Molecular pathology of chromophobe renal cell carcinoma: A review

Abstract

Abstract: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.Key words: chromophobe renal cell carcinoma, diagnosis, electron microscopy, histology, molecular markers. Prehistory and epidemiologyBased on its morphological and electron-microscopic characteristics, chromophobe renal cell carcinoma (RCC) was delineated among experimental kidney tumors nitrosomorpholine-induced in rats.1 In 1985, Thoenes et al. described the first human renal carcinomas as an analogy to the cases in rodents showing similar morphology.2 They noticed a 4.6% incidence of the chromophobe variant in a series of 697 renal cell carcinoma cases. Initially, diagnosis of chromophobe RCC appeared to be straightforward as a result of its characteristic light microscopic features. The same authors 3 years later described an eosinophilic variant of chromophobe RCC, which can easily be confused with renal oncocytoma or "eosinophilic" clear cell carcinoma based on morphological characteristics.3 The latter discovery is also related to its close phenotypic similarity to "eosinophilic" clear cell carcinoma on the one hand and to oncocytoma on the other hand. Presently, chromophobe RCC is considered to account for approximately 5% of all cases of renal cell carcinoma. The mean age of incidence with chromophobe RCC in a series of 104 patients reported by Cindolo et al. 4 was in the sixth decade (58 years), with a range in age of 27-86 years, and the number of men and women was roughly equal. Mortality was less than 10%.

Clinicians’ Real World Perceptions of Pre-Nephrectomy Diagnostic Biopsy Performance as a Driver of Reduction in Unnecessary Surgeries in Renal Tumors

“…Preoperative biopsy of kidney tumors is not widely employed (6–9) with only about 10% of all nephrectomies preceded by a diagnostic biopsy. This problem is longstanding, and despite several academic center based studies suggesting adequate histopathological resolution is possible in this setting (25–27), diagnostic uncertainty in the differentiation of benign RO from malignant chRCC (9,10) and in additional cases even with eosinophilic clear-cell RCCs (ccRCC) remains a clear contributing factor to low rates of biopsy in routine practice. Recent reviews by Ng et al (8) and Yusenko (9,10) both concluded that there was no reliable diagnostic marker or IHC algorithm suitable for reliable differential diagnosis of renal tumors.…”

“…This problem is longstanding, and despite several academic center based studies suggesting adequate histopathological resolution is possible in this setting (25–27), diagnostic uncertainty in the differentiation of benign RO from malignant chRCC (9,10) and in additional cases even with eosinophilic clear-cell RCCs (ccRCC) remains a clear contributing factor to low rates of biopsy in routine practice. Recent reviews by Ng et al (8) and Yusenko (9,10) both concluded that there was no reliable diagnostic marker or IHC algorithm suitable for reliable differential diagnosis of renal tumors. Ng et al (8) concluded as had Liu and Fanning (26), that there is a group of renal tumors, notably ROs and small chRCCs, where increased confidence in diagnosis would defer or totally eliminate the need for surgical intervention.…”

“…This is attributed at least in part to the fact that less than 10% of patients undergo a pre-operative diagnostic biopsy prior to having a nephrectomy for a presumed renal cancer (6). These low rates of pre-operative biopsy are largely attributed to less than desirable diagnostic accuracy by histology and immunohistochemistry in this setting (9, 10). …”

Non–Clear Cell Renal Cell Carcinoma: How New Biological Insight May Lead to New Therapeutic Modalities

“…Oncocytoma and chRCC are different tumors with different genomic profiles [42,43]. CD82/KAI1 is a marker for distinguishing chRCCs from other types of renal cell tumors, especially from renal oncocytomas with an overlapping phenotype [44].…”

Chromophobe renal cell carcinoma: analysis of 53 cases

“…CRCC has its own histological, immunohistochemical, and cytogenetic characteristics (Yusenko 2010). By light microscopy, the tumor cells have a compact growth pattern and the cytoplasm stains lightly with hematoxylin and eosin staining.…”