Occurrence of ocular melanoma thirteen years after skin melanoma: two separate primaries or metastatic disease? A case solved with NRAS and CDKN2A (INK4A-ARF) mutational analysis

Küsters‐Vandevelde, Heidi V.N.; Keunen, J. E. E.; Wesseling, Pieter; Verdijk, Marian A. J.; Ligtenberg, Marjolijn J. L.; Blokx, Willeke A.M.

doi:10.1007/s00428-007-0555-8

Cited by 7 publications

(5 citation statements)

References 12 publications

(13 reference statements)

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“…In addition, these NRAS and BRAF mutations are preserved in the progression of cutaneous melanomas 35 . This is an infrequent problem, since as a rule of thumb a melanoma metastasis is far more likely than a new primary non‐cutaneous melanoma in a patient with a previous history of cutaneous melanoma, 36 even in case of a long interval or a peculiar metastatic pattern 34 . Similarly, this BRAF and RAS mutation analysis might be of use in case of visceral melanoma localization in patients with a blank history for cutaneous melanoma to support a diagnosis of primary mucosal melanoma.…”

Section: Clinical Applications Of Cytogenetics In Melanocytic Tumoursmentioning

confidence: 98%

“…In addition to CDKN2A testing, in some cases RAF or RAS mutation analysis could be performed, possibly together with KIT mutation analysis in case of a clinical problem in differentiating visceral metastasis of cutaneous melanoma from a new primary non‐cutaneous melanoma (as we described in a case in 2008) 34 . Cutaneous melanomas frequently harbour either BRAF or NRAS mutations and these are uncommon in non‐cutaneous types.…”

Section: Clinical Applications Of Cytogenetics In Melanocytic Tumoursmentioning

confidence: 99%

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Molecular cytogenetics of cutaneous melanocytic lesions – diagnostic, prognostic and therapeutic aspects

2009

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Blokx W A M, van Dijk M C R F & Ruiter D J (2010) Histopathology56, 121–132 Molecular cytogenetics of cutaneous melanocytic lesions – diagnostic, prognostic and therapeutic aspects This review intends to update current knowledge regarding molecular cytogenetics in melanocytic tumours with a focus on cutaneous melanocytic lesions. Advantages and limitations of diverse, already established methods, such as (fluorescence) in situ hybridization and mutation analysis, to detect these cytogenetic alterations in melanocytic tumours are described. In addition, the potential value of more novel techniques such as multiplex ligation‐dependent probe amplification is pointed out. This review demonstrates that at present cytogenetics has mainly increased our understanding of the pathogenesis of melanocytic tumours, with an important role for activation of the mitogen‐activated protein kinase (MAPK) signalling pathway in the initiation of melanocytic tumours. Mutations in BRAF (in common naevocellular naevi), NRAS (congenital naevi), HRAS (Spitz naevi) and GNAQ (blue naevi) can all cause MAPK activation. All these mutations seem early events in the development of melanocytic tumours, but by themselves are insufficient to cause progression towards melanoma. Additional molecular alterations are implicated in progression towards melanoma, with different genetic alterations in melanomas at different sites and with varying levels of sun exposure. This genetic heterogeneity in distinct types of naevi and melanomas can be used for the development of molecular tests for diagnostic purposes. However, at the moment only few molecular tests have become of diagnostic value and are performed in daily routine practice. This is caused by lack of large prospective studies on the diagnostic value of molecular tests including follow‐up, and by the low prevalence of certain molecular alterations. For the future we foresee an increasing role for cytogenetics in the treatment of melanoma patients with the increasing availability of targeted therapy. Potential targets for metastatic melanoma include genes involved in the MAPK pathway, such as BRAF and RAS. More recently, KIT has emerged as a potential target in melanoma patients. These targeted treatments all need careful evaluation, but might be a promising adjunct for treatment of metastatic melanoma patients, in which other therapies have not brought important survival advantages yet.

