1.Clinical cytogeneticist, Department of Clinical Genetics, Academic Hospital Groningen, Ant. Deusinglaan 4, 9713 AW Groningen, the Netherlands
Variants can be assigned to all these basic types which are characterized by augmentation of mitochondria leading to a stronger eosinophilia or granularity, respectively, of the cytoplasm. Spindle-shaped/pleomorphic variants as a result of sarcomatoid transformation can also be deduced from all the basic types.The differential diagnosis between renal cell adenomas and carcinomas has been a matter of controversy for long time. Although initially Bells rule generally was followed (3 cm: carcinoma), this appeared unreliable and is still a matter of debate.
Most papillary renal adenomas and carcinomas are characterized by a unique combination of autosomal trisomies with trisomy 17. Papillary adenomas specifically show a -Y,+7,+17 chromosomal pattern as well as trisomy 3 or gain of the long arm of chromosome 3, probably reflecting malignant transformation. Trisomy of chromosomes 12, 16, 20 as well as loss of the extra copy of chromosome 17 or loss of 17p are associated with progression from the adenoma into the carcinoma stage, i.e. papillary renal cell carcinomas. The high incidence of loss of the Y chromosome combined with the strong male preponderance suggests that loss of specific sequences harboured on the Y chromosome probably is important for developing this subtype.
A small subset of papillary RCC is characterized by X; autosome translocations. The t(X;1)(p11.2;q21), resulting in a fusion of the transcription factor TFE3 on the X chromosome, with a novel gene, designated PRCC, on chromosome 1, appears to be a specific primary anomaly characterizing a distinct subgroup of papillary RCC with common RCC like features as clear cytoplasma. These tumors occur preferentially in young (male) adults and children.
Metanephric adenoma or adenofibroma shows gain of chromosomes 7 and 17 with Y chromosome loss suggesting a relationship with papillary renal cell adenomas and carcinomas.
In renal oncocytoma several genetic subsets can be distinghuished: one with mixed populations of normal and abnormal karyotypes without any cytogenetic similarity (yet), a group defined by (variant) translocations involving 11q13, and one with specifically defined numerical anomalies, in particular loss of chromosomes 1, and Y/X.
The finding of mitochondrial DNA changes and the loss of Y/X in both renal oncocytoma and chromophobe carcinoma might indicate progression from renal oncocytoma to chromophobe renal cell carcinomas through additional chromosome losses, also explaining the occasionally malignant behavior of renal oncocytomas.
Chromophobe renal carcinomas show multiple losses of entire chromosomes, i.e. loss of chromosomes 1, 2, 6, 10, 13, 17, 21, and the Y or X chromosome, leading to a low chromosome number.
Collecting duct carcinomas do not show consistent chromosomal abnormalities as yet: probably involvement of the short arm of chromosome 8 related to poor prognosis and loss of the long arm of chromosome 13 as well as loss of part of the long arm of chromosome 1q32.Losses of chromosome1 material seem to be a hallmark for all distal nephron tumors.
Sarcomatoid transformation in RCC represents the highest form of dedifferentiation and can in principle be derived from all the basic cell types. Cytogenetic data on sarcomatoid RCC is scarce: some show structural abnormalities of chromosomes 1, 5, 16, and 19 and losses of 3p, 4(q), 6q, 8p, 9, 13, 14, 17p, and gain of 5, 12, and 20 as well as TP53 mutations.
Eva van den Berg ; Stephan Storkel
Kidney: Renal cell carcinoma: an overview
Atlas Genet Cytogenet Oncol Haematol. 2003-06-01
Online version: http://atlasgeneticsoncology.org/solid-tumor/5021/kidney-renal-cell-carcinoma-an-overview