Cutaneous Primary NUT Carcinoma With BRD3-NUTM1 Fusion

The Hippo pathway in cancer: YAP/TAZ and TEAD as therapeutic targets in cancer

“…However, it is apparent that fusion partners play a role in tumour development, with C-terminal fusion fragments exhibiting frequent conservation of nuclear localisation signal (NLS) and TAD motifs [ 98 , 115–118 ] ( Figure 2 ), as demonstrated by glutamine-rich and highly acidic regions historically associated with TF-binding transactivation domains [ 119 , 120 ]. This is further evidenced by a case of porocarcinoma reported with a BRD3-NUTM1 fusion, independent of YAP rearrangement [ 121 ]. Collectively, these findings emphasise directly that YAP and TAZ, in combination with functional fragments of select fusion partners, are essential drivers in a subset of rare cancer varieties, likely in a highly context-specific manner, given the relative absence of YAP/TAZ fusions in cancer types arising from different tissues.…”

Fusion‐positive skin/adnexal carcinomas

“…More recently, a skin adnexal carcinoma with follicular infundibular differentiation harboring a novel BRD3::NUTM2B fusion was reported. 35 The tumor originated in the shoulder of a 7-year-old girl and was associated with positive sentinel lymph node, but follow-up revealed an unremarkable course at 23 months. That case was histologically different from porocarcinoma based on the higher degree of cellular differentiation with variable amounts of eosinophilic cytoplasm, presence of focal clear-cells, multiple keratocystic structures showing follicular infundibular differentiation (also in the lymph node metastasis), and lack of connection with the epidermis.…”

“…More recently, a skin adnexal carcinoma with follicular infundibular differentiation harboring a novel BRD3::NUTM2B fusion was reported 35 . The tumor originated in the shoulder of a 7‐ year‐old girl and was associated with positive sentinel lymph node, but follow‐up revealed an unremarkable course at 23 months.…”

“…That case was histologically different from porocarcinoma based on the higher degree of cellular differentiation with variable amounts of eosinophilic cytoplasm, presence of focal clear-cells, multiple keratocystic structures showing follicular infundibular differentiation (also in the lymph node metastasis), and lack of connection with the epidermis. 35 On the other hand, the low-grade cytology, scarcity of mitoses, absence of necrosis, and of perineural and lymphovascular invasion were considered in line with the indolent behavior and arguments against NUT carcinoma. 35 The authors concluded that the tumor they were reporting does not fit into any existing cutaneous adnexal carcinoma entity but might represent a variant in the spectrum of infundibular carcinomas.…”

“…35 On the other hand, the low-grade cytology, scarcity of mitoses, absence of necrosis, and of perineural and lymphovascular invasion were considered in line with the indolent behavior and arguments against NUT carcinoma. 35 The authors concluded that the tumor they were reporting does not fit into any existing cutaneous adnexal carcinoma entity but might represent a variant in the spectrum of infundibular carcinomas.…”