Dunn Andrew L J, Gardner Jerad M, Kaley Jennifer R, Bellamy William, Shalin Sara C
Chief Resident (A.L.J.D.), Associate Professor (J.M.G., S.C.S.), Assistant Professor (J.R.K.), Professor (W.B.), Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR.
Am J Dermatopathol. 2018 Jul;40(7):469-478. doi: 10.1097/DAD.0000000000001014.
Recent studies have identified kinase fusions in Spitzoid melanocytic neoplasms, and approximately 10% of Spitzoid neoplasms harbor anaplastic lymphoma kinase (ALK) rearrangements and corresponding ALK immunoreactivity. Deep penetrating nevi (DPN), a subset of melanocytic neoplasms, have histologic and immunohistochemical overlap that have historically supported classification of DPN with blue/cellular blue nevi (CBN). However, HRAS mutations have rarely been detected in DPN, thereby also linking them to Spitz nevi. The purpose of this study was to see if DPN or CBN possess ALK rearrangements, thereby providing more evidence that these melanocytic lesions may be pathogenetically related to Spitzoid neoplasms. Using ALK immunohistochemistry as a surrogate for ALK rearrangement, the authors examined 26 DPN, 30 CBN, and 4 conventional blue nevi. ALK immunoreactive cases underwent fluorescent in situ hybridization to investigate for the presence of ALK gene rearrangement. Patchy and focal ALK immunostaining was found in only 1 case of DPN (1/26, 3.8%). Seven cases of CBN (7/30; 23%) showed ALK immunostaining (6 focal/patchy, 1 strong and diffuse). Fluorescent in situ hybridization using ALK break-apart probes showed various degrees of gain of 2p23 and rare ALK break-apart signals. Four CBN showed ALK rearrangement in 2%-4% of cells. Two cases of CBN showed gain of 2p23 in 10%-20% of cells. In our study, ALK rearrangements are uncommon in both CBN and DPN, making ALK an unlikely driver in tumorigenesis and classification of these melanocytic variants. However, our study did identify ALK molecular changes and immunohistochemical staining patterns that have not been previously described in CBN or DPN.
近期研究已在Spitz样黑素细胞肿瘤中鉴定出激酶融合，约10%的Spitz样肿瘤存在间变性淋巴瘤激酶（ALK）重排及相应的ALK免疫反应性。深部浸润性痣（DPN）是黑素细胞肿瘤的一个亚型，其组织学和免疫组化表现有重叠，这在历史上支持将DPN与蓝色/细胞性蓝色痣（CBN）归为一类。然而，DPN中很少检测到HRAS突变，因此也将它们与Spitz痣联系起来。本研究的目的是观察DPN或CBN是否存在ALK重排，从而提供更多证据表明这些黑素细胞病变在发病机制上可能与Spitz样肿瘤相关。作者采用ALK免疫组化作为ALK重排的替代指标，检测了26例DPN、30例CBN和4例传统蓝色痣。对ALK免疫反应阳性的病例进行荧光原位杂交，以研究ALK基因重排情况。仅1例DPN（1/26，3.8%）发现斑片状和局灶性ALK免疫染色。7例CBN（7/30；23%）显示ALK免疫染色（6例为局灶性/斑片状，1例为强阳性弥漫性染色）。使用ALK断裂分离探针进行的荧光原位杂交显示2p23有不同程度的扩增，且罕见ALK断裂分离信号。4例CBN在2%-4%的细胞中显示ALK重排。2例CBN在10%-20%的细胞中显示2p23扩增。在我们的研究中，ALK重排在CBN和DPN中均不常见，这使得ALK不太可能是这些黑素细胞变异型肿瘤发生和分类的驱动因素。然而，我们的研究确实发现了CBN或DPN中以前未描述过的ALK分子变化和免疫组化染色模式。
