Differentiation of oncocytoma from chromophobe renal cell carcinoma (RCC): can novel molecular biomarkers help solve an old problem?

Abstract

Standard treatment of renal neoplasms remains surgical resection, and nephrectomy for localised renal cell carcinoma (RCC) still has the best chance of cure with excellent long-term results. For smaller renal masses, especially stage T1a tumours less than 4 cm, nephron-sparing surgery is often employed. However, small incidentally detected renal masses pose an important diagnostic dilemma as a proportion of them may be benign and could be managed conservatively. Renal oncocytoma is one such lesion that may pose little risk to a patient if managed with routine surveillance rather than surgery. Additionally, lower-risk RCC, such as small chromophobe RCC, may be managed in a similar way, although with more caution than the renal oncocytomas (RO). The ability to differentiate ROs from chromophobe RCCs, and from other RCCs with a greater chance of metastasis, would guide the physician and patient towards the most appropriate management, whether nephron-sparing surgical resection or conservative surveillance. Consistent accurate diagnosis of ROs is likely to remain elusive until modern molecular biomarkers are identified and applied routinely. This review focuses on the differentiation of renal oncocytomas and chromophobe RCCs. It summarises the history, epidemiology and clinical presentation of the renal neoplasms, explains the diagnostic dilemma, and describes the value, or not, of current molecular markers that are in development to assist in diagnosis of the renal neoplasms.

Characteristics of the Peritumoral Pseudocapsule Vary Predictably With Histologic Subtype of T1 Renal Neoplasms

“…As has been well established, these tumor subtypes are two distinct but potentially related entities with some evidence for a similar line of differentiation. Some, but not all tumors, exhibit overlap in morphology 26,27 . Overlap in PC behavior may be due to similar histogenesis.…”

Diagnostic criteria for oncocytic renal neoplasms: a survey of urologic pathologists

“…Surprisingly, the existing literature on this antibody demonstrates disparate results, with some studies reporting consistent positivity in oncocytoma and others reporting negative, or largely negative, results. [6] We suspect that this reflects threshold selection, as the vast majority of the tumor cells in oncocytoma are negative, with scattered positivity only in single cells and small clusters of cells. [15] If a binary reporting system is used, this could be interpreted as Table 1), although there was not agreement on an amount of positivity that excluded oncocytoma.…”

“…[5] For the classic appearance of chromophobe renal cell carcinoma, there is little similarity to oncocytoma; however, it is well known that the eosinophilic variant [3] may cause a diagnostic challenge in distinguishing it from oncocytoma. Despite the fact that numerous techniques for differentiating these two tumor histologies have been explored over the years, including histochemical stains, immunohistochemistry, chromosomal changes, molecular assays, and electron microscopy, [6] it remains unknown if uniform diagnostic criteria are used by urologic pathologists in practice.…”

Renal Mass Biopsy in the Era of Surgical Alternatives

“…Vimentin is typically negative in oncocytomas and in chromophobe RCCs, but positive in ccRCCs. CK7 is usually positive in chromophobe RCC and negative in oncocytomas and clear cell RCC [44]. However, none of the histologic markers, or combinations of them, is universally accurate in diagnosing oncocytomas.…”