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.     

Carcinosarcoma and squamous cell carcinoma of the renal pelvis associated with nephrolithiasis: a case report of each tumor type

Both squamous cell carcinoma and carcinosarcoma of the renal pelvis are uncommon. We report on two cases, one carcinosarcoma and one squamous cell carcinoma of the renal pelvis. In the patient with squamous cell carcinoma of the left kidney, the tumor was neither detectable on preoperative radiological evaluation nor grossly visible in the surgical specimen. This patient, a 56-year-old man, presented with left lumbar pain, hematuria, fever, 4-5 kg weight loss, and untreated nephrolithiasis of the left kidney that had been diagnosed 20 years earlier. The second patient, an 87-year-old woman, also had a long history of left kidney nephrolithiasis and presented with left lumbar pain and hematuria. Both patients underwent nephrectomy for removal of the non-functioning hydronephrotic left kidney. In both cases, microscopic examination of the surgical specimen revealed squamous metaplasia and dysplasia in the pelvicalyceal mucosa, and islands of atypical squamous cells in the renal parenchyma. In the second case, the kidney also showed sarcomatous changes in the pelvis.     

Fine needle aspiration biopsy of renal mucinous tubular and spindle cell carcinoma: Report of two cases

Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare renal tumor. Here we report two cases of MTSCC which were initially evaluated by fine needle aspiration biopsy (FNAB) and followed by surgical resection of the tumors. The cytomorphologic features of MTSCC were characterized by aggregates of relatively uniform, predominantly oval to spindle cells intermixed with abundant metachromatic myxoid matrix. Only rare epithelioid tumor cells with vacuolated cytoplasm were present. Immunohistochemically, the tumor cells were positive for CK7, CK19, CD10, vimentin, E‐cadherin, alpha‐methyl CoA racemase, and negative for CK903 and CK20. EMA and carbonic anhydrase IX immunoreactivity was seen in one of the two cases. Multiple chromosomal losses involving chromosomes 1, 2, 17 and likely chromosome 7 were revealed by fluorescence in situ hybridization (FISH). These cytomorphologic, immunophenotypic, and cytogenetic features were helpful for including this entity in the differential diagnosis of renal cell carcinomas. Diagn. Cytopathol. 2010. © 2009 Wiley‐Liss, Inc.     

肾细胞癌中抑癌基因PTEN的表达及生物学意义

目的 :研究抑癌基因PTEN在肾细胞癌的表达及其生物学意义。方法 :应用免疫组织化学S P法检测 5例正常肾组织、18例癌旁肾组织和 40例肾细胞癌组织中抑癌基因PTEN的表达。结果 :5例正常肾组织和 18例癌旁肾组织均有较强的PTEN蛋白的表达 ,二者PTEN蛋白的表达强度、阳性细胞的分布形式无差异。抑癌基因PTEN在肾细胞癌中的表达不同于正常肾组织和癌旁肾组织 ,12 5 %的肾细胞癌呈PTEN蛋白阴性 ;17 5 %的肾细胞癌PTEN蛋白呈弱阳性 ;70 %的肾细胞癌PTEN蛋白呈阳性或强阳性 ,与癌旁组织PTEN蛋白的染色强度无差异。PTEN蛋白阴性的肾细胞癌 ,肾门淋巴结转移率为80 % ;PTEN蛋白阳性的肾细胞癌 ,肾门淋巴结转移率为 2 0 %。PTEN蛋白阴性肾细胞癌的肾门淋巴结转移率与PTEN阳性肾细胞癌的肾门淋巴结转移率比较 ,差异有显著性 (P <0 0 5 )。结论 :肾细胞癌中存在着抑癌基因PTEN的表达缺失和异常 ;抑癌基因PTEN的表达异常可能与肾细胞癌的发生、发展有关 ,抑癌基因PTEN是肾细胞癌的一种新的相关基因。     

A case of a novel entity: eosinophilic solid and cystic renal cell carcinoma

Eosinophilic solid and cystic renal cell carcinoma (ESC-RCC) is a relatively newly described entity characterized by specific morphological features and a consistent immunohistochemical profile. The vast majority of cases are sporadic, but tumours with identical histological appearances have been reported in patients with tuberous sclerosis complex (TSC). The distinction between a sporadic or syndrome associated ESC-RCC is not possible without, at a minimum, exploring the patient's clinical context and family history. We present a case of a young female patient who presented with bilateral renal tumours, one of which has been diagnosed as ESC-RCC, and is awaiting genetic testing to exclude underlying TSC.     

