A Rare Presentation of Dual Renal Tumours: Clear Cell Renal Cell Carcinoma with Paraganglioma
We present here a case of a single kidney tumour that revealed two distinct microscopic pictures, one of a clear cell renal cell carcinoma (CCRCC) and the other of a paraganglioma of the kidney.
A 30-year-old female presented to the out patient department of Goa Medical College, Bambolim, Goa, with chief complaints of lower back pain predominantly on the right flank for 6 months. The patient also had a history of loss of appetite, weight loss, and fatigue for the past four months. Patient had no history of any chronic illness.
On examination there were no significant findings. Laboratory and radiological investigations were done. Abdominal ultrasound and computed tomography revealed a tumour in the right kidney. The patient had a tumour resection and partial nephrectomy done. The specimen was sent to the Department of Pathology for histopathological examination.
Gross: The specimen of partial nephrectomy measuring 5 x 4 x 3 centimetres (cm), already cut open. Cut section showed a well-circumscribed tumour mass measuring 3.5 x 3 cm, cut section of which showed areas of haemorrhage, necrosis, and calcification. The capsule could be easily stripped off.
Microscopy: Multiple sections from the kidney revealed a well-circumscribed tumour mass (Figure 1) showing two distinct patterns:
1) Large clear cells arranged in sheets (Figure 2)
2) Round to oval cells with abundant granular cytoplasm arranged in small nests and separated by delicate fibrous stroma (Figures 3 and 4). This pattern is also called the Zellballen pattern.
Surrounding kidney and capsule revealed congestion. Margins were free.
Diagnosis was established as a dual tumour of clear cell renal cell carcinoma (CCRCC) of the right kidney with a paraganglioma (Figure 5). The patient was advised to do a whole-body scan and screening of family members also advised.
Immunohistochemically, renal cell carcinoma shows reactivity for epithelial markers such as keratin, epithelial membrane antigen (EMA),and carcinoembryonic antigen (CEA).[1,2] Paraganglioma shows positivity for chromogranin, synaptophysin. Reticulin highlights nesting pattern.
Molecular Genetics: A distinctive cytogenetic abnormality found in most cases of clear cell renal cell carcinoma is a terminal deletion of the short arm of chromosome 3, beginning at 3p13.
The presence of two distinct patterns in a single kidney tumour is a rare entity. Some studies suggest that germline SDHB mutations (succinate dehydrogenase complex iron sulfur subunit B) can predispose to early-onset kidney cancers in addition to paragangliomas.
Germline mutations affecting the Krebs cycle enzyme, succinate dehydrogenase (SDH), can also cause an inherited tumour susceptibility syndrome. Thus, inherited mutations in SDHB, SDHC, and SDHD genes (encoding subunits of SDH) are associated with a high risk of head and neck paragangliomas and/or adrenal and extra-adrenal pheochromocytomas. Very rarely, germline mutations in SDHB have been found in patients with RCC and a personal or family history of pheochromocytoma and/or paraganglioma.
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