Final Diagnosis -- Invasive Urothelial Carcinoma with Predominant Sarcomatoid Differentiation

FINAL DIAGNOSIS   INVASIVE UROTHELIAL CARCINOMA WITH PREDOMINANT SARCOMATOID DIFFERENTIATION

DISCUSSION

Sarcomatoid carcinoma (spindle cell, metaplastic) is a high-grade neoplasm of the bladder in which a malignant epithelial component (of transitional, glandular, squamous or undifferentiated type) coexists with areas having a sarcoma-like appearance. The latter may have a non-specific spindle cell or pleomorphic look (sometimes admixed with osteoclast-like giant cells) or may exhibit specific features of mesenchymal differentiation (rhabdomyosarcoma, chondrosarcoma, osteosarcoma, liposarcoma). When such features are present the tumor may be described as carcinosarcoma (but this seems to be a variation of the same basic process).

Sarcomatoid carcinoma is a rare tumor in the urinary bladder (< 100 cases reported in the literature) and accounts for approximately 0.3% of all bladder malignancies. Association with cyclophosphamide and radiation therapy was described.

Most patients are elderly males (50-77 years old); death rate is about 50%. The male-female ratio is approximately 3:1, and the most common presenting symptom is gross hematuria.

Grossly, these tumors are often large and polypoid, dull grey with infiltrative margins.

Microscopically they resemble similar tumors in upper aerodigestive tract; they are high grade tumors with sarcomatoid and carcinomatoid components; sarcomatoid component has spindled, round and pleomorphic giant cells, with myxoid or sclerosing areas; carcinomatoid component has papillary or nonpapillary high grade urothelial carcinoma, adenocarcinoma, squamous cell carcinoma or small cell carcinoma. The obvious epithelial component is sometimes present only in the form of carcinoma in situ on the surface and at the periphery of the invasive sarcoma-like tumor.

Immunohistochemistry:
Positive stains: keratin and EMA (both components), variable CEA, HCG
Negative stains: smooth muscle actin (usually), desmin (usually), calponin, caldesmon

The sarcomatoid phenotype retains the epithelial nature of the cells by immunohistochemistry or electron microscopy. Recent molecular studies suggest a monoclonal origin for both components and a possible role for the tumor suppressor gene p16 in the pathogenesis of this tumor.

The differential diagnosis of sarcomatoid carcinoma of the bladder includes pure sarcoma, carcinoma with pseudosarcomatous stroma, and prostate carcinoma extending into the bladder. Pure sarcomas can be excluded based on the unequivocal presence of an epithelial component. High mitotic rate and the presence of atypical mitoses argue against a carcinoma with pseudosarcomatous stroma. Immunohistochemical stains for prostate-specific antigen and prostatic acid phosphatase should be used to exclude an invasive, poorly differentiated prostatic adenocarcinoma (Figure 8).

The tumor behaves as a high-grade malignancy with advanced initial stage and unfavorable outcome. Involvement of ureter and renal pelvis may occur. Metastases develop in regional lymph nodes and distantly and they may consist of only the epithelial or the sarcoma-like component. Prognosis depends on depth of invasion and it is much poorer than ordinary TCC.

Treatment is surgery.

REFERENCES

1. WHO Pathology and Genetics of Tumors of the Urinary System and Male Genital Organs, 2004
2. Rosai and Ackerman's Surgical Pathology, ninth edition
3. Ikegami H, et al, Sarcomatoid carcinoma of urinary bladder: a clinicopathologic and immunohistochemical analysis of 14 patients, Hum Pathol. 2000 Mar;31(3):332-40
4. Torenbeek R., et al, Sarcomatoid carcinoma of the urinary bladder. Clinicopathologic analysis of 18 cases with immunohistochemical and electron microscopic findings, Am J Surg Pathol. 1994 Mar;18(3):241-9.
5. Omeroglu A., et al, A carcinosarcoma/sarcomatoid carcinoma arising in a urinary bladder diverticulum, Arch Pathol Lab Med. 2002 Jul;126(7):853-5.
6. Mukhopadhyay S. et al, Carcinosarcoma of the urinary bladder following cyclophosphamide therapy: evidence of monoclonal origin and chromosome 9p allelic loss, Arch Pathol Lab Med. 2004 Jan;128(1):e8-11.

Contributed by Anca Florea, MD and Anil Parwani, MD, PhD