Table 1. The 2022 WHO classification of PitNETs, 5th edition.
| PitNET type | Subtype | Transcription factors | Hormones | LMWK | |
|---|---|---|---|---|---|
| PIT1-lineage PitNETs | |||||
| Somatotroph tumors | Densely granulated | PIT1 | GH, α-subunit | Perinuclear | |
| Sparsely granulated | PIT1 | GH | Fibrous bodies (>70%) | ||
| Lactotroph tumors | Sparsely granulated | PIT1, ERα | PRL (paranuclear dot-like) | Weak or negative | |
| Densely granulated | PRL (difuse cytoplasmic) | Weak or negative | |||
| Mammosomatotroph tumor | PIT1, ERα | GH (predominant), PRL, α-subunit | Perinuclear | ||
| Thyrotroph tumor | PIT1, GATA3 | α-subunit, βTSH | Weak or negative | ||
| Mature plurihormonal PIT1-lineage tumor | PIT1, ERα, GATA3 | Monomorphic tumor cells with predominant GH expression and variable PRL, βTSH, and α-subunit | Perinuclear | ||
| Immature PIT1-lineage tumor | PIT1, ERα, ATA3 | Monomorphic tumor cells with focal/variable staining for no hormones, or one or more of GH, PRL, βTSH, and/or α-subunit | Focal/variable | ||
| Acidophil stem cell tumor | PIT1, ERα | Monomorphic tumor cells with PRL (predominant) and GH (focal/variable) | Scattered fibrous bodies | ||
| Mixed somatotroph and lactotroph tumor* | PIT1, ERα† | Somatotroph tumor component: GH±α-subunit depending on tumor subtype; lactotroph tumor component: PRL (diffuse or paranuclear depending on the subtype) | Tumor subtype characteristic | ||
| TPIT-lineage PitNETs | |||||
| Corticotroph tumors | Densely granulated | TPIT, NeuroD1(β2) | ACTH and other POMC | Strong, always diffuse | |
| Derivates | |||||
| Sparsely granulated | Variable (often diffuse) | ||||
| Crooke cell tumor | Intense ring-like perinuclear | ||||
| SF1-lineage PitNETs | |||||
| Gonadotroph tumor | SF1, ERα, GATA3 | α-subunit, βFSH, βLH, or none | Variable or negative | ||
| PitNETs without distinct cell lineage | |||||
| Plurihormonal tumor | Multiple combinations | Multiple combinations in a monomorphous tumor population | Variable | ||
| Null cell tumor | None | None | Variable | ||
*These tumors are composed of two morphologically and immunohistochemically distinct tumor cell populations; †Positive in the lactotroph tumor component. PitNET, pituitary neuroendocrine tumor; LMWK, low molecular weight cytokeratin; PIT1, pituitary-specific positive transcription factor 1; GH, growth hormone; ERα, estrogen receptor α; PRL, prolactin; GATA3, GATA-binding protein 3; SF1, steroidgenoic factor 1; GATA, binding protein 3; TPIT, T-box family member TBX19; ACTH, adrenocorticotropic hormone; POMC, pro-opiomelanocortin; FSH, follicle-stimulating hormone; LH, luteinizing hormone