Tumors of Perivascular Cells

Definition

The myopericytoma family of tumors encompasses a group of histologically overlapping lesions, which span a spectrum from “ infantile hemangiopericytoma ” (now felt to represent the cellular phase of myofibroma in young children), to classical myofibroma / myofibromatosis in children and in adult s , and to somewhat more glomoid-appearing lesions, termed myopericytoma and glomangiopericytoma. The distinction between some of these entities can at times be rather subjective, and is generally not of great significance, given their similar morphologic, genetic, and clinical features. However, documentation of multifocal or familial disease is important.

Gross Findings

Myofibromas and myopericytomas appear grossly as nonspecific soft tissue masses. Central necrosis and calcification may be apparent in myofibroma and infantile myofibromatosis.

Microscopic Findings

Myofibromas are distinctly zonated lesions, with peripheral hyalinized, distinctly myoid-appearing areas surrounding a central core of smaller, pericyte-like primitive appearing cells ( Fig. 8.1A–C ). The primitive cells are ovoid to spindled with less cytoplasm than the myoid component, whereas the cells in the peripheral zone are spindled with tapered nuclei and grow in fascicles or in a whorled pattern. The cytoplasm and stroma may have a basophilic, pseudo-chondroid appearance in the peripheral/myoid areas ( Fig. 8.1C ). The central zone of myofibroma may be highly cellular, mitotically active and may show necrosis, features that may suggest a sarcoma if one does not identify the better differentiated myoid zones. A branching, staghorn vascular pattern is frequently present in the central zone. Tumors previously referred to as “infantile hemangiopericytoma” represent cellular myofibromas consisting entirely or almost entirely of this central zone, often with necrosis and calcification ( Figs 8.1D and 8.2A ). Myofibromas in adults often show a “reversed” pattern of zonation, with a central rather than peripheral myoid zone, or may show a disorganized admixture of myoid and primitive-appearing areas ( Fig. 8.1B ). There is usually proportionately more of a myoid component than a primitive component in adult cases. All myofibromas may show extension into small blood vessels at the periphery of the lesion ( Fig. 8.2B–C ). Calcifications may be present. A rare, distinctive subset of myofibromas shows high cellularity, a fascicular growth pattern, and only scattered small myoid nodules, and may easily be mistaken for a spindle cell sarcoma ( Fig. 8.3A–B ). These tumors often harbor SRF-RELA fusions.

Myopericytoma and glomangiopericytoma are best thought of as lesions that have hybrid features somewhere between myofibroma and glomus tumor. These lesions are typically composed of distinctly myoid-appearing, short, eosinophilic, spindled cells, which are arranged around a branching, staghorn vasculature; the vessels may be thin- or thick-walled ( Fig. 8.4A–C ). Lesional cells may be seen around vessels outside of the main tumoral mass. Myoid balls, reminiscent of the myoid zones in myofibroma, are often present, as are distinctive areas of concentric perivascular growth ( Fig. 8.4D ). In some cases, the cells are more glomoid (corresponding to glomangiopericytoma ), and the histologic features of these cases overlap significantly with those of glomus tumors showing smooth muscle differentiation, so-called glomangiomyoma.

A small number of myopericytomas have been reported to show histologic features of malignancy, including cytological atypia, high mitotic activity, and aggressive invasion of surrounding tissues ( Fig. 8.5A ). The histologic features of such lesions, which may be referred to as malignant myopericytoma, overlap with those of malignant glomus tumors. Exceptionally rare patients present with numerous (sometimes dozens) of discrete, benign-appearing myopericytomas involving a limb, so-called “myopericytomatosis” ( Fig. 8.5B ).

Immunohistochemistry

The peripheral, more myoid appearing, zone of myofibromas and all tumor cells of myopericytoma and glomangiopericytoma are strongly positive for smooth muscle actin ( Fig. 8.1E ) and may also show variable degrees of expression of caldesmon. Desmin is rarely expressed by the tumor cells. The central primitive zone of myofibromas shows less expression of smooth muscle actin. CD34 and S100 protein are negative in tumor cells.

Molecular Genetics

PDGFRB mutations are key driver events in myopericytoma and myofibroma and are present in at least 70% of sporadic cases, as well as in familial cases. As noted above, highly cellular myofibromas frequently harbor the SRF-RELA fusion gene.