title: Imaging mass spectrometry assists in the classification of diagnostically challenging atypical Spitzoid neoplasms.
abstract: BACKGROUND
  Previously, using imaging mass spectrometry (IMS), we discovered proteomic differences between Spitz nevi and Spitzoid melanomas.
  
  
  OBJECTIVE
  We sought to determine whether IMS can assist in the classification of diagnostically challenging atypical Spitzoid neoplasms (ASN), to compare and correlate the IMS and histopathological diagnoses with clinical behavior.
  
  
  METHODS
  We conducted a retrospective collaborative study involving centers from 11 countries and 11 US institutions analyzing 102 ASNs by IMS. Patients were divided into clinical groups 1 to 4 representing best to worst clinical behavior. The association among IMS findings, histopathological diagnoses, and clinical groups was assessed.
  
  
  RESULTS
  There was a strong association between a diagnosis of Spitzoid melanoma by IMS and lesions categorized as clinical groups 2, 3, and 4 (recurrence of disease, metastases, or death) compared with clinical group 1 (no recurrence or metastasis beyond a sentinel node) (P < .0001). Older age and greater tumor thickness were strongly associated with poorer outcome (P = .01).
  
  
  CONCLUSIONS
  IMS diagnosis of ASN better predicted clinical outcome than histopathology. Diagnosis of Spitzoid melanoma by IMS was strongly associated with aggressive clinical behavior. IMS analysis using a proteomic signature may improve the diagnosis and prediction of outcome/risk stratification for patients with ASN.
authors: Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut. Electronic address: rlazova97@gmail.com.
authors: Rossitza
authors: R
authors: Lazova
authors: Protea Biosciences Inc, Morgantown, West Virginia.
authors: Erin H
authors: EH
authors: Seeley
authors: Dermatopathologie Friedreichshafen, Friedrechshafen, Germany.
authors: Heinz
authors: H
authors: Kutzner
authors: Melanoma Institute Australia, Sydney, Australia; Sydney Medical School, University of Sydney, Sydney, Australia; Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney, Australia.
authors: Richard A
authors: RA
authors: Scolyer
authors: Department of Dermatology, University of Rochester Medical Center, School of Medicine and Dentistry, Rochester, New York.
authors: Glynis
authors: G
authors: Scott
authors: Department of Dermatology, Medical University of Graz, Graz, Austria.
authors: Lorenzo
authors: L
authors: Cerroni
authors: Department of Dermatology, Medical University of Graz, Graz, Austria; Kempf und Pfaltz Histologische Diagnostik, Zürich, Switzerland.
authors: Isabella
authors: I
authors: Fried
authors: Rabkin Dermatopathology Laboratory, Tarentum, Pennsylvania.
authors: Milena E
authors: ME
authors: Kozovska
authors: Department of Dermatology, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio; Cleveland Skin Pathology Laboratory Inc, Beachwood, Ohio.
authors: Arlene S
authors: AS
authors: Rosenberg
authors: Department of Pathology, MD Anderson Cancer Center, Houston, Texas.
authors: Victor G
authors: VG
authors: Prieto
authors: Department of Pathology, Emory University School of Medicine, Atlanta, Georgia; Children's Healthcare of Atlanta, Atlanta, Georgia.
authors: Bahig M
authors: BM
authors: Shehata
authors: Department of Surgery, Emory University School of Medicine, Atlanta, Georgia.
authors: Megan M
authors: MM
authors: Durham
authors: Department of Pathology, Emory University School of Medicine, Atlanta, Georgia; Children's Healthcare of Atlanta, Atlanta, Georgia.
authors: Gina
authors: G
authors: Henry
authors: Universidad Complutense de Madrid Facultad de Medicina, Madrid, Spain.
authors: Jose L
authors: JL
authors: Rodriguez-Peralto
authors: Universidad Complutense de Madrid Facultad de Medicina, Madrid, Spain.
authors: Erica
authors: E
authors: Riveiro-Falkenbach
authors: Miraca Life Sciences, Newton, Massachusetts; Department of Dermatology, Tufts University School of Medicine, Boston, Massachusetts.
authors: Jochen T
authors: JT
authors: Schaefer
authors: Department of Pathology and Laboratory Medicine, Tufts Medical Center, Boston, Massachusetts.
authors: Richard
authors: R
authors: Danialan
authors: Dermatopathologie Praticien Hospitalier, Département de Pathologie, Hôpital Necker-Enfants Malades, Paris, France.
authors: Sylvie
authors: S
authors: Fraitag
authors: Viollier Morges SA Lausanne, Lausanne, Switzerland.
authors: Sonja
authors: S
authors: Vollenweider-Roten
authors: DermDX New England, Boston, Massachusetts; Beacon Pathology, Dover, Massachusetts.
authors: Alireza
authors: A
authors: Sepehr
authors: Department of Pathology, Hospital Obrero Nro 1, La Paz, Bolivia.
authors: Martin
authors: M
authors: Sangueza
authors: Department of Pathology, University of British Columbia, Vancouver, British Columbia, Canada.
authors: Nouf
authors: N
authors: Hijazi
authors: Department of Pathology, University of Chile, Santiago, Chile.
authors: Yamile
authors: Y
authors: Corredoira
authors: Department of Dermatology, University of Rochester Medical Center, School of Medicine and Dentistry, Rochester, New York; Muhlbauer Dermatopathology Laboratory, Pittsford, New York.
authors: Rachel
authors: R
authors: Kowal
authors: Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Olga M
authors: OM
authors: Harris
authors: Department of Dermatology, Universidad Peruana Cayetano Heredia, Lima, Peru.
authors: Francisco
authors: F
authors: Bravo
authors: Department of Dermatology, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors: Alan S
authors: AS
authors: Boyd
authors: Department of Biostatistics, Yale University School of Public Health, New Haven, Connecticut.
authors: Ralitza
authors: R
authors: Gueorguieva
authors: Mass Spectrometry Research Center, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors: Richard M
authors: RM
authors: Caprioli
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D013058:Mass Spectrometry; D008545:Melanoma / Q000737:chemistry / Q000000981:diagnostic imaging* / Q000556:secondary*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000737:chemistry / Q000000981:diagnostic imaging* / Q000473:pathology*; D018332:Nevus, Epithelioid and Spindle Cell / Q000737:chemistry / Q000000981:diagnostic imaging* / Q000473:pathology*; D011506:Proteins / Q000032:analysis; D012189:Retrospective Studies; D018570:Risk Assessment; D021701:Sentinel Lymph Node Biopsy; D012878:Skin Neoplasms / Q000737:chemistry / Q000000981:diagnostic imaging* / Q000473:pathology*; D016896:Treatment Outcome; D047368:Tumor Burden; D055815:Young Adult
chemical_list: D011506:Proteins
keywords: Spitz nevus; Spitzoid melanoma; atypical Spitzoid neoplasm; histopathology; imaging mass spectrometry; mass spectrometry