Medical and Pediatric Oncology 23:437440 (1994)

Malignant Peripheral Primitive Neuroectodermal Tumor (PNET) of the Kidney

Yoram Mor, MD, Dvora Nass, MD, Cil Raviv, MD, Yoram Neumann, MD,

Ofer Nativ, MD, and Benad Goldwasser, MD

We describe a 61-year-old patient with gression of the tumor was encountered and primitive neuroectodermal tumor (PNET) the patient died within six months with arising from the kidney. Despite intensive widespread disease. This appears to be the treatment including surgery, combination first recorded case of PNET of the kidney. chemotherapy and radiotherapy, rapid pro- o ~ ~ ~ ~ i l e y - ~ i s s , inc.

Key words: primitive neuroectodermal tumor, kidney neoplasms, nephrectomy

INTRODUCTION

The term primitive neuroectodermal tumor (PNET) is used for a group of small, round cell neoplasms presumed to be derived from the neural crest [ 11. These tumors may originate in the central nervous system or peripherally. The peripheral type, which occurs at various sites outside the central nervous system, may be found along the geni- tourinary tract, in the testis, ovary and uterus. However, to the best of our knowledge, a case of PNET of the kidney has never before been described.

CASE REPORT

A 61-year-old male patient, with a history of border- line hypertension and ischemic heart disease, initially presented with left flank pain radiating to the ipsilateral groin and thigh, severe fatigue and a 20 pound weight loss during the previous six weeks. Physical examination revealed a palpable mass in the left upper abdomen of an otherwise healthy patient. Results of complete blood count, serum chemistry panel and urinalysis were within normal limits. Excretory urography revealed a nonfunc- tioning left kidney. Computerized tomography (CT) of the abdomen demonstrated a large tumor with central necrosis which was confined to the left renal parenchyma without renal vein involvement. Severe dilatation of the left collecting system and upper two-thirds of the ureter were noted, terminating in an obstructive pelvic mass. The mass (5 X 7 cm), located along the iliac vessels, was suspected as metastatic lymphadenopathy. Cystoscopy and barium enema were unremarkable. Chest X-ray and bone scan showed no evidence of further metastatic dis- ease.

The patient underwent abdominal exploration through a left subcostal incision with a presumed diagnosis of 0 1994 Wiley-Liss, Inc.

renal cell carcinoma. Intraoperatively , a large solid mass occupying the whole kidney and hydroureteronephrosis was present. Regional lymph nodes were grossly nega- tive. The nodular mass along the left iliac vessels was found to be irresectable; thus, only a left radical nephrec- tomy was performed. Pathological examination revealed a 415 g kidney composed of gray, firm tissue replacing the normal parenchyma and invading the renal vein and the perirenal space, Microscopically, the tumor was formed of small and medium, round, oval and spindle cells with irregular nuclei and ill-defined cytoplasmic borders. The cells were arranged in cords, embedded in fibrous tissue and showed numerous mitotic figures and extensive areas of necrosis (Figs. 1,2). Those findings would correspond to an anaplastic , blastemic predomi- nant Wilms’ tumor. Since this rare and very high grade neoplasm is expected to spread early, combination che- motherapy including adriamycin, actinomycin D, vin- cristine and cytoxane, was initiated. The patient, how- ever, continued to suffer from severe abdominal pain and four months postoperatively , severe paraparesis accom- panied by urinary and fecal incontinence appeared. CT of the spine disclosed a discrete bony lesion at the level of D, vertebra, compressing the spinal cord. Palliative local radiation therapy was employed. Both the rapid progress of the disease and the unresponsiveness to intensive che-

From the Departments of Urology (Y .M., G.R., O.N. , and B.G.), Pathology (D.N.) and Hematology (Y.N.), Chaim-Sheba Medical Center, Tel-Hashomer and Sackler School of Medicine, Tel-Aviv Uni- versity, Tel-Aviv, Israel.

Received March 22, 1993; accepted December 16, 1993

Address reprint requests to Dr. Yoram Mor, Department of Urology, Chaim Sheba Medical Center, Tel-Hashomer 52621, Israel.

438 Mor et al.

Fig. 1. Renal tumor formed of sheets of small cells with central necrosis. H&E, reduced from X200.

Fig. 2. Microscopic view of tumor consisted of small cells with dark nuclei, ill-defined cytoplasmic border and numerous mitoses. H&E, reduced from x 400.

motherapy led us to reassess the pathologic diagnosis by consulting the National Wilms’ Tumor Study Pathology Center. Based upon the microscopic appearance and im- munostains using peroxidase-anti-peroxidase method and antisera against the following antigens: neuron-specific enolase (NSE; DAKO, Denmark)-positive; low molec- ular weight cytokeratin (DAKO, Denmark)-negative; chromogranin (DAKO, Denmark)-positive; vimentin (DAKO, Denmarkbnegative; and synaptophysin (Sigma, USA)-negative, the diagnosis of PNET of kid- ney was established (Fig. 3). Despite additional chemo- therapy and radiotherapy, the patient died 6 months after the initial diagnosis.

