Soft-Tissue Perineurioma of the Bulbar Conjunctiva

Perineuriomas are rare peripheral nerve sheath tumors composed exclusively of neoplastic perineurial cells and showing distinctive morphologic, ultrastructural, and immunophenotypic features that distinguish them from other nerve sheath tumors. Perineuriomas can be broadly divided into 2 histological categories: an intraneural group and a more common extraneural or soft-tissue group.¹ Most of these neoplasms are benign, but perineuriomas of low-grade malignant potential and malignant form have also been reported.^2,3 Soft-tissue perineurioma clinically manifests as a painless nodule, occurs mostly in superficial soft tissue, and only infrequently affects deep soft tissue of the extremities or trunk. Rare examples arising at visceral locations have been reported.^4,5 There are no reported cases in the English-language literature of perineuriomas affecting the conjunctiva.

A 47-year-old man had a painless, slowly growing mass in the right bulbar conjunctiva since 3 months before admission. He underwent surgical removal of a 1.0-cm nodule. Grossly, the specimen consisted of tissue fragments with aggregated dimensions of 1.0 × 0.8 × 0.3 cm that were brownish and firm. Microscopical examination revealed a nonencapsulated subepithelial spindle cell proliferation composed of elongated cells with wavy nuclei and long, slender, eosinophilic cytoplasmic processes. The tumor cells showed an interweaving fascicular growth pattern and focal storiform arrangement, with hypercellular areas and mild cytologic atypia. There were 7 mitotic figures per 10 high-power fields and no necrosis (Figure 1). Immunohistochemical studies showed reactivity for epithelial membrane antigen (EMA) (titer, 1:150 [Dako Corp, Glostrup, Denmark]; antigen retrieval titer, 1:20 [Trilogy; Cell Marque Corp, Rocklin, California] for 40 minutes with heating at 95°C), glucose transporter protein 1 (GLUT-1) (titer, 1:200 [Cell Marque Corp]), and protein gene product 9.5 (titer, 1:100 [Neomarkers Inc, Fremont, California]); showed reactivity focally for claudin-1 (prediluted [Dako Corp]) and collagen IV (titer, 1:100 [Biogenex, Andhra Pradesh, India]); and showed negative results for AE1/3 (titer, 1:50 [Cell Marque Corp]), actin (titer, 1:30 [Cell Marque Corp]), CD34 (titer, 1:100 [Dako Corp]), and S-100 protein (titer, 1:4000 [Bio SB, Inc, Santa Barbara, California]). Ki-67 (titer, 1:25 [Cell Marque Corp]) labeled approximately 10% of the neoplastic cells (Figure 2). Based on the morphologic and immunohistochemical findings, the diagnosis of a perineurioma with atypical histological features in the bulbar conjunctiva was made. After the resection, the patient was lost to follow-up.

Although perineurial cell proliferation may be suspected histologically with routine hematoxylin-eosin staining, a definite identification needs the demonstration of perineurial cell features using immunohistochemical studies. The morphologic criteria include spindle cells with curved or wavy thin nuclei and thin, elongated cytoplasmic processes, arranged in lamellae, and a storiform growth pattern forming loose whorls and bundles. By immunohistochemistry, perineurial cells stain positive for EMA, GLUT-1, and claudin-1; may stain positive for protein gene product 9.5 and CD34; and stain negative for S-100 protein, CD57, and neurofilaments.⁶

Perineuriomas are benign soft-tissue neoplasms, but atypical and malignant examples have been reported.^1,3,4 According to Hornick and Fletcher,¹ cases with atypical pleomorphic cytologic results that show abrupt transition from typical cytomorphologic findings and storiform architecture to markedly hypercellular areas with a fascicular growth pattern and diffuse infiltration of adjacent skeletal muscle have been classified as atypical perineuriomas. Hornick and Fletcher also state that the mitotic count is variable. These histological features have no clinical significance and may be comparable to the degenerative changes observed in ancient schwannoma.¹ In benign and atypical forms of perineurioma, surgical resection with free margins is curative; only 5% of cases have shown recurrence, and there are no reported cases with metastases.^1,4,5

The differential diagnosis of soft-tissue perineurioma includes cellular schwannoma (S-100 protein +; CD34 +/−; EMA −), low-grade fibromyxoid sarcoma of Evans (S-100 protein −; EMA +/−; CD34 −), solitary fibrous tumor (CD34 +; S-100 protein −; EMA −), and benign fibrous histiocytoma or low-grade malignant fibrous histiocytoma (CD34 −; S-100 protein −; EMA −; CD68 +). Immunohistochemical studies will help separate these 4 entities.^1-6

To our knowledge, this is the first case of atypical perineurioma arising in the bulbar conjunctiva reported in the English-language literature.

Correspondence: Dr Ortiz-Hidalgo, Department of Pathology, The American British Cowdray Medical Center, Sur 136 No. 116, Col Las Americas, Mexico DF 01120, Mexico (cortiz@abchospital.com).

Financial Disclosure: None reported.