Perivascular Epithelioid Cell Tumor of the Orbit

Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal neoplasms comprising angiomyolipoma, lymphangiomyomatosis, and clear cell “sugar” tumor of the lung.¹ In 1992, the term PEC was introduced to characterize distinct HMB45-positive cells that seemed to originate from blood vessel walls.² Zamboni et al² coined the term PEComa to describe a pancreatic clear cell sugar tumor lesion indistinguishable from lung clear cell sugar tumor. Recently, PEComas have been recognized at various sites, most often in middle-aged female patients.³ PEComas are characterized by typical chromosomal imbalances, suggesting PECs as distinct tumor cells.⁴

A single case of orbital PEComa has been reported in a 9-year old child.⁵ Here we report a PEComa in the orbit of a 54-year-old patient.

A 54-year-old male patient had a slowly progressing, painless swelling of the right temporal lower eyelid (Figure, A). Ophthalmological examination results of the healthy patient were otherwise normal. Orbital examination showed a soft fluctuant mass in the anterior inferotemporal orbit without overlying cutaneous changes. Orbital ultrasonography and computed tomography revealed a highly reflective, demarcated, hyperdense, contrast-enhancing, round lesion measuring 1.5 × 1.0 × 1.0 cm. The tumor with large feeder vessels was completely excised through an anterior orbitotomy with subciliary incision. No recurrence was detected during 17 months of follow-up.

The tumor was well delineated with a yellow cut surface (Figure, B). Light microscopy revealed a thin fibrous capsule and lymphocytic infiltrates (Figure, C). Solid and trabecular tumor cell aggregates showed intimate association with a ramified vascular network (Figure, D). The tumor cells were large with a clear to eosinophilic granular cytoplasm, round to oval nuclei with prominent nucleoli, and diffuse cell borders. Few cells contained melanin.

The melanocytic markers HMB45 and MART1 (melan A) (Figure, E) were strongly expressed, as were CD10 and CD68. Staining results for the pancytokeratin marker AE1/3, desmin, S-100 protein, CD31, actin, CD117, microphthalmia transcription factor, and chromogranin were negative. Vimentin stained single large cells likely not belonging to the tumor. The proliferation index (ki67) was very low (< 1%).

PEComas are composed of epithelioid, sometimes spindled cells with clear to eosinophilic granular cytoplasm in association with blood vessel walls. Characteristic features are HMB45 and MART1 expression, variable expression of muscle markers, and no cytokeratin or S-100 protein expression.⁶ In a recent comprehensive review,³ expression patterns were as follows: HMB45, 100% of PEComas; MART1, 41%; smooth muscle actin, 59%; S-100 protein, 11%; desmin, 31%; cytokeratin, 0%; and CD117, 33%. In our case, we detected melanocytic markers but no epithelial or smooth muscle markers.

The differential diagnosis of clear cell tumors is vast and comprises clear cell tumors of the lung, kidney, or female genital tract, which can be ruled out in the absence of epithelial markers.

As PEComas may produce melanin, malignant melanoma and pigmented paraganglioma are important differential diagnoses. Orbital melanoma is rare and includes primary orbital melanoma, secondary orbital melanoma by extension from adjacent structures, and metastatic melanoma. PEComas expressing S-100 protein usually also stain for smooth muscle antigen.³ In our case, the lack of nuclear polymorphism or S-100 protein staining and low mitotic activity make the diagnosis of melanoma unlikely. The epithelioid cell structure resembles paraganglioma, but the lack of neurosecretory granules or staining for chromogranin and S-100 protein argue against it.

PEComas generally show a benign course, although rare cases of malignant PEComas have been published.¹ Necrosis, a high mitotic rate, a size larger than 7 cm, an infiltrative growth pattern, and a remarkable hypercellularity may indicate malignant PEComa.³ These characteristics were absent in our specimen. Because of its rarity, the clinical features, biological behavior, and best treatment of orbital PEComa are currently unclear. As most PEComas are benign, primary excision and regular follow-up seem reasonable.

Correspondence: Dr R. Guthoff, Department of Ophthalmology, University of Wuerzburg, Josef-Schneider-Strasse 11, 97080 Wuerzburg, Germany (r.guthoff@uni-wuerzburg.de).

Author Contributions: Dr R. Guthoff had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Financial Disclosure: None reported.

Additional Contributions: Christopher D. M. Fletcher, MD, FRCPath, confirmed the diagnosis.