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Proc (Bayl Univ Med Cent). 2017 April; 30(2): 205–208.
PMCID: PMC5349830

Primitive neuroectodermal tumors of the kidney

Abstract

Ewing's sarcoma/primitive neuroectodermal tumor (ES/PNET) rarely occurs as a primary renal tumor. The disease affects young adults and children and has an aggressive course. The clinical presentation and imaging of these tumors are nonspecific, and they often present at an advanced stage. We present the clinical features, imaging, diagnosis, and treatment of 7 cases of renal PNET (4 men, 3 women; median age, 32 years). Common presenting symptoms were flank or abdominal pain and a mass in the abdomen. On imaging, a large heterogenous infiltrating renal mass with areas of calcification, hemorrhage, and necrosis and tumor thrombus can give a clue to the diagnosis of renal PNET. Immunohistochemistry and molecular studies are essential to confirm the diagnosis. The prognosis of renal ES/PNET is generally poor. Radical nephrectomy combined with chemotherapy and radiotherapy is the standard treatment for renal PNET. An early and accurate diagnosis is crucial for the proper management of these aggressive tumors.

Ewing's sarcoma/primitive neuroectodermal tumors (ES/PNET) are a group of small round cell tumors primarily affecting the bone and soft tissues. Very rarely, they can occur as a primary renal tumor (1). The disease commonly affects young adults and children and runs an aggressive course (2). Molecular studies have established that ES and PNET are part of the same tumor family and exhibit similar biologic behavior. Most of the literature on renal PNET consists of isolated case reports. The clinical presentation and imaging of these tumors are nonspecific, and they often present at an advanced stage. We present the clinical features, imaging, diagnosis, and treatment of 7 cases of renal PNET treated in our center.

METHODS

This is a retrospective analysis of 7 patients diagnosed with PNET of the kidney treated in the Department of Medical Oncology at Regional Cancer Center, Trivandrum, during a 15-year period. The case records of the patients were studied with respect to clinical presentation, diagnosis, treatment received, and survival.

RESULTS

The details of the 7 cases are summarized in Table 1. In our series, the median age was 32 years (range 16–73 years), and there were 4 women and 3 men. In all the patients except one, the presenting symptom was abdominal pain and a huge mass in the abdomen. In one case (#1), the renal mass was detected during antenatal checkup when investigating fetal bradycardia. Most of the patients presented at an advanced stage, and 4 out of 7 had metastatic disease at presentation involving the lungs and bone. Computed tomography (CT) imaging details were available in 5 of our cases and showed heterogenous hypodense mass lesions arising from the upper or lower poles of the kidney with areas of hemorrhage and necrosis; 3 cases also had calcifications. Histopathological examination showed a small round blue cell neoplasm in all the cases, and immunohistochemistry, which was available in 5 cases, was positive for CD99.

Table 1.
Summary of clinical presentation and treatment of 7 patients with renal primitive neuroectodermal tumor
Figure 1.
(a) Plain CT scan of the abdomen, axial view, showing a large isodense lesion involving the right kidney causing contour distortion and enlargement. (b) Contrast-enhanced CT image showing moderately enhancing nonhomogeneous mass with involvement of the ...
Figure 2.
(a) Hematoxylin and eosin stain (40×) showing the neoplasm composed of large nests of cells with a moderate amount of cytoplasm, moderately pleomorphic nuclei with granular chromatin, and areas of geographic necrosis, with thin vascular channels ...
Figure 3.
Contrast-enhanced CT of the abdomen showing a large irregular heterogeneously enhancing mass lesion arising from the upper pole of the right kidney, with multiple specks of calcification within.
Figure 4.
Technetium-99m scintigraphy bone scan showing increased uptake over the lateral margin of the left orbital ridge.

Only 3 of our cases had localized disease, and all underwent radical nephrectomy; however, only 2 received adjuvant chemotherapy with vincristine, doxorubicin, cyclophosphamide/ifosfamide, etoposide (VDE/IE), and one received adjuvant irradiation to the primary site. Among our 4 cases with metastatic disease, 3 presented following radical nephrectomy, 3 received chemotherapy, and 3 were given palliative irradiation to the metastatic site. Two patients did not receive any systemic treatment after radical nephrectomy, and their follow-up details were not known. Among the 5 patients who received chemotherapy, 4 were alive beyond 1 year, and one is alive in remission at 15 months. The survival of our patient group ranged from 6 months to 18 months.

