Spitz Nevi Display Allelic Deletions

Bogdan, I; Burg, G; Böni, R.

doi:10.1001/archderm.137.11.1417

Cited by 23 publications

(16 citation statements)

References 24 publications

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“…16 This is not surprising given that typical Spitz nevi can also have loss of heterozygosity of 9p. 21,22 Consistent with this data, 3 patients in our cohort had heterozygous 9p21 deletion, and although SLN biopsy was not performed in any of the cases, all patients were alive without disease progression; although follow-up time was quite short (average of 5 months) (#7, #9, and #11). This may explain the lack of correlation between metastases and deletion of 9p21 in a study of 28 ASTs by Cesinaro et al 21 who did not specify if the aberration was heterozygous deletion.…”

Section: Discussionsupporting

confidence: 84%

Clinical Follow-up of Atypical Spitzoid Tumors Analyzed by Fluorescence In Situ Hybridization

Egnatios¹,

Ferringer

2016

The American Journal of Dermatopathology

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Many neoplasms with spitzoid features remain enigmatic, especially those with intermediate grade features or "atypical spitzoid tumors" (ASTs). Fluorescence in situ hybridization (FISH) has emerged as a complementary technique to conventional microscopy, with certain chromosomal patterns conveying diagnostic information. In this study, we examined 36 ASTs analyzed by FISH for specific abnormalities in chromosomes 6, 9, and 11. Aberrations were detected in 11 cases, 7 of which met FISH criteria for spitzoid melanoma. These had homozygous deletion of 9p21, partial deletion of 11q13, gain of 6p25, and gain of 11q13. All 3 patients with positive sentinel lymph nodes, including one with progression beyond the sentinel lymph node, had homozygous deletion of chromosome 9p21, but there were no deaths in an average of 28 months of follow-up of these cases. Other aberrations in the chromosomal pattern of ASTs were heterozygous deletion of 9p21, partial deletion of 6p23, and tetraploidy. We found that ASTs, including those eventually diagnosed as spitzoid melanoma, had a more indolent course in our cohort than conventional malignant melanoma. Moreover, the addition of FISH results led to a more definitive diagnosis in 7 cases, 4 of which had abnormalities on FISH consistent with spitzoid melanoma.

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Section: Discussionsupporting

confidence: 84%

Clinical Follow-up of Atypical Spitzoid Tumors Analyzed by Fluorescence In Situ Hybridization

Egnatios¹,

Ferringer

2016

The American Journal of Dermatopathology

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“…45 Loss of heterozygosity Two independent studies have recently demonstrated loss of heterozygosity on chromosome 9p with DNA polymorphic markers in two of 27 and five of five 'Spitz nevi'. 46,47 The latter findings provide additional evidence for the close relationship between Spitz tumors and melanoma.…”

Section: Special Techniquesmentioning

confidence: 86%

The Spitzoid lesion: rethinking Spitz tumors, atypical variants, ‘Spitzoid melanoma' and risk assessment

2006

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Although much remains to be learned about Spitzoid lesions, there is increasing evidence that these tumors may be a type of melanocytic neoplasm distinct from conventional melanocytic nevi and malignant melanoma. In the current communication, the author has attempted to describe accurately the state-of-the-art surrounding these lesions, their nomenclature, and assessment of risk. Acknowledging the peculiar nature of Spitzoid lesions, the author prefers the term Spitz tumor rather than 'Spitz nevus' (except perhaps for the most typical lesions) and argues against using the term 'Spitzoid melanoma' until more information is available to justify such a term. The author also believes that patients are best served by the comprehensive evaluation of Spitzoid lesions and their classification into three categories: (1) Spitz tumor without significant abnormality, (2) Spitz tumor with one or more atypical features (atypical Spitz tumor), including those judged to have indeterminate biological potential, and (3) malignant melanoma, rather than the two categories of 'Spitz nevus' and melanoma. Only rigorous characterization of sufficient numbers of Spitzoid lesions and long-term follow-up of patients will provide truly objective information for the formulation of optimal guidelines for the management of patients with these lesions.

