Updated December 16, 2008

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A 57-year-old woman presented with hematuria. Radiographic studies revealed a left renal mass, and a radical nephrectomy was performed. The enlarged kidney was almost entirely replaced by an ovoid, 14.5 cm long, 8.5 cm diameter, firm tumor having a lobulated, pale gray-tan cut surface with areas of yellow-green necrosis. There was no gross evidence of vascular invasion or of renal pelvic extension. The tumor cells were smooth muscle actin (+) and cytokeratin (-).

Archive Case and Diagnosis: This case first appeared as Performance Improvement Program in Surgical Pathology (PIP) 2005, Case 05 and is a leiomyosarcoma.

Criteria for Diagnosis and Comments:
This spindle cell neoplasm of the kidney shows the morphology of a smooth muscle tumor. It has a circumscribed border with the adjacent renal parenchyma and is composed of alternating cellular fascicles of spindle cells with blunt-ended, non-tapering nuclei and eosinophilic cytoplasm. There is variable, frequently marked pleomorphism, including multinucleated tumor giant cells. The presence of mitoses, including atypical forms, and foci of tumor necrosis further characterize this tumor as a high grade leiomyosarcoma.

Leiomyosarcoma (LMS) of the kidney is a rare lesion, comprising only 0.5% of all primary renal malignancies. However, among renal sarcomas LMS accounts for 50-60% of cases. Most occur in adults, and patients usually present with flank pain, hematuria and a mass. Tumors are usually large, solid, gray-white, soft to firm and focally necrotic. They may arise from the renal capsule, renal parenchyma, pelvic muscularis, or the main renal vein.

The cells of low grade lesions typically resemble those of nonneoplastic smooth muscle. High grade lesions are pleomorphic and can appear undifferentiated, requiring immunohistochemical stains to separate them from other sarcomas, the more common being sarcomatoid renal cell carcinoma (RCC) and from atypical forms of angiomyolipoma (AML). LMS typically expresses smooth muscle actin, desmin, calponin and h-caldesmon and are negative for cytokeratin (AE1/AE3), S100 protein, and HMB-45.

LMS of the kidney is an aggressive tumor with a 5-year survival rate of 29-36%; most patients die of disease within 1 year of diagnosis. Small size (<5 cm), low histologic grade, and renal-limited disease are associated with the most favorable outcome.

The presence of necrosis, nuclear pleomorphism and more than a rare mitotic figure distinguish LMS from leiomyoma, which is typically encountered in adults as incidental, small (millimeter-sized) capsular tumors at autopsy. Rarely, leiomyomas are large (up to 37 kg) and may have calcification and cystic change, but necrosis should not be present. In addition to staining for actin and desmin, some capsular leiomyomas focally express HMB-45, suggesting a relationship to AML and other tumors derived from the perivascular epithelioid cell.

AML is composed of an admixture of adipose tissue, abnormal blood vessels and variably differentiated smooth muscle. In most instances, its distinctive and familiar histology allows for a straightforward diagnosis. Histologic variation in the components of AML can, however, lead to an error in diagnosis, particularly if the tumor is not well sampled, and differentiation from other tumors is necessary when the relative proportion of the three components becomes extreme or any of the components shows pleomorphism.

The perivascular cells represent the "myo" portion of AML, show the most variable histology and most frequently appear as spindle cells and rounded epithelioid cells with variable atypia. In addition, many lesions have immature muscle cells, including leiomyoblasts. The presence of nuclear pleomorphism and mitotic activity in AML is not evidence of malignancy. Only rare cases of true sarcomatous transformation (usually high grade leiomyosarcoma) with pulmonary metastases have been reported. Excluding the monotypic epithelioid variant which may have malignant potential with a risk for invasion and metastasis, AML can be regarded as a benign mesenchymal neoplasm. Furthermore, the presence in regional lymph nodes, extension into the renal vein/vena cava, or involvement of perirenal tissue is not indicative of malignant progression.

