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ALK Rearrangements Are Infrequent in Cellular Blue Nevus and Deep Penetrating Nevus

Dunn, Andrew L. J., MD; Gardner, Jerad M., MD; Kaley, Jennifer R., MD; Bellamy, William, PhD; Shalin, Sara C., MD, PhD

The American Journal of Dermatopathology: July 2018 - Volume 40 - Issue 7 - p 469–478
doi: 10.1097/DAD.0000000000001014
CME Article

Abstract: 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.

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.

Correspondence: Andrew L. J. Dunn, MD, Chief Resident, Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (e-mail:

Supported by the University of Arkansas for Medical Sciences, Department of Pathology.

All authors and staff in a position to control the content of this CME activity and their spouses/life partners (if any) have disclosed that they have no financial relationships with, or financial interests in, any commercial organizations pertaining to this educational activity.

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