PMID- 24698967
OWN - NLM
STAT- MEDLINE
DCOM- 20140801
LR  - 20220330
IS  - 1532-0979 (Electronic)
IS  - 0147-5185 (Print)
IS  - 0147-5185 (Linking)
VI  - 38
IP  - 7
DP  - 2014 Jul
TI  - Clinical and pathologic findings of Spitz nevi and atypical Spitz tumors with ALK 
      fusions.
PG  - 925-33
LID - 10.1097/PAS.0000000000000187 [doi]
AB  - Spitz tumors represent a group of melanocytic neoplasms that typically affect 
      young individuals. Microscopically, the lesions are composed of cytologically 
      distinct spindle and epithelioid melanocytes, with a range in the architectural 
      display or the cells, their nuclear features, and secondary epidermal or stromal 
      changes. Recently, kinase fusions have been documented in a subset of Spitz 
      tumors, but there is limited information on the clinical and pathologic features 
      associated with those lesions. Here, we report a series of 17 patients (9 male, 8 
      female) with spitzoid neoplasms showing ALK fusions (5 Spitz nevi and 12 atypical 
      Spitz tumors). The patients' ages ranged from 2 years to 35 years (mean=17 y; 
      median=16 y). Most lesions were located on the lower extremities and presented 
      clinically as polypoid nodules. All tumors were compound melanocytic 
      proliferations with a predominant intradermal growth. Tumor thickness ranged from 
      1.1 to 6 mm (mean=2.9 mm; median=2.5 mm). The most characteristic histopathologic 
      feature of the tumors (seen in all but 2 lesions) was a plexiform dermal growth 
      of intersecting fascicles of fusiform melanocytes. All but 2 tumors were 
      amelanotic. All tumors were strongly immunoreactive for ALK. The ALK 
      rearrangements were confirmed in all cases by fluorescence in situ hybridization 
      (FISH), and the fusion partner was determined by quantitative polymerase chain 
      reaction as TPM3 (tropomyosin 3) in 11 cases and DCTN1 (dynactin 1) in 6 cases. 
      None of the 8 tumors that were analyzed by FISH for copy number changes of 6p, 
      6q, 9p, or 11q met criteria for melanoma. Two patients underwent a sentinel lymph 
      node biopsy, and in both cases melanocyte nests were found in the subcapsular 
      sinus of the node. Array comparative genomic hybridization of these 2 tumors 
      revealed no chromosomal gains or losses. In conclusion, our study revealed that 
      Spitz nevi/tumors with ALK rearrangement show a characteristic plexiform 
      morphology and that ALK immunohistochemistry and FISH enable the accurate 
      identification of this morphologic and genetic distinct subset of spitzoid 
      neoplasms.
FAU - Busam, Klaus J
AU  - Busam KJ
AD  - *Department of Pathology  section signHuman Oncology and Pathogenesis Program, Memorial 
      Sloan-Kettering Cancer Center, New York, NY daggerDermatopathologie Friedrichshafen, 
      Friedrichshafen, Germany double daggerDepartment of Dermatology, Medical University Graz, 
      Graz, Austria.
FAU - Kutzner, Heinz
AU  - Kutzner H
FAU - Cerroni, Lorenzo
AU  - Cerroni L
FAU - Wiesner, Thomas
AU  - Wiesner T
LA  - eng
GR  - P30 CA008748/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Surg Pathol
JT  - The American journal of surgical pathology
JID - 7707904
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (DCTN1 protein, human)
RN  - 0 (Dynactin Complex)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (TPM3 protein, human)
RN  - 0 (Tropomyosin)
RN  - EC 2.7.10.1 (ALK protein, human)
RN  - EC 2.7.10.1 (Anaplastic Lymphoma Kinase)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Anaplastic Lymphoma Kinase
MH  - Biomarkers, Tumor/analysis/*genetics
MH  - Biopsy
MH  - Child
MH  - Child, Preschool
MH  - DNA Copy Number Variations
MH  - Dynactin Complex
MH  - Female
MH  - Gene Dosage
MH  - *Gene Fusion
MH  - Gene Rearrangement
MH  - Genetic Predisposition to Disease
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Lymphatic Metastasis
MH  - Male
MH  - Microtubule-Associated Proteins/genetics
MH  - Nevus, Epithelioid and Spindle Cell/enzymology/*genetics/pathology
MH  - Phenotype
MH  - Polymerase Chain Reaction
MH  - Receptor Protein-Tyrosine Kinases/analysis/*genetics
MH  - Skin Neoplasms/enzymology/*genetics/pathology
MH  - Tropomyosin/genetics
MH  - Young Adult
PMC - PMC5042334
MID - NIHMS708433
EDAT- 2014/04/05 06:00
MHDA- 2014/08/02 06:00
PMCR- 2016/09/29
CRDT- 2014/04/05 06:00
PHST- 2014/04/05 06:00 [entrez]
PHST- 2014/04/05 06:00 [pubmed]
PHST- 2014/08/02 06:00 [medline]
PHST- 2016/09/29 00:00 [pmc-release]
AID - 10.1097/PAS.0000000000000187 [doi]
PST - ppublish
SO  - Am J Surg Pathol. 2014 Jul;38(7):925-33. doi: 10.1097/PAS.0000000000000187.