Benign |
Schwannoma | Focal palisading; spindled or wavy nuclei with pointed ends and fine, smooth chromatin; Fibrillary, fibrotic, or myxoid stroma; rare atypia | Diffuse, strong S100 and SOX10; Pancytokeratin staining is common; GFAP and CD34 is variable |
Desmoid tumor (fibromatoses) | Long fascicular fragments; Bland spindled fibroblasts/myofibroblasts; Oval nuclei with even chromatin | Nuclear β-catenin staining; CTNNB1 or APC mutations in up to 75% of cases; Patchy SMA staining, and rare desmin staining |
Leiomyoma | Irregular contoured cohesive fragments; Bland ovoid nuclei with blunted ends; Dense cytoplasm with distinct boundaries | Positive for SMA and desmin; Negative for S100, c-kit, DOG1, β-catenin, and ALK |
Solitary fibrous tumor | Discohesive fragments, irregular fascicles; Bland spindle cells, pale indistinct cytoplasm; Fusiform nuclei, prominent collagenous stroma | CD34, STAT6 (nuclear), BCL2, EMA positive; Negative for pancytokeratin, S100, desmin, c-kit; Characteristic NAB2::STAT6 fusion |
Inflammatory fibroblastic tumor | Fibroblast-like to epithelioid cells; Prominent nuclear atypia and nucleoli; Abundant plasma cells and lymphocytes | Positive for SMA and ALK; ALK gene rearrangements |
Malignant |
Malignant peripheral nerve sheath tumor | Fascicles of spindle or epithelioid cells; Enlarged slender, wavy nuclei; Marked pleomorphism and mitoses | S100 and SOX10 show patchy positivity |
Leiomyosarcoma | Hypercellular; fascicles and dispersed cells; Blunt-ended nuclei, eosinophilic cytoplasm; Mitoses and necrosis | Positive for SMA and desmin; Negative for S100, c-kit, DOG1, β-catenin, and ALK |
Type A thymoma | Spindled cells with oval nuclei and inconspicuous nucleoli; Type AB: admixed with lymphocytes | Positive for pancytokeratin, p63, and p40 |
Lymphangioleiomyomatosis | Spindled to cuboidal cells with oval nuclei and minimal atypia | Positive for SMA, HMB45, melan-A, ER and PR; Negative for pancytokeratin and S100 |
Synovial sarcoma | Monophasic: Uniform spindle cells with ovoid nuclei. Biphasic: Spindle and epithelioid cells in varying proportions | Positive for BCL2, EMA, pancytokerain, and CD99; TLE1 positivity is highly specific, negative for CD34; Characteristic SS18::SSX fusion |
Sarcomatoid mesothelioma | Hypocellular smears; few cohesive fragments of atypical spindle cells, ranging from bland to pleomorphic, occasionally collagenous stroma | Positive often for low molecular weight cytokeratin, vimentin, WT1, D2-40, and calretinin; BAP1 is often retained in sarcomatoid form; Homozygous deletion of 9p21 (CDKN2A) |
Spindle cell carcinoma | Fascicles and single spindle cells with pleomorphism, mitosis, and necrosis | Positive for vimentin, variable cytokeratin and TTF1 staining; MET exon 14-skipping mutations |
Spindle cell melanoma | Whorls and single slender spindle cells; Variable nuclear pleomorphism; melanin pigment | Positive for S100, SOX10, and MART1; BRAF p.V600E |
Spindle cell neuroendocrine tumor | Single cells, uniform ovoid or spindle nuclei: +/− plexiform vessels Carcinoid v. atypical carcinoid; +/− atypia, necrosis, mitosis | Positive for neuroendocrine markers; MEN1 mutations |
Pulmonary artery intimal sarcoma | Loosely cohesive fascicles of malignant-appearing spindle cells; Variable nuclear atypia | Variable mesenchymal differentiation, may be positive for desmin, SMA, myogenin, S100, ERG, and CD31; MDM2, PDGFRA, and KIT amplifications |