Renal tumors: diagnostic and prognostic biomarkers

Abstract

The International Society of Urological Pathology convened a consensus conference on renal cancer, preceded by an online survey, to address issues relating to the diagnosis and reporting of renal neoplasia. In this report, the role of biomarkers in the diagnosis and assessment of prognosis of renal tumors is addressed. In particular we focused upon the use of immunohistochemical markers and the approach to specific differential diagnostic scenarios. We enquired whether cytogenetic and molecular tools were applied in practice and asked for views on the perceived prognostic role of biomarkers. Both the survey and conference voting results demonstrated a high degree of consensus in participants' responses regarding prognostic/predictive markers and molecular techniques, whereas it was apparent that biomarkers for these purposes remained outside the diagnostic realm pending clinical validation. Although no individual antibody or panel of antibodies reached consensus for classifying renal tumors, or for confirming renal metastatic disease, it was noted from the online survey that 87% of respondents used immunohistochemistry to subtype renal tumors sometimes or occasionally, and a majority (87%) used immunohistochemical markers (Pax 2 or Pax 8, renal cell carcinoma [RCC] marker, panel of pan-CK, CK7, vimentin, and CD10) in confirming the diagnosis of metastatic RCC. There was consensus that immunohistochemistry should be used for histologic subtyping and applied before reaching a diagnosis of unclassified RCC. At the conference, there was consensus that TFE3 and TFEB analysis ought to be requested when RCC was diagnosed in a young patient or when histologic appearances were suggestive of the translocation subtype; whereas Pax 2 and/or Pax 8 were considered to be the most useful markers in the diagnosis of a renal primary.

FIGURE 1

CAIX immunohistochemistry in RCC. A, Circumferential membrane staining of tumor cells in a clear cell RCC. B, Basolateral delineation of clear cell papillary renal carcinoma cells, with sparing of the apical surfaces.

FIGURE 2

Needle aspiration of a retroperitoneal mass in a man with a history of RCC and pancreatic neuroendocrine tumor. A, Low magnification of the cell block preparation shows groups of eosinophilic tumor cells. B, Higher magnification shows variably sized vesicular nuclei with distinct nucleoli and ample pink cytoplasm. C, Immunohistochemical analysis with RCC marker shows a few cells with cytoplasmic membrane reactivity. D, Pax 8 immunohistochemistry reveals distinct nuclear reactivity confirming a primary renal origin of the retroperitoneal recurrence.

FIGURE 3

A, Needle biopsy of an adrenal mass with alveolar nests of clear cells. Immunohistochemical analysis shows diffuse reactivity of the cells for CD10 (B) and Pax 2 (C).

FIGURE 4

A, Nephrectomy specimen from a woman with a history of breast cancer, containing a hemorrhagic friable tumor mass extending from one renal pole along the subcapsular renal cortex to the opposite renal pole. B, Light microscopy of the tumor in the kidney reveals anastomosing trabeculae and tubules. C, ER immunohistochemistry shows diffuse nuclear reactivity. D, Light microscopy from the original primary breast carcinoma shows fused tubular and cribriform structures.

FIGURE 5

A 69-year-old man, with a history of renal cancer 11 years ago, presented with a 1cm right lung nodule, which was investigated with fine-needle aspiration under computed tomography guidance. A, Cell block preparation shows tumor cells with pink cytoplasm. B, Higher magnification of tumor cells with pink cytoplasm and nuclei that are vesicular and hyperchromatic. C, Immunohistochemical analysis with RCC marker shows strong cytoplasmic reactivity. D, Pax 2 immunohistochemistry reveals strong nuclear staining, confirming a metastasis to the lung from a primary renal tumor.

FIGURE 6

A, Chromophobe RCC consists of nests of cells with abundant pink cytoplasm and irregular hyperchromatic nuclei with irregular nuclear contours. B, Hale colloidal iron stain shows fine microvacuolated positive staining within the cytoplasm of the tumor cells.

FIGURE 7

TFE immunohistochemistry shows positive nuclear staining in a case of translocation RCC.