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

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.

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 whole-body 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.

The postoperative period was uneventful. The patient presented after 1 month with severe breathlessness, anasarca, and hypotension. Chest x-ray showed canonball metastasis in the lungs with bilateral pleural effusion. Finally, the patient died due to left ventricular failure.

Sarcomatoid RCC, first reported by Farrow et al in 1968,7 represents a high-grade transformation or dedifferentiation of any of the well-defined variants of RCC.1 The overall incidence of this change is reported to be 8% to 10%.2 The specific incidence of sarcomatoid change in chromophobe RCC has been variously reported to range from 2% to 55% and has been reported to be higher than that seen in other variants of RCC.8 However, in the largest series, which consists of a multi-institutional clinicopathologic analysis of 101 cases of sarcomatoid RCC,2 the incidence is not higher than for the other histologic types and is reported to be 9%. Maximum association of sarcomatoid RCC in the literature is reported to be with collecting duct carcinoma: 25% to 29%.2,3 

The specimen in the present case showed typical tan-brown areas in the large part of the tumor, which on sampling revealed classic chromophobe areas. The sarcomatoid component appeared as distinctly more grayish and fleshy, with a fibrous cut surface. This is the classic appearance described in the literature.2 Necrosis in our specimen was confined only to these areas.

In all of the major series of sarcomatoid RCCs2,3,7 and the other isolated reports4,8 and short series,9–11 consisting of about 275 cases of sarcomatoid change in RCC, the sarcomatoid component resembles a malignant tumor of mesenchymal differentiation, such as fibrosarcoma, malignant fibrous histiocytoma, or undifferentiated sarcoma. There are fewer than 10 cases reported to have the presence of heterologous elements, such as chondrosarcomatous, osteoarcomatous, and rhabdomyosarcomatous components.2–4,7,12 Sometimes, the entire tumor may be composed of sarcomatoid elements, and immunohistochemical or ultrastructural evidence of its epithelial derivation needs to be established to prove that it is not a primary renal sarcoma.4 To date, there is no report of other epithelial elements being found within the sarcomatoid areas. Hence, to the best of our knowledge, the present case of squamous epithelial differentiation within the sarcomatoid elements is the first case to be reported. However, an association of collecting duct carcinoma and a chromophobe RCC with or without an associated sarcomatoid component has been well documented, because both are histogenetically derived from the distal nephron.5 A composite tumor composed of squamous carcinoma of the renal pelvis with a sarcomatoid RCC has been documented in the literature.13 In our case, the dilated renal pelvis stretched over the tumor was clean and smooth walled and did not show any evidence of tumor. The remnant kidney also showed hydronephrosis, and the pelvicalyceal system and ureter were dilated.

Presence of the sarcomatoid component signals an ominous prognosis independent of the type of epithelial component of the RCC.2 The extent of this component may range from 1% to 99% of the tumor.2,3 In our case, sarcomatoid areas constituted about 50% of the tumor. In the literature, the percentage of sarcomatoid elements (>50%), angioinvasion, and high TNM stage were correlated adversely with survival.2 Our patient had all 3 poor prognostic indicators.

The patient had pulmonary metastasis at presentation that rapidly progressed, succumbing to her disease within 1 month of the removal of the renal tumor. This is compatible with the natural course of evolution and biology of disease.

The extent of surgery or addition of adjuvant treatment does not significantly alter prognosis of sarcomatoid RCC. However, one of the series claims a slightly better outcome with doxorubicin and interferons.3 Our patient died within 1 month of her debulking surgery and did not receive any adjuvant treatment. Recently, there has been an intense study of c-kit expression in sarcomatoid RCC and evaluation of the possible use of imatinib (STI-571) as a treatment option in advanced disease, which is usually the case with these tumors.14 In this light, we extensively studied c-kit expression and found that none of the epithelial, sarcomatoid, or dedifferentiated areas marked for c-kit. Hence, in our opinion, study of the c-kit expression as well as targeted treatment with imatinib require further evaluation. As was expected, the chromophobe elements in the tumor showed strong membrane positivity for kidney-specific cadherin, indicating its derivation from the distal nephron,15 whereas the dedifferentiated sarcomatoid and squamous areas were uniformly negative for the marker.

In conclusion, we report an unusual occurrence of squamous differentiation in a sarcomatoid chromophobe RCC. Although all the clinical features of our case confirm to the standard findings reported in literature, the presence of squamous differentiation within sarcomatoid areas has not been previously reported.