Differential diagnosis for diagnostically challenging bland-appearing spindle cell lesions of the breast.
| Diagnosis | Key histological features | SMA | CD34 | Other IHC | Ancillary tests | Behaviour |
| Reactive spindle cell nodule | Haemosiderin deposition, fat necrosis, foreign body giant cell reaction and inflammatory cell infiltrate | + | – | Reactive | ||
| Inflammatory pseudotumour | Inflammatory cell infiltrate | + | – | ~50% ALK+ | Rearrangement of 2p23 (ALK) in ALK+ cases | Reactive |
| Desmoid-type fibromatosis | Long sweeping fascicles of spindle cells with infiltrative growth, open thin-walled vessels | + | – | β-catenin+ | CTNNB1 mutation analyses | Locally aggressive |
| Low-grade fibromatosis-like spindle cell carcinoma | Small clusters of epithelioid cells among spindle cells with mild atypia and infiltrative growth | + | – | pancytokeratin +p63+ | Malignant | |
| Low-grade myofibroblastic sarcoma | Mild focal atypia and infiltrative growth | + | – | fibronectin+ | Fibronectin fibrils and fibronexus junctions in ultrastructural studies | Malignant |
| Nodular fasciitis | Tissue culture-like appearance and extravasated erythrocytes | + | – | Rearrangement of 17p13 (USP6) | Reactive | |
| Pseudoangiomatous stromal hyperplasia | Pseudovascular spaces | +/− | + | PR+, CD31– | Reactive | |
| Myofibroblastoma | Well-circumscribed spindle cell lesion with collagen bands and adipose tissue component | +/− | + | PR+, RB1− | Deletion of 13q14 (RB1) | Benign |
| Fibroadenoma | Admixed benign glandular and stromal elements | +/− | + | Benign | ||
| Phyllodes tumour | Admixed glandular and stromal elements with leaf-like fronds, stromal overgrowth, cytologic atypia, increased mitoses and heterologous elements | +/− | + | Benign or malignant | ||
| Benign fibroblastic spindle cell tumour | Haphazardly arranged fascicles of spindle cells and keloid-like collagen fibres | – | + | RB− | Deletion of 13q14 (RB1) | Benign |
| Spindle cell lipoma | Admixed spindle cells and mature adipocytes | – | + | RB1− | Deletion of 13q14 (RB1) | Benign |
| Solitary fibrous tumour | Branching ‘staghorn’ vasculature | – | + | STAT6+ | Rearrangement of 12q13 (STAT6) | Benign or malignant |
| Dermatofibrosarcoma protuberans | Storiform arrangement of spindle cells with infiltrative growth | – | + | t(17;22)(q22;q13) producing COL1A1-PDGFB fusion | Locally aggressive, rare metastasis | |
| Low-grade fibromyxoid sarcoma | Collagenised hypocellular areas and cellular myxoid nodules | – | – | Rearrangement of 16p11 (FUS) | Malignant |
.+, positive; –, negative; ALK, ALK receptor tyrosine kinase; COL1A1, collagen type I alpha 1 chain;CTNNB1, catenin beta 1;FUS, FUS RNA binding protein;IHC, immunohistochemistry; PDGFSB, platelet derived growth factor subunit B; PR, progesterone receptor;RB1, RB transcriptional corepressor 1;SMA, smooth muscle actin;STAT6, signal transducer and activator of transcription 6;USP6, ubiquitin-specific peptidase 6.