Inflammatory Soft Tissue Tumors: A Wolf in Sheep's Clothing.

Rottmann, Douglas; Perry, Kyle D · Arch Pathol Lab Med · 2026

review · Level V

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Abstract

The diagnosis of soft tissue tumors is becoming increasingly complex as the number of entities and associated ancillary studies continues to increase. Mesenchymal tumors with prominent associated inflammation are challenging, given that the pathologist might not consider soft tissue entities in the differential diagnosis. This review will cover selected inflammatory soft tissue tumors commonly encountered in surgical pathology practice or associated with recurrent diagnostic pitfalls, namely,inflammatory well-differentiated liposarcoma/atypical lipomatous tumor, angiomatoid fibrous histiocytoma, myxoinflammatory fibroblastic sarcoma, inflammatory myofibroblastic tumor, and mass-forming fibroinflammatory lesions, as well as key vascular tumors with associated inflammation. To review inflammatory soft tissue tumors most commonly encountered in surgical practice or prone to significant diagnostic challenges. This article will also cover relevant ancillary studies and provide a brief differential diagnosis. Literature review through PubMed search. With advancements in musculoskeletal medicine leading to more targeted treatments, precise histologic classification is key to improving patient outcomes. This is particularly important for inflammatory soft tissue lesions, as some malignant conditions may be mistaken for reactive processes. Achieving an accurate diagnosis relies on identifying morphologic characteristics, considering the clinical presentation, and using appropriate ancillary studies.