Rossitza Lazova1, Erin H Seeley2, Heinz Kutzner3, Richard A Scolyer4, Glynis Scott5, Lorenzo Cerroni6, Isabella Fried7, Milena E Kozovska8, Arlene S Rosenberg9, Victor G Prieto10, Bahig M Shehata11, Megan M Durham12, Gina Henry11, Jose L Rodriguez-Peralto13, Erica Riveiro-Falkenbach13, Jochen T Schaefer14, Richard Danialan15, Sylvie Fraitag16, Sonja Vollenweider-Roten17, Alireza Sepehr18, Martin Sangueza19, Nouf Hijazi20, Yamile Corredoira21, Rachel Kowal22, Olga M Harris23, Francisco Bravo24, Alan S Boyd25, Ralitza Gueorguieva26, Richard M Caprioli27. 1. Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut. Electronic address: rlazova97@gmail.com. 2. Protea Biosciences Inc, Morgantown, West Virginia. 3. Dermatopathologie Friedreichshafen, Friedrechshafen, Germany. 4. Melanoma Institute Australia, Sydney, Australia; Sydney Medical School, University of Sydney, Sydney, Australia; Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney, Australia. 5. Department of Dermatology, University of Rochester Medical Center, School of Medicine and Dentistry, Rochester, New York. 6. Department of Dermatology, Medical University of Graz, Graz, Austria. 7. Department of Dermatology, Medical University of Graz, Graz, Austria; Kempf und Pfaltz Histologische Diagnostik, Zürich, Switzerland. 8. Rabkin Dermatopathology Laboratory, Tarentum, Pennsylvania. 9. Department of Dermatology, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio; Cleveland Skin Pathology Laboratory Inc, Beachwood, Ohio. 10. Department of Pathology, MD Anderson Cancer Center, Houston, Texas. 11. Department of Pathology, Emory University School of Medicine, Atlanta, Georgia; Children's Healthcare of Atlanta, Atlanta, Georgia. 12. Department of Surgery, Emory University School of Medicine, Atlanta, Georgia. 13. Universidad Complutense de Madrid Facultad de Medicina, Madrid, Spain. 14. Miraca Life Sciences, Newton, Massachusetts; Department of Dermatology, Tufts University School of Medicine, Boston, Massachusetts. 15. Department of Pathology and Laboratory Medicine, Tufts Medical Center, Boston, Massachusetts. 16. Dermatopathologie Praticien Hospitalier, Département de Pathologie, Hôpital Necker-Enfants Malades, Paris, France. 17. Viollier Morges SA Lausanne, Lausanne, Switzerland. 18. DermDX New England, Boston, Massachusetts; Beacon Pathology, Dover, Massachusetts. 19. Department of Pathology, Hospital Obrero Nro 1, La Paz, Bolivia. 20. Department of Pathology, University of British Columbia, Vancouver, British Columbia, Canada. 21. Department of Pathology, University of Chile, Santiago, Chile. 22. Department of Dermatology, University of Rochester Medical Center, School of Medicine and Dentistry, Rochester, New York; Muhlbauer Dermatopathology Laboratory, Pittsford, New York. 23. Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. 24. Department of Dermatology, Universidad Peruana Cayetano Heredia, Lima, Peru. 25. Department of Dermatology, Vanderbilt University School of Medicine, Nashville, Tennessee. 26. Department of Biostatistics, Yale University School of Public Health, New Haven, Connecticut. 27. Mass Spectrometry Research Center, Vanderbilt University School of Medicine, Nashville, Tennessee.
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.
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.
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