Primary Ewing´s sarcoma/Primitive neuroectodermal tumor of the kidney. An infrequent finding

Sarcoma de Ewing primario/Tumor neuroectodérmico primitivo renal. Un hallazgo infrecuente

David Parada^1,3, Alí Godoy², Francisco Liuzzi², Karla B. Peña¹, Aramis Romero¹ and Arelí M. Parada³

¹Department of Anatomic Pathology, Vargas Hospital. Caracas. Venezuela.
²Service of Surgery 1. Vargas Hospital. Caracas. Venezuela.
³School of Medicine, “José María Vargas”. Central University of Venezuela. Caracas. Venezuela.

SUMMARY

Objetive: Ewing´s sarcoma/Primitive neuroectodermal tumor (ES/PNET) is an extraordinarily rare primary tumor in the kidney. We re-port herein the clinical, histological, and immunohisto-chemical features of a primary renal ES/PNET.
Methods: A 19-year old male referred a two weeks history of constant, colic, left flank pain, and fever. A left radical nephrectomy was performed. Gross pathologic examination showed pink-tan, lobulated solid tumor, lo-calized at the superior pole.
Results: Histologically, the tumor was solid with necrosis. The neoplastic cells showed a small amount of clear cytoplasm, and had vesicular nuclei with small nucleoli. Immunohistochemical studies showed strongly and diffusely positive staining for CD99 in a membranous pattern.
Conclusions: This case represents a typical ES/PNET, affecting a young male patient. Adequate diagnosis is important because this neoplasm has an aggressive behaviour.

Keywords: Kidney. Ewing´s Sarcoma. Primitive neuroectodermal tumor. CD99. Immunohistochemestry.

RESUMEN

Palabras clave: Riñón. Sarcoma de Ewing. Tumor neuroectodérmico primitivo. CD99. Inmunohistoquímica.

Introduction

The round cell tumors of the kidney include a wide range of unrelated neoplasms with overlapping morphologic features and different prognostic/therapeutic implications. In this group of tumors, Ewing´s sarcoma/primitive neuroectodermal tumor (ES/PNET) is an extremely rare primary tumor in the kidney (1). They ussually affect young adults, with slight male predominance, are large at presentation and tend to be highly aggressive tumors (1,2).

Immunohistochemical studies has proven to be valuable in the differencial diagnosis of renal round cell tumors, although some of these entities lack a characteristic immunophenotype (1). Herein we report the clinical, histological e immunohistochemical findings in a new case of primary Ewing´s sarcoma/Primitive neuroectodermal tumor of the kidney.

Case Report

A 19-year-old male referred a two weeks history of constant, colic, left flank pain, and fever. His medical history was unremarkable. Abdominal physical examination demonstrated epigastric and left upper quadrant abdominal pain, at the superficial and profound palpation. The urinalysis was unremarkable. An abdominal ultrasonography and an abdominal computerized tomography were performed (Figure 1A), followed by a left radical nephrectomy. The patient is alive after surgical intervention and he is receiving chemotherapy with vincristine, doxorubicin, cyclophosphamide, isofosphamide and ectoposide.

The resected left kidney was fixed in buffer formalin pH 7.2, and tissue preparations were made by the routine procedure to hematoxylin-eosin stain. Paraffin-embedded preparation was stained immunohistochemically using the enzyme-conjugated polymer system (EnVision System, Dako,Glostrup, Denmark). For specific immunohistochemical details see Table I.

Results

Pathologics findings

Gross pathologic examination showed pink-tan, lobulated solid tumor (maximun diameter: 7.5 cm), localized at the superior pole, wich replaced the normal renal parenchima and had necrotic areas (Figure 1B). No renal vein invasion was grossly identified.

