Types Of Renal Tumors Research Articles

Ancillary Diagnostic Techniques in the Evaluation of Adult Epithelial Renal Neoplasms

The role played currently by the different ancillary diagnostic techniques in the diagnosis of adult epithelial renal tumors continues to be debated. It has also become clear that in some instances light microscopic appearance alone cannot be used to classify these neoplasms into specific categories with the degree of precision required for therapeutic purposes. Renal cell carcinoma (RCC) subtypes may share common histologic characteristics but exhibit different biological behavior and response to therapy which clearly indicates the crucial role that advanced pathologic speciation plays in the current assessment of these neoplasms. Although immunohistochemistry is widely used for the purpose of categorizing renal tumors because of its widespread availability, the immunoprofiles of the various types of renal neoplasms overlap significantly, making definitive diagnostic determinations difficult and challenging at times. This manuscript will address how ancillary diagnostic techniques can be incorporated into the routine evaluation of neoplastic renal masses to improve classification. Both cytology and surgical specimens will be addressed, as fine needle aspiration (FNA) is being used with preference in many cases in the diagnosis of renal masses. Surgical and cytopathologists must intelligently select the ancillary diagnostic technique/s that will provide the information needed to solve the differential diagnosis under consideration in a given case. However, in some cases >1 of these techniques should be used to make an accurate diagnosis with the aim of arriving at an unequivocal diagnosis. The identification of specific signaling pathways that are defective in certain types of renal neoplasms has made possible the design of target-specific therapies that are directed towards the aberrant pathways associated with the defective proteins found in these tumors. This makes the exact classification of these neoplasms and the detection of these aberrant proteins targeted for treatment an absolute requirement for the application of these molecular-based therapeutic interventions. The role that the pathologic assessment plays in the classification of renal tumors becomes more important than ever to take advantage of this and similar new molecular-oriented therapies.

Stage I clear cell sarcoma of the kidney: is it the time for a less intensive adjuvant treatment?

Clear cell sarcoma of the kidney (CCSK) is a rare type of renal tumor, comprising 2% to 5% of all primary renal tumors in children. Despite the label of "unfavorable" tumor, with recent multimodality treatment schedules, including radiotherapy and multi-agent chemotherapy, disease free survival rates approaching 80% can be achieved. Younger age at tumor diagnosis and advanced-stage disease represent adverse prognostic factors. Of note, as a consequence of oncologic therapies a number of surviving patients have suffered from late sequelae on the musculoskeletal, gastrointestinal, hepatic, endocrine and cardiovascular function, or developed second tumors. Improved survival rates and a deeper knowledge of iatrogenic complications have promoted the awareness of a sequential reduction of treatment intensity, at least for low-stage CCSK, above all focusing on the abolition of flank radiation therapy (RT). It is fundamental to recognize that the rarity of this tumor calls for international cooperation trough controlled clinical trials, and without forgetting the key importance of a correct histological diagnosis and adequate surgical staging. The recent recognition of CCSK specific chromosomal translocation might help to guide targeted therapies complementary to conventional chemotherapy and radiotherapy.

New and emerging renal tumors

The International Society of Urological Pathology (ISUP) 2012 Consensus Conference on Adult Renal Neoplasia made recommendations regarding the diagnosis and classification of new and emerging adult renal tumors. There was consensus that five entities should be recognized as new histological types: tubulocystic renal cell carcinoma (RCC), acquired cystic disease-associated RCC, clear cell (tubule) papillary RCC, MiT family translocation RCC [in particular t(6;11) RCC] and hereditary leiomyomatosis-associated RCC. In addition, three rare epithelial carcinomas were considered emerging or provisional entities: thyroid-like follicular RCC; succinate dehydrogenase B deficiency-associated RCC; and ALK-translocation RCC. There were also a number of suggested modifications to existing WHO 2004 categories with the new classification. This new classification of renal neoplasia is known as the ISUP Vancouver Classification. These new renal tumor types have clinicopathological and molecular features that are distinct from those included in 2004 WHO classification. Correct diagnosis and classification of these new renal tumor entities have important implications for patient management.

Utility of apparent diffusion coefficients in the evaluation of solid renal tumors at 3T.

