We present a case with a retroperitoneal mass that was first thought to be a malignant mesenchymal tumor on intraoperative frozen section but was then diagnosed as sarcomatoid CRCC with osteosarcomatous differentiation on paraffin sections.
Personal and family history revealed nothing of significance and laboratory values were also within normal limits. A tissue 1.5x1x0.5 cm in size obtained from the intraabdominal mass before the surgical excision showed atypical spindlelike cells making up long fascicules (Figure 2). The mass was reported as ‘Malignant; consistent with mesenchymal tumor' and resected. Macroscopically, the mass was 18x18x11 cm in size and sections showed a solid dirty yellow tumor with widespread necrotic areas. A separate solid gray, bonedensity area 6 cm in diameter at the external surface of the tumor was noted (Figure 3). Microscopic evaluation of the tumor revealed typical CRCC areas consisting of polygonal cells containing centrally-located round hyperchromatic nuclei and pale, granular, eosinophilic cytoplasm and faint cytoplasmic margins. The cells formed solid islands, together with large, pleomorphic, polyhedral or spindlelike atypical cells with hyperchromatic nuclei and osteoblast morphology. Indifferentiated sarcoma and osteosarcoma areas were noted next to CRCC areas (Figure 4A,B; 5A,B). Immunohistochemical evaluation revealed that carcinoma areas had a profile that supported CRCC by staining positively with cytokeratin (CK) 8-18, CK7, and EMA, and negatively with CD10 and vimentin. Sarcoma areas stained focally with CK and diffusely with vimentin while there was no staining with CD34, S-100, Actin, and HHF-35 (Figure 6A,B). The diagnosis was therefore ‘sarcomatoid CRCC with osteosarcomatous differentiation'. Chemotherapy was planned but the patient died due to surgical complications before treatment was started.
Figure 2: Atypical spindle-type cells making up long fascicles on frozen section.
Figure 4A,B: Chromophobe renal cell carcinoma areas.
Figure 5A,B: Transition areas from chromophobe renal cell carcinoma to osteosarcoma.
RCC with sarcomatoid differentiation is not a separate histological entity and it just signifies the differentiation of the epithelial component that may be present in all RCC subtypes to a higher grade tumor resembling a sarcoma characterized by spindle cells with atypical cytological features[1,6,9].
Sarcomatoid differentiation is seen most commonly in CRCC among the RCC subtypes at a rate of 9%[2,9]. Peralta-Venturina et al. have studied 100 kidney tumors and found the rates for sarcomatoid differentiation to be 8% in conventional RCC, 9% in chromophobe RCC, 3% in papillary RCC, 29% in collecting duct carcinoma and 11% in unclassified RCC[8]. The sarcoma component usually consists of areas of malignant fibrous histiocytoma, fibrosarcoma and undifferentiated sarcoma[5]. Less than 10 cases have been reported with a heterologous element such as chondrosarcoma, osteosarcoma or rhabdomyosarcoma[7]. There are 3 case reports in the English literature of CRCC cases containing osteosarcoma-like areas[1,5,9] and two of these tumors had a retroperitoneal mass as in our case[5,9]. The tumor protruded from the lower half of the kidney, causing abdominal spread and pulmonary[5,9] and hepatic[5] metastases in both cases, leading to death due to widespread disease. The other case was limited to the kidney but had invaded the perirenal fatty tissue and renal vein. Hepatic, pulmonary and bone metastases developed three months after the surgery, necessitating radiotherapy and chemotherapy[1]. Itoh et al.[5] have interpreted the positive staining with CK and EMA in the sarcoma areas in their own case and other sarcomatoid RCC cases reported in the literature[7,10] as being due to a metaplastic change of the osteosarcoma-like component that can morphologically mimic osteosarcoma. Immunohistochemical analysis of our case also revealed diffuse staining with vimentin and positive staining of a few cells with cytokeratin in the sarcoma areas.
The presence of a sarcomatoid component has been reported to be associated with an increased risk of metastasis and an unfavorable prognosis[3,7-9]. The CRCC cases with sarcomatoid differentiation in the literature have shown distant organ metastases such as to the bone, liver, lung and lymph nodes[10].
Nagashima et al. have published a CRCC case with sarcomatoid differentiation who died due to systemic metastases 14 months after the diagnosis and histopathological investigation of the metastatic foci showed a tumor with a sarcomatoid appearance that did not contain an epithelial element[11].
Quiroga-Garza et al. have published a CRCC cases with sarcomatoid differentiation while a metastatic periaortic lymph node similarly revealed tumor with a sarcomatoid appearance[1]. These results support the presence of a tumor progression pathway from chromophobe to sarcomatoid RCC. Careful postoperative follow-up for potential histological progression of CRCC to the sarcomatoid subtype has been suggested[11]. Klatte et al. have reported that a sarcomatoid component accompanies 50% of metastatic CRCC cases, that these cases have a tendency to have hepatic metastases, unresponsiveness to immunotherapy and that the prognosis is unfavorable[6].
The tumor in the form of a retroperitoneal mass in our case was almost totally excised and the left kidney left alone as the MR images and the peroperative findings did not provide a clear picture and the tumor's frozen section report was malignant mesenchymal tumor. No non-tumoral kidney tissue was observed in the macroscopic and microscopic investigation of the tumor.
In conclusion, CRCC with osteosarcomatous differentiation is a very rare tumor and can be encountered as a retroperitoneal mass with a rapid and progressive course. RCC with sarcomatoid differentiation should therefore always be considered for retroperitoneal tumors that look like mesenchymal tissue on histology and the medical and surgical treatment of the patient should be planned taking this possibility into account.
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