Cytokeratin 7: a useful adjunct in the diagnosis of chromophobe renal cell carcinoma

AIMS: The histopathological diagnosis of chromophobe renal cell carcinoma can present a diagnostic challenge, as these tumours can resemble either conventional renal cell carcinoma or oncocytoma. The aim of this study was to determine whether cytokeratin 7 expression is of practical use in the distinction of these three entities. METHODS AND RESULTS: A total of 40 cases previously diagnosed as either chromophobe renal cell carcinoma, conventional renal cell carcinoma or oncocytoma were identified. A representative section of each was stained with H&E and cytokeratin 7. Following independent review of the cases by three pathologists, a consensus diagnosis for each case was reached and the pattern of cytokeratin 7 staining was assessed. There were 12 cases of chromophobe renal cell carcinoma in the study, all of which showed a characteristic peripheral membrane pattern of staining for cytokeratin 7. Seventeen of the 18 cases of conventional renal cell carcinoma studied were negative for cytokeratin 7, while one case showed weak focal staining of <5% of the cells. The 10 cases of oncocytoma showed patchy weak to moderate cytoplasmic expression of cytokeratin 7, without the characteristic peripheral membrane accentuation seen in the chromophobe carcinomas. CONCLUSIONS: Immunohistochemical staining for cytokeratin 7 appears to be a useful adjunct in the diagnosis of chromophobe renal cell carcinoma, and in distinguishing this tumour from both oncocytoma and conventional renal cell carcinoma.     

Fine‐needle aspiration of tubulocystic renal cell carcinoma

We report two cases of tubulocystic renal cell carcinoma, a rare renal tumor the cytology of which has not been previously reported. Both aspirates were cellular and contained large sheets of cells with abundant granular cytoplasm, distinct cell borders and intracellular windows, distinct to prominent nucleoli, rare intracytoplasmic vacuoles, and rare nuclear grooves. Cells with variable amounts of cytoplasm were also arranged in small groups, some of which resembled spherules. The large sheets of cells with windows appeared specific for tubulocystic carcinoma; the spherules could easily be confused with a papillary renal cell carcinoma.     

Clear cell papillary renal cell carcinoma: a review

The disease concept of clear cell (tubulo) papillary renal cell carcinoma (CCP-RCC) as a distinct subtype of renal cell carcinoma has been recently established. First described in the setting of end stage renal disease, this tumor type is more frequently recognized and encountered in a sporadic setting. In this article, we provide an overview of the recent understanding of this tumor. Macroscopically, tumors are well circumscribed with well-developed tumor capsule. Histologically, the tumor cells are cuboidal to low columnar cell with clear cytoplasm and papillary and tubulo-papillary configuration. Immunohistochemically, tumor cells generally show diffuse expression for cytokeratin 7, CA9 (cup-shaped pattern), HIF-1, GLUT-1 and high molecular weight cytokeratin, but negative for AMACR, RCC Ma and TFE3. CD10 is negative or focally positive in most tumors. Genetically, this tumor has no characteristics of clear cell RCC or papillary RCC. Prognostically, patients with CCP-RCC behave in an indolent fashion in all previously reported cases. In conclusion, although this tumor has been integrated into recent International Society of Urologic Pathology Classification of renal neoplasia, both aspects of disease concept and clinical behavior are yet to be fully elucidated. Further publications of large cohorts of patients will truly help understand the biologic potential and the molecular underpinnings of this tumor type.     