We assessed the usefulness of apparent diffusion coefficients (ADCs) for solid renal tumor imaging using diffusion-weighted magnetic resonance imaging (DWI) at 3T. This retrospective study assessed ADCs of 31 patients with renal tumors that were imaged using preoperative DWI. DWI was performed with the b values of 50, 500, and 1000 s/mm(2), using a 3T magnetic resonance imaging (MRI) system (MAGNETOM Trio, 3T, Siemens Healthcare, Erlangen, Germany). The ADC map was calculated using the b values of 50 and 1000 s/mm(2). ADCs of the different tumors were compared according to the Tukey-Kramer test. The tumors were diagnosed as clear cell renal cell carcinoma (RCC; n = 20), papillary RCC (n = 1), infiltrating urothelial carcinoma (UC) of the kidney (n = 4), cystic RCC (n = 1), poorly differentiated carcinoma (n = 1), and angiomyolipoma (AML; n = 4). The mean ADC of clear cell RCC was significantly higher than that of infiltrating UC of the kidney (1.423 vs. 0.931 × 10(-3) mm(2)/s; P < 0.05), and the mean ADC of AML was significantly lower than that of clear cell RCC (0.674 vs. 1.423 × 10(-3) mm(2)/s; P < 0.01). ADCs used in DWI at 3T may be useful for differentiation of different types of solid renal tumors.

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)].

Genome-Wide Promoter Methylome of Small Renal Masses

The majority of renal cell carcinoma (RCC) is now incidentally detected and presents as small renal masses (SRMs) defined as ≤4 cm in size. SRMs are heterogeneous comprising several histological types of RCC each with different biology and behavior, and benign tumors mainly oncocytoma. The varied prognosis of the different types of renal tumor has implications for management options. A key epigenetic alteration involved in the initiation and progression of cancer is aberrant methylation in the promoter region of a gene. The hypermethylation is associated with transcriptional repression and is an important mechanism of inactivation of tumor suppressor genes in neoplastic cells. We have determined the genome-wide promoter methylation profiles of 47 pT1a and 2 pT1b clear cell, papillary or chromophobe RCC, 25 benign renal oncocytoma ≤4 cm and 4 normal renal parenchyma specimens by Infinium HumanMethylation27 beadchip technology. We identify gene promoter hypermethylation signatures that distinguish clear cell and papillary from each other, from chromophobe and oncocytoma, and from normal renal cells. Pairwise comparisons revealed genes aberrantly hypermethylated in a tumor type but unmethylated in normal, and often unmethylated in the other renal tumor types. About 0.4% to 1.7% of genes comprised the promoter methylome in SRMs. The Infinium methylation score for representative genes was verified by gold standard technologies. The genes identified as differentially methylated implicate pathways involved in metabolism, tissue response to injury, epithelial to mesenchymal transition (EMT), signal transduction and G-protein coupled receptors (GPCRs), cancer, and stem cell regulation in the biology of RCC. Our findings contribute towards an improved understanding of the development of RCC, the different biology and behavior of histological types, and discovery of molecular subtypes. The differential methylation signatures may have utility in early detection and particularly differential diagnosis for prognostic stratification as well as identify novel gene and pathway targets for therapeutic intervention.

Expression of carbonic anhydrase IX, PAX2 and PAX8 and their association with clinicopathologic characteristics in renal epithelial tumors

To study the expression of carbonic anhydrase IX (CAIX), PAX2 and PAX8 in different types of renal epithelial tumor and their association with clinicopathologic characteristics. Immunohistochemical study by EnVision method was performed in order to assess the expression of CAIX, PAX2 and PAX8 in 155 cases of renal cell carcinoma and 4 cases of metastatic clear cell renal cell carcinoma (CCRCC). Ninety-six cases of non-neoplastic renal parenchymal tissue adjacent to CCRCC, 8 cases of clear cell hepatocellular carcinoma and 2 cases of clear cell hidradenoma were used as controls. CAIX was commonly expressed in CCRCC (94.0%, 63/67), of which 77.8% (49/63) showed strong positivity. CAIX was focally positive in papillary renal cell carcinoma, collecting duct carcinoma and urothelial carcinoma of renal pelvis. It was negative in chromophobe renal cell carcinoma, oncocytoma and adjacent non-neoplastic renal tissue. CAIX was also strongly expressed in the 4 cases of metastatic CCRCC. Focal expression of CAIX was demonstrated in the 8 cases of clear cell hepatocellular carcinoma and 2 cases of clear cell hidradenoma. The expression of CAIX in CCRCC did not correlate with tumor grading, clinical staging and presence of distal metastasis. On the other hand, PAX2 showed positive expression in different types of renal epithelial tumor, clear cell hepatocellular carcinoma and clear cell hidradenoma in various degrees. In contrast, PAX8 was commonly expressed in all types of renal epithelial tumor, with the exception of urothelial carcinoma of renal pelvis. PAX8 was not expressed in clear cell hepatocellular carcinoma and clear cell hidradenoma. Regarding diagnosis of CCRCC, CAIX demonstrated high sensitivity and specificity. PAX2 showed high specificity but low sensitivity. PAX8 was sensitive and specific in the diagnosis of renal epithelial tumor. CAIX is a useful immunohistochemical marker with high specificity and sensitivity in distinguishing CCRCC from other types of renal epithelial tumor and clear cell tumors of non-renal origin. PAX2 is a marker with high sensitivity and low specificity for diagnosis of renal epithelial tumors. PAX8 is typically expressed in renal epithelial tumors. The combined detection of CAIX, PAX2 and PAX8 is useful in the diagnosis and differential diagnosis of renal epithelial tumors.

