Spindle Cell Tumor/Sarcoma Subtyping

Subtyping of spindle cell tumors and sarcomas requires integration of clinicopathologic parameters together with immunohistochemical studies. A useful initial approach to these tumors is the identification of one or more of the following subclasses of markers:

Cytokeratins, markers of epithelial differentiation, in soft tissue tumors: Within sarcomas, there are two classes of cytokeratin expression: (a) the kind observed in the small subset of sarcomas displaying true epithelial differentiation (e.g., synovial sarcomas and epithelioid sarcomas); and (b) tumors displaying 'anomalous' cytokeratin expression, e.g., leiomyosarcoma, melanoma, angiosarcoma.

Markers of smooth muscle differentiation: The principal markers of muscle differentiation are also antibodies to the intermediate filament, desmin, and to muscle-specific actin isoforms (e.g., antibodies 1A4 and HHF-35). Such antibodies are most useful in identifying tumors such as leiomyosarcomas, although smooth muscle actin expression can be seen in other tumors such as gastrointestinal stromal tumors and tumors showing myofibroblastic differentiation.

Markers of myofibroblastic differentiation: Myofibroblasts are distinguished from true smooth muscle cells by their 'partial' muscle immunophenotype, usually smooth muscle actin positive and desmin negative. Furthermore, the former is usually expressed in a characteristic peripheral, wispy pattern. Soft tissue tumors characterized by myofibroblastic differentiation include nodular fasciitis and myxofibrosarcoma.

Markers of nerve sheath differentiation: The principal markers of nerve sheath differentiation are antibodies to S100 protein, CD57, and the p75-NTR nerve growth factor receptor. They are most helpful in confirming the diagnosis of benign and malignant nerve sheath tumors. None of these markers, however, are specific for nerve sheath differentiation, and must be used in combination with other markers. p75-NTR is also an excellent marker of spindle cell and desmoplastic melanoma, which is generally negative for expression of melanoma-specific antigens.

H&E	p75-NTR Spindle cell melanoma positive for expression of the p75-NTR nerve growth factor receptor.

Markers of endothelial differentiation: Endothelial markers include von Willebrand factor (the co-factor of the clotting factor VIII, often erroneously referred to as 'F. VIII'), CD34, CD31, and the FLI-1 gene product, with varying sensitivities and specificities. As a practical issue, it is best to employ both a highly specific (e.g., CD31) and a highly sensitive (e.g., CD34) marker to assess the presence of endothelial differentiation in histologic and clinical settings where the diagnosis of a vasoformative tumor is being entertained.

Other useful markers in identifying soft tissue tumors: While not specific for a cell or tumor type, the presence and even pattern of expression of type IV collagen can be helpful in identifying specific soft tissue tumor subtypes, as only a subset of sarcomas manifest type IV collagen expression; furthermore, the pattern of type IV collagen expression can provide evidence to help identify selected spindle cell tumors. In addition, it can be the only marker of some tumors without specific markers (e.g., liposarcoma).

Beta catenin is normally a cell membrane-associated protein. However, alterations in the APC/beta catenin pathway which occur in fibromatoses result in abnormal nuclear localization of this protein. Only a restricted subset of spindle cell tumors, including fibromatoses, show this unique distribution of beta catenin.

CD117 (c-kit) is a highly specific marker for gastrointestinal stromal tumors.

Spindle Cell Tumors of the Skin: One of the most frequent sites of presentation of spindle cell tumors is in the skin, where there is a relatively restricted (and distinctive) differential diagnosis which includes atypical fibroxanthoma, dermatofibroma, dermatofibrosarcoma protuberans, leiomyoma/leiomyosarcoma, melanoma, and spindle cell squamous cell carcinoma. These tumors can be subclassified using a panel of antibodies that includes antibodies to p63 or cytokeratin 5, CD34, muscle actins, desmin, S100, and F. XIIIa.

Requisition Forms | Tests Offered | Sending Specimens