Clear cell papillary renal cell carcinoma: a clinicopathological study emphasizing ultrastructural features and cytogenetic heterogeneity

Clear cell papillary renal cell carcinoma (CCPRCC) is a recently recognized renal neoplasm, which was initially described in end-stage renal disease (ESRD), but some cases have been reported in otherwise normal kidneys. We report a series of 11 CCPRCC (age range, 33-72 years; male-to-female ratio, 8:3). Follow-up was available for 8 patients. No patients developed local recurrence, distant or lymph-node metastasis, or cancer death. Histologically, all tumors exhibit morphologic features typical of CCPRCC including a mixture of cystic and papillary components, covered by small to medium-sized cuboidal cells with abundant clear cytoplasm. All 11 cases exhibited moderate to strong positivity for CK7, CA9, Vim, and HIF-1α, coupled with negative reactions for CD10, P504S, and RCC. We did not find any VHL gene mutations in all 11 cases. Losses of chromosomes 3 (monoploid chromosome 3) was detected in 3 cases. Ultrastructurally, the tumor cells composed of numerous glycogens with scanty cell organelles, reminiscent of clear cell renal cell carcinoma (CCRCC). In conclusion, the coexpression of CA9 and HIF-1α in the absence of VHL gene abnormalities in CCPRCC suggests activation of the HIF pathway by mechanisms independent of VHL gene mutation. Losses of chromosomes 3 (monosomies chromosome 3) was detected in 3 cases suggesting that at least some of these lesions have demonstrated abnormalities of chromosomes 3. Ultrastructurally, CCPRCC composed of numerous glycogens with scanty cell organelles, reminiscent of CCRCC suggesting the close pathogenesis relationship of CCPRCC with CCRCC.     

Pancreatic acinar cell carcinoma with pleomorphic and spindle cells: An autopsy-proven case

Pancreatic acinar cell carcinomas are glandular and have amphophilic/eosinophilic cytoplasm, presenting acinar, solid, and trabecular structures. Unusual histological features of acinar cell carcinoma are known, such as oncocytic, pleomorphic, spindle, and clear cell variants, but their clinical significance has not been well described. A man in his 70s was referred to our hospital because of elevated serum pancreatic enzymes. Contrast-enhanced abdominal computed tomography revealed slight swelling of the pancreatic head and suspension of the main pancreatic duct in the pancreatic body. He died only 14 days after admission. Gross findings at autopsy showed an ill-defined tumor located in the pancreatic head, involving the gastric and duodenal walls. Peritoneal dissemination, liver metastases, and lymph node metastases were also observed. Microscopically, tumor cells had moderate-to-severe nuclear atypia and amphophilic cytoplasm showing pleomorphism, and diffusely proliferated in solid pattern without lumina, were admixed with spindle cells. Immunohistochemically, tumor cells including pleomorphic and spindle cells were positive for B-cell lymphoma/leukemia 10 and trypsin. Consequently, the diagnosis was pancreatic acinar cell carcinoma with pleomorphic and spindle cells. We encountered a rare variant of pancreatic acinar cell carcinoma with pleomorphic and spindle cells. Clinically, our case showed rapid progression.     

Oncocytic renal cell carcinoma having papillotubular growth: rare morphological variant of papillary renal cell carcinoma

Herein is described a unique renal cell tumor with previously unreported morphological and immunohistochemical features. The patient was a 78-year-old Japanese man. A huge left renal tumor was found on ultrasound during evaluation of left abdominal distention. The tumor was macroscopically characterized by a non-infiltrative border, pale yellow to grayish color, foci of hemorrhage and partial edematous change. Histologically the tumor had an extensive small tubular growth pattern often with papillary fronds mainly composed of oncocytic cells with deeply eosinophilic granular cytoplasm. Clear vacuolated cells were scattered among the oncocytic cells. The present case had an unusual immunohistochemical profile for all known types of renal cell tumors, but both the oncocytic cells and the clear vacuolated cells were strongly immunoreactive for α-methylacyl-coenzyme A racemase. It is concluded that the tumor may be a candidate for a rare variant of papillary renal cell carcinoma. Further cases having similar features are awaited for a definitive classification of this tumor as a previously undescribed tumor type.     