CD133 Staining Detects Acute Kidney Injury and Differentiates Clear Cell Papillary Renal Cell Carcinoma from Other Renal Tumors

CD133 has recently been characterized as a progenitor cell marker in the kidney. However, the expression of this marker has not been thoroughly investigated in kidney injury and variants of renal tumors for pathology practice. We quantified CD133 expression in kidney biopsies from patients with acute renal failure and compared staining intensity with serum creatinine levels. CD133 expression levels were also evaluated in several subtypes of renal neoplasms. Normal adult renal parenchyma showed CD133 expression in parietal epithelium and in less than 5% of the epithelial cells in proximal and distal nephron tubules. However, CD133 was diffusely upregulated in the injured proximal and distal tubular epithelium and the CD133 expression scores in renal tubules were significantly correlated with serum creatinine levels. Amongst the renal tumors, CD133 was diffusely expressed in clear cell papillary renal cell carcinoma but was only focally present in other types of renal tumors. In summary, CD133 is a useful marker to detect renal tubular injury and to differentiate clear cell papillary renal cell carcinoma from other tumor types.

Abstract LB-107: Mitochondrial DNA mutations are diagnostic markers of renal oncocytomas.

Abstract Oncocytomas are mostly benign tumors of epithelial origin, characterized by dense accumulation of defective mitochondria. To date, no nuclear gene has been found to be responsible for these tumors, but a correlation of the oncocytic phenotype with the occurrence of disruptive mitochondrial DNA (mtDNA) mutations, mostly affecting genes encoding for proteins of Complex I of the respiratory chain (NADH dehydrogenase), has been shown in sporadic oncocytomas of different organs, including renal oncocytomas (RO). Kidney cancer is made up of a number of tumors that present with a different histology and clinical course. They are caused by different genes, and therefore therapy needs to be adapted for each type of renal tumor. Imaging techniques are usually not sufficient to distinguish between benign and malignant forms of renal cell cancer (RCC). In addition, it is difficult to differentiate benign ROs from malignant forms of RCCs in samples from biopsies, because they share ultrastructural appearances, including abnormal mitochondria with altered cristae. Therefore, a reliable diagnostic tool would be invaluable to guide clinicians in the management of patients with RCC of unclear phenotype. In our current work we tested whether mtDNA mutations can be used as diagnostic tools to distinguish between benign ROs and more aggressive forms of RCC. We sequenced the entire mtDNA in 36 samples that included sporadic, bilateral and multifocal as well as familial ROs and 30 non-oncocytic RCCs of different histologies. Moreover, the mitochondrial copy number was determined in all samples by real-time PCR. Furthermore, we sequenced the mtDNA from biopsies and compared it to the mtDNA sequence of the resected tumor. We found a strong correlation between the presence of disruptive mtDNA mutations affecting complex I genes and the oncocytic phenotype in renal tumors. Additionally, oncocytomas showed significantly higher mtDNA copy number when compared to other RCCs. We also show that the mtDNA sequences from the biopsies correspond to the sequence of the tumor itself and are predictive of the phenotype. Hence, we propose that sequencing of the mitochondrial genome, supported by the analysis of the mtDNA copy number, may be used as a diagnostic tool to distinguish between benign and aggressive forms of RCCs to guide physicians in choosing the appropriate treatment for patients. Citation Format: Martin Lang, Cathy D. Vocke, Maria J. Merino, Laura S. Schmidt, Marston W. Linehan. Mitochondrial DNA mutations are diagnostic markers of renal oncocytomas. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-107. doi:10.1158/1538-7445.AM2013-LB-107

