Tumors of soft tissue are among the most challenging in surgical pathology. There are several reasons for this: they are rare, so you see few in training; they are overlapping in morphology; they do not always obey the principles that help you to identify malignant potential in carcinomas; and each entity has at least three names, four variants, and seven mimickers. However, we will cover some of the names you will hear most commonly. The tumors are broken down into lines of differentiation, with the caveats that there are some tumors that do not differentiate along any known lineage (grouped separately) and that many soft tissue tumors dedifferentiate into the same final common malignant pathway, the entity formerly known as malignant fibrous histiocytoma (MFH). In many instances, MFH is simply a generic dedifferentiated sarcoma, the high-grade form of any one of a number of precursor lesions. The good news is, once it is that high grade, the origin becomes sort of academic.
When diagnosing a soft tissue lesion, especially in its initial presentation, you must always walk yourself through the mental game of, “what else could this be?” It is a good habit for any organ system but especially in the field of sarcomas and spindle cell lesions. For lesions that do not look clearly malignant (by which we mean they lack nuclear atypia and necrosis), you must always consider that it might be a reactive lesion. For lesions with bizarre and huge nuclei, despite the malignant look, you must consider benign entities with degenerative atypia (such as an ancient schwannoma). For lesions in or near an organ, such as in visceral sites, you must always ask yourself if it could be a carcinoma masquerading as a sarcoma. For spindle cell lesions anywhere, you must ask yourself if it could be melanoma. Some of these questions require immunostains to answer, some just a skeptical eye.