Immunohistomorphologic and molecular cytogenetic analysis of a carcinosarcoma of the urinary bladder

Abstract

Carcinosarcomas of the urinary bladder are malignant biphasic tumors with an epithelial and a spindle cell component. For the histogenesis of the two components, a biclonal and a monoclonal origin are discussed. We present the immunomorphology and molecular cytogenetics of such a case. The immunohistology of biopsies of the urinary bladder revealed a poorly differentiated urothelial carcinoma (GIII) and a co-existing pleomorphic, spindle cell leiomyosarcoma (GIII). The two components were microdissected and further analyzed for gains and losses of chromosomal material using comparative genomic hybridization. In addition, loss of heterozygosity analyses were included. The tumor components revealed as overlapping core aberrations losses on the short arm of chromosome 9 and on the long arm of chromosome 11. However, both components showed additional aberrations exclusively detected in one of the components. The occurrence of overlapping aberrations strongly argues for a monoclonal origin of this tumor with a common ancestor. The additional aberrations of the components point to an independent and divergent course of tumor progression in both components.

TP53 mutational analysis supports monoclonal origin of biphasic sarcomatoid urothelial carcinoma (carcinosarcoma) of the urinary bladder

“…22 More recently, concordant X-chromosome inactivation and significant overlap in loss of heterozygosity were reported in separately microdissected components of sarcomatoid carcinoma of the urinary bladder in a study by Sung et al, 23 supporting a monoclonal origin for both components. Gronau et al 24 obtained similar results, finding that the tumor components showed overlapping chromosomal alterations as well as additional nonoverlapping alterations. These secondary mutational aberrations were thought to represent events significant in the divergence occurring after the initial tumorigenesis.…”

“…These secondary mutational aberrations were thought to represent events significant in the divergence occurring after the initial tumorigenesis. 24 Although TP53 mutations are common in urothelial carcinomas, particularly in high-grade and highstage cancers, TP53 mutation analysis has not previously been utilized to evaluate the molecular characteristics of the morphologically distinct components of sarcomatoid carcinoma of the urinary bladder. TP53 exons 5-8, corresponding to the DNAbinding domain, are considered to be the region most frequently harboring point mutations in bladder carcinomas.…”

K-ras gene mutational analysis supports a monoclonal origin of biphasic pleomorphic carcinoma of the lung

“…3,7,[13][14][15]17,19,22 In different anatomical sites, most, but not all, of these tumors composed of carcinoma and sarcoma or sarcoma-like components are considered monoclonal growths (the so-called divergent hypothesis) rather than true collision tumors (convergent hypothesis). 20,[23][24][25][26][27][28][29][30][31] In turn, these monoclonal growths may originate from a single ancestor undergoing divergent epithelial and mesenchymal differentiation early during the neoplastic transformation (combination theory), or the full-blown carcinoma cells undergo sarcomatoid changes during tumor progression (conversion theory). 21,[23][24][25] In the lung, a monoclonal origin has been suggested for carcinosarcoma and blastoma using diverse molecular strategies, such as X chromosome inactivation, 24 microsatellite analysis, 29 and mutational genotyping of p53 gene, 28 whereas little is known about clonality of pulmonary pleomorphic carcinomas.…”

Partial cystectomy: Is it a reliable option for the treatment of bladder

“…They usually present as well-circumscribed grayish firm nodules. 5 Bladder leiomyosarcoma has always been considered a highly aggressive tumour. Most patients are already in the advanced pathologic stage when the tumour is detected; less than 15% of tumours are identified in the T1 stage.…”