Pure malignant rhabdoid tumor of the left kidney in an adult: A case report and review of the literature

Malignant rhabdoid tumors of the kidney (MRTKs) are extremely rare. Pure MRTKs in adult patients are particularly rare and have not been previously reported in China. Due to the non-specific clinical symptoms, it is difficult but also essential to be able to give a definite diagnosis. The present study reports a case of pure adult malignant rhabdoid tumor in a patient’s left kidney with characteristic clinicopathological features. Considering the fact that the characteristic findings are often not observed in clinical symptom and imaging studies, the histological features, immunohistochemical staining and cytogenetic studies may aid in confirming the diagnosis of pure MRTKs. Although pure adult MRTKs remain extremely uncommon, it is necessary to consider this possibility when such types of renal tumors are encountered.

Composite tumor of metanephric adenoma and Wilms’ tumor of the kidney: A case report and review of the literature

Metanephric adenoma (MA) and Wilms’ tumor (WT) are two distinct types of renal tumors. Composite MA and WT of the kidney are extremely rare. Here, a rare case of composite MA and WT of the kidney in a 36-year-old male is described. MA and WT each have their own histopathological features, respectively, and they focally share morphological similarities, which can be a diagnostic challenge. Immunohistochemistry is useful in the differential diagnosis of MA and WT. The histopathological features and differential diagnosis of the composite tumor are emphasized here to promote a better and broader understanding of this less understood subject.

Review of tubulocystic carcinoma of the kidney with focus on clinical and pathobiological aspects

Tubulocystic carcinoma of the kidney (TCK) is a recently established entity in renal neoplastic pathology. This review aims to give an overview of the clinical and pathobiological aspects of TCK. Grossly, the TCKs are well-demarcated multicystic lesions giving a "wrapped bubble" or "spongy" appearance. Microscopically, the tumors are composed of multiple, variably sized cysts separated by thin fibrous septa lacking ovarian stroma or desmoplastic reaction. The cysts are lined by tumor cells with eosinophilic cytoplasm and nuclear atypia of variable, but not infrequently of high grade corresponding to Fuhrman grade 3. A frequent association with papillary tumors has been reported. Recent molecular genetic studies of TCK have revealed distinct features separating this subset of renal cell carcinomas (RCCs) from other types of renal tumors including collecting duct carcinoma of Bellini and renal medullary carcinoma as well as pointing towards a close kinship with papillary RCC. Tubulocystic carcinoma of the kidney generally pursues an indolent clinical course. However, several cases with aggressive clinical behavior have been reported. We strongly feel that there is enough clinicopathological evidence to corroborate TCK as a separate entity and that it should be incorporated into the next WHO classification of renal tumors as a separate neoplastic category.

Clear cell sarcoma of the kidney: A review

Clear cell sarcoma of the kidney (CCSK) is a rare renal tumour that is observed most often in children under 3years of age. Only a few large series of CCSK have been reported and patients with CCSK are often included among patients with other types of childhood renal tumours. The purpose of this paper is to review the published series and case reports of CCSK and to create an up-to-date overview of clinical and histological features, genetics, treatment, and outcome.

Distinct Cytoplasmic Expression of KL-6 Mucin in Chromophobe Renal Cell Carcinoma: A Comparative Immunohistochemical Study with Other Renal Epithelial Cell Tumors

The presence of cytoplasmic sialyl glycoproteins is a conspicuous feature in chromophobe renal cell carcinoma (RCC). We compared the immunohistochemical expression of sialyl glycoproteins in chromophobe RCC with that in other types of renal tumors. Formalin-fixed, paraffin-embedded tissues of surgically resected renal tumors (chromophobe RCC, 14 cases [10 cases of classic type and 4 cases of eosinophilic variant]; oncocytoma, 7 cases; and clear cell RCC, 9 cases) and kidneys from immature infants (4 cases) were immunostained with antibodies against sialyl glycoproteins (anti-KL-6 and anti-sialyl MUC1 antibodies). Cytoplasmic expression of KL-6 and sialyl MUC1 was distinctive in the chromophobe RCC and renal oncocytoma cells, and in the intercalated cells in collecting duct epithelia. Apical-surface staining of these sialyl glycoproteins was predominantly observed in clear RCC, in the epithelia of the distal tubule and collecting duct, and in the neonatal renal proximal tubule, but not in those of the adult renal proximal tubule. The above-mentioned observations provide additional evidence for similar phenotypic profiles of chromophobe RCC and renal oncocytoma, and the intercalated cells in collecting ducts and the oncofetal expression of sialyl glycoproteins in clear cell RCC. KL-6 is a potential tumor marker for renal tumors.

