A conventional-type epithelioid sarcoma (ES) it is mostly seen in the distal extremities (commonly hand) of young adults. On histomorphology, it displays a typical "granuloma-like" pattern of tumor cells surrounding a necrotic focus [1
Lately, a non-conventional subtype of ES has been identified with a differing clinical profile and a polyphenotypic differentiation, termed as the "proximal-type" ES. It is more frequently seen in the pelvis, perineum and genital tract of young to middle aged adults. On histology, it usually lacks the conventional "granuloma-like appearance". In addition to presence of oval to polygonal cells, it shows characteristic large cells with 'rhabdoid' traits [4
The present case was identified as a perineal mass in a middle-aged male. The outside slide on review revealed a multi nodular tumor comprising oval to polygonal cells arranged predominantly in cohesive sheet like pattern. Interspersed were large cells with abundant cytoplasm, vesicular nuclear chromatin and prominent nucleoli. A wide panel of IHC makers was performed to sort out a diagnosis from an equally wide range of differentials, including metastasis from a poorly differentiated carcinoma, a rhabdomyosarcoma, a melanoma, an epithelioid leiomyosarcoma, an epithelioid angiosarcoma, an epithelioid malignant peripheral nerve sheath tumor (MPNST), an epithelioid gastrointestinal stromal tumor (GIST), a conventional ES, an anaplastic large cell lymphoma (ALCL), a synovial sarcoma, an extra-renal rhabdoid tumor and a mesothelioma. In the clinico-radiologic metastatic work-up, no definite mass was identified in the solid organs as well as in the gastrointestinal (GI) tract. In addition, CEA levels were found to be normal. No glandular or squamoid areas were seen in the tumor. Further, on IHC, lack of CK20 and CEA expression made a possibility of a metastatic adenocarcinoma from the GI tract as less likely. CD 34 positivity further substantiated a diagnosis of an ES over a carcinoma, as well as a synovial sarcoma, the latter which is known to express epithelial and mesenchymal markers [5
]. Apart from this dual immunoreactivity, no biphasic tumor cell pattern was noted. Lack of S-100 and HMB-45 ruled out the possibilities of an epithelioid MPNST and a melanoma. Desmin was found to be focally positive as has been seen by Guillou et al in 62.5% of their cases of proximal-type ES [4
]. Possibility of an epithelioid rhabdomyosarcoma was discarded considering strong immunoreactvity for CK, CK7 and EMA along with Myo D-1 negativity. An epithelioid leiomyosarcoma was ruled out in view of SMA negativity. An epithelioid GIST seemed another differential, but lack of C-KIT was helpful in considering this close differential diagnosis, less likely.
An interesting observation in the tumor was a 'pseudoangiosarcomatous' pattern, as has been noted in some cases by Guillou et al [4
]. Lack of CD31 ruled out the possibility of an epithelioid angiosarcoma [7
]. In addition, diffuse EMA and CK expression helped in considering a diagnosis of an epithelioid angiosarcomas as less likely, which can rarely show focal expression for these markers [5
]. Lack of LCA along with diffuse positivity for CK ruled out an ALCL. Apart from the non-contributory findings in terms of any body cavity lesions, calretinin negativity ruled out a mesothelioma. In this way, a diagnosis of proximal-type ES was based on the presence of larger/rhabdoid cells in a tumor, with an otherwise epithelioid morphology, exhibiting a polyphenotypic expression with mesenchymal markers (vimentin, CD34); a myogenic marker (desmin) along with epithelial markers (CK, CK7, EMA). There have been infrequent studies and case reports on this tumor [4
]. Ultrastructurally, the rhabdoid cells noted in this tumor have been found to be displaying paranuclear, well-delineated filamentous aggregates, indenting the nucleus eccentrically along with tonofilaments around the cytoplasmic inclusion that in itself is a result of the filamentous aggregates [4
]. In view of lack of fresh tissue, we could not perform an ultrastructural analysis. Nevertheless, the distinct cytoplasmic inclusions were well noted on conventional staining. The 'rhabdoid' histology has been seen in carcinomas and melanomas [11
]. In cases of proximal-type ES, it forms an intrinsic part of the tumor morphology. However, its prognostic significance remains unclear [8
]. Another close differential, which was entertained, was the rhabdoid tumor itself. In terms of its biological behavior, like its renal counterpart, an extra-renal rhabdoid tumor (ER RT) is quite aggressive and lethal. However, it is commonly known to occur in younger children. An ER RT shows inactivating mutations/deletions of both the alleles of tumor suppresser genes hSNF5/IN11
on chromosome 22q11.2 [12
]. Similar deletion has also been noted in proximal-type ES [13
]. It has been proposed that considering the aberrations on chromosome 22 as an epiphenomenon, proximal-type ES might be actually representing a form of a "complex" rhabdoid tumor [12
]. There have been few studies dealing with the genetics of this subtype of ES, including a recent case report by Lee et al [14
], who reported chromosomal gains of 5q32-qter, 12q24qter, and 22q by comparative genomic hybridization in this tumor.
The importance of identifying this subtype lies in its aggressive behavior was seen in our patient who, despite adjuvant CT/RT did not get rid of the local lesion. Although, fortunately he did not develop any metastatic lesions in view of the adjuvant treatment, the persistence of the tumor suggests a possibility of unclear margins of the first excision that was performed elsewhere.
Certain prognostic factors, including tumor size have been recognized in proximal-type ES [8
]. Current accumulated data indicate that the presence of rhabdoid features in malignant tumors is related to an aggressive behavior, multimodal therapy resistance, a rapidly fatal outcome. At the same time it has been postulated that whether this grim prognosis is related to rhabdoid vs non-rhabdoid cell ratio with in the tumor is unclear [11
]. In our case, the recurrent mass revealed an increase in the number of larger cells. It would be worthwhile to identify more of such cases clinical outcomes. Further, genetic studies would be helpful in establishing insights into the molecular events responsible for the polyphenotypic expression of this tumor with an uncertain differentiation.