In cases where leiomyosarcoma is a diagnostic consideration, the identification of "arterialized" veins or the presences of perivascular collarettes and "hair-on-end" myocytes can be helpful in making the correct diagnosis of AML. In addition, AML has a unique immunophenotype. It not only expresses smooth muscle markers (muscle-specific actin, smooth muscle actin, calponin and desmin [50% of cases]) but is also immunoreactive for both melanosome and melanoma markers (HMB-45, HMB-50, CD63 and Melan-A [MART-1]). AML is consistently negative for epithelial antigens (cytokeratins and EMA).

Sarcomatoid RCC should always be included in the differentiated diagnosis of a malignant spindle cell neoplasm of the kidney. It is not a distinct histologic subtype of RCC but may arise in any of the four distinct subtypes of adult RCC - conventional (clear cell), papillary (chromophil), chromophobe, and collecting duct carcinoma. Although frequently undifferentiated, the sarcomatoid component can resemble malignant fibrous histiocytoma or fibrosarcoma and contain heterologous elements, including rhabdomyosarcomatous, chondrosarcomatous or osseous differentiation. The sarcomatoid component may predominate, but adequate sampling will generally reveal a carcinomatous element. Tumors composed exclusively of sarcomatoid or spindled elements without a recognizable epithelial component should be categorized as unclassified RCC. The immunoprofile of sarcomatoid RCC is extremely important in that it allows separation of this tumor from other entities that may mimic it. It is immunoreactive for cytokeratin (AE1/AE3) (94% of cases), vimentin (56% of cases), and EMA (50% of cases). Sarcomatoid collecting duct carcinomas may express high molecular weight cytokeratin (34BE12) as well as mark for UEA-1 lectin. A leiomyosarcoma-like histologic appearance in sarcomatoid RCC was not observed in the study by dePeralta-Venturina and colleagues. Therefore, a malignant appearing spindle cell neoplasm with histologic and immunophenotypic smooth muscle features is most likely a leiomyosarcoma or AML.

Both sarcomatoid RCC and sarcomatoid urothelial carcinoma can have similar histologic features and immunophenotype (cytokeratin and vimentin +). Thorough sampling will usually reveal nests of better differentiated invasive urothelial carcinoma or areas characteristic of papillary urothelial carcinoma or urothelial carcinoma in situ. Concurrent glandular, squamous and poorly differentiated histology, desmoplasia, epicenter of the tumor in the pelvicaliceal system, and history of urothelial carcinoma are helpful in this differential diagnosis.

Inflammatory myofibroblastic tumor (IMT) clinically mimics malignancy and should be included in the differential diagnosis of spindle cell tumors of the kidney. Absence of cellular atypia and necrosis and rarity of mitoses help to distinguish IMT from renal LMS with focal myxoid change. Three histologic patterns can be seen in IMTs with one pattern predominating in the majority of tumors: 1) loosely organized spindle cells admixed with small blood vessels and inflammatory cells in a myxoid background, 2) spindle cell proliferation admixed with variable amounts of dense collagen, lymphoid aggregates often forming follicles, and plasma cells, 3) hypocellular fibrous tissue with dense "keloid-like" fibrosis and sparse inflammatory cells. Immunohistochemically there is diffuse positivity for vimentin; smooth muscle actin and muscle specific actin (HHF-35) are positive in the majority of cases (focal or diffuse). Desmin, CD34 and pankeratin have been negative in all cases tested, as was ALK-1 (Kapusta et al.) In studies of non-renal IMT, ALK-1 abnormalities have been reported in 37-60% of cases by immunohistochemistry and FISH, with ALK-1 positive cases in younger patients (children and young adults).

Solitary fibrous tumor is another benign mimic of a renal sarcoma. Cellularity is variable and consists of a proliferation of uniformly bland spindle cells in a haphazard, storiform, short fascicular or hemangiopericytoma-like growth pattern and less cellular dense collagenous bands. Immunostaining for CD34, bcl-2 and CD99 confirms the diagnosis.