Renal Tumors Associated With Germline SDHB Mutation Show Distinctive Morphology

Germline succinate dehydrogenase B (SDHB) mutation causes pheochromocytoma/paraganglioma syndrome type 4 (PGL4). PGL4 is characterized by pheochromocytoma and paraganglioma, type 2 (SDHB negative) gastrointestinal stromal tumors and renal tumors, which are usually classified as carcinoma. We report 4 kindreds with 5 PGL4-associated renal tumors. Four of the tumors occurred before the age of 30 years, 4 were in the left kidney, 3 were in female patients, and 4 demonstrated consistent but previously unrecognized morphology. The tumors were composed of cuboidal cells with bubbly eosinophilic cytoplasm and indistinct cell borders. Many of the cells displayed distinctive cytoplasmic inclusions, which were vacuolated or contained eosinophilic fluid-like material. The cells were arranged in solid nests or in tubules surrounding central spaces. The tumors were well circumscribed or lobulated and frequently showed cystic change. Benign tubules or glomeruli were often entrapped at the edges of the tumors. The fifth tumor lacked these features but displayed sarcomatoid dedifferentiation. Immunohistochemistry for SDHB was completely negative in all 4 available tumors. Death from metastatic disease occurred in the patient with dedifferentiated tumor 1 year after diagnosis, whereas the other 4 tumors were cured by local excision alone (mean follow-up, 11 y; range, 2 to 30 y). We conclude that morphology supported by negative immunohistochemistry for SDHB can be used to identify kindreds with germline SDHB mutations (PGL4 syndrome) presenting with this unique type of renal tumor. These renal tumors appear to have a good prognosis after complete excision unless there is sarcomatoid dedifferentiation.

Re-evaluation of histological type by immunohistochemical and genetic study of transcription factors (TFE3 and TFEB) of VHL gene mutation-negative clear cell renal cell carcinoma and other special types of renal tumor

Translocation-type renal carcinoma has been recently discovered, and it is possible that this tumor may have been previously diagnosed as other types of renal tumor. We have subjected 41 renal tumors, including VHL gene mutation-negative clear cell renal cell carcinoma (RCC), papillary RCC, and chromophobe RCC, to immunohistochemistry of transcription factor E3 (TFE3) and TFEB. All tumors were histologically evaluated by additional immunohistochemical study. As a result, 5 tumors showed a positive reaction for TFE3 with a range from 1+ to 2+ in intensity. No tumors were positive for TFEB. In 5 tumors immunohistochemically positive for TFE3, chimeric transcripts including ASPL-TFE3, PRCC-TFE3, CLTCTFE3, PSF-TFE3, or Nono-TFE3 were not detected. The diagnosis of 6 tumors was changed by reevaluation through retrospective histological and immunohistochemical study. In 4 of 6 tumors, the diagnosis of clear cell RCC was changed to chromophobe RCC. In 1 tumor, oncocytoma was detectable, and RCC with rhabdoid features and sarcomatoid changes was detected in 1 tumor. Finally, the cutoff value of TFE3 immunohistochemistry should be more than 2+ with a wide range. The translocation-type renal carcinoma seems to be quite rare.

Primary Ewing’s Sarcoma of the Kidney in a 73-Year-Old Man

Objective. Ewing's sarcoma of the kidney is rare and is usually found in young adults. We present here a single case study of Ewing's sarcoma found in an elderly man. Material and methods. A 73-year-old man underwent routine surgery for hydrocoele of the testis. He developed urinary obstruction symptoms, and radiological examinations revealed a tumour in the right kidney. Results. Microscopical, immunohistochemical, and molecular pathological analysis of the tumour was consistent with Ewing's sarcoma. FISH showed rearrangement of chromosomes 22q12 (EWSR1). The patient subsequently underwent nephrectomy followed by 6 adjuvant chemotherapy cycles. Follow-up after 7 months shows no recurrence. Conclusion. This case report presents not only the rare finding of Ewing's sarcoma in the kidney, but also the occurrence of this tumour entity in an elderly patient. Treatment options for the different types of renal tumours are vastly different and the need for a correct diagnosis is, therefore, vital.

