| Abstract|| |
Small cell carcinoma is a malignancy primarily recognized in the bronchopulmonary region. Extrapulmonary locations are extremely uncommon. We report here a case of renal tumor encountered in a 34-year-old female, with extensive metastases in liver, lung and bone. Histological examination was most compatible with primitive neuroectodermal tumor (PNET) small cell carcinoma. There were negative immunohistochemcal markers for cytokeratin, any hormonal peptides and epithelial membrane antigens, which is consistent with the designation of the neoplasm as PNET. Previously reported cases have all been in the elderly and, to the best of our knowledge, this is the first case of proven PNET of the kidney described in a young female.
Keywords: Kidney tumor, Small cell carcinoma, PNET.
|How to cite this article:|
Radhi A, Ratnakar K S, Al Durazi M, Khalifa F. Primitive Neuroectodermal Tumor or Small Cell Carcinoma of the Kidney, a Rare Neoplasm: Case Report. Saudi J Kidney Dis Transpl 2002;13:506-10
|How to cite this URL:|
Radhi A, Ratnakar K S, Al Durazi M, Khalifa F. Primitive Neuroectodermal Tumor or Small Cell Carcinoma of the Kidney, a Rare Neoplasm: Case Report. Saudi J Kidney Dis Transpl [serial online] 2002 [cited 2020 Oct 21];13:506-10. Available from: https://www.sjkdt.org/text.asp?2002/13/4/506/33107
| Introduction|| |
Small cell carcinoma of lung is a wellrecognised entity with endocrine differentiation and characterized by rapid progression. [¹] The occurrence of this tumor in extrapulmonary sites is seen with rarity.
During the last decade, tumors with similar morphological features were encountered at several extrapulmonary locations such as the oesophagus, prostate, endometrium, urinary bladder, pancreas and parotid gland. ,,,,,
Capella et al  first reported small cell tumor of the kideney followed by Tetu et al,  and Essenfeld et al  who added five more cases. Their cases were in the elderly.
We report here a young female who was proven by histology and immunnohistochemistry to have primitive neuroectodermal tumor (PNET) small cell carcinoma.
| Case Report|| |
A 34-year old Bahraini woman was admitted to the surgical department with a three-month history of generalized body aches, night fever and left flank pain. Abdominal CT scan revealed a left renal mass [Figure - 1]. On September 20, 2000, the patient underwent left radical nephrectomy. At operation, an extensive, left renal tumour, predominantly medullary and hilar in location with extension into inferior vena cava and involving the hilar nodes, was excised.
The left nephrectomy specimen contained a tumor measuring 13 x 10 x 8 cm predominantly occupying the renal pelvis and infiltrating the upper pole. The tumor was soft, uniformly gray-white colored and showed areas of necrosis and hemorrhage. The cortex was clearly demarcated and distinctly discernible at several points. The renal vessels and perinephric fat were infiltrated by the tumor. Formalin fixed, paraffin embedded tissue sections were stained with hemotoxylin and eosin, periodic acid Schiff (PAS), and Mason Fontana's silver stain. Several sections were submitted to immunohistochemical markers, which included carcino-embryonic antigen (CEA), desmin, S100, monoclonal neuron specific enolase (NSE), leukocyte common antigen
(LCA), cytokeratin and epithelial membrane antigen (EMA). Sections from different sites showed similar findings. The lesion was composed of infiltrating round, oval or small spindle-cells with scanty cytoplasm and dark nuclei (Figures 2 and 3). In some areas, broad bands of collagen separated the sheets of cells, while in other areas, the cells were closely packed with no appreciable stroma. The cells had prominent nucleoli and frequent mitosis (10-15/HPF). Wide areas of hemorrhage and necrosis were noticed and no recognizable structures of identifiable mesenchymal elements were seen. The tumor extended into the perinephric fat and involved the renal vessels. Special stains and immunohistochemical marker studies revealed acid Schiff positive cytoplasm, argyrophilic granules, and positive S100 and NSE reactions. Other markers were negative (CEA, cytokeratin, EMA, Desmin, and LCA).
One month later, the patient was readmitted with hemoptysis and pain in the left lower extremity. CT scans revealed liver matastases, retroperitoneal lymphadenopathy, small left pleural effusion and few illdefined pulmonary lesions. Bone scan revealed bone metastases. Complete blood picture showed normocytic normochromic anemia.
Blood chemistry showed total proteins 76 g/l, albumin 21g/l, globulins 55 g/l, total bilirubin 19 µmol/l, alkaline phosphatase 563 U/l, gamma glutamyl transpeptidase 851 U/l, calcium 2.87 mmol/l, phosphorus 1.5 mmol/l, magnesium 0.76 mmol/l and urea 9.7 mmol/l. Plasma creatinine and electrolytes were within normal limits.
