-
摘要: NUT癌(NUT Carcinoma)是一种罕见的起源不明的具有高度侵袭性的恶性肿瘤,其以伴有NUTM1 基因染色体重排为主要特点,病理表现为具有突然和局灶性鳞状分化低分化或未分化癌,FISH检测见NUTM1 基因重排可明确诊断,NUT癌预后较差,临床上并未明确治疗方案,治疗方式多为手术、放疗及化疗。本文报道1例74岁鼻腔鼻窦NUT癌患者,临床表现为右侧鼻塞伴面部肿胀,鼻窦CT及MRI示右侧鼻腔及上颌窦软组织密度影伴骨质破坏,入院后行鼻窦肿物活检术,术后病理FISH染色结果示BRD4/NUT融合t(15,19),予序贯同步放化疗2个疗程后肿物显著减小,2个月后肿物再次迅速增长侵及硬腭影响进食,行上颌骨部分切除术,术后2个月患者因肿瘤转移累及全身脏器衰竭死亡,生存期11个月,现对本病例的临床特征和诊疗经过进行报告及相关文献复习。Abstract: NUT Carcinoma(NC) is a rare malignant tumor of unknown origin, which is highly aggressive. It is characterized by chromosome rearrangement accompanied by NUTM1 gene. The pathological manifestations were sudden and focal squamous in poorly differentiated or undifferentiated carcinoma. NUTM1gene rearrangement can be used to diagnose NC. The prognosis of NUT cancer is poor. Clinically, there is no established treatment plan. treatment options mainly comprise surgery, radiotherapy and chemotherapy. A 74-year-old patient with NC of the nasal cavity and sinuses was reported. Her clinical presentation was right nasal congestion with facial swelling. Sinus CT and MRI showed soft tissue density in the right nasal cavity and maxillary sinus with bone destruction. After admission, the patient underwent nasal endoscopic biopsy, and the postoperative pathological FISH staining showed BRD4/NUT fusion t(15, 19). The tumor was significantly reduced after two courses of sequential chemoradiotherapy. Two months later, the patient underwent a partial maxillary resection due to the rapid regrowth of sinusoidal mass, invading the hard palate. The patient died 2 months after surgery due to multiple organ failure resulted from tumor metastasis, with a survival time of 11 months. The clinical characteristics, diagnosis and treatment of this case were reported and related literature was reviewed.
-
Key words:
- NUT carcinoma /
- clinical diagnosis /
- treatment /
- prognosis /
- sinus tumor
-
[1] French CA. NUT Carcinoma: Clinicopathologic features, pathogenesis, and treatment[J]. Pathology international, 2018, 68: 583-595. doi: 10.1111/pin.12727
[2] Kubonishi I, Takehara N, Iwata J, et al. Novel t(15;19)(q15;p13) chromosome abnormality in a thymic carcinoma[J]. Cancer Res, 1991, 51(12): 3327-3328.
[3] French CA, Miyoshi I, Kubonishi I, et al. BRD4-NUT fusion oncogene: a novel mechanism in aggressive carcinoma[J]. Cancer Res, 2003, 63(2): 304-307.
[4] Sholl LM, Nishino M, Pokharel S, et al. Primary Pulmonary NUT Midline Carcinoma: Clinical, Radiographic, and Pathologic Characterizations[J]. J Thorac Oncol, 2015, 10(6): 951-959. doi: 10.1097/JTO.0000000000000545
[5] Shehata BM, Steelman CK, Abramowsky CR, et al. NUT midline carcinoma in a newborn with multiorgan disseminated tumor and a 2-year-old with a pancreatic/hepatic primary[J]. Pediatr Dev Pathol, 2010, 13(6): 481-485. doi: 10.2350/09-10-0727-CR.1
[6] Bishop JA, French CA, Ali SZ. Cytopathologic features of NUT midline carcinoma: A series of 26 specimens from 13 patients[J]. Cancer Cytopathol, 2016, 124(12): 901-908. doi: 10.1002/cncy.21761
[7] French CA, Kutok JL, Faquin WC, et al. Midline carcinoma of children and young adults with NUT rearrangement[J]. J Clin Oncol, 2004, 22(20): 4135-4139. doi: 10.1200/JCO.2004.02.107
[8] Mengoli MC, Longo FR, Fraggetta F, et al. The 2015 World Health Organization Classification of lung tumors: new entities since the 2004 Classification[J]. Pathologica, 2018, 110(1): 39-67.
