Sarcomatoid urothelial carcinoma of the bladder with osseous metaplasia: bone in urinary bladder

Abstract

Sarcomatoid urothelial carcinoma is a rare aggressive malignant neoplasm of the urinary bladder. It usually presents at an advanced stage and thus carries a poor prognosis. These tumours are usually managed with multimodal therapies such as cystectomy and chemotherapy. In the present case, a 72-year-old man presented with gross haematuria and was diagnosed as sarcomatoid urothelial carcinoma with chondrosarcomatous differentiation and extensive stromal osseous metaplasia. The patient was managed with transurethral resection of bladder tumour (TURBT), followed by intravesical chemotherapy. The patient is doing well post 14 months follow-up. Hence, complete TURBT with chemotherapy is also a viable option for patients who prefer to preserve bladder.

Background

Sarcomatoid urothelial carcinoma (UC) is an uncommon variant of urothelial malignancies with a dismal prognosis. They behave aggressively and exhibit separate malignant epithelial and mesenchymal components. In the past, some pathologists have preferred to use the term ‘carcinosarcoma’ when the sarcomatous component displayed specific mesenchymal differentiation such as osteosarcoma, chondrosarcoma or leiomyosarcoma.¹ Sarcomatoid UC can show unusual stromal reactions in the form of psuedosarcomatous stroma, or stromal osseous or cartilaginous metaplasia.² We herein encountered a unique case of UC of the bladder with chondrosarcomatous differentiation along with extensive stromal osseous metaplasia detected on transurethral resection of the bladder tumour (TURBT). In the present case, there was the presence of both benign bone and a malignant cartilaginous component. These components although commonly known to occur separately in UCs rarely present as benign and malignant components in the same tumour. To the best of our understanding, this is a unique case with these varied histomorphological findings.

Case presentation

A 72-year-old man presented with gross haematuria associated with the passage of blood clots for 2 months. The patient had a history of smoking and occasional tobacco chewing for 50 years and did not have any history of drug allergy.

Investigations

His urine microscopic examination revealed numerous red blood cells and urine cytology was suspicious of a high-grade UC (PARIS grade IV). His ultrasonography and contrast-enhanced CT of the kidney-urinary bladder region revealed an intraluminal polypoidal growth in the urinary bladder with internal vascularity arising from the left posterolateral wall measuring 4.8×4.2×5.2 cm with multiple echogenic coarse calcific foci within it (figure 1A, B). The growth did not show any positional variation with clinical stage T2N0M0.

Figure 1.

Contrast-enhanced CT images: (A) axial section shows a polypoidal enhancing soft tissue mass (arrow) in the urinary bladder lumen arising from the left lateral wall with multiple foci of calcifications; (B) coronal image shows three polypoidal enhancing soft tissue masses (arrows) with the largest lesion showing calcifications.

Treatment

The patient was planned for TURBT and the specimen was submitted for histopathological examination, which revealed a high-grade papillary UC. In addition to the carcinomatous component, the tumour stroma contained multiple bony trabeculae of variable sizes, separated by loose fibrous connective tissue. Osteoid and bony trabeculae were lined by large cells with ample cytoplasm and multinucleated giant cells consistent with osteoblasts and osteoclasts, respectively. Mineralisation of the bone was identified. Along with this, large areas of malignant cartilaginous differentiation were identified. Spindled mesenchymal cells with hyperchromatic nuclei exhibiting marked pleomorphism, conspicuous nucleolus and high mitotic activity were seen (figure 2A–D). The epithelial component of the tumour was immunoreactive for pancytokeratin and cartilage for S100 protein. The tumour was non-muscle invasive and separately sent deep muscle was also free of tumour. The case was discussed in multidisciplinary meet and all agreed for restage TURBT. After 2 weeks, it was performed and biopsy revealed only fibrosis without any evidence of malignancy. Following this, a decision was taken to administer intravesical chemotherapy with follow-up, as the patient opted to preserve his bladder.

Figure 2.

(A) Microphotograph showing both the areas of carcinoma and sarcoma 4×; (B) Microphotograph showing chondrosarcomatous differentiation 4×; (C) Microphotograph showing high-grade nuclear features 40×; (D) Microphotograph showing stromal osseous metaplasia 10×.

Outcome and follow-up

A final diagnosis of high-grade UC with chondrosarcomatous differentiation and extensive stromal osseous metaplasia was made (pT1 stage). Later, the patient was treated with intravesical mitomycin C 40 mg weekly for 6 weeks. After its completion, cystoscopy was performed which was normal and instillation of chemotherapy was continued monthly for next 1 year. The patient is doing well in follow-up with no recurrence.

