reported, suggesting a link between these two tumor types, but this link remains incompletely understood and controversial. MIFSs have also been reported to coexist with pleomorphic hyalinizing angiectatic tumor, but the precise classification of these unusual tumors remains the subject of debate.
A complex karyotype including a reciprocal t(1;10)(p22;q24) was initially reported in MIFS, followed by a report of a reciprocal t(1;10) in a case of HFLT and a hybrid MIFS/HFLT with der(10)t(1;10). The breakpoints in chromosomes 1 and 10 cluster in TGFBR3 and in or near OGA (MGEA5), respectively, but do not result in an expressed fusion gene. The t(1;10) has been detected in most HFLT cases and appears much more common in hybrid HFLT-MIFS tumors than in classic MIFS. Although these findings resulted in the proposal of an initial pathogenetic link between MIFS and HFLT, suggesting that they represent a morphological continuum or pathological spectrum, later studies have questioned this hypothesis, postulating that these two entities are unrelated and that hybrid HFLT-MIFS tumors more likely represent sarcomatous progression in HFLT, rather than true MIFS. Additionally, one third of MIFSs demonstrate BRAF-related fusions, which were not detected in any of the HFLTs tested. Another common genetic event in both MIFS and HFLT is the presence of a 3p11.1-p12.1 amplicon, including the VGLL3 gene.

Tumors are lobulated and variably gelatinous, fleshy, or firm, typically attaining a size of roughly 3 cm.

These tumors are infiltrative and multinodular, being centered in the subcutaneous tissue in most cases. They are characterized histologically by dense inflammation merging with stroma varying from myxoid to hyalinized and containing sheets and small foci of epithelioid and spindled cells. Some lesions contain foamy histiocytes, giant cells, and haemosiderin. The cellularity is quite variable between lesions. Amid the inflammatory background, scattered bizarre cells with large vesicular nuclei and macronucleoli reminiscent of Reed–Sternberg cells or virocytes are present. Many cells show degenerated smudged chromatin. Pseudolipoblasts akin to those encountered in myxofibrosarcoma with cytoplasmic mucopolysaccharide matrix compressing nuclei may be seen. The spindle cells often coalesce at the periphery of myxoid lobules to form a reticular pattern as they merge with myxoid tissue. The inflammatory infiltrate is mixed, consisting of lymphocytes, plasma cells, histiocytes, and eosinophils in varying proportions. Emperipolesis may be present. Despite the cytological atypia, mitotic activity is minimal. Immunohistochemistry is unhelpful.

Cytological preparations show large epithelioid cells with macronucleoli and lipoblast-like features enmeshed in myxoid stroma with prominent inflammation and spindle cells.

Local recurrences are common and often repeated. Metastases are rare, occurring in < 1% of cases after multiple recurrences. Initial complete excision is the best predictor of a favorable outcome.

Not clinically relevant

Essential: typical distal extremity location; atypical fibroblastic cells with macronucleoli; variably myxoid and hyalinized matrix with a mixed inflammatory infiltrate.

Desirable: pseudolipoblasts.