Shared chromosome 21q loss in a mixed subtype renal cell carcinoma: composite or collision tumor?

Clear cell renal cell carcinoma (CCRCC) and papillary renal cell carcinoma (PRCC) are the two most frequently encountered subtypes of renal cell carcinoma (RCC). Rarely, these two entities are identified intermingled within the same mass and have been labeled either collision tumors juxtaposed by random chance or composite tumors that have arisen from a common tumorigenic precursor cell. Regarding this distinction, authors have commonly relied upon macroscopic, histologic, and clinicopathologic findings, which may be prone to subjectivity. Objective molecular evidence has been lacking. We present a renal tumor showing a mixed CCRCC and PRCC with corroborating histologic, immunophenotypic, chromosomal microarray analysis (CMA), and next-generation sequencing (NGS) analysis for the respective tumor components, including classic findings of chromosome 3p loss and VHL mutation within the CCRCC component and gain of chromosomes 7 and 17 within the PRCC component. Of novel interest, CMA revealed a shared loss of chromosome 21q in both components with no other identifiable shared or overlapping mutations. This report adds unique evidence supporting the possibility of a true composite renal cell carcinoma composed of two commonly recognized subtypes. This finding may help to inform early molecular pathogenetic mechanism of RCC tumorigenesis.

Applications of Digital Polymerase Chain Reaction (dPCR) in Molecular and Clinical Testing.

BACKGROUND: Digital polymerase chain reaction (dPCR) is an accurate and sensitive molecular method that can be used in clinical diagnostic, prognostic, and predictive tests. The key component of the dPCR method is the partitioning of a single reaction into many thousands of droplets, nanochannels or other nano- or picoliter-sized reactions. This results in high enough sensitivity to detect rare nucleic acid targets and provides an absolute quantification of target sequences or alleles compared to other PCR-based methods. CONTENT: An increasing number of dPCR platforms have been introduced commercially in recent years and more are being developed. These platforms differ in the method of partitioning, degree of automation, and multiplexing capabilities but all can be used in similar ways for sensitive and highly accurate quantification of a variety of nucleic acid targets. Currently, clinical applications of dPCR include oncology, microbiology and infectious disease, genetics, and prenatal/newborn screening. Commercially available tests for clinical applications are being developed for variants with diagnostic, prognostic, and therapeutic significance in specific disease types. SUMMARY: The power of dPCR technology relies on the partitioning of the reactions and results in increased sensitivity and accuracy compared to qPCR. More recently, the sensitivity of dPCR has been applied to the detection of known variants in cell-free DNA and circulating tumor DNA. Future clinical applications of dPCR include liquid biopsy, treatment resistance detection, screening for minimal residual disease, and monitoring allograft engraftment in transplanted patients.