Legrand Mélanie, Louveau Baptiste, Osio Amélie, Tallet Anne, Calonje Eduardo, Scoazec Jean-Yves, de la Fouchardiere Arnaud, Tirode Franck, Von Deimling Andreas, Busam Klaus, Shah Ahmed, Flaman Ashley, Jouenne Fanélie, Mourah Samia, Pissaloux Daniel, Lantuejoul Sylvie, French Christopher A, Goto Keisuke, Cribier Bernard, Dehner Carina A, Alomari Ahmed K, Fletcher Christopher Dm, Hanna John, Macagno Nicolas, Battistella Maxime, Kervarrec Thibault
Department of Pathology, Centre Hospitalier Universitaire de Tours, Université de Tours, Tours, France.
Université Paris Cité, Paris, France.
Histopathology. 2025 Sep;87(3):375-387. doi: 10.1111/his.15444. Epub 2025 Mar 24.
NUT carcinoma is a rare malignant neoplasm characterised by recurrent NUTM1 rearrangements, initially reported in the midline. Recently, 10 cases of cutaneous NUT carcinoma with adnexal differentiation harbouring BRD3::NUTM1, NSD3::NUTM1, BRD4::NUTM1 or BRD3::NUTM2B fusions have been reported. Accordingly, 'NUT adnexal carcinoma' (NAC) has been introduced as a provisional tumour entity to the fifth edition of the WHO Classification of Skin Tumours.
We report the histopathological, molecular genetic and epigenetic features of seven additional cases of NAC.
The cohort consisted of four female and three male patients with a median age of 58 years. Follow-up was available for six cases, and documented diffuse metastatic spreading leading to death at 18 months after diagnosis for one case. Histopathological examination in all cases revealed dermal/subcutaneous neoplasms composed of poorly differentiated cells with large irregular vesicular nuclei and at least focally prominent nucleoli. All cases showed areas of duct/gland formation. Using immunohistochemistry, all tumours showed diffuse NUT expression with co-expression of SOX10 in five cases. P63 and P40 were diffusely positive in one case and confined to the periphery of the tumour nests in five cases. Molecular analysis showed BRD4::NUTM1 fusions (n = 3), BRD3::NUTM1 fusions (n = 3) and NSD3::NUTM1 (n = 1). Although being close to this latter group, methylation and transcriptional analysis revealed that NAC formed a unique cluster distinct from extracutaneous NUT carcinoma and NUTM1-rearranged porocarcinoma.
Our results further support the existence of primary cutaneous NAC and suggest that it may represent an entity distinct from extracutaneous NUT carcinoma.
NUT癌是一种罕见的恶性肿瘤，其特征为NUTM1反复重排，最初报道于中线部位。最近，已有10例具有附件分化的皮肤NUT癌病例被报道，这些病例存在BRD3::NUTM1、NSD3::NUTM1、BRD4::NUTM1或BRD3::NUTM2B融合。因此，“NUT附件癌”（NAC）已被作为一个临时肿瘤实体引入到《世界卫生组织皮肤肿瘤分类》第五版中。
我们报告另外7例NAC的组织病理学、分子遗传学和表观遗传学特征。
该队列包括4名女性和3名男性患者，中位年龄为58岁。6例患者有随访记录，其中1例在诊断后18个月记录到弥漫性转移扩散导致死亡。所有病例的组织病理学检查均显示真皮/皮下肿瘤，由分化差的细胞组成，细胞核大且不规则呈泡状，至少局灶性核仁明显。所有病例均显示有导管/腺体形成区域。采用免疫组织化学方法，所有肿瘤均显示NUT弥漫性表达，5例同时表达SOX10。1例P63和P40弥漫性阳性，5例局限于肿瘤巢周边。分子分析显示BRD4::NUTM1融合（n = 3）、BRD3::NUTM1融合（n = 3）和NSD3::NUTM1（n = 1）。尽管与后一组接近，但甲基化和转录分析显示NAC形成了一个独特的聚类，与皮肤外NUT癌和NUTM1重排的汗孔癌不同。
我们的结果进一步支持原发性皮肤NAC的存在，并表明它可能是一种与皮肤外NUT癌不同的实体。
