STSs are often difficult to categorize pathologically, and subsequently require significant expertise and experience on the part of the pathologist. The pathologist provides the surgeon with information that is critical to the appropriate management of the patient. This information includes the histologic grade and subtype of the tumor as well as the status of the clinical margins following resection. By definition, a grossly positive margin is one in which the surgical margin appears involved to the naked eye, and this is confirmed by microscopic examination. A margin should be considered microscopically positive when the tumor is close to or involves the surgical margin on microscopic exam.
The surgeon and pathologist should not hesitate to seek a second opinion when there is a question about the diagnosis or histopathology of a soft tissue tumor. Review at a center with expertise in the diagnosis of STS is frequently necessary and appropriate.
STSs arise from undifferentiated connective tissue (MFH), fibrous tissue (desmoid, fibrosarcoma), joints (tendosynovial, chordoid, epithelioid, and clear cell sarcoma), muscle (leiomyosarcoma, rhabdomyosarcoma), fat (liposarcoma), vessels (lymphangiosarcoma, hemangiopericytoma) and nerves (malignant peripheral nerve tumor, primitive neuroectodermal tumor). Chondrosarcoma and osteogenic sarcoma can also arise in soft tissue (extraskeletal osteogenic sarcoma). Within histologic subtypes the clinical behavior of a STS varies with size, grade and location.
Tumor grade is the best indicator of the potential for a STS to metastasize. Management of the patient is simplified by utilization of a grading system that distinguishes between high and low grade tumors only. High grade tumors have a very high likelihood of metastasizing (> 50%) compared to low grade tumors (< 15%). The distinction between high and low grade is made based on cellular differentiation (well vs. poor), cellularity (hypocellular vs. hypercellular), stroma (abundant vs. scant), vascularity (hypo- vs. hypervascular), necrosis (minimal vs. much), and number of mitoses per 10 high power fields (< 5 vs. > 5).
STSs may contain both high and low grade components. This commonly occurs in "de-differentiated liposarcoma" in which a low grade liposarcoma recurs with areas of high grade tumor. When over 20% of the tumor contains high grade elements it should be classified and managed as a high grade sarcoma.
The technique of immunohistochemistry is based on the propensity of tissues of specific histogenesis to express specific cell surface antigens. Antibodies are used to identify these cell surface proteins. Immunohistochemistry is very useful in the pathologic diagnosis of STS, particularly with regard to histiogenic subtype. It can be used on paraffin-embedded or frozen tissues and is particularly useful in distinguishing between highly undifferentiated melanoma, lymphoma, carcinoma, and sarcoma. A panel of antibodies is used to determine the specific type of sarcoma, as within categories there is considerable variation in antigen expression. A simplified description of commonly used antibodies in the immunohistochemical analysis of STS and other tumors is provided below.
Vimentin is expressed by a variety of tumors of mesodermal and neuroectodermal origin, including many carcinomas, melanoma, and most STSs. Epithelial membranes and cells of epidermal origin will stain positive for cytokeratin, as will most carcinomas. STSs are usually cytokeratin-negative and vimentin positive. The demonstration of cytokeratin and epithelial membrane antigen (EMA), although characteristic of carcinoma, can also be seen with epithelioid and synovial sarcoma. Factor VIII-related antigen is produced by endothelial cells and can be very useful in the diagnosis of poorly differentiated angiosarcoma. Desmin is an extremely useful
marker for muscle tumors. The vast majority of rhabdomyosarcomas stain positively, even when poorly differentiated. Myoglobin, though found exclusively in skeletal muscle, is less sensitive than desmin.
Neuron-specific enolase is an antigen found on the surface of cells of neural crest origin. It is expressed in neuroblastoma, APUDomas, ganglioneuromas, and ganglioneuroblastomas. Neurofilament and S-100 are useful in distinguishing between tumors of neuronal origin (neurofilament positive ) or nerve sheath origin (S-100 positive). While S-100 immunoreactivity is seen in chondrocytes, adipocytes and Schwann cells, the differential diagnosis of a particular STS rarely involves more than one of these histologic subtypes.
Certain chromosomal abnormalities occur in particular subtypes of STS. Cyto-genetic analysis can provide the correct pathologic diagnosis in poorly differentiated tumors that lack immunohistochemical markers. These are listed in Table 4.5.
Electron microscopy is a valuable technique for categorizing the small number of tumors that are negative for immunohistochemical markers. Lipid may be appreciated in liposarcomas, while clear cell sarcomas often contain melanosomes.
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