Squamous Differentiation in a Sarcomatoid Chromophobe Renal Cell Carcinoma: An Unusual Case Report With Review of the Literature

Archives of Pathology & Laboratory Medicine, Oct 2008 by Viswanathan, Seethalakshmi, Desai, Sangeeta B, Prabhu, S R, Amin, Mahul B

We describe an extremely rare occurrence of a squamous differentiation in a sarcomatoid chromophobe renal cell carcinoma in a 45-year-old woman with nodal and lung metastasis at presentation. The tumor on histology showed all 3 components intimately admixed with each other, which to the best of our knowledge is the first such case to be reported in the literature. The renal pelvis was smooth walled and uninvolved. Kidney-specific cadherin was positive in the chromophobe renal cell carcinoma areas and negative in the sarcomatoid and squamous areas.

(Arch Pathol Lab Med. 2008;132:1672-1674)

Sarcomatoid change represents a high-grade transformation or dedifferentiation in any of the classical variants of renal cell carcinoma (RCC), including chromophobe RCC, and is not a distinct histologic entity.1 The histologic features seen are usually of a high-grade spindle cell tumor of mesenchymal differentiation, with a variable proportion of epithelial elements of RCC.2-4 A coexistent aggressive component in the form of collecting duct carcinoma or a squamous carcinoma with a chromophobe RCC has been described.5,6 We describe a case of squamous differentiation in a chromophobe RCC with sarcomatoid change. To the best of our knowledge, this is the first case to be reported in the literature.

REPORT OF A CASE

A 45-year-old female patient, postmenopausal, presented with an abdominal lump that increased progressively for 10 years and significantly impeded her routine activity. She had severe loss of weight and appetite. Besides being a diabetic, she had no other significant history. On examination, she was moderately built, extremely malnourished, with pallor and clubbing. She was observed to have fullness in the right half of the abdomen.

On investigation, the patient's hemoglobin was 6.4 g/dL, and her total white blood cell count was 13 800/µL. Results of wholebody bone scintigraphy were normal. Pulmonary function tests showed mild restrictive disease.

Ultrasonography and a computed tomography scan showed a large, well-defined solid mass with few cystic spaces extending from the inferior margin of the liver to the right iliac fossa and arising from the anterior and inferior aspects of the right kidney. The mass was vascular, and increased blood flow was seen through it. Dilated veins were noted around the mass. The right renal vein and artery were unremarkable. Enlarged retroperitoneal nodes were present. Both of the lungs showed nodular lesions, which represented metastasis from the renal primary. The D12 to L1 vertebrae showed lytic lesions. The tumor was clinically Robson stage IV due to the presence of lung metastasis at presentation.

A right nephrectomy with excision of tumor was performed. We received a specimen of kidney with the tumor measuring 20 × 14 × 12 cm and adjacent uninvolved kidney measuring 8 × 8 × 3 cm. The entire specimen weighed 2.2 kg. The tumor was well encapsulated, ovoid, and firm in consistency. The cut surface was predominantly solid, yellow, tan, and fleshy, with few cystic areas. Large, irregular, gray-white firm areas with associated hemorrhage and necrosis were identified in the midst of the tumor. At one end, the dilated pelvis was identified. The remnant kidney showed a markedly dilated pelvicalyceal system (Figure 1). The cortical surface showed occasional irregular scars. The ureter identified was dilated with thickened walls and measured 8 cm in length.

On microscopy, sections from the brown-tan areas showed a cellular tumor composed of tumor cells arranged predominantly in nests and sheets. These nests were separated by delicate fibrovascular septae. The majority of the individual cells were polygonal with abundant eosinophilic cytoplasm and a prominent perinuclear halo, giving the cells a classic "vegetable cell" appearance. Nuclei appeared crinkled, and mitosis was not identified. These were areas typical of chromophobe RCC. The periphery of a large number of these nests showed more closely packed cells with scanty cytoplasm and hyperchromatic rounded nuclei. In places, the nests were composed of a greater proportion of these basaloid cells. Sections from the large, firm, gray-white areas on gross morphology showed spindled, more anaplastic tumor cells arranged in fascicles and whorls separated by hyalinized collagen morphologically resembling a sarcoma. Pleomorphism and mitosis were identified in abundance, and necrosis was seen (Figure 2). Amid these sarcomatoid areas were seen nests, sheets, and cords of cells with distinct squamous differentiation, including keratinization and formation of pearls (Figure 3). There was intimate admixture of the chromophobe, sarcomatoid, and squamous elements. The squamous elements were not identified in one area, but were multifocally seen arising within the sarcomatoid areas. Adjacent kidney showed evidence of oncocytosis, reactive changes in the entrapped renal tubules, and features of chronic pyelonephritis. Immunohistochemistry demonstrated the sarcomatoid areas, including the squamous component, to be diffusely positive for cytokeratin, epithelial membrane antigen, and vimentin, whereas c-kit was diffusely negative in all of the areas-chromophobe, spindly sarcomatoid, and squamous elements. The chromophobe elements showed membrane positivity for kidney-specific cadherin, whereas the sarcomatoid area and area with squamous differentation were uniformly negative for the marker.