Chromophobe renal cell carcinoma with sarcomatoid change. A case report

Chromophobe renal cell carcinoma (RCC) is a newly established entity of renal neoplasm with histological and molecular biological features different from those of common RCCs. Chromophobe RCC shows characteristically cloudy and reticular cytoplasm and cellular features resembling distal nephron. Its prognosis has been reported to be more favorable than that of common RCCs. Recently, however, several cases have been reported which showed sarcomatoid change to present poor prognosis. Here we present a case of chromophobe RCC with sarcomatoid change which was once resected surgically. The surgically resected tumor was histologically composed of chromophobe epithelial cell sheets and sarcomatoid elements. The former showed positivity for colloid iron staining, and was immunohistochemically positive for E-cadherin and epithelial membrane antigen (EMA), whereas the latter was positive for vimentin instead of colloid iron and E-cadherin. EMA was focally positive in the sarcomatoid element. The patient died with systemic metastases 14 months after the operation. Histologically, the metastatic tumors were composed only of sarcomatoid element lacking epithelial element. Based on these findings and previous reports, this case supports the existence of a tumor progression pathway from chromophobe to sarcomatoid RCC. It is necessary to perform careful postoperative investigation of chromophobe RCC due to its possible histological progression to the sarcomatoid subtype.     

Chromophobe renal cell carcinoma

Chromophobe renal cell carcinoma (RCC) is a recently established subtype of RCC, which has rarely been reported in Japan. In this communication, the authors report two Japanese cases of chromophobe RCC together with the immunohistochemical findings. The tumors were composed of sheets and cribriform glands formed by tumor cells with cloudy and reticular cytoplasm. Ultrastructurally, the cytoplasm was filled with numerous microvesicles. The tumor cells were positive for cytokeratin, epithelial membrane antigen, and Tamm-Horsfall protein. Occasionally, LeuM1-positive cells were also noted. Vimentin was negative, unlike the usual RCC. Reactivity for peanut agglutinin was more frequent than that to Lotus tetragonolobus agglutinin. The results of this study suggest that the tumor cellq possessed phenotypes similar to the distal nephron rather than to the proximal tubular cells.     

Chromophobe cell carcinoma and renal cell neoplasms with mucin-like changes

Hale's colloidal iron staining of 8 chromophobe cell carcinomas (CCC) was compared with that of non-chromophobe renal cell carcinomas (RCC), renal oncocytomas, and renal adenomas. Six non-chromophobe RCC showing diffuse and moderate cytoplasmic staining contained extensive areas with translucent cytoplasm as observed in CCC. Seventeen of 25 conventional RCC of the clear cell variant (randomly chosen from 130 cases), 21 of 26 RCC with areas of chromophilic cytoplasm, and 16 of 20 papillary RCC, 7 of 14 adenomas and 14 of 16 oncocytomas displayed focal areas with mild to moderate staining of the cytoplasm. Hale's colloidal iron staining was partially reduced by digestion with neuramidase but not with hyaluronidase. This positive staining demonstrated glycoproteins containing sialylated glycoconjugates, probably a type of acid epithelial mucin. We suggest that there is a spectrum of mucin-like changes in typical CCC representing RCC with extensive and marked "mucin-like changes". The eosinophilic variant of CCC and some RCC with extensive chromophobe cell features represent renal neoplasms with moderate changes. The other RCC, oncocytomas and papillary renal neoplasms with mild to moderate staining with Hale's colloidal iron represent renal neoplasms with focal mucin-like changes. RCC with extensive chromophobe cell features may pose a differential diagnostic problem with CCC.     

Chromosomal gains in the sarcomatoid transformation of chromophobe renal cell carcinoma.

The hallmark of chromophobe renal cell carcinoma is multiple chromosomal losses from among chromosomes 1, 2, 6, 10 and 17. Chromophobe renal cell carcinoma with distant metastases or sarcomatoid transformation are uncommon and little is known about their chromosomal abnormalities. We collected six sarcomatoid chromophobe renal cell carcinomas and three primary chromophobe renal cell carcinomas with distant metastases. A cytogenetic analysis by fluorescent in situ hybridization on paraffin-embedded tissue was performed using centromeric probes for chromosomes 1, 2, 6, 10 and 17. We found more than one signal in four of six (66%) sarcomatoid chromophobe renal cell carcinomas, in both sarcomatoid and adjacent epithelial components. Both primary chromophobe renal cell carcinomas and matched metastases showed single signals for all chromosomes studied in two cases and no abnormalities in the remaining case. We concluded that: (1) both epithelial and sarcomatoid components of sarcomatoid chromophobe renal cell carcinoma show different genetic abnormalities from those characteristic of chromophobe renal cell carcinoma; (2) sarcomatoid chromophobe renal cell carcinomas frequently have multiple gains (polysomy) of chromosomes 1, 2, 6, 10 and 17; (3) distant metastases show the same genetic patterns, usually chromosomal losses (monosomy), found in the primary tumors.     

