Nerve sheath myxoma (neurothekeoma) of the skin: light microscopic and immunohistochemical reappraisal of the cellular variant.

Nerve sheath myxoma (NSM) is a rare cutaneous neoplasm, the histogenesis of which is controversial. Fifteen cases of NSM were studied by routine light microscopy and with a broad panel of immunohistochemical stains. NSM were classified into three groups based on cellularity, mucin content and growth pattern. 1) The hypocellular (myxoid) type (5/15 cases) showed frequent encapsulation or sharp circumscription. Immunohistochemically this type was strongly positive for S-100 protein and collagen type IV and variably positive for epithelial membrane antigen. 2) The cellular type (4/15 cases) had scant mucin and ill-defined nodular or infiltrating growth. Immunostaining showed positive reaction for neuron specific enolase (2/4), Leu-7 (1/4) and smooth muscle specific actin (2/4), and was negative with the other antibodies. 3) The "mixed type" (6/15 cases) had variable cellularity and mucin content with poor demarcation and variable immunolabeling. We conclude that: 1) there are major light microscopic and immunohistochemical differences between the classical hypocellular (myxoid) and the cellular forms of NSM (neurothekeoma); 2) while the immunohistochemical results support the presence of nerve sheath differentiation in the classical forms of NSM, and to some extent in the mixed forms, there is an absence of convincing evidence of neural differentiation in the cellular variant by either light microscopy or immunohistochemistry; 3) the variable immunophenotypes suggest that differentiation other than neural may take place in CNT.