Subtyping of renal cortical neoplasms in fine needle aspiration biopsies using a decision tree based on genomic alterations detected by fluorescence in situ hybridization

Abstract

ObjectivesTo improve the overall accuracy of diagnosis in needle biopsies of renal masses, especially small renal masses (SRMs), using fluorescence in situ hybridization (FISH), and to develop a renal cortical neoplasm classification decision tree based on genomic alterations detected by FISH.Patients and MethodsEx vivo fine needle aspiration biopsies of 122 resected renal cortical neoplasms were subjected to FISH using a series of seven-probe sets to assess gain or loss of 10 chromosomes and rearrangement of the 11q13 locus. Using specimen (nephrectomy)-histology as the ‘gold standard’, a genomic aberration-based decision tree was generated to classify specimens. The diagnostic potential of the decision tree was assessed by comparing the FISH-based classification and biopsy histology with specimen histology.ResultsOf the 114 biopsies diagnostic by either method, a higher diagnostic yield was achieved by FISH (92 and 96%) than histology alone (82 and 84%) in the 65 biopsies from SRMs (<4 cm) and 49 from larger masses, respectively. An optimized decision tree was constructed based on aberrations detected in eight chromosomes, by which the maximum concordance of classification achieved by FISH was 79%, irrespective of mass size. In SRMs, the overall sensitivity of diagnosis by FISH compared with histopathology was higher for benign oncocytoma, was similar for the chromophobe renal cell carcinoma subtype, and was lower for clear-cell and papillary subtypes. The diagnostic accuracy of classification of needle biopsy specimens (from SRMs) increased from 80% obtained by histology alone to 94% when combining histology and FISH.ConclusionThe present study suggests that a novel FISH assay developed by us has a role to play in assisting in the yield and accuracy of diagnosis of renal cortical neoplasms in needle biopsies in particular, and can help guide the clinical management of patients with SRMs that were non-diagnostic by histology.

Small renal masses in the era of personalized medicine: Tumor heterogeneity, growth kinetics, and risk of metastasis

“…Several studies have been performed by means of fluorescence in situ hybridization, and one field of research is aimed at defining which set of alterations can be held as "typical" of specific tumor subtypes. Anyway, this procedure is still investigational [16,[18][19][20][21].…”

Ancillary studies in fine needle aspiration of the kidney

“…Nevertheless, in the past decade pathologists have acquired more knowledge, especially regarding individual subtypes of RCC. [1][2][3][4] Many of these newer subtypes of RCC either require or are much easier to diagnose with additional ancillary testing, [4][5][6][7][8][9][10][11][12][13][14][15][16] and increasingly tumors with mixed features are being recognized. 17,18 No specific prognostic markers are available for RCC, although the correct identification of the specific subtype of RCC does more clearly define the prognosis of the patient.…”