Genomic comparison of malignant melanoma and atypical Spitz tumor in the pediatric population

Church, Alanna J.; Moustafa, Danna; Pinches, R. Seth; Hawryluk, Elena B.; Schmidt, Birgitta

doi:10.1111/pde.14935

Cited by 6 publications

(5 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…During the early stages of molecular research on nevi, it became apparent that MAPK pathway activation results from BRAF mutations in common nevi and small congenital nevi [29], NRAS mutations in medium-sized congenital nevi [29], GNAQ or GNA11 mutations in blue nevi [30], and HRAS mutations in a subset of Spitz nevi [31]. Spitz melanomas often exhibit more mutations than Spitz melanocytomas and Spitz nevi, resulting in a higher tumor mutational burden (TMB), occasionally including a UV mutational signature [32].…”

Section: Early Findings Including Hras Alterationsmentioning

confidence: 99%

Spitz Melanocytic Tumors: A Fascinating 75-Year Journey

Chatzopoulos,

Syrnioti,

Linos

2024

Genes

View full text Add to dashboard Cite

Over the last 75 years, our understanding of Spitz lesions has undergone substantial evolution. Initially considered a specific type of melanoma, the perception has shifted towards recognizing Spitz lesions as a spectrum comprising Spitz nevi, Spitz melanocytomas, and Spitz melanomas. Spitz lesions are known for posing a significant diagnostic challenge regarding the distinction between benign neoplasms displaying atypical traits and melanomas. A comprehensive understanding of their molecular basis and genomic aberrations has significantly improved precision in classifying and diagnosing these challenging lesions. The primary aim of this review is to encapsulate the current understanding of the molecular pathogenesis and distinct clinicopathologic characteristics defining this intriguing set of tumors.

show abstract

Section: Early Findings Including Hras Alterationsmentioning

confidence: 99%

Spitz Melanocytic Tumors: A Fascinating 75-Year Journey

Chatzopoulos,

Syrnioti,

Linos

2024

Genes

View full text Add to dashboard Cite

show abstract

“…Cases showing a mutation of the TERT promoter show a less favorable prognosis [79]. A high TMB (>5 mut/Mb), measured by NGS, is associated with a less favorable biologic behavior [80]. In addition, tumors that exhibit histopathological features typical of Spitz tumors but harbor BRAF V600E , NRAS or NF1 mutations often exhibit aggressive biological behavior and a less favorable outcome [24,34].…”

Section: Risk-associated Parameters In Spitz Tumorsmentioning

confidence: 99%

Spitz Tumors and Melanoma in the Genomic Age: A Retrospective Look at Ackerman’s Conundrum

Urso

2023

Cancers

View full text Add to dashboard Cite

After 25 years, “Ackerman’s conundrum”, namely, the distinction of benign from malignant Spitz neoplasms, remains challenging. Genomic studies have shown that most Spitz tumors harbor tyrosine and serine/threonine kinase fusions, including ALK, ROS1, NTRK1, NTRK2, NTRK3, BRAF and MAP3K8, or some mutations, such as HRAS and MAP3K8. These chromosomal abnormalities act as drivers, initiating the oncogenetic process and conferring basic bio-morphological features. Most Spitz tumors show no additional genomic alterations or few ones; others harbor a variable number of mutations, capable of conferring characteristics related to clinical behavior, including CDKN2A deletion and TERT-p mutation. Since the accumulation of mutations is gradual and progressive, tumors appear to form a bio-morphologic spectrum, in which they show a progressive increase of clinical risk and histological atypia. In this context, a binary classification Spitz nevus-melanoma appears as no longer adequate, not corresponding to the real genomic substrate of lesions. A ternary classification Spitz nevus-Spitz melanocytoma-Spitz melanoma is more adherent to the real neoplastic pathway, but some cases with intermediate ambiguous features remain difficult to diagnose. A prognostic stratification of Spitz tumors, based on the morphologic and genomic characteristics, as a complement to the diagnosis, may contribute to better treatment plans for patients.

show abstract

“…Morphologically, there are substantial overlaps between the subtypes but also between borderline lesions such as the group of atypical Spitz tumors. An exact diagnosis is often only possible by combining morphology, immunohistochemistry, and an additional molecular workup (Church et al., 2022; Raghavan, Peternel, et al., 2020).…”

Section: Introductionmentioning

confidence: 99%

Characterization of PRAME immunohistochemistry reveals lower expression in pediatric melanoma compared to adult melanoma

Forchhammer,

Aebischer,

Lenders

et al. 2024

Pigment Cell Melanoma Res

View full text Add to dashboard Cite

Pediatric melanomas are rare tumors that have clinical and histological differences from adult melanomas. In adult melanoma, the immunohistochemical marker PRAME is increasingly employed as a diagnostic adjunct. PRAME is also under investigation as a target structure for next‐generation immunotherapies including T‐cell engagers. Little is known about the characteristics of PRAME expression in pediatric melanoma. In this retrospective study, samples from 25 pediatric melanomas were compared with control groups of melanomas in young adults (18–30 years; n = 32), adult melanoma (>30 years, n = 30), and benign melanocytic nevi in children (0–18 years; n = 30) with regard to the immunohistochemical expression of PRAME (diffuse PRAME expression >75%/absolute expression). Pediatric melanomas show lower diffuse PRAME expression (4%) and lower absolute PRAME expression (25%) compared to young adult melanomas (15.6%/46.8%) and adult melanomas (50%/70%). A significant age‐dependent expression could be observed. An analysis of event‐free survival shows no prognostic role for PRAME in pediatric melanoma and young adult melanoma, but a significant association with diffuse PRAME expression in adulthood. The age dependency of PRAME expression poses a potential pitfall in the diagnostic application of melanocytic tumors in young patients and may limit therapeutic options within this age group. The immunohistochemical expression of the tumor‐associated antigen PRAME is an increasingly important diagnostic marker for melanocytic tumors and is gaining attention as a possible immunotherapeutic target in melanoma. As the available data primarily stem from adult melanoma, and given the clinical and histological distinctions in pediatric melanomas, our understanding of PRAME expression in this specific patient group remains limited. The age‐dependent low PRAME expression shown here constrains the use of this marker in pediatric melanoma and may also limit the use of immunotherapeutic strategies against PRAME in young patients.

show abstract

Genomic comparison of malignant melanoma and atypical Spitz tumor in the pediatric population

Cited by 6 publications

References 30 publications

Spitz Melanocytic Tumors: A Fascinating 75-Year Journey

Spitz Melanocytic Tumors: A Fascinating 75-Year Journey

Spitz Tumors and Melanoma in the Genomic Age: A Retrospective Look at Ackerman’s Conundrum

Characterization of PRAME immunohistochemistry reveals lower expression in pediatric melanoma compared to adult melanoma

Contact Info

Product

Resources

About