Restrospective reappraisal of the prognostic classification of spitzoid melanocytic neoplasms after BRAF and NRAS mutation characterisation: a single institution experience

Author:

Moysset Irene12,Castrejon Natalia3,Garcia‐Herrera Adriana234,Castillo Paola234,Marginet Marta3,Teixido Cristina2345,Podlipnik Sebastian6,Albero‐Gonzalez Raquel234ORCID,Montironi Carla35,Navarro Judit3,Rovira Carlota7,Puig Susana2468,Carrera Cristina2468,Alos Llucia234

Affiliation:

1. Department of Pathology Consorci Sanitari Integral Barcelona Spain

2. University of Barcelona Barcelona Spain

3. Department of Pathology Hospital Clinic of Barcelona Barcelona Spain

4. August Pi I Sunyer Biomedical Research Institute (IDIBAPS) Barcelona Spain

5. Molecular Biology Core Hospital Clinic Barcelona Barcelona Spain

6. Department of Dermatology Hospital Clínic of Barcelona Barcelona Spain

7. Department of Pathology Hospital Sant Joan de Déu Barcelona Spain

8. Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) Instituto de Salud Carlos III Madrid Spain

Abstract

AimsThe current WHO classification of melanocytic tumours excludes neoplasms showing BRAF or NRAS mutations from the Spitz category. This study aimed to review and reclassify atypical melanocytic tumours with spitzoid morphological features diagnosed between 2009 and 2021 in our hospital after expanding the molecular profile, including BRAF and NRAS mutations in all cases.Methods and resultsA total of 71 neoplasms showing spitzoid features (Spitz‐like) and atypia were included. The risk of progression of tumours was first studied by integrating the morphology, immunohistochemistry (p16, Ki67, HMB45 and PRAME) and fluorescence in‐situ hybridisation (FISH) results (melanoma multiprobe and 9p21). In a second step, after expanding the molecular study, including BRAF and NRAS mutational status, the neoplasms were finally classified into four subgroups: atypical Spitz tumour (AST, n = 45); BRAF‐mutated naevus/low‐grade melanocytoma with spitzoid morphology (BAMS, n = 2); Spitz melanoma (SM, n = 14); and BRAF or NRAS mutated melanoma with spitzoid features (MSF, n = 10). Follow‐up of patients revealed uneventful results for AST and BAMS. Only one SM presented lymph node metastasis after 134 months. Conversely, patients with MSF showed an unfavourable outcome: three developed lymph node metastases after a mean time of 22 months, with one patient presenting distant metastasis and dying of the disease 64 months from diagnosis. The progression‐free survival showed significant differences between the four groups of spitzoid tumours (P < 0.001) and between both melanoma subtypes (P = 0.012).ConclusionsThe classification and prognostication of atypical neoplasms with spitzoid features requires the integration of histomorphology with the molecular investigation of tumours, which should include BRAF and NRAS mutational status.

Funder

HORIZON EUROPE Health

Publisher

Wiley

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