Division of Anatomic Pathology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
Virchows Arch. 2021 Jan;478(1):21-30. doi: 10.1007/s00428-020-03011-3. Epub 2021 Jan 6.
NUT carcinoma, also known as NUT midline carcinoma, is an aggressive malignancy mainly affecting the midline structures of younger patients and almost invariably leading to death within a few months of the diagnosis. Morphologically, NUT carcinoma consists of sheets of monomorphous small or medium size cells with scant cytoplasm, commonly featuring areas of abrupt squamous differentiation with keratinization. Immunohistochemistry for NUT protein is sensitive and specific, typically showing a speckled nuclear reactivity, assisting in diagnosis. The molecular background of NUT carcinoma includes the reciprocal translocation t(15;19) leading to expression of the BRD4-NUT fusion transcript with oncogenic properties. Other less common genes may occasionally be fused with NUT not only in NUT carcinoma but also in other soft tissue tumors, highlighting the fact that NUT-rearranged tumors may represent a larger and more diverse family of neoplasms. Thoracic SMARCA4-deficient undifferentiated tumors are aggressive malignancies diagnosed more often in young male smokers, which often lead to death within a few months. SMARCA4-deficient tumors show undifferentiated morphology with occasional hepatoid and rhabdoid features. Immunohistochemically, the hallmark of diagnosis is loss of expression of SMARCA4 (BRG1). Concurrent loss of SMARCA2 expression, as well as expression of one or more stem cell markers SOX2, CD34, or SALL4 is common. Truncating mutations in SMARCA4, a catalytic subunit of the mammalian BAF (SWI/SNF) complex, are the dominant oncogenic molecular event underlying the pathogenesis of these tumors. SMARCA4 deficiency can also be seen as a passenger somatic event in multiple solid neoplasms manifesting as focal dedifferentiation and rhabdoid morphology.
神经内分泌肿瘤（NUT）癌，也称为 NUT 中线癌，是一种侵袭性恶性肿瘤，主要影响年轻患者的中线结构，几乎无一例外地在诊断后几个月内导致死亡。从形态上看，NUT 癌由形态单一的小或中等大小的细胞片组成，细胞质稀少，常见突然出现角化的鳞状分化区域。NUT 蛋白的免疫组织化学染色具有敏感性和特异性，通常显示斑驳的核反应性，有助于诊断。NUT 癌的分子背景包括导致 BRD4-NUT 融合转录本表达的相互易位 t(15;19)，具有致癌特性。其他不太常见的基因偶尔也可能与 NUT 融合，不仅在 NUT 癌中，而且在其他软组织肿瘤中也是如此，这突出了一个事实，即 NUT 重排肿瘤可能代表一个更大、更多样化的肿瘤家族。胸 SMARCA4 缺陷未分化肿瘤是侵袭性恶性肿瘤，在年轻男性吸烟者中更常见，通常在几个月内导致死亡。SMARCA4 缺陷肿瘤具有未分化的形态，偶尔具有肝细胞样和横纹肌样特征。免疫组织化学检查，诊断的标志是 SMARCA4（BRG1）表达缺失。同时缺失 SMARCA2 表达，以及一个或多个干细胞标志物 SOX2、CD34 或 SALL4 的表达也很常见。SMARCA4 截断突变，一种哺乳动物 BAF（SWI/SNF）复合物的催化亚基，是这些肿瘤发病机制中的主要致癌分子事件。SMARCA4 缺失也可以作为一种乘客体细胞事件，在多种实体肿瘤中表现为局灶性去分化和横纹肌样形态。