DISCUSSION

Peripheral primitive neuroectodermal tumor (PNET) is a rare entity proposed only in the late 1970s. It describes a

group of neoplasms which arise from primitive neuroec- todermal cells and previously defined as peripheral neu- roepithelioma, peripheral neuroblastoma, peripheral medulloepithelioma, etc. [ 11. Reviewing the literature, only about one hundred cases with certain diagnosis based upon valid histological, immunocytochemical and cytogenetic criteria have been reported. Classically, PNET occurs in children and young adults, although all age groups may be affected [2]. The tumor usually arises in the chest wall and in the paraspinal region, though less common origins including bones, limbs and genitouri- nary tract have also been described [ 1-31. Histologically, the tumor is composed of small dark cells arranged in cords or clusters, with or without rosettes or pseudoro- settes [4,5]. Neurosecretory granules, microtubules and numerous peripheral microfilaments are observed in elec- tron microscopy [2]. Positive immunocytochemical staining for neuron-specific enolase (NSE), S- 100 pro- tein and vimentin facilitate the diagnosis but are not pathognomonic [ 1,2]. Likewise, the cytogenetical find- ings demonstrating chromosomal reciprocal translocation t(ll:22) (q24;q12) and intense expression of the MIC, gene may be found but are not specific [6]. Conceivably, diagnosis of PNET still raises difficulties in certain cases and is also supported by excluding other small round cell neoplasms.

Only few cases involving the genitourinary tract have been reported, originating in the uterus, ovary and testi- cle [7-141. With regard to their histogenesis, the gonadal PNETs may express either the pluripotentiality of the germ cells or malignant transformation within the neuro- ectodermal component of a mature teratoma [ 1,11,13,14]. Reasonable explanation for the genesis of PNETs which arise in other peripheral sites, such as uterus or kidney, is more challenging. Several theories have been proposed [ 151 including the presence of aberrant neural crest cells, dedifferentiation of native neural elements and monoder- ma1 differentiation of a teratoma (which is extremely rare in the kidney). Those concepts are supported by descrip- tions of neural elements in other renal neoplasia including rhabdoid and Wilms’ tumors [16,17], and by reports about embryonal renal tumors associated with nervous system tumors (so-called central nervous system-renal neoplasia) [ 181.

Peripheral PNET is a highly aggressive neoplasm which tends to recur locally and to metastasize early to regional lymph nodes, lungs, liver, bone and bone mar- row. Being unresponsive to various treatment modalities, prognosis for patients with PNET is poor. In the Memo- rial Sloan Kettering experience with 54 patients, favor- able results were noted with early surgical intervention, intensive chemotherapeutic drugs active against PNET (especially cyclophosphamide) and radiation therapy for local control [2]. Overall, survival ranges from 1 to 160

PNET of the Kidney 439

Fig. 3. idase, reduced from X400.

Microscopic view of neuron-specific enolase-positive staining of tumor cells with immunoperox-

months with distinctively poor prognosis among patients with distant metastases at diagnosis [2,15].

In summary, PNET of the kidney, which is described for the first time herein, should be included in the differ- ential diagnosis of small round cell renal tumors, espe- cially whenever an aggressive clinical course is encoun- tered. Early diagnosis, radical surgery and adjuvant treatment may improve the precognized poor prognosis.

ACKNOWLEDGMENTS

immunocytochemistry, electron microscopy and molecular probes. Cancer 63:2515-2521, 1989.

4. Erlanson RA, Cordon-Cardo C: Neoplasms of complex or uncer- tain histogenesis. In Azar HA (ed): “Pathology of Human Neo- plasms.” New York: Raven, 1988, pp. 5 3 3 4 1 1.

5. Lieberman PH: Primitive neuroectodermal tumor. In: “Proceeding of the Forty-Fifth Annual Anatomic Pathology Slide Seminar.” Chicago: American Society of Clinical Pathology, 1981, pp. 100- 105.

6. Ambros IM, Ambros PF, Strehl S, Kovar H, Gadner H, Salzer- Kuntschik M: MIC, is a specific marker for Ewing sarcoma and peripheral primitive neuroectodermal tumors. Cancer 67: 1886- 1893, 1991.

Dr. Iris Goldberg for performing the immunostains.

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