Clear cell carcinoma of minor salivary glands

Two cases of carcinoma of the minor salivary glands are presented in which most cells had clear cytoplasm. Both patients had clinical histories in excess of 10 years and, in the one case with adequate follow-up, no recurrence had occurred after a further 11 years. Both tumours were locally invasive. The clear cells contained small amounts of glycogen, but no intracytoplasmic mucin. Immunohistochemical and ultrastructural studies showed epithelial features, with no evidence of myoepithelial differentiation. These tumours were very similar to the small number of previously reported cases, which were all considered to be low-grade carcinomas. Amongst the differential diagnoses, the most important is metastatic clear cell carcinoma of the kidney and this can only be confidently excluded clinically or by the use of imaging techniques. In summary, we consider intraoral clear cell carcinoma to be a distinct tumour of low malignant potential.     

Rare renal tumor--mucinous tubular and spindle cell carcinoma

We report a rare case of renal tumor--mucinous tubular and spindle cell carcinoma in a 65-year-old man. The tumor, located in the right kidney, was well circumscribed. Microscopically, the tumoral proliferation was composed of cuboidal cells arranged in tubules, with abrupt transition to spindle cell morphology in a myxoid stroma. Because of the favorable prognosis with this type of tumor, mucinous tubular and spindle cell carcinoma must be differentiated from papillary renal cell carcinoma, especially the variant with sarcomatoid dedifferentiation.     

肾脏黏液性管状和梭形细胞癌临床病理学观察

目的 探讨肾脏黏液性管状和梭形细胞癌的临床病理学特征、免疫表型及鉴别诊断。方法 应用常规病理、免疫组化方法观察1例肾脏黏液性管状和梭形细胞癌并复习相关文献。结果 肿物与周围肾组织分界清楚，组织学特点是排列呈管状的上皮样细胞，片状的梭形细胞和黏液性间质，无明显核的异型性，缺乏坏死。免疫组化：CK、EMA、vimentin阳性，SMA、desmin、S-100蛋白、HMB45等阴性。结论 肾脏黏液性管状和梭形细胞癌是WHO新确定的一类罕见的低度恶性肾上皮性肿瘤，预后较好，要与后肾腺瘤、肉瘤样癌和集合管癌等疾病相鉴别。     

Clear-cell papillary renal cell carcinoma: 24 cases of a distinct low-grade renal tumour and a comparative genomic hybridization array study of seven cases

Adam J, Couturier J, Molinié V, Vieillefond A & Sibony M
(2011) Histopathology 58, 1064–1071
Clear‐cell papillary renal cell carcinoma: 24 cases of a distinct low‐grade renal tumour and a comparative genomic hybridization array study of seven cases Aims: To report clinicopathological and genomic characteristics of (ccpRCC), a rare, recently characterized renal tumour entity. Methods and results: Twenty‐four renal tumours identified as ccpRCC were collected. Data from comparative genomic hybridization on microarrays (array‐CGH) were obtained for seven of these. Most tumours (58%) occurred in the absence of renal disease. Mean patient age was 58.1 years. Tumours were small (mean size: 2.4 cm) and classified as pT1. Histological characteristics consisted of tubules and papillae lined by a single layer of small clear cells harbouring low‐grade nuclei (Fuhrman grades 1 or 2). Architectural variations, with compact areas (41% of cases) and a micro‐ or macrocystic pattern (67% of cases) were observed frequently. Immunostaining demonstrated diffuse, strong expression of cytokeratin 7 and vimentin, whereas CD10, racemase, RCC antigen, translocation factor E3, TFE3 and translocation factor EB were consistently negative. In seven tumours, array‐CGH detected no chromosomal imbalances. Conclusions: Clear‐cell papillary renal cell carcinoma (ccpRCC) were differentiated from other renal neoplasms by a specific constellation of histopathological and immunohistochemical features, without characteristic genomic imbalances. Clinical, histopathological and genomic data suggested that these tumours have a low potential for malignancy.     

