Table 5.
Differential diagnoses of AFH.
| Diagnosis | Morphology | IHC | Common Genetic Alterations |
|---|---|---|---|
| Histiocytic lesions | Diverse; histiocytes; and multinucleated giant cells | Diverse (depending on entity); CD68, CD163, and FXIIIA | Diverse (depending on entity); activating MAPK signaling mutations (BRAF, NRAS, KRAS, ARAF, and MAP2K1) |
| Follicular dentritic sarcoma | Fascicles/whorls/storiform pattern; oval-spindle cells with small nucleoli and syncytial borders; nuclear pseudoinclusions; binucleate (often) or multinucleate (rare) forms; and admixed lymphocytic infiltrate with perivascular lymphocytic cuffs | CD21, CD23, CD35, and D2-40 | Highly diverse mutational profile |
| Small, blue round-cell tumors See Table 1 and Table 2 |
Cells with small round-oval-spindle cells with scant cytoplasm | Diverse (depending on entity) | Diverse (depending on entity) |
| Epithelioid fibrous histiocytoma | Polypoid; epidermal collarette; epithelioid cells with vesicular nuclei, small nucleoli, and amphophilic cytoplasm | FXIIIA, EMA, and ALK | ALK rearrangements (various fusion partners) |
| Aneurysmatic fibrous histiocytoma | Epidermal hyperplasia and basal layer pigmentation; circumscribed, dermal based proliferation; haphazard arrangement of ovoid spindle cells; admixed foam and giant cell; central blood-filled cystic space; and abundant hemosiderin deposition | FXIIIA, SMA | Not specific |
| Rhabdomyosarcoma | Monomorphic primitive round cells with variable rhabdomyoblastic differentiation (depending on subtype) | Desmin, myogenin, and MyoD1 | Diverse (depending on subtype); PAX3/PAX7-FOXO1 fusions (ARMS); alterations of RAS signaling pathway (embryonal RMS) |
| Rhabdoid tumor | Solid pattern; rounded-polygonal cells with vesicular nuclei and prominent nucleoli; and eosinophil hyaline-like cytoplasmic inclusions | Diverse; keratins, EMA, CD99, synaptophysin, SALL4, glypican-3, and INI1 loss | SMARCB1 biallelic loss |
| Inflammatory myofibroblastic tumor | Fascicular pattern (variable); plump-spindle cells with vesicular nuclei and small nucleoli; amphophilic cytoplasm; oedematous-myxoid-fibrous stroma; and mixed inflammatory infiltrate | SMA, calponin, desmin, keratin (focal), ALK, and ROS1 | ALK rearrangements (various fusion partners); ROS1, NTRK3, RET, or PDGFRB rearrangements |
| Carcinoma | Sheets/nests/trabecula; round-oval-epithelioid cells with nuclear atypia and variable amount of cytoplasm | Pankeratins, lineage specific markers (depending on site of origine) | Diverse (depending on site of origin) |
| Meningeoma | Highly diverse (according to subtype and grade): lobulated; whorled, fascicular pattern; spindle or plump syncytial cells; intranuclear pseudoinclusions; and psammoma bodies | EMA, S100, and PR | Monosomy 22; NF2 deletions |
| Extraskeletal myxoid chondrosarcoma | Multinodular; lace-like/reticular pattern; round-spindle monomorphic cells; eosinophilic cytoplasm; and myxoid matrix | Non-specific; S100 (focal) | NR4A3-EWSR1-/TAF15/TCF12/TFG |
| Myoepithelioma (syncytial) | Cutaneous; poorly marginated; syncytial growth; sheets of uniform ovoid-histiocytoid-epithelioid cells; and minimal stroma | S100, EMA, GFAP, SMA, and calponin | EWSR1-PBX3 |
| Myxoid liposarcoma | Lobulated; primitive uniform round-ovoid cells; variable number of lipoblasts; myxoid stroma; and plexiform vasculature (chicken wire) | DDIT3 | FUS/EWSR1-DDIT3 |