Not all granular cell tumors show schwann cell differentiation: a granular cell leiomyosarcoma of the thumb, a case report.

Abstract

To the Editor: Tumors with a granular cell phenotype (GCT) encompass a wide variety of cutaneous, deeper, or visceral lesions (1); show different behavior, ranging from benign (as the congenital gingival GCT) (2) to atypical and malignant (3); and demonstrate varying differentiations despite their uniform morphologic appearance (4). Most adult GCTs are currently thought to be of schwannian origin, whereas congenital GCTs are of uncommitted mesenchymal cell origin (4). The case we describe is of an 18-year-old woman who presented with a painful swelling in the subungual region of the terminal phalanx of the right thumb, 1 cm in diameter. The excised fragmented tissue was whitish and firm, entirely composed of plump cells with centrally placed, oval to round vesicular nuclei, with clumped chromatin and a central nucleolus and coarsely granular eosinophilic periodic acid Schiff-diastase negative cytoplasm. The growth patterns varied from ribbons or nests, divided by fibrous septa (Fig. 1), to bundles of elongated granular cells, more often seen at the periphery of the fragments (Fig. 2). There were one to two mitotic figures per 10 high power fields (inset, Fig. 2) and a middle nuclear pleomorphism, without necrotic areas. A diagnosis of malignant granular cell tumor was made. Immunohistochemical phenotype of the first surgical specimen showed reactivity for vimentin and muscle actin (clone HHF35) (Fig. 3), and negative results for cytokeratin (Cam 5.2), desmin, neuron specific enolase, and S-100 protein. Ultrastructural study, performed on paraffin-embedded tissue, showed nests of polygonal to spindle-shaped cells, with cytoplasm engulfed by secondary lysosomes and glycogen. Focally, bundles of contractile filaments (Fig. 4) and micropinocytotic vesicles were present. Sparse interstitial cells with angular bodies (Gaucher-like bodies) were observed. The ultrastructural picture was consistent with granular tumor with a smooth-muscle differentiation.FIG. 1: The biopsy of a thumb lesion showed ribbons and a nest of plumped cells with centrally placed, round to oval nuclei and coarsely granular eosinophilic cytoplasm.FIG. 2: At the periphery of the fragments, bundles of elongated granular cell predominated; inset: a mitotic figure.FIG. 3: A bundle of elongated granular cells, cut en face, showed granular positivity for HHF-35 stain (Immunoperoxidase).FIG. 4: Ultrastructural findings: a neoplastic cell shows a bundle of contractile filaments with fusiform densities. Vacuoles representing secondary lysosomes are visible in the adjacent cell (×28000).The subsequent terminal phalanx amputation showed a subungual focus of well differentiated leiomyosarcoma, with granular change (Fig. 5). The tumor had haphazardly oriented or interweaving fascicles of spindle cells with pleomorphic nuclei. When cut en face, the fascicles showed distinct cellular outlines and perinuclear clear zones.FIG. 5: Well-differentiated leiomyosarcoma of the amputated thumb with nuclear pleomorphism and focal granular change (arrow).The patient is alive and disease free 2 years after amputation. Light and electron microscopic findings in our case clearly supported smooth muscle origin: a focal fascicular growth pattern, actin positivity, and microfilaments in electron microscopy on the first specimen. The amputation specimen showed typical haphazardly oriented or interweaving fascicles, which, when cut en face, typically show distinct cellular outlines and perinuclear clear zones, allowing us to define the lesion as cutaneous leiomyosarcoma with granular changes. To our knowledge, thirteen granular cell leiomyosarcomas have been reported (Table 1). Leiomyosarcomas (LMSs) of the skin are rare (2), accounting for less than 5% of sarcomas in adults (8). The extremities are typically involved (2). Despite the histologic resemblance, the LMSs arising in the skin typically behave in an indolent manner, with limited infiltration of subcutaneous tissues and without metastases, and do not cause death. Conversely, tumors arising in the subcutaneous tissues pursue an aggressive course, with local recurrences and distant metastases, and they lead to death, as do soft tissues LMSs (8).TABLE 1: Clinicopathologic features of 13 granular cell leiomyosarcomas As Table 1 shows, all but one (case 12, ref. 5) dermal granular cell LMS have had an indolent course, whereas three patients of nine with deeper and soft tissues LMSs with granular change died of disease. Maria Sironi, M.D. Agnese Assi, M.D. Department of Pathology; Legnano General Hospital-USL 34; Legnano, Italy Gianandrea Pasquinelli, M.D. Giovanna Cenacchi, M.D. Department of Experimental Pathology; Section of Cytopathology and Ultrastructural Diagnosis; S. Orsola Hospital; Bologna, Italy