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Section: Clinical Applications Of Cytogenetics In Melanocytic Tumoursmentioning

confidence: 98%

Section: Clinical Applications Of Cytogenetics In Melanocytic Tumoursmentioning

confidence: 99%

Molecular cytogenetics of cutaneous melanocytic lesions – diagnostic, prognostic and therapeutic aspects

2009

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“…To our knowledge, a germline mutation of CDKN2A/P16 INK4A has been identified in only one family combining cases of both uveal and cutaneous melanomas among more than 90 uveal melanoma families [11] and in only one sporadic case of uveal melanoma in a series of 385 unselected cases [15]. However, it is noteworthy that the differential diagnosis between primary uveal melanoma and ocular metastasis from cutaneous melanoma may be difficult and this hypothesis cannot be ruled out in the two patients identified with a CDKN2A/P16 INK4A mutation [26]. In the study conducted by the Melanoma Genetics Consortium (GenoMEL), a CDKN2A/P16 INK4A mutation was identified in 190 of 466 (41%) melanoma-prone families with at least three relatives with malignant cutaneous melanoma [13].…”

Section: Discussionmentioning

confidence: 79%

Contribution of CDKN2A/P16 INK4A, P14 ARF, CDK4 and BRCA1/2 germline mutations in individuals with suspected genetic predisposition to uveal melanoma

et al. 2010

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Uveal melanoma arises from melanocytes of the uveal tract (iris, ciliary body and choroid) and represents the most common intraocular malignancy in adults. Some rare clinical situations (young age at diagnosis, bilateral or multifocal forms, association with cutaneous malignant melanoma and/or familial aggregations of melanomas) are suggestive of genetic susceptibility. The aim of this study was to evaluate the contribution of CDKN2A/P16INK4A, P14ARF and CDK4 gene germline mutations in a series of patients with uveal melanoma recruited in a single institution with a clinical presentation indicative of genetic predisposition. Molecular analyses were proposed to 36 patients and were performed in 25 cases. The contribution of BRCA1/2 gene germline mutations in patients with uveal melanoma and a personal and/or family history of breast/ovarian cancers was also evaluated. Molecular analysis of BRCA1/2 genes was proposed to 35 patients and was performed in 25 patients. No deleterious germline mutation was identified in either group of patients. These results indicate that the CDKN2A/P16INK4A, P14ARF, CDK4 genes are not responsible for the vast majority of genetic susceptibility to uveal melanoma. They also suggest that one case of uveal melanoma in a family with a history of breast cancer is not sufficient to justify BRCA1/2 genetic testing when the classical criteria for molecular analysis are not present. International studies are ongoing in melanoma-prone families in an attempt to identify uveal melanoma susceptibility loci and genes.

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“…Ocular metastasis of melanoma is rare, but is thought to be more likely in cases of widespread metastatic disease 7. The choroid is the most common site of involvement of metastases from cutaneous melanoma, representing 46% of cases.…”

Section: Discussionmentioning

confidence: 99%

Suprachoroidal and vitreous haemorrhage as a presenting feature of metastatic melanoma

et al. 2023

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A man in his 70s presented with right ocular pain, vision loss and temporal headache 4 days after undergoing laser peripheral iridotomy. The patient had lost 10 lbs over the preceding 6 weeks and had a medical history significant for a previously excised melanoma of the left arm. During the course of investigations, the patient was referred to oncology for workup, ultimately leading to a diagnosis of metastatic melanoma. Visceral metastases were identified in the lungs, right anterior fourth rib, left femoral distal diaphysis and medial side of the right globe. The patient decompensated and died shortly after his first radiotherapy treatment.This is the first published report of suprachoroidal haemorrhage secondary to metastasis from suspected cutaneous melanoma. The case highlights the importance of considering malignancy on the differential diagnosis for a suprachoroidal haemorrhage of unknown aetiology and involving oncology early for workup and treatment.

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Occurrence of ocular melanoma thirteen years after skin melanoma: two separate primaries or metastatic disease? A case solved with NRAS and CDKN2A (INK4A-ARF) mutational analysis

Cited by 7 publications

References 12 publications

Molecular cytogenetics of cutaneous melanocytic lesions – diagnostic, prognostic and therapeutic aspects

Molecular cytogenetics of cutaneous melanocytic lesions – diagnostic, prognostic and therapeutic aspects

Contribution of CDKN2A/P16 INK4A, P14 ARF, CDK4 and BRCA1/2 germline mutations in individuals with suspected genetic predisposition to uveal melanoma

Suprachoroidal and vitreous haemorrhage as a presenting feature of metastatic melanoma

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