[9] Stevens TM, Morlote D, Xiu J, et al. NUTM1-rearranged neoplasia: a multi-institution experience yields novel fusion partners and expands the histologic spectrum[J]. Mod Pathol, 2019, 32(6): 764-773. doi: 10.1038/s41379-019-0206-z
[10] Giridhar P, Mallick S, Kashyap L, et al. Patterns of care and impact of prognostic factors in the outcome of NUT midline carcinoma: a systematic review and individual patient data analysis of 119 cases[J]. Eur Arch Otorhinolaryngol, 2018, 275(3): 815-821. doi: 10.1007/s00405-018-4882-y
[11] Lee JK, Louzada S, An Y, et al. Complex chromosomal rearrangements by single catastrophic pathogenesis in NUT midline carcinoma[J]. Ann Oncol, 2017, 28(4): 890-897. doi: 10.1093/annonc/mdw686
[12] French CA, Ramirez CL, Kolmakova J, et al. BRD-NUT oncoproteins: a family of closely related nuclear proteins that block epithelial differentiation and maintain the growth of carcinoma cells[J]. Oncogene, 2008, 27(15): 2237-2242. doi: 10.1038/sj.onc.1210852
[13] French CA, Rahman S, Walsh EM, et al. NSD3-NUT fusion oncoprotein in NUT midline carcinoma: implications for a novel oncogenic mechanism[J]. Cancer Discov, 2014, 4(8): 928-941. doi: 10.1158/2159-8290.CD-14-0014
[14] Alekseyenko AA, Walsh EM, Zee BM, et al. Ectopic protein interactions within BRD4-chromatin complexes drive oncogenic megadomain formation in NUT midline carcinoma[J]. Proc Natl Acad Sci USA, 2017, 114(21): E4184-E4192.
[15] Shiota H, Elya JE, Alekseyenko AA, et al. "Z4" Complex Member Fusions in NUT Carcinoma: Implications for a Novel Oncogenic Mechanism[J]. Mol Cancer Res, 2018, 16(12): 1826-1833. doi: 10.1158/1541-7786.MCR-18-0474
[16] Grayson AR, Walsh EM, Cameron MJ, et al. MYC, a downstream target of BRD-NUT, is necessary and sufficient for the blockade of differentiation in NUT midline carcinoma[J]. Oncogene, 2014, 33(13): 1736-1742. doi: 10.1038/onc.2013.126
[17] Huang QW, He LJ, Zheng S, et al. An Overview of Molecular Mechanism, Clinicopathological Factors, and Treatment in NUT Carcinoma[J]. Biomed Res Int, 2019, 2019: 1018439.
[18] Bauer DE, Mitchell CM, Strait KM, et al. Clinicopathologic features and long-term outcomes of NUT midline carcinoma[J]. Clin Cancer Res, 2012, 18(20): 5773-5779. doi: 10.1158/1078-0432.CCR-12-1153
[19] 涂晓敏, 任建君, 赵宇. 头颈鳞状细胞癌危险因素及遗传风险的研究进展[J]. 临床耳鼻咽喉头颈外科杂志, 2022, 36(5): 391-396. https://lceh.whuhzzs.com/article/doi/10.13201/j.issn.2096-7993.2022.05.015
[20] Lee T, Cho J, Baek CH, et al. Prevalence of NUT carcinoma in head and neck: Analysis of 362 cases with literature review[J]. Head Neck, 2020, 42(5): 924-938. doi: 10.1002/hed.26067
[21] 黄志刚, 文卫平, 毛薇, 等. 头颈肿瘤的综合治疗策略[J]. 临床耳鼻咽喉头颈外科杂志, 2023, 37(9): 673-690. https://lceh.whuhzzs.com/article/doi/10.13201/j.issn.2096-7993.2023.09.001
[22] Haack H, Johnson LA, Fry CJ, et al. Diagnosis of NUT midline carcinoma using a NUT-specific monoclonal antibody[J]. Am J Surg Pathol, 2009, 33(7): 984-991. doi: 10.1097/PAS.0b013e318198d666
[23] Fujioka N, French CA, Cameron MJ, et al. Long-term survival of a patient with squamous cell carcinoma harboring NUT gene rearrangement[J]. J Thorac Oncol, 2010, 5(10): 1704-1705. doi: 10.1097/JTO.0b013e3181ebaa20
[24] Stathis A, Zucca E, Bekradda M, et al. Clinical Response of Carcinomas Harboring the BRD4-NUT Oncoprotein to the Targeted Bromodomain Inhibitor OTX015/MK-8628[J]. Cancer Discov, 2016, 6(5): 492-500. doi: 10.1158/2159-8290.CD-15-1335
计量
- 文章访问数: 89
- 施引文献: 0