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  • Early tubular differentiation in WT lacks

    2019-12-03

    Early tubular differentiation in WT lacks lumen formation and, therefore, sometimes can be confused with rosettes of ES/PNET or neuroblastoma. However, tubular structure usually has Lopinavir neatly aligned to form a single layer around the future lumen, whereas neuroblastic rosettes are arranged more randomly [3]. MIC2 and FLI-1 expression and WT-1 positivity on IHC are useful markers in distinguishing between the two [13]. Lymphoma can involve the kidney primarily and may present as renal mass and show presence of undifferentiated round cells on microscopy. However, it lacks monotonous nuclei, presence of cytoplasmic glycogen, and rosettes, which are present in PNET. The cells in lymphoma usually dissect through the interstitium with relative preservation of renal structures [21]. Immunohistochemically, LCA is the common denominator for lymphomas. Classic neuroblastoma can present as a primary intrarenal neoplasm or can secondarily involve the kidney. Presence of neuropil or ganglionic differentiation coupled with immunohistochemical expression of antibody NB84 and absence of MIC2 strongly favors a neuroblastoma [22]. The ES/PNET family of tumors is defined by highly recurrent chromosomal translocation [23]. EWS-FLI, that is, t[11;22][q24;q12], is found to be the most common type of translocation. This translocation is characterized by fusion of EWS gene, which is located on chromosome 22q12 with the FLI-1 gene, located on chromosome11q24. The chimeric EWS-FLI-1 fusion protein, formed as a result of the aforementioned translocation, is localized to the nucleus and is a more powerful transcription activator than normal FLI-1. EWS-ERG translocation, that is, t[21;22][q12;q12], is the second most common translocation documented in 10% of cases [23]. Some other rare translocations have also been discovered; they include t[21;22][q12;q12], t[7;22][p22;q12], t[17;22][q12;q12], and t[2;22][q33;q12] [23], [24]. EWS-FLI-1 is the most heterogeneous gene fusion in cancer. The 2 most common fusions join EWS exon 7 in frame with either exon 6 (type 1 fusion) or exon 5 (type 2 fusion) of FLI-1. Other types of fusion transcript are designated by different exons involved (eg, type 10-5). Similarly, at least 4 different structural types of the rarer EWS-ERG fusion have been described [23], [24]. Zoubek et al [25] and de Alava et al [26] had reported an association of the type I EWS-FLI-1 fusion with longer relapse-free survival in ES/PNET regardless of stage of disease. In the present study, 5 of the 10 patients with metastasis had EWS-FLI-1 type 1 translocation, a single case had EWS-FLI-1 type 2, and another case had EWS-FLI-1 types 1 and 2 translocation. EWS-FLI-1 type 2 translocation was identified in 1 of 4 cases with recurrent disease in which Lopinavir RT-PCR was performed. Because of less number of cases, prognostic significance of detected translocations in the present study remains uncertain. RT-PCR is considered to be an objective diagnostic test in conjunction with light/electron microscopic and immunohistochemical evaluation. Fluorescent in situ hybridization (FISH) can also be used for translocation studies. Bridge et al [27] observed FISH as a more sensitive and reliable ancillary technique than RT-PCR for the diagnosis of EWS/PNET in FFPE tissue. In addition, with the help of FISH, additional information regarding fusion transcript subtype can be obtained.
    Acknowledgment
    Introduction Ewing sarcoma (ES) is a bone and soft tissue tumor that encompasses tumors formerly known as Askin\'s tumor, Peripheral Neuroectodermal Tumor (PNET) and the Ewing Sarcoma Family of Tumors (ESFT) (Hawkins et al., 2011). This disease is most common in the second decade of life with an annual incidence of about 225 cases in North America in children between 1 and 20years of age (Esiashvili et al., 2008). Patients with Ewing sarcoma who present with localized disease have a favorable 5-year event free survival of around 70% due to the advent of multimodal therapy that includes chemotherapy, surgery and/or radiation (Grier et al., 2003, Paulussen et al., 2008). Unfortunately, patients with bone and bone marrow metastatic disease or recurrent disease have a less than 20% overall survival rate (Bernstein et al., 2006, Esiashvili et al., 2008, Leavey et al., 2008). Therefore, there is a great need to develop new approaches or therapies for the treatment of this tumor that target the biology of the disease.