Table 1.
Summary of 26 cases of NUTM1-rearranged neoplasia
| Case | Submitting diagnosis | Final diagnosis | Age, sex | Clinical primary site | Gene fusiona | NUT IHC | IHC positive | IHC negative |
|---|---|---|---|---|---|---|---|---|
| 1 | Poorly differentiated neoplasm, favor large cell neuroendocrine carcinoma | NUT carcinoma with large cell neuroendocrine carcinoma-like features | 39, F | Paranasal sinuses | BRD4-NUTM1 | NT | CAM5.2, SYN | Pankeratin |
| 2 | Poorly differentiated carcinoma, non-small cell type | NUT carcinoma | 46, M | Mediastinum | BRD4-NUTM1 | NT | p63, CK7 | TTF1, CHR, SYN, B72.3, CD5 |
| 3 | Metastatic squamous cell carcinoma | NUT carcinoma | 13, M | Bone (proximal humerus) | X-NUTM1 | NT | n/a | n/a |
| 4 | Large cell neuroendocrine carcinoma | NUT carcinoma, with large cell neuroendocrine carcinoma-like features | 36, M | Lung and chest | BRD4-NUTM1 | NT | p63, CK5/6 focal, SYN | CHR, TTF1, Napsin A, Pankeratin, S100, CD56, CK20 |
| 5 | Undifferentiated malignant neoplasm | NUT carcinoma | 12, M | Soft tissue (neck) | BRD4-NUTM1 | NT | AE1/AE3, CK5/6, CAM5.2, CK19, patchy p63, SYN, CD99 | CHR, desmin, SMA, myogenin, GFAP, CD34, HMB45, MelanA, CD20, CD3, CD79a, CD30, ALK1, TDT, INI-1 retained |
| 6 | Poorly differentiated squamous cell carcinoma | NUT carcinoma | 49, M | Frontal sinus | BRD4-NUTM1 | NT | p63, CK5/6, CK7, p16 | TTF1, SYN, CHR |
| 7 | Favor NUT midline carcinoma | NUT carcinoma | 48, M | Ethmoid sinus, orbit | BRD4-NUTM1 | NT | AE1/AE3, EMA | SYN, CHR, TTF1, GFAP |
| 8 | Nonkeratinizing squamous cell carcinoma | NUT carcinoma | 30, M | Floor of mouth, glottis | BRD4-NUTM1 | NT | AE1/AE3, p63, CK5/6, SYN, p16 | CHR, OCT3/4 |
| 9 | Undifferentiated carcinoma with abrupt squamous differentiation | NUT carcinoma | 49, M | Sinonasal | BRD4-NUTM1 | NT | PanCK, p63, CD99 | CHR, SYN, S100 |
| 10 | Poorly differentiated carcinoma with squamous and glandular differentiation | NUT carcinoma with squamous and glandular differentiation | 44, M | Lung | BRD4-NUTM1 | NT | PanCK, TTF1 (patchy weak), p63, CK5/6, p16 | Napsin A, CK20 |
| 11 | Poorly differentiated/high-grade carcinoma | NUT carcinoma | 32, F | Ovary and lung | BRD4-NUTM1 | NT | AE1/AE3 | PLAP, CD30, S100, CHR, SYN, Calretinin, inhibin, MelanA |
| 12 | Undifferentiated carcinoma | NUT carcinoma | 67, F | Nasal and maxillary sinus | BRD4-NUTM1 | NT | p63, SYN | CHR, S100, CD99, CK7, CK5/6, Desmin, CD34 |
| 13 | Undifferentiated malignant neoplasm | Malignant neoplasm of uncertain lineage with BRD4-NUTM1 | 47, F | Sphenoid sella | BRD4-NUTM1 | NT | None | p40, EMA, CK5/6, SYN, CHR, PLAP, OCT3/4, Melan-A, CD34, desmin, FLI1, CD68, CD30 |
| 14 | Poorly differentiated non-small cell carcinoma with squamous features | NUT carcinoma | 44, M | Pleura | BRD4-NUTM1 | Pos | p63, patchy TTF1, CK5/6 | Napsin A |
| 15 | Poorly differentiated squamous cell carcinoma | NUT carcinoma | 56, F | Skull Base | BRD4-NUTM1 | Pos | CAM5.2 | CHR, SYN, CD56 |
| 16 | Squamous cell carcinoma | NUT carcinoma | 56, F | Lacrimal sac | BRD4-NUTM1 | Pos | CK5/6, p63 | BER-EP4 |
| 17 | Basaloid carcinoma | NUT carcinoma | 36, M | Lung (hilar) | NSD3-NUTM1 | NT | p63 | TTF1, SYN, CHR |
| 18 | Poorly differentiated carcinoma | NUT carcinoma | 35, M | Lung | BRD3-NUTM1 | Pos | n/a | n/a |
| 19 | Poorly differentiated carcinoma | NUT carcinoma | 45,M | Lung | BRD4-NUTM1 | Pos | n/a | n/a |
| 20 | Spindle cell sarcoma with features of myxoid chondrosarcoma metastatic to liver | NUT sarcoma with features of myxoid chondrosarcoma metastatic to liver | 63, F | Lung primary | MGA-NUTM1 | Pos | n/a | n/a |
| 21 | Small round blue cell malignancy | NUT rearranged tumor with a small round cell pattern | 38, F | Lung | BRD4-NUTM1 | NT | SYN | CHR, CAM5.2, STAT6, CD99, CD45, desmin, SMA, S100, CD34 |
| 22 | Extraosseous osteosarcoma | NUT sarcoma with a small round/epithelioid cell pattern, and scant fibrous matrix, high-grade | 65, F | Colon (cecum) | MXD4-NUTM1 | Pos | Vimentin | AE1/AE3, EMA, CK19, CK20 |
| 23 | Squamous cell carcinoma | NUT carcinoma | 74, M | Lung, mets to liver | NSD3-NUTM1 | Pos | CK5/6, p63, CD56 | CK7,NapsinA,TTF1 |
| 24 | NUT midline carcinoma | NUT Carcinoma | 29, M | Mediastinum | BRD4-NUTM1 | Pos | AE1/3, Cam5.2, CK7, CK20, EMA, p63 | n/a |
| 25 | NUT midline carcinoma | NUT sarcoma with a round-oval cell pattern and fibrous matrix | 61, M | Chest wall/pleural | MGA-NUTM1 | Pos | Weakly positive for CD34 in a subset of cells | Pankeratin, CD45, CD43, calretinin, desmin, myogenin, S100, AFP, CD30, CD43, CD45, CD68, PLAP |
| 26 | Extraskeletal myxoid chondrosarcoma, solid variant | NUT sarcoma with features of extraskeletal myxoid chondrosarcoma with a solid pattern | 48, M | Foot (lung metastasis 4 years later) | X-NUTM1 | Pos | Estrogen receptor, minimal dot-like keratin positivity (AE1/AE3 cocktail) | GFAP, S100, SMA |
NT not tested, n/a not available, IHC immunohistochemistry, SYN synaptophysin, CHR chromogranin, PanCK pan-cytokeratin, SMA smooth muscle actin, X unknown partner
a
Cases 1–13: fusions identified by FISH
a
Cases 14–25: fusions identified by Archer
a
Case 26: NUT break-apart FISH only. Identified by NUT IHC screening of a tissue microarray composed of cases previously diagnosed as extraskeletal myxoid chondrosarcoma