Discussion

Sarcomatoid differentiation is an infrequent variant of UC of the bladder with its incidence ranging from 0.1% to 0.3%.^{3 4} Sarcomatoid carcinomas are biphasic malignancies with both epithelial and mesenchymal components. The exact genesis of these neoplasms remains a contentious matter in histopathology. According to the commonly acknowledged theories, these tumours may arise either from a pluripotent neoplastic cell or maybe collision tumours, in which both epithelial and mesenchymal components arise autonomously.

In 2004, WHO clubbed all the previously distinct biphasic malignant tumours, including carcinosarcomas, under the heading of sarcomatoid carcinoma.⁵ This was done because of the molecular evidence showing that a monoclonal population of cells was responsible for the differentiation of the tumour into mesenchymal and epithelial components. This monoclonal cell line develops multiple genomic changes similar to each clone and, at some point during the tumour progression, undergoes divergent differentiation into mesenchymal and epithelial components.⁶ These transitions from an epithelial-to-mesenchymal phenotype are because of the induction of transcription factors and are known as epithelial-to-mesenchymal transition. This transformation, including alteration or loss of epithelial cell–cell junctions, helps explain the aggressive clinical course which is very typical of sarcomatoid carcinoma, as it leads to increased invasiveness and metastatic potential. This classification was further revised by WHO in 2016 to incorporate some new entities such as ‘invasive UC with divergent differentiation’ that includes those tumours arising from urothelial tract, with the presence of ‘usual type’ UC beside some other morphologies.⁷ Such variants have vital prognostic and therapeutic implications for both the urologist and oncologist and present many diagnostic challenges for the pathologist.

Sarcomatoid variant of UC presents in elderly patients with a mean age of 66 years with a male to female ratio of 3:1.¹ They do not have any specific presenting symptoms and usually present with microscopic or gross haematuria, along with other variable symptoms such as dysuria, nocturia, urinary retention or abdominal pain, as are with conventional UC.

Macroscopically, they usually present as large polypoidal growths, usually involving the fundus and lateral walls of the urinary bladder. On microscopy, they should have both epithelial and mesenchymal malignant components. On immunohistochemistry, the carcinomatous component is immunoreactive for epithelial membrane antigen (EMA) and pancytokeratins, while the mesenchymal component is positive for vimentin.

In one of the large case series (n=41) by Lopez-Beltran et al, heterologous elements may be present in the sarcomatoid variant of UC.⁸ The most frequent element encountered was osteosarcoma, followed by chondrosarcoma, and rarely rhabdomyosarcoma, angiosarcoma or liposarcoma. In the present case, heterologous component was present in both benign and malignant form, which has not been reported previously.

There is no standardised treatment protocol for sarcomatoid carcinomas due to their rarity, and patients are often treated alike to patients with conventional UC. Many authors suggest cystectomy should be performed even for early-stage disease (T1) rather than intravesical therapy to avoid the risk of tumour progression and the potential for incomplete tumour removal in a TURBT specimen.⁹ Multimodal therapy, usually consisting of cystectomy, followed by adjuvant chemotherapy and/or radiation, is the usual approach, yet the effectiveness of these treatments has not been well studied.¹⁰ In the present case, the patient desired to preserve the bladder, hence after completion TURBT, intravesical chemotherapy was chosen and in the follow-up of more than a year, he is recurrence free. Continued research and multicentre prospective studies are necessary to fully understand sarcomatoid carcinomas of the urinary bladder, the underlying pathophysiology, and new targeted therapies.

In conclusion, sarcomatoid variant of UC is an uncommon type of tumour associated with poor outcome in contrast to classical UC. Such rare pathology needs to be reported and clubbed to get an overall picture of its biology and prognosis.

Learning points.

• Sarcomatoid urothelial carcinoma is a rare and aggressive variant with poor prognosis as compared with conventional urothelial carcinoma.

• Cell of origin for invasive carcinoma and sarcoma in the bladder is same.

• Early detection and prompt management is necessary to avoid its spread and metastasis.

• Multidisciplinary meeting is required for planning the management of such unusual cases and patient’s desire also needs to be considered.

• Though the best treatment is radical in high-grade tumour with sarcomatoid differentiation, but for opting bladder conservative approach, the patient must be compliant for intravesical therapy and strict surveillance.