Chen T Y, Keeney M G, Chintakuntlawar A V, Knutson D L, Kloft-Nelson S, Greipp P T, Garrity J A, Salomao D R, Garcia J J
Mayo Clinic School of Medicine, Mayo Clinic Rochester, MN, USA.
Department of Laboratory Medicine and Pathology, Mayo Clinic Rochester, MN, USA.
Eye (Lond). 2017 May;31(5):720-725. doi: 10.1038/eye.2016.307. Epub 2017 Jan 13.
PurposeAdenoid cystic carcinoma (ACC) represents ~10-15% of salivary neoplasms and almost universally exhibits a lethal clinical course. ACC is also known to occur in the lacrimal gland. ACC is characterized by its heterogeneous morphology and may demonstrate tubular, cribriform, and/or solid architectural patterns. Unfortunately, these histopathological features are not specific to ACC and can be seen in other salivary gland-type neoplasms, introducing a diagnostic dilemma. The discovery of fusion transcripts has revolutionized the diagnosis, surveillance, and treatment of epithelial malignancies. In several anatomic subsites ACC is frequently characterized by a fusion transcript involving genes MYB and NFIB; more specifically, t(6;9)(q22-23;p23-24). This study explores the incidence of MYB rearrangement in cases of lacrimal gland ACC using fluorescent in situ hybridization.Materials and methodsRetrospective clinical and histopathological review of 12 cases of lacrimal gland ACC seen at Mayo Clinic over a 25-year period (1990-2015) was performed. Demographic and clinical data were obtained from medical records. Surgical pathology archival material including H&E slides and immunostains was re-examined. Formalin-fixed paraffin-embedded material was further evaluated using immunohistochemistry when appropriate. Fluorescent in situ hybridization (FISH) using a MYB break-apart probe was applied to all histologically confirmed cases of ACC and benign salivary gland parenchyma.ResultsThe median patient age was 53.6 years (range 12-64) and distributed equally by gender (six male and six female). Rearrangement of MYB was identified using FISH in seven cases (58%). Twenty-five sections of benign salivary gland parenchyma showed no evidence of MYB rearrangement. Primary surgical resection was most common treatment, and 78% of the patient received adjuvant radiation therapy. Median overall survival (OS) was 11 years. Rearrangement of MYB did not affect OS.ConclusionsIn summary, our results indicate that the MYB rearrangement defines a significant subset of lacrimal gland ACCs. Importantly, FISH for MYB rearrangement may be used as a diagnostic tool during pathological examination of lacrimal gland neoplasms. Our results showed no relationship between rearrangement status and clinical outcome. Lastly, the presence of t(6;9) in ACC may provide a platform for molecular-targeting strategies in the future.
目的
腺样囊性癌（ACC）约占涎腺肿瘤的10%-15%，几乎普遍呈现致命的临床病程。ACC也见于泪腺。ACC具有形态异质性，可表现为管状、筛状和/或实性结构模式。不幸的是，这些组织病理学特征并非ACC所特有，在其他涎腺型肿瘤中也可见到，这带来了诊断难题。融合转录本的发现彻底改变了上皮性恶性肿瘤的诊断、监测和治疗。在几个解剖部位，ACC常具有涉及MYB和NFIB基因的融合转录本；更具体地说，是t(6;9)(q22-23;p23-24)。本研究采用荧光原位杂交技术探讨泪腺ACC病例中MYB重排的发生率。
材料与方法
对梅奥诊所25年间（1990 - 2015年）所见的12例泪腺ACC病例进行回顾性临床和组织病理学检查。从病历中获取人口统计学和临床数据。重新检查包括苏木精-伊红（H&E）切片和免疫染色在内的手术病理存档材料。必要时，对福尔马林固定石蜡包埋材料进一步进行免疫组织化学评估。使用MYB断裂分离探针的荧光原位杂交（FISH）技术应用于所有经组织学确诊的ACC病例和涎腺良性实质组织。
结果
患者年龄中位数为53.6岁（范围12 - 64岁），性别分布均衡（男性6例，女性6例）。采用FISH技术在7例（58%）病例中检测到MYB重排。25份涎腺良性实质组织切片未显示MYB重排迹象。手术切除是最常见的治疗方法，78%的患者接受了辅助放疗。总生存（OS）期中位数为11年。MYB重排不影响OS。
结论
总之，我们的结果表明，MYB重排在泪腺ACC中定义了一个重要的亚组。重要的是，检测MYB重排的FISH技术可在泪腺肿瘤病理检查时用作诊断工具。我们的结果显示重排状态与临床结局之间无关联。最后，ACC中t(6;9)的存在可能为未来的分子靶向策略提供一个平台。
