Fine and Stout[3
] in 1956 suggested that extraskeletal osteosarcomas show behavior similar to primary osteogenic osteosarcoma in the bone. Subsequent studies have indicated that extraskeletal osteosarcoma should be considered clinically and therapeutically separate from osteogenic osteosarcoma.[4
] Osteosarcoma, by definition, is a malignant tumor showing osteoid production and is known to occur in the 7th
decade. It is more common in males (male to female ratio: 4:1). Some have a history of radiation therapy for urothelial carcinoma. The time interval between radiotherapy and development of sarcoma can be long, with a mean interval of 12 years. Most osteosarcomas arise in the trigone region, although cases have been reported in the renal pelvis and ureter as well. They present as solitary, large, polypoid, gritty, often deeply invasive, variably hemorrhagic mass, with size varying between 2 cm and 15 cm (median: 6.5 cm).
Histologically, tumors are composed of malignant cells surrounding variably calcified, woven bone lamellae. Foci of chondrosarcomatous differentiation or spindle cell areas may also be observed. The differential diagnosis includes urothelial carcinoma with osseous metaplasia and sarcomatoid variant of urothelial carcinoma (carcinosarcoma). The cytologic atypia differentiates osteosarcoma from stromal osseous metaplasia occurring in some urothelial carcinomas. A recognizable malignant epithelial component is diagnosis of sarcomatoid carcinoma even when osteoid is present The diagnosis of osteosarcoma should only be made after excluding all these possibilities, as osteosarcoma has worse prognosis than the other two disease entities.
Criteria for the diagnosis of primary extraskeletal osteosarcoma by Allan et al.,[5
] are: (1) the presence of a uniform morphological pattern of sarcomatous tissue that excludes the possibility of malignant mesenchymoma, (2) the production of malignant osteoid or bone by the sarcomatous tissue, and the (3) ready exclusion of an osseous origin.
Immunohistochemical analysis in osteosarcoma is negative for pan-cytokeratin 7 and 20, epithelial membrane antigen, as well as a smooth muscle actin, desmin, CD34, and CD68. Vimentin[6
] and p53 are strongly expressed in more than 95% of the neoplastic cells. In our case, vimentin was diffusely positive and cytokeratin was negative.
In carcinosarcoma, the immunostains for keratin or ultrastructural presence of desmosomes are seen, and can confirm their true carcinomatous nature with the presence of at least focal epithelial differentiation. The signs and symptoms are non-specific and include hematuria, dysuria, polyuria, and flank pain.
Primary tumor in the bladder on imaging may be detected either as a thickening of the bladder walls or as an intra-luminal mass. On CT, intra-luminal tumors may occasionally show fine calcifications. Sensitivity of CT in detecting the bladder carcinomas is in the range of 79-89%, and has a specificity ranging from 91% to 94.7%.[7
] The high specificity enables direct referral for rigid cystoscopy and biopsy thus expediting diagnosis and treatment.
The treatment protocol depends on the depth of invasion, which is categorized as superficial, muscle invasive, or hyperinvasive. Superficial malignancies may be treated with electrocautery or instillation of Bacille Calmette-Guérin. Hyperinvasive tumors necessitate radical cystectomy with chemoradiation. For muscle-invasive tumors, radical cystectomy with or without chemotherapy has been the traditional standard, but, in an effort to improve the quality of life by avoiding urinary diversion procedures, the bladder-sparing trimodality therapy of transurethral resection of bladder tumor, systemic chemotherapy, and concurrent radiation therapy has increasingly been used in selected patients. As our patient already had pulmonary metastasis, surgical treatment was deferred and systemic chemotherapy (ifosfamide and doxorubicin) was being administered. Osteosarcoma of the urinary bladder is a rare aggressive tumor with poor prognosis. Majority of the patients have advanced stage at presentation and die within 6 months, most from the effects of local spread (urinary obstruction, uremia, secondary infection, etc.) and often with lung metastases. The stage of the disease at the time of diagnosis is the best predictor of survival.