Mucinous tubular and spindle cell carcinoma of kidney is probably a variant of papillary renal cell carcinoma with spindle cell features

Mucinous tubular and spindle cell carcinoma is a rare and newly described type of renal cell carcinoma (RCC) with a relatively indolent behavior. However, its histogenetic origin or line of differentiation remains unclear. Twelve cases of mucinous tubular and spindle cell carcinoma were identified and retrieved from the files of 3 institutions. Detailed morphological features, as well as their immunohistochemical profile established with markers of proximal renal tubules (RCC marker antigen, CD15, and alpha-methylacyl-CoA racemase) and of distal renal tubules (kidney-specific cadherin and cytokeratin 7), were studied. The age range of the patients was 35 to 73 years with a median of 56 years. The male to female ratio was 1:3. All of the patients were alive with follow-up between 4 and 38 months. All the tumors were confined to the kidney with a mean tumor size of 6.9 cm (range, 1.8-17 cm). The tumors were composed of variable proportions of tubular and spindle cell areas with focal to prominent mucinous or myxoid stroma. Foamy macrophages were seen in 10 cases and were prominent in 4 cases. A focal compressed tubulopapillary growth pattern was seen in 10 cases. The tumor cells were uniformly cuboidal with ovoid to round nuclei and inconspicuous nucleoli (Furhman nuclear grade 3 in 6 cases). Focal necrosis was seen in 3 cases. Immunostains showed that tumors were positive for RCC marker antigen (11/12), alpha-methylacyl-CoA racemase (11/12), CD15 (8/12), CD10 (2/12), kidney-specific cadherin (1/12), and cytokeratin 7 (11/12). Its morphological features as well as a strong preferential expression of proximal tubule markers suggest that this tumor is a type of RCC with proximal tubular differentiation, which appears closely related to or represents a morphological variant of papillary RCC.     

Mucinous tubular and spindle-cell carcinoma of the kidney

4 cases (2 males and 2 females) of mucinous tubular and spindle-cell carcinoma of the kidney were studied. The patients' age was 43 to 87 years. Microscopically, this tumor comprised two major cell populations. One of them involved spindle cells with a sparse cytoplasm, which were arranged in the fascicular pattern, often resembling low-grade smooth muscle tumors. The other population was small cuboidal cells with round nuclei and an eosinophilic cytoplasm. The mitotic activity was low. Only one tumor had both cell components. The other three tumors were represented by the second type cells. Immunohistochemical staining with avidin-biotin was performed by using cytokeratin, vimentin, SMA, p53, Bcl 2, EMA, and CD10. All cases were stained positively with antibodies to the cytokeratins AE1-AE2 and vimentin. The expression of EMA, Bcl 2, and CK7 was varying in different tumors. Responses to smooth muscle actin, p53, CK20, and CD10 were negative in all cases. Mucinous tubular and spindle-cell carcinoma of the kidney should be differentiated from angiomyolipoma with the preponderance of a leiomyomatous component, renal smooth muscle neoplasms, metanephrotic adenoma, and renal cell carcinoma with sarcomatoid differentiation.     

