Perineurioma

Not clinically relevant

Soft tissue perineuriomas share pathogenetic mechanisms with other nerve sheath tumors. Deletion of 22q12 and mutations in NF2 (encoding the tumor suppressor merlin [NF2]) are the most frequently reported genetic alterations, similar to in schwannomas and meningiomas. Deletion of 17q11 (including NF1) is also a recurrent event in soft tissue perineurioma. Other reported chromosomal alterations include a three-way chromosome 2, 9, and 4 translocation involving ABL1; various chromosomal losses; and a rearrangement involving 10q24 in a soft tissue perineurioma of the foot. Alterations in 10q24 are recurrent events in sclerosing perineuriomas. Malignant perineurial tumors have been less well characterized: loss of chromosome 13q and small deletions of chromosomes 3, 6, and 9 have been reported in 2 cases of low-grade malignant perineurial tumor.

Soft tissue perineuriomas are well circumscribed but unencapsulated. The cut surface is usually firm or rubbery and yellow, tan, or white. A small subset of tumors show a gelatinous appearance. Size ranges from < 1 to 20 cm, although most tumors are between 1.5 and 8 cm. The mean size of superficial tumors is 3 cm, compared with 7 cm for deep-seated tumors.

Soft tissue perineuriomas typically show a predominantly storiform or whorled growth pattern. Other distinctive architectural features include long fascicles with tumor cells arranged in a lamellar fashion and perivascular growth. The tumor cells are usually slender spindle cells with wavy or tapering nuclei, indistinct nucleoli, and characteristic delicate bipolar cytoplasmic processes. Some perineuriomas contain shorter, ovoid tumor cells. The stroma is usually collagenous; about 20% of cases contain at least focally myxoid matrix, which is occasionally abundant. Mitotic activity is typically scarce or absent. Occasional soft tissue perineuriomas show degenerative nuclear atypia, including pleomorphic and multinucleated cells, some with nuclear pseudoinclusions. Plexiform architecture has rarely been reported. Sclerosing perineuriomas are composed of cords of small epithelioid to spindle cells in a dense collagenous stroma. Reticular perineuriomas are composed of interconnected, elongated spindle cells with a lacy or reticular architecture. Rare perineuriomas contain cells with intracytoplasmic vacuoles, mimicking lipoblasts. The very rare malignant perineuriomas (perineurial malignant peripheral nerve sheath tumors) show cytoarchitectural features similar to benign soft tissue perineuriomas, in addition to hypercellularity, nuclear atypia and hyperchromasia, and a high mitotic count.

By immunohistochemistry, perineuriomas consistently express EMA, which ranges from weak and focal to strong and diffuse. Claudin-1 and GLUT1 are also often positive. CD34 is expressed in about 60% of soft tissue perineuriomas. Staining for S100, SOX10, and GFAP is negative. In addition to EMA, sclerosing perineuriomas may show limited staining for keratin.

There is little experience with cytological diagnosis of these lesions, but FNA specimens are said to be paucicellular, with smears containing fragments of myxoid stroma.

Conventional perineuriomas of soft tissue (and sclerosing and reticular subtypes), including those with degenerative nuclear atypia, are benign and only rarely recur locally. Malignant perineuriomas may sometimes metastasize, but they appear to behave in a less aggressive fashion than conventional malignant peripheral nerve sheath tumors.

Not clinically relevant

Essential: storiform, whorled, and lamellar architecture; elongated, slender spindle cells with bipolar cytoplasmic processes; expression of EMA; variable claudin-1, GLUT1, and CD34.