Table 10.
Differential diagnoses of LGFMS.
| Diagnosis | Morphology | IHC | Common Genetic Alterations |
|---|---|---|---|
| Desmoid-type fibromatosis | Long, sweeping fascicles; slender uniform spindle cells; pale cytoplasm; and parallel to fascicles thin-walled blood vessels with perivascular edema | Beta-catenin (nuclear), SMA, and desmin (focal) | CTNNB1 or APC mutations |
| Nodular fasciitis | Plump spindle cells; tissue-culture aspect; extravasated erythrocytes; lymphocytes; and sometimes osteoclast-like giant cells | Non-specific: SMA, CD68, and desmin (focal) | USP6 rearrangements (diverse fusion partners) |
| Ossifying fibromyxoid tumor (mostly benign, rarely malignant) | Multilobulated; nests/cords of uniform round-spindle cells; indistinct cytoplasm; no atypia (rarely high nuclear grade in malignant lesions); fibromyxoid stroma; partial rim of mature bone; and atypical osteoid in malignant tumors | S100, desmin, GFAP (focal), and pankeratin (rare) | PHF1 rearrangements (diverse fusion partners) |
| Neurofibroma | Nodular or diffuse growth; variable admixture of perineurial cells, schwann cells and fibroblasts; hyperchromasia; usually no atypia or mitoses; and myxoid-collagenous stroma with “shredded-carrot” collagen | S100, SOX10, CD34, and EMA | NF1 deletions |
| Perineurioma | Nodular; non-encapsulated; circumscribed or infiltrative; whorled/storiform/fascicular pattern; and slender spindle cells with bipolar cytoplasmic extensions and uniform oval or elongated nuclei | EMA, GLUT1, CD34, and Claudin 1 | TRAF7 mutations (intraneural perineurioma); NF1/2 deletions |
| Desmoplastic fibroblastoma | Paucicellular; bland stellate-spindle cells; and abundant collagenous-myxocollagenous stroma | FOSL1, SMA (focal) | t(2;11) |
| Malignant peripheral nerve sheath tumor | Fascicles of monomorphic atypical spindle cells with perivascular accentuation and alternating cellularity; pleomorphism is possible; staghorn vessels; geographic necrosis; and heterologous differentiation | S100, SOX10 (focal), and loss of H3K27me3 | Inactivating mutations of NF1, CDKN2A/B, EED, and SUZ2 |
| Fibroma nuchae | Paucicellular; bland spindle cells; thick collagen bundles; and entrapped adipose tissue and/or small nerves | CD34 | Not relevant |
| Intramuscular (cellular) myxoma | Myxoid stroma; hypocellular; uniform spindle-stellate cells; inconspicuous vessels; and infiltration into skeletal muscle | CD34 | GNAS mutations |
| Dermatofibrosarcoma protuberans | Dermal based; cellular, storiform pattern of uniform spindle cells; encasement of skin appendages; and infiltration in subcutaneous fat with honeycombing | CD34 | COL1A1-PDGFB (most often); COL6A3-PDGFD or EMILIN2-PDGFD (rare) |
| NTRK-rearranged spindle cell neoplasm (emerging) | Wide spectrum of morphologies and histological grades; most often haphazardly arranged monomorphic spindle cells; variable stromal/perivascular hyalinization; and infiltrative growth into fat | S100, CD34 (co-expression), and NTRK | NTRK1-3 rearrangements (diverse fusion partners); RAF1 or BRAF fusions (rare) |