CASE REPORT

Int J Clin Oncol (2007) 12:160–162 © The Japan Society of Clinical Oncology 2007DOI 10.1007/s10147-006-0632-z

Naoki Yamamoto · Shinichi Maeda Yoshikazu Mizoguchi

Malignant paraganglioma arising from the kidney

Abstract Paragangliomas are rare neoplasms arising from undifferentiated cells of the primitive neural crest. We report a case of a 34-year-old patient with renal para-ganglioma. Complete surgical resection of the tumor was performed without intraoperative incident. The diagnosis was made based on immunohistochemical and ultramicro-scopic analyses. The postoperative course was uneventful. Based on the obtained results, we discuss the clinical aspects of the case and the diagnosis.

Key words Kidney · Malignant · Paraganglioma

Introduction

Paraganglioma arising from the kidney is rare. We describe a case of a patient with renal paraganglioma. There have been only 11 cases reported in the literature up to 2005.

Case report

A 34-year-old woman with no signifi cant medical history consulted us because of right upper quadrant pain. Physical examination was notable only for fl ank tenderness upon palpation. The clinical triad of headache, palpitations, and diaphoresis – common to pheochromocytoma – was not observed. Computed tomography (CT) demonstrated a solid mass with an attenuation similar to that of the liver

without a cystic compartment in the upper pole of the right kidney. The mass demonstrated slight homogeneous en-hancement compared to what is expected for renal paren-chyma. The mass was separate from the right adrenal gland (Fig. 1). With a provisional diagnosis of renal cell carcino-ma, laparotomy was performed. The tumor was located in the upper pole of the right kidney and was well encapsu-lated. An examination during surgery showed the tumor had no involvement with neighboring organs or with the renal vein. There was no peritoneal dissemination or liver metastasis. The right adrenal gland and the kidney with the tumor were removed en bloc.

The gross appearance of the nephrectomized right kidney was deformed by a solid lesion, 60 × 60 mm in size. Microscopically, the tumor consisted of a defi ned nest made up of spindle- and oval-shaped cells (“Zellballen”). The in-dividual cells were characterized by moderately abundant cytoplasm and nuclear atypia. Argentaffi n cells and argyro-phil cells were not detected by Masson-Fontana or Grime-lius staining. We determined by immunohistochemistry that the tumor did not express carcinoembryonic antigen (CEA), serotonin, or epithelial membrane antigen (EMA). Susten-tacular cells were positive for S-100 protein. Ultramicro-scopically, the tumor cells contained many dense-core neurosecretory granules, 150 to 250 nm in size, and a few microfi laments (Fig. 2B). Although metastasis to adjacent lymph nodes was confi rmed, there appeared to be no adre-nal involvement. On the basis of these fi ndings, malignant paraganglioma arising from the renal parenchyma was di-agnosed histologically.

The patient underwent irradiation to the renal bed in conjunction with chemotherapy (cyclophosphamide and vincristine). The patient has been disease-free for 5 years.

Discussion

The differential diagnosis of spindle-cell-predominant renal tumor includes sarcomatoid renal cell carcinoma, primary

N. Yamamoto (*)1 · S. MaedaDepartment of Urology, Toyota Memorial Hospital, Toyota, Japan

Y. MizoguchiDepartment of Pathology, Fujitagakuen, Toyoake, Japan

1 Present address: Department of Urology, Gifu University Hospital, 1-1 Yanagito, Gifu 501-1194, JapanTel. +81-58-230-6341; Fax +81-58-230-6339e-mail: yamanao@gifu-u.ac.jp

Received: May 1, 2006 / Accepted: October 29, 2006

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is achieved by demonstrating a complete absence of staining for EMA. In general, paraganglioma cells are ar-gyrophilic and argentaffi n-negative, and the chief cells lo-cated in the cell balls are positive for chromogranin, synaptophysin, neuron-specifi c enolase, serotonin, and neu-rofi lament; they are S-100 protein negative by immunohis-tochemistry. In the present patient, we proved that the tumor had high expression of chromogranin in the oval-shaped cells, while no expression of CEA, serotonin, or EMA was demonstrated. The cells in the tumor were argentaffi n-negative and sustentacular cells had a positive reaction to S-100 protein, an important feature in the differentiating diagnosis from other endocrine neoplasms. These were appropriate fi ndings to make the diagnosis of paraganglioma. The presence of many intracellular dense-core neurosecretory granules, 150 to 250 nm in size, and a few microfi laments confi rmed the fi nal pathological diagnosis.

There has been confusion surrounding the term “pheo-chromocytoma”, leading to variations in nomenclature. The main source of this confusion is the use of the term “pheo-chromocytoma” for any catecholamine-secreting paragan-glioma, i.e., extraadrenal pheochromocytoma. A search of the literature revealed 5 reported cases of intrarenal para-ganglioma1 and 6 reported cases of intrarenal pheochromo-cytoma up to 2005,2,3 We could not accurately diagnose the present case due to a lack of symptoms of catecholamine excess. Five of the 11 reported cases involved clinical mani-festations of catecholamine hypersecretion,1–3 while the remaining cases did not. Renal cell carcinoma can cause paraneoplastic endocrinopathy with hypertension, but with no associated catecholamine elevation.4 It is important to keep in mind that an intrarenal mass in a hypertensive pa-tient might be a paraganglioma.1,2 It is necessary to continue to observe the progress of clinical investigation in this area.

Metastasis to adjacent lymph nodes helped us to confi rm the diagnosis of malignancy. Even after excision, a malig-nant pheochromocytoma cannot be diagnosed reliably on histological grounds,2 and thus extensive surgical evaluation of the tumor is required to ascertain the presence of local invasion or metastases.

We performed intensive multiagent chemotherapy with irradiation. Because there is no histological criterion for malignancy in this neoplasm, it would be prudent to con-sider every case of paraganglioma as potentially malignant and to monitor each patient carefully for an extended peri-od after removal of the primary tumor. Elder et al.5 have reported that the treatment of malignant paraganglioma with cyclophosphamide, vincristine, and dacarbazine (CVD) improves or stabilizes the disease. At present, this combina-tion chemotherapy (CVD) is a valid option for the treat-ment of malignant pheochromocytoma and abdominal paraganglioma. However, because of the small number of cases and the unpredictable clinical course (sometimes pro-longed over many years) of malignant pheochromocytoma, the effectiveness of treatment with alpha methylparatyro-sine, chemotherapy, and radiotherapy remains diffi cult to evaluate.6

Fig. 1. Computed tomography (CT) revealed a solid tumor in the up-per pole of the right kidney. The tumor was slightly enhanced

A

B

Fig. 2. A The microscopic appearance shows spindle-shaped or cres-cent cells forming integrated groups that give the appearance of mes-enchymal clusters. B An electron micrograph shows dense-corded granules and intracellular adhesions resembling desmosomes in the cytoplasm of the tumor cells. A H&E, ×200; B ×10 000

leiomyosarcoma, primary malignant peripheral nerve sheath tumor, primary neuroepithelial tumors, paragangli-oma, and mesoblastic nephroma. Differentiating sarco-matoid renal cell carcinoma from the other diagnoses

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References

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