Final Diagnosis -- A 5-year-old boy with epithelioid sarcoma

DIAGNOSIS  Epithelioid sarcoma.


First described in 1970 (2), epithelioid sarcoma accounts for less than 1% of soft tissue sarcomas (11). It arises from multipotential mesenchymal cells able to express both epithelial and mesenchymal immunophenotype (7), and typically shows a slow-growing pattern. Epithelioid sarcoma occurs more frequently in the upper limbs, usually involving the extremities (hand and wrist) of young to middle-aged male adults (4, 7, 11). This "classic" form of epithelioid sarcoma is composed by cells varying from spindle to round and epithelioid, with necrotic areas. A recently reported "proximal"-type variant is characterized by higher aggressiveness and preferential location in proximal-axial and deep regions (1, 4). In a recent study, frequent deletions of INI1 gene have been detected in the proximal-type variant, by both real-time quantitative PCR analysis and immunohistochemistry (9). Interestingly, the recognition of INI1 deletion in this extradural clival tumor with rhabdoid features reminds one of the atypical teratoid/rhabdoid tumor (AT/RT), a high malignant pediatric brain neoplasm, typically containing rhabdoid cells and divergent differentiation along epithelial, mesenchymal, neuronal or glial pathways. AT/RTs are associated with inactivation of INI1 gene. Moreover, very similar morphological and immunohistochemical findings (including INI1 deletion) have been reported in both malignant renal and extra-renal rhabdoid tumors, thus making the differential diagnosis difficult and problematic (6). In the present case, AT/RT was ruled out because of the extracerebral and extradural location. Furthermore, epithelioid sarcoma was considered more likely than extra-renal rhabdoid tumor on the basis of the cellular morphology and the presence of extensive geographic necrosis.

Despite their slow growth, epithelioid sarcomas tend to spread locally, infiltrating regional lymph nodes and can present as multinodular and/or metastatic disease (5). The reported recurrence rate is as high as 70%. Treatment is primarily by wide local excision, followed by adjuvant radiotherapy; however, even in cases of primary amputation of an affected limb, no survival advantage has been observed (11).

To our knowledge, this is the first report of an epithelioid sarcoma involving the clivus in a pediatric patient. The presence of a large and aggressive tumor in the skull base of a child, centered in the clivus along the midline, gives rise to a large differential diagnosis. However, skull base tumors are less common in children than in adult populations, and there are clear differences in the differential diagnoses of the two populations (12). In this case, the neuroradiological findings and the patient's age actually suggested clival chordoma, craniopharyngioma or rhabdomyosarcoma as the most likely diagnosis. Chondrosarcoma, lymphoma, aggressive meningioma, plasmocytoma, and metastasis were considered much less likely in this age group (3).

The neuroimaging characteristics of the lesion, however, did not allow a clear presumptive diagnosis. Actually, while the location and the age well suited the first hypothesis of a chordoma, the neuroradiology did not reveal other findings commonly encountered in such tumors (8, 10). Furthermore, chordomas are classically characterized by high T2-signal, reflecting the high fluid component and the vacuolated cellular components (3) while in the present case the mass was homogeneously hypointense on T2-images, suggesting the high cellularity which was subsequently confirmed by the microscopic examination. Alternatively, the low T2-signal could have been the result of a predominant chondroid or fibrous component, even though it is usually associated with a less homogeneous basal signal and contrast enhancement. Although typical of the pediatric age, the craniopharyngioma was radiologically excluded on the basis of the clival involvement, the lack of the classic signal heterogeneity, and the absence of cystic components (3). On the other hand, a rhabdomyosarcoma was hard to rule out, since it usually shows a low T2-signal and a local aggressiveness, like the present case. However, the nasopharyngeal and skull base involvement is generally more extensive than the one found in our patient. Besides, the rhabdomyosarcoma was quite easily ruled out by histology, based on the morphology of neoplastic cells and the INI1 deletion demonstrated by immunohistochemistry.

The final diagnosis required histologic examination which showed epithelioid neoplastic cells, with rounded nuclei and abundant eosinophilic cytoplasm, numerous mitoses, a high proliferative index and areas of necrosis. Immunohistochemistry, demonstrating a positive stain for vimentin, cytokeratins, and EMA, and the failure of BAF-47 antibody to stain neoplastic nuclei (suggesting INI1 deletion), were in favor of epithelioid sarcoma. This report adds epithelioid sarcoma to the differential diagnosis of both clival tumors and pediatric skull base tumors.


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Contributed by Benedetta Ludovica Pettorini, MD, Federica Novegno, MD, Alessandro Cianfoni, MD, Luca Massimi, MD, Pasquale De Bonis, MD, Giuseppe Esposito, MD, Massimo Caldarelli, MD, Gianpiero Tamburrini, MD, Concezio Di Rocco, MD, Felice Giangaspero, MD§, Libero Lauriola, MD

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