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Abstract：
BACKGROUND: ETV6 gene rearrangement is the molecular hallmark of secretory carcinoma (SC), however; the nature, frequency, and clinical implications of atypical ETV6 signal patterns by fluorescence in situ hybridization (FISH) has not yet been systematically evaluated in salivary gland neoplasms.
METHODS: The clinical, histopathologic, immunohistochemical and molecular features of seven salivary SCs, including four cases with atypical ETV6 FISH patterns, were retrospectively analyzed along with a critical appraisal of the literature on unbalanced ETV6 break-apart in SCs.
RESULTS: The patients were four males and three females (31-70 years-old). Five presented with a painless neck mass and two patients with recurrent disease had a history of a previously diagnosed acinic cell carcinoma of the buccal mucosa. Histologically, there were varied combinations of microcystic, papillary, tubular, and solid patterns. All tumors were diffusely positive for S100 and/or SOX10, while 2 cases also showed luminal DOG1 staining. Rearrangement of the ETV6 locus was confirmed in 5/7 cases, of which 3 cases showed classic break-apart signals, 1 case further demonstrated duplication of the ETV6 5`end and the other loss of one copy of ETV6. Two cases harbored ETV6 deletion without rearrangement. Two of the 4 cases with atypical ETV6 FISH patterns represented recurrent tumors, one with widespread skeletal muscle involvement, bone and lymphovascular invasion. Surgical treatment resulted in gross-total resection in all 7 cases, with a median follow up of 9.5 months post-surgery for primary (n = 3) and recurrent disease (n = 1).
CONCLUSIONS: Duplication of the distal/telomeric ETV6 probe represented the most common (26/40; 65%) variant ETV6 break-apart FISH pattern in salivary SC reported in the literature and appears indicative of an aggressive clinical course.
METHODS: The clinical, histopathologic, immunohistochemical and molecular features of seven salivary SCs, including four cases with atypical ETV6 FISH patterns, were retrospectively analyzed along with a critical appraisal of the literature on unbalanced ETV6 break-apart in SCs.
RESULTS: The patients were four males and three females (31-70 years-old). Five presented with a painless neck mass and two patients with recurrent disease had a history of a previously diagnosed acinic cell carcinoma of the buccal mucosa. Histologically, there were varied combinations of microcystic, papillary, tubular, and solid patterns. All tumors were diffusely positive for S100 and/or SOX10, while 2 cases also showed luminal DOG1 staining. Rearrangement of the ETV6 locus was confirmed in 5/7 cases, of which 3 cases showed classic break-apart signals, 1 case further demonstrated duplication of the ETV6 5`end and the other loss of one copy of ETV6. Two cases harbored ETV6 deletion without rearrangement. Two of the 4 cases with atypical ETV6 FISH patterns represented recurrent tumors, one with widespread skeletal muscle involvement, bone and lymphovascular invasion. Surgical treatment resulted in gross-total resection in all 7 cases, with a median follow up of 9.5 months post-surgery for primary (n = 3) and recurrent disease (n = 1).
CONCLUSIONS: Duplication of the distal/telomeric ETV6 probe represented the most common (26/40; 65%) variant ETV6 break-apart FISH pattern in salivary SC reported in the literature and appears indicative of an aggressive clinical course.
摘要：
背景：ETV6基因重排是分泌性癌（SC）的分子标志，然而；自然，频率,和通过荧光原位杂交（FISH）的非典型ETV6信号模式的临床意义尚未在唾液腺肿瘤中进行系统评估。
方法：临床，组织病理学,七种唾液SC的免疫组织化学和分子特征，包括4例非典型ETV6FISH模式，回顾性分析以及对SCs中不平衡ETV6破裂的文献的批判性评估。
结果：患者为4名男性和3名女性（31-70岁）。5例表现为无痛性颈部肿块，2例复发性疾病患者有先前诊断为颊粘膜腺泡细胞癌的病史。组织学上,有不同的微囊细胞组合，乳头状，管状,和坚实的图案。所有肿瘤均为S100和/或SOX10弥漫性阳性，而2例也显示腔DOG1染色。在5/7例中证实了ETV6基因座的重排，其中3例显示典型的分裂信号，1例进一步证明了ETV65'端的重复和另一个ETV6的一个拷贝的丢失。2例存在ETV6缺失，无重排。4例具有非典型ETV6FISH模式的患者中有2例代表复发性肿瘤，一个广泛参与骨骼肌的人，骨和淋巴管浸润。手术治疗7例全部切除，原发性（n=3）和复发性疾病（n=1）的中位随访时间为术后9.5个月。
结论：远端/端粒ETV6探针的重复代表了文献中报道的唾液SC中最常见的（26/40;65％）变体ETV6分裂FISH模式，并且似乎表明积极的临床过程。
方法：临床，组织病理学,七种唾液SC的免疫组织化学和分子特征，包括4例非典型ETV6FISH模式，回顾性分析以及对SCs中不平衡ETV6破裂的文献的批判性评估。
结果：患者为4名男性和3名女性（31-70岁）。5例表现为无痛性颈部肿块，2例复发性疾病患者有先前诊断为颊粘膜腺泡细胞癌的病史。组织学上,有不同的微囊细胞组合，乳头状，管状,和坚实的图案。所有肿瘤均为S100和/或SOX10弥漫性阳性，而2例也显示腔DOG1染色。在5/7例中证实了ETV6基因座的重排，其中3例显示典型的分裂信号，1例进一步证明了ETV65'端的重复和另一个ETV6的一个拷贝的丢失。2例存在ETV6缺失，无重排。4例具有非典型ETV6FISH模式的患者中有2例代表复发性肿瘤，一个广泛参与骨骼肌的人，骨和淋巴管浸润。手术治疗7例全部切除，原发性（n=3）和复发性疾病（n=1）的中位随访时间为术后9.5个月。
结论：远端/端粒ETV6探针的重复代表了文献中报道的唾液SC中最常见的（26/40;65％）变体ETV6分裂FISH模式，并且似乎表明积极的临床过程。
