title: Spitz Tumors: Comparison of Histological Features in Relationship to Immunohistochemical Staining for ALK and NTRK1.
abstract: Spitz tumors are a group of melanocytic neoplasms with distinct morphological features that tend to affect young individuals. Distinguishing benign from malignant Spitz tumors can be challenging, but cytogenetic and molecular tests have contributed to improvements in diagnostic accuracy. Spitz tumors harbor diverse genetic alterations, including mutations in HRAS, loss of BAP1, or kinase fusions in ROS1, NTRK1, ALK, BRAF, and RET genes. Limited data exist on the correlation between histopathological features and kinase fusions. Here, we describe the histopathological features of 105 Spitz tumors (Spitz nevi and atypical Spitz tumors), comparing lesions according to their immunoreactivity for ALK or NTRK1. Intersecting fascicular growth of fusiform melanocytes was seen in all but one ALK-positive tumor (27 of 28 or 96.4%), whereas it was infrequent in NTRK1-positive tumors (5 of 20 or 25.0%) and tumors negative for both ALK and NTRK1 (96.4% vs 25.0% vs 8.7%, P < .0027). There was a trend toward ALK-positive tumors being amelanotic compared with NTRK1-positive tumors and combined ALK-/NTRK1-negative tumors (89.3% vs 45% vs 47.4%, respectively, P = .1023) and lacking epithelioid cell morphology (0% vs 45.0% vs 41%, respectively, P = .6985). In conclusion, this study confirms that although not specific, the growth pattern of intersecting fascicles of amelanotic fusiform melanocytes is strongly associated with ALK expression.
authors.affiliation: University of California Davis, Sacramento, CA, USA Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Maija
authors.initials: M
authors.lastname: Kiuru
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Achim
authors.initials: A
authors.lastname: Jungbluth
authors.affiliation: Dermatopathologie Friedrichshafen, Friedrichshafen, Germany.
authors.forename: Heinz
authors.initials: H
authors.lastname: Kutzner
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Wiesner
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, NY, USA busamk@mskcc.org.
authors.forename: Klaus J
authors.initials: KJ
authors.lastname: Busam
mesh_terms: D000293:Adolescent; D000328:Adult; D000077548:Anaplastic Lymphoma Kinase; D014408:Biomarkers, Tumor / Q000032:analysis*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008544:Melanocytes / Q000473:pathology; D008875:Middle Aged; D018332:Nevus, Epithelioid and Spindle Cell / Q000175:diagnosis* / Q000473:pathology; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis / Q000096:biosynthesis*; D020917:Receptor, trkA / Q000032:analysis / Q000096:biosynthesis*; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000473:pathology; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA
keywords: ALK; NTRK1; Spitz nevus; immunohistochemistry