Clear cell papillary renal cell carcinoma: a clinicopathologic analysis of 6 cases

Clear cell papillary renal cell carcinoma (CCPRCC) is a newly described variant of renal cell carcinoma (RCC) which is composed mainly of cells with clear cytoplasm arranged in cystic and papillary patterns. We report the clinicopathologic features, prognosis and differential diagnosis of 6 Clear Cell Papillary Renal Cell Carcinomas. The clinical information and follow-up data were analyzed. The patients were six males with median age of 52.5 years. Case 1 revealed dense calcification and ossification. Cases 2 and 3 contain a variably prominent smooth muscle stromal component. CA-IX, CK7, PAX-8 and VIM were positive in all cases. TFE3 and AMACR were not expressed in any tumor. CD10 was negative in 5 of 6 cases .The patients were followed for 13~55 months with no local tumor recurrences and tumor metastasis. The CCPRCC was associated with a more favorable outcome. These were low-grade and low-stage renal tumors. No lymph node or distant metastasis of the six tumors.     

Pigmented microcystic chromophobe renal cell carcinoma

We report a case of a 60-year-old female with a pigmented microcystic chromophobe renal cell carcinoma (PMCRCC). The tumor was 4.5cm in diameter, and was located in the right kidney. Grossly, on cross section, the tumor was light gray with multiple small brown to black pigmented foci up to 0.2cm in diameter. Histologically, the tumor showed a microcystic arrangement with cribriform areas and formation of adenomatous structures. The microcystic and cribriform areas were composed of larger pale cells and smaller eosinophilic cells, with cytological features of conventional chromophobe renal cell carcinoma (CRCC). The cytological features of the cells within the adenomatous structures were different. These cells were mostly columnar with nuclei at the base, and had a variable amount of pale to eosinophilic cytoplasm. There were foci of ample brown pigmentation located in the cytoplasm of the tumor cells and extracellularly. In addition, microscopic calcifications were present. Immunohistochemically, the tumor cells were positive for EMA, E-cadherin, cytokeratin CAM5.2, and cytokeratin AE1/AE3. Cytokeratin 7 was positive only focally. S-100 protein, melan A, HMB 45, vimentin, and CD117 were negative. PMCRCC is a rare tumor. To the best of our knowledge, only one series containing 20 cases of this variant of CRCC has been described to date. The important feature is that PMCRCC seems to have a relatively benign biological behavior, and distant metastases and sarcomatoid transformation are absent.     

Targeted next‐generation sequencing and non‐coding RNA expression analysis of clear cell papillary renal cell carcinoma suggests distinct pathological mechanisms from other renal tumour subtypes

Clear cell tubulopapillary renal cell carcinoma (CCPRCC) is a recently described rare renal malignancy that displays characteristic gross, microscopic and immunohistochemical differences from other renal tumour types. However, CCPRCC remains a very poorly understood entity. We therefore sought to elucidate some of the molecular mechanisms involved in this neoplasm by carrying out targeted next‐generation sequencing (NGS) to identify associated mutations, and in addition examined the expression of non‐coding (nc) RNAs. We identified multiple somatic mutations in CCPRCC cases, including a recurrent [3/14 cases (21%)] non‐synonymous T992I mutation in the MET proto‐oncogene, a gene associated with epithelial‐to‐mesenchymal transition (EMT). Using a microarray approach, we found that the expression of mature (n = 1105) and pre‐miRNAs (n = 1105), as well as snoRNA and scaRNAs (n = 2214), in CCPRCC cases differed from that of clear cell renal cell carcinoma (CCRCC) or papillary renal cell carcinoma (PRCC) tumours. Surprisingly, and unlike other renal tumour subtypes, we found that all five members of the miR‐200 family were over‐expressed in CCPRCC cases. As these miRNAs are intimately involved with EMT, we stained CCPRCC cases for E‐cadherin, vimentin and β‐catenin and found that the tumour cells of all cases were positive for all three markers, a combination rarely reported in other renal tumours that could have diagnostic implications. Taken together with the mutational analysis, these data suggest that EMT in CCPRCC tumour cells is incomplete or blocked, consistent with the indolent clinical course typical of this malignancy. In summary, as well as describing a novel pathological mechanism in renal carcinomas, this study adds to the mounting evidence that CCPRCC should be formally considered a distinct entity. Microarray data have been deposited in the GEO database [GEO accession number (GSE51554)]. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.