Chromophobe renal cell carcinoma with extensive calcification and ossification

A 39-year-old woman presenting with microscopic hematuria was found to have an extensively calcified mass in the upper pole of the right kidney. Gross and histologic examination of the nephrectomy specimen revealed a 9.3-cm renal tumor composed of solid trabecular sheets of polygonal epithelial cells with clear cytoplasm and distinct cell borders characteristic of a chromophobe renal cell carcinoma. Electron microscopy showed the presence of numerous intracytoplasmic microvesicles, thereby confirming the diagnosis. However, the unique additional feature of this tumor included the presence of dense calcification and ossification throughout the tumor. To our knowledge, we report the first case of chromophobe renal cell carcinoma with the concomitant presence of extensive calcification and ossification. A literature review on chromophobe renal cell carcinoma with either calcification or ossification is performed.     

Chromophobe renal cell carcinoma with neuroendocrine differentiation

Chromophobe renal cell carcinoma was described by Thoenes et al. in 1986, and associations with carcinoma of collecting ducts, conventional renal cell carcinoma and sarcomatoid renal cell carcinoma have been described. We report a case of chromophobe renal cell carcinoma which showed neuroendocrine differentiation. This is the first known case to be clearly identified as such. The patient was a 56‐year‐old man with constant right flank pain and hematuria; CT scan revealed an 8.5 cm non‐homogeneous mass involving the right kidney. Right radical nephrectomy was performed. The tumor showed a mixture of classical and eosinophilic patterns of chromophobe cell carcinoma. Additionally, it showed insular, glandular and rosetoid‐like formations embedded in a dense eosinophilic hyaline stroma. The cells were cuboid or cylindrical with well‐defined boundaries, finely stippled chromatin and a small nucleolus. The appearance of the cytoplasm varied from faintly eosinophilic to coarsely granular eosinophilic. Immunohistochemically, the neuroendocrine areas were reactive for C‐kit, epithelial membrane antigen, cytokeratin, cytokeratin 7, chromogranin A, neuron‐specific enolase, CD56 and S‐100 protein. Our case represents a typical chromophobe carcinoma with neuroendocrine differentiation. Additionally, the immunohistochemical profile in both types of lesion suggests a common origin from renal tubular cells.     

Immunohistochemistry and lectin histochemistry in sarcomatoid renal cell carcinoma: a comparison with classical renal cell carcinoma

We investigated the expression of various cell markers in renal cell carcinoma, concentrating particularly on the sarcomatoid variety, using lectin and immunohistochemical techniques. The sarcomatoid variant showed stronger staining in a higher proportion of cases for vimentin and reduced positivity for epithelial membrane antigen, in comparison with classical renal cell carcinoma. All sarcomatoid tumours reacted with at least one cytokeratin, enabling them to be distinguished from true renal sarcomas; this is of diagnostic value when a panel of markers is used. Overall a similar pattern of markers is seen in sarcomatoid and classical renal cell carcinoma using lectin and immunohistochemistry, suggesting that the sarcomatoid variant arises as a metaplastic change rather than having a different histogenesis.     

Acquired cystic disease-associated renal cell carcinoma with sarcomatoid change and rhabdoid features

Acquired cystic disease (ACD)–associated renal cell carcinoma (RCC) is a recently described entity. To the best of our knowledge, there are no reports of ACD-associated RCC with sarcomatoid and rhabdoid changes. In this article, we present the first case of such a tumor. A 56-year-old Japanese man has received long-term hemodialysis and had a history of right renal cancer. Following the discovery of metastatic cancer in the thoracic wall, detailed imaging studies revealed a mass in the left kidney. The histologic examination of the left renal tumor showed ACD-associated RCC with sarcomatoid change and rhabdoid features. Immunohistochemically, intracytoplasmic globular inclusions in rhabdoid cells were positive for vimentin and cytokeratin CAM5.2. The G-band karyotype showed the following changes: 46, X, +X. −Y[1]/43, idem, add(2)(q31), −6, −9, −14, −15, +16, −22, +mar1[6]/46, XY[2]/abnormal cell[11]. In conclusion, pathologists and urologists should be aware that rhabdoid features may occur in ACD-associated RCC and that the loss of chromosomes 9 and 14 may occur during the process of sarcomatoid change in ACD-associated RCC.     

