Genomic Landscape of Spitzoid Neoplasms Impacting Patient Management

Abstract

Spitzoid neoplasms are a distinct group of melanocytic proliferations characterized by epithelioid and/ or spindle shaped melanocytes. Intermediate forms that share features of both benign Spitz nevi (SN) and Spitz melanoma, i.e., malignant Spitz tumor (MST) represent a diagnostically and clinically challenging group of melanocytic lesions. A multitude of descriptive diagnostic terms exist for these ambiguous lesions with atypical Spitz tumor (AST) or Spitz tumor of uncertain malignant potential (STUMP) just naming two of them. This diagnostic gray zone creates confusion and high insecurity in clinicians and in patients. Biological behavior and clinical course of this intermediate group still remains largely unknown, often leading to difficulties with uncertainties in clinical management and prognosis. Consequently, a better stratification of Spitzoid neoplasms in benign and malignant forms is required thereby keeping the diagnostic group of AST/STUMP as small as possible. Ancillary diagnostic techniques such as immunohistochemistry, comparative genomic hybridization, fluorescence in situ hybridization, next generation sequencing, micro RNA and mRNA analysis as well as mass spectrometry imaging offer new opportunities for the distinct diagnosis, thereby allowing the best clinical management of Spitzoid neoplasms. This review gives an overview on these additional diagnostic techniques and the recent developments in the field of molecular genetic alterations in Spitzoid neoplasms. We also discuss how the recent findings might facilitate the diagnosis and stratification of atypical Spitzoid neoplasms and how these findings will impact the diagnostic work up as well as patient management. We suggest a stepwise implementation of ancillary diagnostic techniques thereby integrating immunohistochemistry and molecular pathology findings in the diagnosis of challenging ambiguous Spitzoid neoplasms. Finally, we will give an outlook on pending future research objectives in the field of Spitzoid melanocytic lesions.

Analysis of Sentinel Node Biopsy and Clinicopathologic Features as Prognostic Factors in Patients With Atypical Melanocytic Tumors

“…Additional techniques to assess molecular genetic alterations, such as comparative genomic hybridization, next-generation sequencing, microRNA and mRNA analysis, and mass spectrometric imaging, will help improve the differential diagnosis and clinical management of AMTs in the near future. 42…”

Standardized diagnostic algorithm for spitzoid lesions aids clinical decision-making and management: a case series from a Swiss reference center

“…Certain spitzoid lesions show evidently benign or malignant clinic and histology, while others present with unclear characteristics and are therefore categorized as lesions of intermediate biologic potential [ 1 ]. These lesions are a challenge for pathologists and clinicians, as there is no consensus on ancillary diagnostics or clinical management [ 2 ]. As patients are typically young [ 2 , 3 ], prediction of the clinical outcome is essential to determine if adjuvant treatment is necessary.…”

Incidence and outcome of Spitzoid tumour of unknown malignant potential (STUMP): an analysis of cases in the Netherlands from 1999 to 2014

“…Subsequently, they represent a diagnostic grey zone and a clinically challenging group. 2,3 The biological behaviour and clinical course of this intermediate group remains largely unknown. This results in a clinical challenge regarding the management of AST/STUMP.…”

“…1 Artificial exposure to UVB while soaking in an indoor salt bath, also called balneophototherapy, could simulate the natural exposure to the sun while bathing in the Dead Sea. 2 However, the evidence underlying clinical efficacy, such as longer remission from disease and higher dermatology-related quality of life, has not yet been clearly evaluated. In a Cochrane review, 3 we evaluated whether balneophototherapy would improve the skin of patients with chronic plaque psoriasis compared with UVB alone.…”

“…Departments of 1 Dermatology;2 Pathology, Amsterdam UMC, Amsterdam, the Netherlands; and 3 Department of Dermatology, Leiden Universitair Medisch Centrum, Leiden, the Netherlands Correspondence: Darryl C.K.S. Tio.…”