Carbonic Anhydrase IX Expression in Renal Neoplasms

Carbonic anhydrase IX (CAIX), a hypoxia-induced protein, is expressed in some renal tumors. We evaluated its immunohistochemical expression in 317 primary and 42 metastatic renal neoplasms (186 clear cell, 52 papillary, 35 chromophobe, 47 unclassified, and 15 Xp11.2 translocation renal cell carcinomas [RCCs]; 26 oncocytomas; 2 metanephric adenomas; 1 urothelial carcinoma; 1 mixed epithelial and stromal tumor; and 1 angiomyolipoma); 7 neoplasms were unknown as to whether they were primary or metastatic. We also correlated expression with tumor type and grade. Variable staining was seen in clear cell, papillary, unclassified, and Xp11.2 translocation carcinomas. One chromophobe carcinoma had focal expression. No staining was seen with other tumors. An association was found between high expression and clear cell vs non-clear cell carcinomas with all cases (P < .01) and primary (P < .01) cases. An association between CAIX expression and grade (P < .01) in primary clear cell carcinomas was found. CAIX expression is more common in clear cell RCC than other renal tumor types and is associated with grade.

Non-clear cell renal carcinoma: comparative analysis of the new and old histological classification in 79 cases

To compare the old classification and 2004 WHO histological classification of renal cell carcinoma, summarize the differences and possible reasons, and correct the traditional pathological concepts of kidney cancer. Specimens of 79 cases histopathologically diagnosed as non-clear cell renal cell carcinomas after radical nephrectomy during 1998 to 2005 in Tianjin Medical University Cancer Hospital were reclassified according to the 2004 WHO renal cell carcinoma histological classification system. After reclassification, there were 14 cases of clear cell renal cell carcinoma (CCRCC), 23 cases of papillary renal cell carcinoma (PRCC), 34 cases of chromophobe renal cell carcinoma (ChRCC), one collecting duct renal cell carcinoma, one unclassified renal cell carcinoma, 5 cases of mixed cell renal cell carcinoma (CCRCC + PRCC 2 cases, CCRCC + ChRCC 2 cases, PRCC + ChRCC 1 case), and one oncocytoma diagnosed. Some chromophobe renal cell carcinomas and papillary renal cell carcinomas were easier to be diagnosed as granular cell renal cell carcinoma in the past. The eosinophilic cytoplasm similar to that in the granular cells, and some confusion between PRCC and ChRCC are the main reasons. The cellular characteristic features of granular renal cell carcinoma can be found in many types of renal tumors. Granular cell renal cell carcinoma is not an independent entity, therefore, it should be removed from the histological classification of renal cell carcinoma. The diagnosis standard of mixed renal cell carcinoma (MRCC) need to be determined and consummated.

Molecular pathology of chromophobe renal cell carcinoma: A review

The recognition of chromophobe renal cell carcinoma (RCC) among other distinct types of renal cell tumors (RCT) based on light-microscopic features, such as cytoplasmic and nuclear characteristics, might pose a dilemma in some cases because of morphological pattern overlapping with renal oncocytoma or conventional RCC. The present article reviews chromophobe RCC with focus on aspects of its molecular pathology, which was shown using ancillary modern microarray-based technology that can distinguish it from its mimics and therefore be helpful for its correct diagnosis. Although the high resolution DNA-microarray analyses excluded with all certainty the occurrence of small specific alterations, the loss of entire chromosomes 2, 10, 13, 17 and 21 occurs exclusively in chromophobe RCC and therefore probes localized at these chromosomes might be used to establish the diagnosis of chromophobe RCC in cases with uncertain histology. The usefulness of proposed candidate genes selected by the global gene expression analyses in the diagnostic pathology is far below expectations. The conflicting staining patterns, together with the poor specificity of used antibodies, leads us to believe that these candidate immunomarkers might not help in the separation of chromophobe RCC, with the exception of CD82, which has recently been suggested to be used for routine histological diagnosis.