Chromophobe renal cell carcinoma with liposarcomatous dedifferentiation - report of a unique case

Sarcomatous transformation of chromophobe renal cell carcinoma (CRCC) is a well recognized phenomenon. Of the published cases with sarcomatous transformation of CRCC, none have shown liposarcomatous differentiation. Out of a cohort of 250 cases of CRCC, 19 (7.6%) showed sarcomatous differentiation. In one case (female, age 46 years), the sarcomatous component of the tumor displayed histological features of a pleomorphic liposar-coma. Light microscopic examination revealed a biphasic pattern with a chromophobe renal cell carcinoma(CRCC) and a high-grade sarcomatous component containing large pleomorphic lipoblasts. In several areas both components were intermingled. The conventional CRCC component showed classic histological features with calcifications, medium-sized polygonal cells arranged in solid-alveolar structures with raisinoid nuclei, pale-eosinophilic flocculent cytoplasm with perinuclear haloes. In addition, a microcystic-adenomatous component had luminal spaces filled with erythrocytes. The CRCC was positive with Hale''s colloidal iron-stain whereas the sarcomatous component was negative. The CRCC component was diffusely positive for cytokeratin 7, parvalbumin and racemase but negative for cy-tokeratin 20, vimentin, CD10, carboanhydrase IX and S100-protein. The pleomorphic liposarcomatous component displayed immunereactivity for CD10, vimentin, racemase and focally for carboanhydrase IX. The proliferative activity (Mib-1/Ki-67) was 5% in the CRCC and 30% in the pleomorphic liposarcomatous component. No immunereactivity for MDM2 or CDK4 was detected.This is the first reported case of a sarcomatoid CRCC where the sarcomatous component displayed features of a pleomorphic liposarcoma. The patient died from widespread metastatic disease 12 months after nephrectomy.     

Chromophobe cell renal carcinoma and its variants--a report on 32 cases

This paper reports on 32 chromophobe cell renal carcinomas observed in 697 renal cell cancers (RCC) of adults (peak in the sixth decade of life). The chromophobe cell-type differs from other types of RCC macroscopically, the cut-surface being predominantly of grey-beige colour. Histologically, there are two variants: one is the typical (light) variant (n = 22) and the other is eosinophilic (n = 10). Both variants have in common (a) reaction of the cytoplasm with Hale's acid iron colloid; (b) electron microscopic detection of cytoplasmic microvesicles (150-300 nm), frequently with 'inner vesicles', and (c) low glycogen content in comparison with the clear cell carcinoma. Immunocytochemical investigations on the intermediate filaments show a positive reaction for cytokeratins No. 18 (uniformly) and Nos. 7 and 19 (to varying extents) for both variants, whereas vimentin was not found in any of these carcinomas, in contrast to the clear-cell type. The cytomorphological grading revealed predominantly G II tumours. A lymph node metastasis was found in one patient. On the basis of the mortality curves determined, the prognosis for patients with chromophobe cell carcinomas is more favourable than that of the clear-cell type. In terms of differential diagnosis, on the one hand, the typical (light) variant of the chromophobe cell RCC must be delimited from the clear-cell RCC, and on the other hand, the eosinophilic variant must be distinguished from the chromophilic or 'granular' RCC. Microscopic, histological, histochemical, electron microscopic, and intermediate filament analysis results document that the chromophobe cell type of RCC is a distinct entity. The implications for the nomenclature of RCC, especially with regard to the 'granular' type, are discussed.     

The evolution of collagen expression in sarcomatoid renal cell carcinoma

The development of a sarcomatoid morphotype is recognized as an extreme form of dedifferentiation in renal cell carcinoma and is associated with a poor prognosis. Although sarcomatoid renal cell carcinoma shows pronounced spindle cell morphology, clear cell renal cell carcinoma may show early spindle cell change with cellular elongation, and the prognostic significance of this is debated. To determine the relationship between sarcomatoid renal cell carcinoma and clear cell renal cell carcinoma showing early spindle cell change, we have investigated collagen expression using immunohistochemistry in these 2 tumor types. Both sarcomatoid renal cell carcinoma and early spindle cell change tumors showed pericellular interstitial expression of collagen types I and III, whereas sarcomatoid renal cell carcinoma also showed cytoplasmic expression of these collagen types. Expression of these collagen types in typical clear cell renal cell carcinoma was, in occasional cases, limited to faint and patchy staining in a pericellular interstitial distribution. Tumor cells did not stain for collagen type IV in sarcomatoid renal cell carcinoma, early spindle cell change, or typical clear cell renal cell carcinoma. In sarcomatoid renal cell carcinoma, there was diffuse pericellular expression of collagen type V and patchy pericellular expression of collagen type VI, whereas early spindle cell change tumors showed patchy pericellular staining with antibodies to collagen type V. Collagen type VI expression in early spindle cell change was largely confined to the vascular adventitia and areas of scarring, although very occasional foci of faint interstitial staining were also seen. In typical clear cell renal cell carcinoma, staining of collagen types V and VI was limited to the vascular adventitia and foci of desmoplasia, whereas no staining of tumor cell cytoplasm were seen. This study has shown that collagen expression of sarcomatoid renal cell carcinoma differs from that of early spindle cell change and provides validating evidence that these 2 morphotypes should not be considered together for classification purposes.     

肾细胞癌伴肉瘤样分化的形态学和免疫表型研究

本文描述5例分别发生在肾透明细胞癌、乳头状肾细胞癌和嫌色细胞癌中的肉瘤样成分的形态学特征及免疫表型。探讨其病理诊断及发生机制。