Genomic analysis of a case of agminated Spitz nevi and congenital‐pattern nevi arising in extensive nevus spilus

Porubsky, Caitlin; Teer, Jamie K.; Zhang, Yonghong; Deschaine, Maria; Sondak, Vernon K.; Messina, Jane L.

doi:10.1111/cup.13082

Cited by 11 publications

(10 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…32 Since then, HRAS has also been recognized as a driver for nevus spilus and investigators have shown that where the HRAS gene resides. 14,16,20,24,25 Since these discoveries, much has been learned about the pathogenesis of Spitz including the fact that a significant majority of Spitz, as well as some other classes of melanocytic neoplasms such as PRKCA fusion melanocytic nevi/ tumors, are the result of genomic fusions. 20,21,[33][34][35] However, there have been very few studies investigating whether fusions can play a role in agminated presentations of melanocytic neoplasms.…”

Section: Discussionmentioning

confidence: 99%

“…[20][21][22][23] ASN have been shown to occur in the setting of nevus spilus as a result of a mosaic HRAS mutation, involving the entire area of the nevus spilus, along with copy number gains of 11p in the focal spitzoid proliferations. 14,16,20,24,25 However, there is limited knowledge regarding the pathophysiology of ASN outside of the setting of nevus spilus, and the potential for genomic fusions to play a role in agminated nevi. 11,15,26 In this study, we present the clinical, histologic, and molecular findings of three cases of agminated melanocytic neoplasms harboring genomic fusions and therefore propose that genomic fusions can play a role in the development of agminated Spitz or other fusion-mediated melanocytic neoplasms.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Agminated presentation of fusion‐driven melanocytic neoplasms

et al. 2023

View full text Add to dashboard Cite

Background: The conventionally understood pathogenesis of agminated Spitz nevi includes a mosaic HRAS mutation followed by copy number gains in 11p. However, we have recently observed agminated presentations of fusion-driven melanocytic neoplasms.Methods: We retrieved cases from our database of benign fusion-induced melanocytic neoplasms with an agminated presentation. Both the primary lesion and the secondary lesion were sequenced. TERT-promoter mutational testing and the melanoma fluorescence in situ hybridization assay were also performed.Results: Three cases were included. Two had a PRKCA fusion (partners ATP2B4 and MPZL1) and one had a ZCCHC8::ROS1 fusion. None of the cases met morphologic or molecular criteria for malignancy. There was no evidence of tumor progression in secondary lesions. The same fusion was identified in the primary and secondary lesions. None of the patients developed evidence of nodal or systemic metastasis. Conclusions:We present accumulating evidence that fusion-driven melanocytic neoplasms can present with an agminated presentation. The differential diagnosis of an agminated presentation versus a locally recurrent or potentially locally metastatic tumor is critical, and accurate diagnosis has significant prognostic and therapeutic consequences for the patient. As with HRAS mutations, fusion-driven melanocytic tumors may have an agminated presentation.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Agminated presentation of fusion‐driven melanocytic neoplasms

et al. 2023

View full text Add to dashboard Cite

show abstract

“…HRAS mutations have also been detected in urothelial and squamous cell carcinomas, adenocarcinomas of various origins, leukemias, and myelodysplastic syndromes (17)(18)(19). HRAS mutations in Spitz melanocytic proliferations are most commonly missense mutations involving codons 61 and 13, with the three most commonly reported mutations being Q61L (2,6,14,20), Q61R (14,(20)(21)(22)(23), and G13R (6,21,(24)(25)(26)(27)(28).…”

Section: P Amplified And/or Hras Mutated Spitz Melanocytic Proliferationsmentioning

confidence: 99%

“…In addition to solitary lesions with typical desmoplastic Spitz nevus morphology, other melanocytic proliferations with HRAS mutations and/or 11p gain have also been described, including agminated Spitz nevi with or without associated nevus spilus (25)(26)(27)(28), recurrent Spitz nevi (30), melanocytic nevi with deep penetrating nevus-like morphology (21), pseudogranulomatous Spitz nevi (31) and a combination of syringocystadenoma papilliferum, tubular adenoma and a Spitz nevus (24). Moreover, the desmoplastic Spitz nevus phenotype is not restricted to HRAS mutated lesions since rare Spitz nevi harboring ROS1, ALK or even a BRAF fusion exhibiting a desmoplastic Spitz nevus morphology have been described (2,32).…”

Section: P Amplified And/or Hras Mutated Spitz Melanocytic Proliferationsmentioning

confidence: 99%

An Update on Molecular Genetic Aberrations in Spitz Melanocytic Proliferations: Correlation with Morphological Features and Biological Behavior

Šekoranja

Pižem

Luzar

2021

ama

View full text Add to dashboard Cite

The aim of the paper is to give an update on molecular genetic aberrations in Spitz melanocytic proliferations with special em- phasis on their correlation with morphological features and biological behavior. The Spitz group of melanocytic proliferations is defined by a combination of distinctive morphological features and driver molecular genetic events. Morphologically, these neoplasms are characterized by large, oval, polygonal, or spindled melanocytes with abundant eosinophilic cytoplasm, vesicular nuclei with prominent nucleoli, often in association with epidermal hyperplasia. Molecular aberrations in Spitz melanocytic proliferations can be divided into two main groups, according to the driver genetic change: 1) 11p amplification/HRAS muta- tion, present in about 20% of cases, and 2) kinase fusions, present in about 50%, further subdivided into tyrosine kinase fusions (ALK, ROS1, NTRK1, NTRK3, MET, RET) or serine-threonine kinase fusions (MAP3K8, BRAF). Driver genetic aberrations can be detected along the whole biological spectrum of Spitz melanocytic proliferations, and are mutually exclusive. Although driver genetic aberrations enable proliferation of melanocytes, additional genetic events (often biallelic inactivation of CDKN2A and TERT promoter mutations) are necessary for the development of overt Spitz malignancy.Conclusions. Recent studies have demonstrated that certain driver genetic aberrations are more often associated with the benign spectrum of Spitz melanocytic proliferations and indolent biological behavior (11p amplification/HRAS mutation, tyrosine kinase fusions). In contrast, some driver aberrations are more frequent in the atypical/malignant spectrum of Spitz melanocytic proliferations with a potential for aggressive biological behavior (serine-threonine kinase fusions). In addition, certain driver aberrations are often associated with distinctive morphological features. However, none of the morphological features is entirely specific for any of these driver genetic aberrations. Immunohistochemistry for ALK, ROS1, and pan-TRK can be used for screening purposes to detect cor- responding fusion proteins.

show abstract

“…Agminated Spitz nevi arise from cutaneous genetic mosaicism. Several reports 2,3 have demonstrated somatic pathogenic HRAS variants in nevus spilus-associated agminated Spitz nevi. Recently, a complex translocation involving TRPM1, PUM1, and LCK has also been implicated 4 ; however, to our knowledge, no other genetic variants of agminated Spitz nevi have been reported.…”

mentioning

confidence: 99%