During this admission, the patient received two cycles of chemotherapy: combination of vincristine, adriamycin and cyclophosphomide. The general condition remarkably improved and the hemoptysis and the legpains disappeared.
| Discussion|| |
Small cell carcinoma of lung is a wellrecognized rapidly progressive tumor.  Several extrapulmonary locations are documented in the literature affecting the pancreas, parotid glands, esophagus, prostate, bladder, and kidneys. Small cell carcinoma of the kidney and renal pelvis, fulfilling the criteria analogous to the pulmonary tumors is of rare occurrence, only six such cases having been described (four tumors in the kidney and two in the renal pelvis) in the literature. ,,
The term "small cell tumor" applied to the cases described earlier lacks specificity; denoting only the presence of uniform small round cells. In the three cases reported by Bernard et al,  two were cytokeratin positive and one was NSE positive with neurosecretory granules confirmed by ultrastructural studies. Essenfeld et al  reported two cases with NSE positivity. Only three reported cases support neuroendocrine origin of the "small cell tumor" of the kidney. Essenfeld et al  reported two cases in which the renal tumors predominantly occupied the renal pelvis, and were associated with transitional cell tumor. Our case differed in that it occurred in a young female with no admixture of transitional cell carcinoma.
Primitive neuroectodermal tumors (PNET) constitute a controversial and poorly defined class of tumors of neuroectodermal origin occuring in the central nervous system and peripheral sites. Though there is continued disagreement on its definition, it is possible to accept PNET as indicating a group of extracranial and extraspinal round cell tumors, being NSE positive uniformly. Neuroblastoma and peripheral neuroepitheliomas, despite morphological similarity with small cell tumor,  exhibit distinct clinical pathologic profiles such as age and site, as well as distinct oncogenic profiles. A thoracopulmonary tumor involving the ribs and interosseous space, Askin tumor, is now accepted as PNET, and is a well recognized entity affecting infants and adolescents.[ 13] Intraosseous PNET, encountered in the diaphyseal location of young adults, also known as the Ewings tumor (sarcoma), is positive for neural markers namely NSE and S100. PNET of bone differs from neurblastoma and peripheral neuroepithelomas, as the lesion lacks overt neural differentiation. However, the Ewings tumour and PNET of bone, inspite of histogenetic and morphological similarity may differ in behavior.  Hence, more detailed studies are usually required.
Small cell tumors of kidney, in view of both rarity and lack of in-vitro studies have confusing oncogenesis. Small cell carcinoma of the lung is a rapidly progressive tumor of the elderly that is related to Kultschitzky cells, the neuroendocrine cells of the bronchial mucosa.  All the cases of small cell carcinomas of the kidney, reported earlier, therefore, justify the term small "cell carcinoma". However, the present case occuring in a 34 year old young female raises the possibility of PNET. PNET lesions having a round cell pattern, as in the present case, totally depend upon immunocytochemistry, (S100+, NSE+, Sliver+ CEA-, EMA-, CYTOKERATIN-LCA-, Desmin-) for the diagnosis.  The authors, therefore, wonder whether this case could be diagnosed as PNET (Primitive Neuroectodermal Tumor) of the kidney (renal pelvis) based on clinical, morphological and immunocytochemical profile, instead of "small cell carcinoma". Oncogenic profiles and follow up studies may ultimately assist in understanding the biologic behavior. At present, irrespective of the terminology, the prognosis tends to be uniformly poor.
Small cell carcinoma and PNET may not be used synonymously since the embryologic origins of the cells differ. However, neural and neuroendocrine differentiation overlaps. Morphologic kinship, chemotherapeutic reponses and dissemination of the disease may follow similar lines with grave prognosis. So far, the authors reporting small cell carcinoma of the kidney have not considered or carried out in vitro studies to rule out the possibility of PNET of kidney. Bronchial carcinoids and small cell (oat cell) carcinomas of the lung, 1 are positive for cytokeratin, EMA and CEA in addition to NSE and S100.
In conclusion, we prefer to label this lesion as a peripheral PNET of the kidney rather than small cell carcinoma for the above-mentioned reasons.
| Acknowledgments|| |
The authors acknowledge with thanks Dr. Krishnan Unni and Dr. J.C. Cheville, Mayo Clinic, Rochester, USA for their advice about the manuscript. We also thank Dr. Ali A. Satir Chairman, Department of Pathology, and Salmaniya Medical Complex for granted his permission to publish this case.
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K S Ratnakar
Consultant, Department of Pathology, Salmaniya Medical Complex, P.O. Box 12, Manama
[Figure - 1], [Figure - 2], [Figure - 3]