A 64-year-old man presented with gross hematuria and vague pain in the left loin. His medical history was unremarkable. Physical examination revealed percussion pain over the left kidney region. Urinalysis showed positive for protein and red blood cells. Abdominal B ultrasonography revealed left hydronephrosis and a hypoechoic mass in the inferior segment of the left ureter. Magnetic resonance imaging (MRI) confirmed left hydronephrosis, a low signal mass in the upper pole of the kidney, and another mass with high T1, low T2 signal in the inferior segment of the left ureter. Imaging examination showed no abnormality elsewhere. A clinical diagnosis of malignancy of the left kidney and the ureter was made, for which a left nephro-ureterectomy was performed.
Gross examination of the nephro-ureterectomy specimen showed pale grayish solid tumor in the enlarged kidney, and the tumor measured 11
cm, causing dilatation of the renal pelvis. The tumor invaded the cortex, medulla, adeps renis and involved 90% of the total kidney, resulting in distortion (Figure
a). And a separate elongated solid tumor mass, 7
cm in size, was present in the inferior segment of the left ureter, being distinct from the tumor in the renal (Figure
b). Microscopically, the renal mass showed a biphasic infiltrative growth pattern with the typic characteristic of mesenchymal chondrosarcoma. It consisted of undifferentiated spindle to oval shaped cells, with hyperchromatic nuclei and scanty cytoplasm mainly arranged in Ewing’s sarcoma-like, lamellar or hemangiopericytoma-like patterns. Other areas demonstrated well defined islands of cartilage. The transformation from the undifferentiated cells to the cartilage cell was abrupt and interlaced(Figure
b). The tumor had invaded the renal pelvis, but there were no evidence of papillary lesion or underlying urothelial carcinoma.
Figure 1 Nephro-ureterectomy specimen showing the large tumor nodule in the kidney. Gross examination showed the tumour involved the whole kidney cortex, medulla, capsule (red arrow) and adeps renis (green arrow) and the ureter was distended by a narrow solid (more ...)
Figure 2 The renal mass consisting of sheets of undifferentiated mesenchymal cells (H&E, 2a), and scattered well demarcated islands of differentiated cartilage (H&E, 2b). Both the undifferentiated tumor cells and cartilaginous islands were immunoreactive (more ...)
The tumor in the distal ureter was microscopically similar to that in the kidney, with the typical biphasic mesenchymal chondrosarcoma component , which constituted bulk of the tumor mass. However, there was a small component exhibiting features of urothelial carcinoma. The urothelial carcinoma showed infiltrative nests, of moderate cytological grade, and displayed foci of squamous cell differentiation with some degree of keratinization (Figure
b). The mucosa adjacent to the tumor showed no evidence of underlying dysplasis or carcinoma in-situ. Extensive sampling of the kidney tumor did not identify a carcinomatous component. Vascular invasion of the chondrosarcoma was detected , but no carcinomous metastasis was detected.
Figure 3 The ureteric tumor revealing a mesenchymal chondrosarcoma, similar to that in the kidney (black arrow), and in addition a synchronous infiltrative urothelial carcinoma (white arrow) (3a),with foci of squamous differentiation and keratinization(3b). The (more ...)
Immunohistochemical staining showed the poor-differentiated tumor cells and cells within the cartilaginous areas in both the kidney (Figure
f) and the ureter were positive for Vimentin, CD99and S-100 protein but were negative for cytokeratin, epithelial membrane antigen ,E-cadherin, Leu7, neuron-specific enolase, SMA, CD34, p63 and desmin. The poor-differentiated tumor cells displayed a higher Ki-67 index than those in the well-differentiated cartilaginous areas. The urothelial carcinoma component within the ureter, the tumor cells were positive for cytokeratin (Figure
c), epithelial membrane antigen, E-Cadherin and negative for Vimentin (Figure
d), S-100 and CD99, enhancing the contrast of synchronous urothelial carcinoma from mesenchymal chondrosarcoma. For FISH analysis, labeled probes specific for chromosomes 3, 7, 17 and for the p16 (9p21) gene (GP Medical Technologies,Ltd, Beijing, China) were used. Two DNA- probes were mixed together as a set double-target FISH and paired as follows: chromosome 3 (fluorescein isothiocyanate) and chromosome 7 (rhodamine), chromosome 17 (fluorescein isothiocyanate) and p16 (rhodamine).In both the urothelial carcinoma and mesenchymal chondrosarcoma components, aneuploidy of chromosome 3, 7 and 17 and loss of p16 gene were observed (Figure
, and Tables
Aneuploidy of chromosome 3(green) and 7(red) in urothelial carcinoma (4a). Aneuploidy of chromosome17(green)and loss of the p16 gene(red) in urothelial carcinoma (4b).
The ratio of gene copy numbers to chromosome 3,7and 17 centromere by FISH probes in urothelial carcinoma and mesenchymal chondrosarcoma
Gene copy numbers of the p16 (9p21) gene by FISH probe
The patient died of the widespread metastases two months after surgery, autopsy was not performed.