DISCUSSION

ES/PNET of the kidney was first reported by Seemayer and colleagues in 1975 (3) and is exceedingly rare. It usually affects young adults at a median age of 28 years and has a male predominance of 3:1 (4, 5). In our series, the median age was 32 years, and the male:female ratio was 4:3. The common presenting symptoms are flank or abdominal pain, mass in the abdomen, and hematuria (6). Patients are usually asymptomatic until the tumor reaches a large size; the maximum diameter of such tumors is often 10 cm (7, 8). Systemic symptoms such as weight loss and fever may also occur (9). Our patients presented similarly, except in one patient in whom the renal mass was detected during antenatal checkup. Most of the patients present at an advanced stage with distant metastasis, which is in concordance with the aggressive behavior of this tumor (4, 10). Common sites of metastasis include the lung, liver, and bone (6). In our series, 4 out of 7 had metastatic disease at presentation involving the lungs and bone.

The imaging characteristics of renal PNET are often nonspecific and overlap with those of other renal tumors, such as renal cell carcinoma, Wilms tumor, neuroblastoma, lymphoma, and desmoplastic small round cell tumor (11). Renal PNETs appear hypoechoic, isoechoic, and /or hyperechoic to the adjacent renal parenchyma on ultrasound and show increased vascularity on Doppler imaging. CT scan shows a large heterogenous mass with areas of hemorrhage or necrosis (12). On magnetic resonance imaging (MRI), the tumor appears as a lobulated isointense and /or hypointense mass on T1-weighted images and as a heterogeneous to hyperintense mass on T2-weighted images, with heterogenous contrast enhancement (6, 12). MRI and CT also help to evaluate renal vein and inferior vena caval involvement. Technetium-99m scintigraphy is useful for the detection of bone metastases (6). CT imaging details were available in 5 of our cases and showed mass lesions arising from the upper or lower poles of the kidney, 3 with calcifications.

Diagnosis of renal PNET is challenging. Although radiological features may be suggestive, biopsy with immunohistochemistry is required to confirm the diagnosis. Renal PNET is characterized by small uniform round cells with dark nuclei, ill-defined cytoplasmic borders, and poorly formed rosette-like structures (9). The histopathologic features overlap with other small round blue cell tumors like neuroblastoma, desmoplastic small round cell tumor, and lymphoma. Immunohistochemistry and molecular studies play a crucial role in differentiating these tumors. PNET shows strong positivity for MIC-2 gene product and CD-99 over the membrane of tumor cells, which is seen in more than 90% of renal PNET cases (7). It is also positive for different neural biomarkers such as S-100, Leu 7, and NSE (13). The immunohistochemistry findings are further supported by the identification of a characteristic EWSR1/FLI1 fusion product that results from a t(11;22) (q24/q22;q12) translocation. This translocation is identified in 90% of cases and unequivocally confirms the diagnosis (7, 14). Among our cases, IHC details were available in 5 patients, and all were positive for CD99.

Renal PNET appears to be a unique clinical entity that behaves more aggressively than PNET arising at other sites. As the tumor is highly aggressive, it is often diagnosed in an advanced stage when it has already involved perinephric fat, hilar lymph nodes, renal veins, and the inferior vena cava. In more advanced stages, the tumor involves the liver, spleen, peritoneum, and lungs. The prognosis for renal ES/PNET is generally poor, with a 5-year disease-free survival of 45% to 55% in localized cases, whereas cases with an advanced stage at presentation have a median relapse-free survival of only 2 years (9, 13, 15).

The treatment for renal ES/PNET is similar to that for ES/PNET elsewhere and includes surgery, chemotherapy, and radiation (6, 10). Surgical options include partial or total nephrectomy with cavotomy in cases of renal vein involvement (6, 14). The diagnosis of renal ES/PNET is often made postoperatively and hence chemotherapy is generally given as an adjuvant. The recommended chemotherapy regimen is vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide and etoposide given for a period of 1 year (16). The role of radiotherapy is not clear, but it may be given in locally advanced disease and in those with positive margins. Despite aggressive therapy, the overall cure rate of renal PNET is only 20% (17). Among the 7 cases reported here, 6 underwent radical nephrectomy, 5 received chemotherapy, and 4 received radiation therapy. Four patients were alive beyond 1 year, and one is alive in remission at 15 months. The survival of our patient group ranged from 6 months to 18 months. Since the overall prognosis of this tumor is poor, an early and accurate diagnosis is crucial for the proper management of these aggressive tumors.

References

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