Table 3:
Workup and differential diagnosis of IDH2 mutated sinonasal tumors.
| Diagnosis | Keratins | P63/p40 | S-100 | Neuro-endocrine markers | P16/HPV | EBER ISH | NUT (IHC) | SMARCB1 (INI) (IHC) | SMARCA4 (BRG1) (IHC) | SMARCA2 (BRM) (IHC) | IDH2 R172 (IHC) | Note |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| IDH2 Sinonasal tumor | + | − | − | +/− | − | − | − | Retained | Retained | Retained | + | IDH2 R172 hotspot mutation, at 15q26.1 locus. |
| HPV-related sinonasal carcinoma | + | + | − | -a | + | − | − | Retained | Retained | Retained | − | Including multiphenotypic sinonasal carcinoma (HPV33+). |
| Sinonasal lymphoepithelial carcinoma | + | + | − | − | − | + | − | Retained | Retained | Retained | − | Syncytial growth. |
| NUT-midline carcinoma | + | + | − | − | − | − | + | Retained | Retained | Retained |
BRD4-NUT fusion protein, t(15;19)(q14;p13.1) or NUT-variant. Abrupt keratinization. |
|
| SMARCB1 deficient SNC | + | + | − | − | − | − | − | Lost | Retained | Retained | − |
hSNF5/INI1 loss (SMARCB1) at 22q11.2 locus. Cytoplasmic vacuoles. Rhabdoid or plasmacytoid cells. |
| SMARCA4 deficient SNC | + | + | − | − | − | − | − | Retained | Lost | Retainedb | − | BRG1 loss (SMARCA4) at 19p13.2, with or without BRM loss (SMARCA2) at 9p24.3 locus. |
| Olfactory neuroblastoma | − | − | + | + | − | − | − | Retained | Retained | Retained | − | − |
| Small cell neuroendocrine carcinoma | + | − | − | + | − | − | − | Retained | Retained | Retained | − | − |
| Large cell neuroendocrine carcinoma | + | − | − | + | − | − | − | Retained | Retained | Retained | − | − |
| IDH2 wild-type LCNEC | + | − | − | + | − | − | − | Retained | Retained | Retained | − | − |
| IDH2 wild-type SNUC or PDC | + | − | − | − | − | − | − | Retained | Retained | Retained | − | − |
| Melanoma | − | − | + | − | − | − | − | Retained | Retained | Retained | − | Melanin pigment, binucleation or multinucleation. Positive for Melan-A, HMB45, SOX10, etc. |
| Diffuse large B-cell lymphoma | − | − | − | − | − | − | − | Retained | Retained | Retained | − | Discohesive cells. Positive for CD20, PAX5, etc. |
a
May be focally positive in HPV-SCC and HPV-LCNEC.
b
May be lost in 13% of cases. SNC: sinonasal carcinoma, SCC: small cell carcinoma, LCNEC: large cell neuroendocrine carcinoma, PDC: poorly differentiated carcinoma, NOS: not otherwise specified.