One of the most frequent morphologies encountered in soft tissue tumors is a spindled cell pattern, in which the tumor cells exhibit slender and elongated nuclei and cytoplasmic borders. These spindle cells can be arranged in haphazard manner (Figs. 2.1 and 2.2) as seen in nodular fasciitis or placed in organized bundles (often termed a “fascicular” or “herringbone pattern” ) as seen in malignant peripheral nerve sheath tumor (Fig. 2.3). Finally, the spindle cells can be arranged in a whirling or storiform architecture, as seen in dermatofibrosarcoma protuberans (Fig. 2.4).

Although mesenchymal in nature, soft tissue tumor cells can have an epithelioid appearance. Morphologically, these cells have cytoplasmic and nuclear borders that are round or oval (Fig. 2.5). Examples of epithelioid type soft tissue neoplasms include epithelioid sarcoma, epithelioid hemangioendothelioma, and epithelioid gastrointestinal stromal tumor. Epithelioid-type sarcomas can be mistaken for poorly differentiated carcinomas , particularly if the pathologist is unaware of the anatomic location or clinical history of the lesion.

Round cell tumors encompass a broad range of soft tissue neoplasms that are made up of cells that have a high nuclear to cytoplasmic ratio, similar to the appearance of a lymphocyte. As hematoxylin will stain the nucleus of a cell violet or blue, round cell neoplasms generally appear blue at low magnification. Examples of round cell soft tissue neoplasms include embryonal rhabdomyosarcoma or Ewing sarcoma (Fig. 2.6). Although these neoplasms have substantially overlapping morphologic appearances, many exhibit unique genetic features that facilitate diagnosis. Round cell tumors can also be confused for neuroendocrine carcinomas or lymphomas .

Many high-grade sarcomas can exhibit pleomorphic or bizarre-appearing cells. The tumor cells of this pattern demonstrate substantial variation in the size and shape of the nuclei (Fig. 2.7). Highly atypical mitoses can often be identified. One of the most frequently occurring pleomorphic soft tissue neoplasms is an undifferentiated high-grade pleomorphic sarcoma, previously designated as “high-grade malignant fibrous histiocytoma (MFH).” Pleomorphic sarcomas must be distinguished from pleomorphic carcinoma, hematolymphoid neoplasms, or melanomas that can have a similar appearance.

Myxoid soft tissue tumors exhibit varying amounts of a background bluish mucoid-like substance (Fig. 2.8). The neoplasms in this pattern can be difficult to differentiate based on architecture, as the tumor cells often freely float in this myxoid material. Examples of these tumors include myxoid liposarcoma, myxofibrosarcoma, and aggressive angiomyxoma.

The endothelial nature of vascular tumors is frequently apparent by the formation of infiltrative vascular channels (Fig. 2.9). Adipocytic tumors can often be identified by obvious fat cells or lipoblasts that contain large clear vacuoles in the cytoplasm (Fig. 2.10). Cartilaginous tumors will exhibit deposition of a blue or pink background chondroid -like matrix (Fig. 2.11). Osseous tumors show at least focal dense and eosinophilic extracellular osteoid material (Fig. 2.12).