DSRCT is a rare neoplasm that affects young patients. It may present a problem in the differential diagnosis with other small round cell tumors. The diagnosis of DSRCT however can be established with correlation of clinical, cytological and immunocytochemical features. The cytological features that we found in the smears obtained by FNA are similar to other descriptions in the literature. Similar to reports of Zeppa et al [11
], we did not detect in our smears fragments of fibrosis or cytoplasmic granules or vacuoles. The finding of stromal fragments, frequently seen in FNA is not a common finding in liquid based preparations [12
One of the characteristics of DSRCTs is its dissemination along serous surfaces. Due to this fact, development of serous effusions is a common clinical finding in DSRCTs patients, with detection of tumor cells in the fluid. In effusions, tumor cells may be present in aggregates but no obviously architectural arrangement is seem.
Demonstration of a divergent phenotype and the reciprocal translocation characteristic of DSRCT are critical to the diagnosis.
In a reported series of 32 cases of DSRCTs [13
], 88% of cases were immunoreactive for AE1/AE3, 84% for NSE, 81% for desmin. These results were similar to other previous studies [2
]. Lae et al [13
] detected positivity to WT1 antibody in 29 out of 32 cases. Our immunohistochemical results are in agreement with other previous studies. Strong membrane expression of HER2/neu and immunoreactivity to c-kit protein are not common findings [14
The establishment of a specific reciprocal translocation t (11; 22)(p13;12) as diagnostic in DSRCT was based on the results of Sawyer et al [9
]. Shen et al [15
] and Roberts et al [16
] described variants of with other chromosome involved in addition to chromosome 11 and 22. The translocation t (11; 22)(p13;12) involve the EWS gene in 22q24 and WT1 gene in 11p13. This translocation produces the chimeric transcript EWS/WT1 and the related WT1 protein, which can be detected by immunohistochemical method.
EWS gene encodes a protein which the precise function and normal role has not yet been elucidated. Recently, Thomas et al [17
] proposed that the protein product of the EWS gene interacts with Brn-3a cellular transcription factor via a direct protein-protein interaction. Native WT1 protein function has not completely known, but it represses transcription in vitro of many genes. WT1 is a tumor-suppressor gene that encodes a protein, which mediates transcriptional repression and interacts with p53 protein [18
], product of another tumor suppressor gene, TP53, frequently deleted or mutated in many human tumors. In absence of intact p53 protein, WT1 acts as a transcriptional activator [19
]. Normal WT1 protein is expressed in tissues, which undergo mesenchymal-epithelial conversion derived from mesoderm, in a specific period of development [20
] and it plays a role in mesothelial formation in embryonic development [21
]. Immunohistochemical detection of WT1 in DSRCTs is predictive of the translocation and it also demonstrates that the chimeric protein is expressed in significant amount in tumour cells 22, 23
. In addiction to consistent WT1 expression, the typical serosal involvement in DSRCT has raised the possibility that this tumor might be a blastematous tumour derived of primitive mesothelium [24
]. Mesothelin is a glycoprotein of unknown function strongly expressed in mesothelial cells. Although lack of specificity of expression of mesothelin for mesothelial origin, the expression of this protein in DSRCT may have some significance on histogenisis of this tumor [25
We detected WT1 immunoreactivity in all tumors tissues and in 2 out of 3 serous effusions with malignant cells, as well as on FNAB smears. The high frequency of DSRCTs with WT1 protein expression suggests that in consensus with clinical tomographic and cytological findings, this antibody may be used to confirm the diagnosis of DSRCT in cytological samples. We observed a negative WT1 reaction in the cytological sample of patient 3. This sample was collected 10 months after the end of chemotherapy protocol. We can hypothesize if chemotherapy hampered a different antigenic pattern in malignant cells, and influenced this result.
Among other small round cell tumors, most of cases of rhabdomyosarcomas and neuroblastomas do not disclose nuclear WT1 staining [26
]. Comparing DSRCT and Ewing Sarcoma/PNET, Hill et al. [28
] detected WT1 nuclear immunoreactivity in all 13 DSRCT cases studied; conversely, all 11 cases of Ewing Sarcoma/PNET were negative. Additionally, Wilm's tumor was demonstrated to present a high percentage of cases with nuclear WT1 staining; for this reason, correlation with clinical findings is necessary to do a differential diagnosis between Wilm's tumour and DSCRT in effusions [26
]. On the other hand, it is important to emphasize that malignant mesothelioma should also be considered in the differential diagnosis, since it can show varied histological appearances including sarcomatoid differentiation with desmoplastic areas, or even resembling undifferentiated sarcomas [29
]. WT1 might also decorate nuclei of both epithelioid or biphasic mesothelioma but in general, WT1 stain most frequently epithelioid mesotheliomas [30
]. The use of a panel of markers can also help in the differential diagnosis.
In conclusion, cytological and immunophenotypical findings in an appropriate clinical context is sufficient to suggest DRSTC, what sounds highly contributive for us, considering the high aggressiveness of this tumor.