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“…Demonstrating the specificity of 9p21 loss was particularly important, as numerous previous studies have documented 9p21 deletions in dysplastic nevi and spitz nevi. 4,23 However, when evaluating these studies in detail, deletions were noted as a loss of a single copy (heterozygous loss) in some cases in as few as 30% of cells. Therefore, in this study we specifically chose to focus on homozygous deletions, which, in our experience, when present uniformly in large aggregates of cells is a finding specific to melanoma.…”

Section: Discussionmentioning

confidence: 99%

“…16 A number of studies to date have shown that both dysplastic nevi and spitz nevi may have heterozygous deletions in a proportion of melanocytic cells evaluated by FISH. 4,23 In addition, in the early stages of probe selection for the current FISH assay, in which heterozygous 9p21 deletions were enumerated in melanoma and nevi, the 9p21 probe was not selected among the top 4 probes for its ability to discriminate melanoma from nevi. However, it has been our subsequent experience that homozygous deletions in 9p21 can be used as a specific marker to differentiate melanoma from nevi.…”

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confidence: 99%

Enhanced Detection of Spitzoid Melanomas Using Fluorescence In Situ Hybridization With 9p21 as an Adjunctive Probe

Gammon

Beilfuss

Guitart

et al. 2012

American Journal of Surgical Pathology

105

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The use of molecular diagnostic methods such as fluorescence in situ hybridization (FISH) for challenging melanocytic neoplasms is becoming more widespread. In light of the diagnostic difficulty they pose, spitzoid melanocytic neoplasms constitute an area of greatest potential utilization. In this study we wished to evaluate the sensitivity of the currently used melanoma FISH probe assay in a group of unambiguous spitzoid melanomas. On the basis of comparative genomic hybridization data, copy number losses at chromosome 9 have long been recognized as a frequent event in melanoma. In this study we wished to evaluate the efficacy of 9p21 as a potential FISH target and then evaluate the added benefit of reflexing the standard melanoma FISH assay, with FISH targeting 9p21 and the centromere of chromosome 9 (Cep9). Cep9 was included as a control to exclude inadequate hybridization or truncation as a source of homozygous deletions. We first studied a training set of 85 melanomas and 58 nevi with FISH targeting 9p21 and Cep9. As per previous methodology, 30 cells were enumerated. In the training set, the nevi had a mean number of cells with homozygous 9p21 loss of 0.97, with a standard deviation of 1.26. The melanomas had a mean of 7.1 and a standard deviation of 6.76. This difference was significant (P=2×10(-12)). On the basis of the training set, we identified a cutoff of 10 homozygous deletions to distinguish between melanoma and nevi. In a subsequent validation set consisting of 76 melanomas and 88 nevi, we found this cutoff to have a sensitivity of 33% and a specificity of 100%. Finally, in our group of 43 unequivocal spitzoid melanomas, standard FISH against chromosomes 6 and 11 was 70% sensitive. Homozygous 9p21 loss was present in 11 of 27 (41%) cases tested. By combining the standard melanoma FISH assay with the 9p21 FISH assay, a combined sensitivity of 85% was found. Among these 27 cases tested with 9p21, there were 7 cases that were negative by the standard melanoma FISH assay but that were positive by 9p21, suggesting that the 9p21 assay may be highly complementary to the standard melanoma FISH assay. Hence, in this study, we validated the efficacy of 9p21/Cep9 as a diagnostic FISH assay in melanoma, and demonstrated its complementary effect to the standard FISH assay. 9p21 may be particularly helpful in lesions with spitzoid morphology.

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Spitz Nevi Display Allelic Deletions

Cited by 23 publications

References 24 publications

Clinical Follow-up of Atypical Spitzoid Tumors Analyzed by Fluorescence In Situ Hybridization

Clinical Follow-up of Atypical Spitzoid Tumors Analyzed by Fluorescence In Situ Hybridization

The Spitzoid lesion: rethinking Spitz tumors, atypical variants, ‘Spitzoid melanoma' and risk assessment

Enhanced Detection of Spitzoid Melanomas Using Fluorescence In Situ Hybridization With 9p21 as an Adjunctive Probe

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