Microscopically, the tumor was solid with necrosis and consisted of vaguely lobulated proliferation of round cells with high nuclear to cytoplasmic ratio (Figure 2, A-D). The surrounding renal parenchyma showed infiltration by the malignant neoplasm, forming broad sheets. The tumor cells were present in groups separated by fibrovascular septae (Figure 2A). The neoplastic cells showed a small amount of clear cytoplasm, and had vesicular nuclei with small nucleoli (Figure 2, B,C). Mitotic figures were commonly found (Figure 2, C,D). Focal Homer-Wright type rosettes were seen (Figure 2, C). No tubule formation, glomeruloid structures, pseudorosettes, cartilagenous, myogenous or spindle component were identified.

Discussion

In the year 1994, Mor and coworkers (3) described a characteristic primary renal neoplasia consistent with the diagnosis of malignant peripheral primitive neuroectodermal tumor. Actually, most of the reported cases have occurred in young adults, with a mean age at presentation beetwen 28 and 34 years (range: 4-69 years) and a slight male predominance (1,2,4). Common symptoms at the presentation were flank pain and/or haematuia (1). In our case, a young male patient with left flank pain were consistent with previous reported findings of primary renal ES/PNET.

One possible source of renal ES/PNET is from neural ramifications that invest the kidney. The inervation of the kidney comes from adrenergic fibers originating in the celiac plexus and accompanying efferent arterioles and descending vasa recta (5). Another possibility is that embryonic neural crest cells migrate into the kidney and subsequently undergo tumorogenesis. An interplay between developing metanephros and neural differentiation factors such as c-ret (6) and neurotrophin-3 (7) is apparent in rodent kidneys and suggests that neural differentiation is essential to nephrogenesis.

Histologically, renal ES/PNET could be a diagnostic challenge because many tumors exhibited features of the so-called small round cell tumor. Malignant lymphoma, rhabdomiosarcoma, renal neuroblastoma, Wilms´ tumor, small cell osteosarcoma, desmoplastic small cell tumor and so, are disease for distinction (1). Therefore, immunohistochemestry has proven to be value in the differential diagnosis of these kidney tumors. The bases for diagnosis of the present case as ES/PNET were: a-) morphology of small round cell tumor was found histologically and b-) immunohistochemically, MIC2 showed strong membrane positivity. Similar features in renal ES/PNET has been previously reported (1,2,4).

Althought histological and immunohistochemical studies are important to reach a definitive diagnosis the chromosomal and moleular analyses could be required. The ES family have chromosomal translocations, t(11;22)(q24;q12), t(21;22) and chimera genes, EWS-FL1, EWS-ERG, EWS-ETV1 or EWS-EIAF as common abnormalities (8,9). Over 85% of ES/PNET are characterized by the translocation t(11;22)(q24;q22) that results in the fusion of the ews gene on chromosome 22 to the fli-1 gene on chromosome 11 (10-13). The chimeric EWS/FLI-1 fusion protein localizes to the nucleus, is a more powerful transcription activator than is normal fli-1 (14).

Primary renal ES/PNET is an aggressive neoplasm with poor prognosis. Metastases are usually absent at the time of first observation, but metastases affect the prognosis little (4). In previous reported cases, the patients died 10.3 months on average after their first diagnosis of the tumor. Radiotherapy or chemotherapy is not effective. Jimenez et al., (1) informed that chemotherapeutic treatment with ifosphamide and/or cyclophosphamide, could be included in treatment protocols for primary kidney ES/PNET. Obviously, further studies will be necessary to determine the precise impact of these drugs on survival in renal ES/PNET.

In summary, we report an additional case of primary renal ES/PNET. Our case confirmed that ES/PNET is a rare neoplasm, affecting young adults with aggressive behavior. It is important to distinguish primary renal ES/PNET from other round cell tumors, given his aggressive behavior. The immunohistochemical study may be valuable in the differential diagnosis of renal round cell tumors.

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Correspondence:
David Parada
Department of Anatomic Pathology ]]> Vargas Hospital
San Francisquito a Monte Carmelo
Esquina El Recodo. San José
Apdo. 1010, Caracas. (Venezuela).
parada@cantv.net

Acepted for publication: June 7th, 2006