Pericyte Antigens in Perivascular Soft Tissue Tumors

Abstract

Introduction Perivascular soft tissue tumors are relatively uncommon neoplasms of unclear line of differentiation, although most are presumed to originate from pericytes or modified perivascular cells. Among these, glomus tumor, myopericytoma, and angioleiomyoma share a spectrum of histologic findings and a perivascular growth pattern. In contrast, solitary fibrous tumor (previously termed hemangiopericytoma) was once hypothesized to have pericytic differentiation. Methods Here, we systematically examine pericyte immunohistochemical markers among glomus tumor (including malignant glomus tumor), myopericytoma, angioleiomyoma, and solitary fibrous tumor. Immunohistochemical staining and semiquantification was performed using well-defined pericyte antigens, including αSMA, CD146, and PDGFRβ. Results Glomus tumor and myopericytoma demonstrate diffuse staining for all pericyte markers, including immunohistochemical reactivity for αSMA, CD146, and PDGFRβ. Malignant glomus tumors all showed some degree of pericyte marker immunoreactivity, although it was significantly reduced. Angioleiomyoma shared a similar αSMA + CD146 + PDGFRβ+ immunophenotype; however, this was predominantly seen in the areas of perivascular tumor growth. Solitary fibrous tumors showed patchy PDGFRβ immunoreactivity only. Discussion In summary, pericyte marker expression is a ubiquitous finding in glomus tumor, myopericytoma, and angioleiomyoma. Malignant glomus tumor shows a comparative reduction in pericyte marker expression, which may represent partial loss of pericytic differentiation. Pericyte markers are essentially not seen in solitary fibrous tumor. The combination of αSMA, CD146, and PDGFRβ immunohistochemical stainings may be of utility for the evaluation of pericytic differentiation in soft tissue tumors.

The pericyte antigen RGS5 in perivascular soft tissue tumors

“…These findings extend our previous observation regarding a shared pericytic immunophenotype within these tumors, including immunoreactivity for αSMA, CD146, and PDGFRβ [10]. In contrast, myofibroma, solitary fibrous tumor and PEComa tumors do not share this pericytic immunophenotype, with absent or weak/focal RSG5 immunoreactivity only.…”

“…To date there is no direct evidence that SFT arises from pericytic cells (see [37] for a review). Previously, we examined αSMA, CD146 and PDGFRβ expression across 10 SFT specimens [10]. No expression of αSMA or CD146 was seen, while patchy PDGFRβ immunoreactivity was found in a subset of SFT (7/10 samples), in line with previously published observations [38].…”

“…More study is required in order to better elucidate the cellular differences between RGS5+ tumors (glomus tumor, myopericytoma, angioleiomyoma) and RGS5–tumors (myofibroma). In our previous study, we found that a minority of soft tissue tumors demonstrate loss of PDGFRβ expression, potentially representing a modified or aberrant pericyte immunophenotype [10]. Lack of RGS5 in myofibroma may represent such aberrant pericyte phenotype, or alternatively could suggest a non-pericytomatous line of differentiation.…”

“…Semi-quantitative grading of immunohistochemical stains was performed with some modification of previous protocols by three blinded independent observers [10]. Intensity of staining was graded on a three point scale (0–3+), defined as follows: 0: absent stain; 1+: weak, focal cytoplasmic staining; 2+: moderate, focal to diffuse cytoplasmic staining; 3+: strong, diffuse cytoplasmic staining.…”

“…Ultrastructural examination has suggested either a modified pericyte or smooth muscle phenotype in glomus tumor [7,8], myopericytoma, and angioleiomyoma [9]. Recently, we reported a shared pericyte immunophenotype among glomus tumor, myopericytoma, and angioleiomyoma, including diffuse immunoreactivity for αSMA, CD146, and PDGFRβ [10]. However, these known pericyte antigens have relatively diverse expression profiles, both in normal and neoplastic tissues (see Shih et al and Palman et al [11,12] for a review).…”