The Principles of Clinical Cytogenetics - Extra Materials - Springer

Cytogenetics of Solid Tumors 439
nomas are difficult to distinguish from oncocytomas and clear cell/granular renal cell carcinomas,
and in such cases, demonstration of the typical hypodiploid karyotype can be diagnostic. Extremely
hypodiploid karyotypes, particularly those with chromosome counts less than 40, are uncommon in
solid tumors generally, and the characteristic group of monosomies found in chromophobe cell carcinomas
has not been described in other renal cell cancer histologies.
Papillary Renal Carcinomas
Approximately 10% of all renal carcinomas are papillary, and the cytogenetic profiles for papillary
renal cell carcinomas are distinctive. The differential diagnosis of papillary renal carcinoma can
be challenging, particularly with respect to distinction from benign renal adenoma or from clear cell
carcinoma. Benign renal adenomas are common tumors that are often discovered incidentally by
radiography, angiography, or at autopsy. It has been proposed that papillary renal neoplasms smaller
than 3 cm be classified as benign adenomas, whereas those larger than 3 cm should be classified as
carcinomas. However, size alone does not permit accurate estimation of malignant potential. Distinction
between adenoma and carcinoma is further confounded by the observation that kidneys involved
by papillary renal cell carcinoma often contain papillary renal adenomas, and the suspicion that papillary
renal cell carcinomas arise from the adenomas has been reinforced by cytogenetic studies.
Renal adenomas and papillary carcinomas contain a similar core group of chromosome aberrations (–Y,
+7, +17), but these are generally the only cytogenetic aberrations seen in the adenomas (150–152),
whereas papillary carcinomas are apt to have acquired several additional aberrations (153). Hence,
cytogenetic studies indicate a continuum of chromosome aberrations in papillary renal cell tumors,
with gain of chromosomes 7 and 17 contributing to the early phases of nonmalignant neoplastic
progression. Kovacs et al. recommend that renal papillary tumors with isolated trisomies 7 and 17
(with or without loss of a sex chromosome) be classified as papillary renal cell adenomas, irrespective
of size (150). The same investigators recommend that papillary renal cell tumors with complex
karyotypic aberrations be classified as carcinomas, even when small in size. However, published
studies provide little or no clinical follow-up data for these cytogenetic subgroups, and it is not yet
known whether karyotypic complexity predicts patient outcome.
The cytogenetic profile can be useful in resolving a differential diagnosis of papillary versus clear
cell/granular renal cell carcinoma. Most papillary renal cell carcinomas contain some nonpapillary
components, and arbitrary cutoffs are used to define the minimal percentage of papillary components
required for diagnosis as true papillary renal cell carcinoma. Reliable distinction between papillary
and nonpapillary renal cell carcinoma is important clinically because papillary carcinomas appear to
have a better prognosis, stage for stage, than do nonpapillary carcinomas (154). As discussed earlier,
the most frequent cytogenetic aberrations in papillary renal cell carcinomas include trisomies of chromosomes
7, 16, and 17, and loss of the Y chromosome; each of these aberrations is found in at least
50% of papillary renal cell carcinomas (see Fig. 8) (155,156). Additional nonrandom chromosome
aberrations, which are found in 10–50% of papillary renal cell carcinomas, include trisomies 3, 8, 12,
and 20 (150). In contrast, clear cell/granular carcinomas rarely have trisomies 16 or 17, but virtually
always have a cytogenetic deletion of 3p14–21, which is found in fewer than 10% of papillary renal
cell carcinomas (132,134).
Pediatric Renal Cell Carcinomas with Xp11.2 or 6p21 Translocations
Pediatric renal cell carcinomas are uncommon, and they differ from adult cases (which most often
have clear cell/granular histology) in that they very often have papillary components. Unlike the
adult papillary renal carcinomas, with their distinctive profile of chromosomal trisomies, the pediatric
renal carcinomas most often have translocations involving the X chromosome and chromosome 6.
These translocations are not restricted to pediatric renal carcinomas, but are also found occasionally
in adult papillary carcinomas (157). The unifying theme for the pediatric carcinoma translocations is that
they target various members of the MiT family of transcription factors. The most frequent translocation is