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Melanoma: HELP
Articles by John William Kelly
Based on 32 articles published since 2008
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Between 2008 and 2019, J. W. Kelly wrote the following 32 articles about Melanoma.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Guideline Clinical practice guidelines for the diagnosis and management of melanoma: melanomas that lack classical clinical features. 2017

Mar, Victoria J / Chamberlain, Alex J / Kelly, John W / Murray, William K / Thompson, John F. ·Victorian Melanoma Service, Alfred Health, Melbourne, VIC victoria.mar@monash.edu. · Victorian Melanoma Service, Alfred Health, Melbourne, VIC. · Peter MacCallum Cancer Centre, Melbourne, VIC. ·Med J Aust · Pubmed #29020893.

ABSTRACT: INTRODUCTION: A Cancer Council Australia multidisciplinary working group is currently revising and updating the 2008 evidence-based clinical practice guidelines for the management of cutaneous melanoma. While there have been many recent improvements in treatment options for metastatic melanoma, early diagnosis remains critical to reducing mortality from the disease. Improved awareness of the atypical presentations of this common malignancy is required to achieve this. A chapter of the new guidelines was therefore developed to aid recognition of atypical melanomas. Main recommendations: Because thick, life-threatening melanomas may lack the more classical ABCD (asymmetry, border irregularity, colour variegation, diameter > 6 mm) features of melanoma, a thorough history of the lesion with regard to change in morphology and growth over time is essential. Any lesion that is changing in morphology or growing over a period of more than one month should be excised or referred for prompt expert opinion. Changes in management as a result of the guidelines: These guidelines provide greater emphasis on improved recognition of the atypical presentations of melanoma, in particular nodular, desmoplastic and acral lentiginous subtypes, with particular awareness of hypomelanotic and amelanotic lesions.

2 Review Clinicopathological characteristics and prognosis of patients with multiple primary melanomas. 2018

Adler, N R / Kelly, J W / Haydon, A / McLean, C A / Mar, V J. ·Victorian Melanoma Service, Alfred Hospital, Melbourne, Victoria, Australia. · School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia. · Department of Medical Oncology, Alfred Hospital, Melbourne, Victoria, Australia. · Department of Anatomical Pathology, Alfred Hospital, Melbourne, Victoria, Australia. · Skin and Cancer Foundation, Carlton, Victoria, Australia. ·Br J Dermatol · Pubmed #28755438.

ABSTRACT: -- No abstract --

3 Review Metastatic pathways in patients with cutaneous melanoma. 2017

Adler, Nikki R / Haydon, Andrew / McLean, Catriona A / Kelly, John W / Mar, Victoria J. ·Victorian Melanoma Service, Alfred Hospital, Melbourne, Vic, Australia. · School of Public Health and Preventive Medicine, Monash University, Alfred Hospital, Melbourne, Vic, Australia. · Department of Medical Oncology, Alfred Hospital, Melbourne, Vic, Australia. · Department of Anatomical Pathology, Alfred Hospital, Melbourne, Vic, Australia. · Skin and Cancer Foundation, Carlton, Vic, Australia. ·Pigment Cell Melanoma Res · Pubmed #27900851.

ABSTRACT: Metastasis represents the end product of an elaborate biological process, which is determined by a complex interplay between metastatic tumour cells, host factors and homoeostatic mechanisms. Cutaneous melanoma can metastasize haematogenously or lymphogenously. The three predominant models that endeavour to explain the patterns of melanoma progression are the stepwise spread model, the simultaneous spread model and the model of differential spread. The time course to the development of metastases differs between the different metastatic routes. There are several clinical and histopathological risk factors for the different metastatic pathways. In particular, patient sex and the anatomical location of the primary tumour influence patterns of disease progression. There is limited existing evidence regarding the relationship between tumour mutation status, other diagnostic and prognostic biomarkers and the metastatic pathways of primary cutaneous melanoma. This knowledge gap needs to be addressed to better identify patients at high risk of disease recurrence and personalize surveillance strategies.

4 Review Atypical Spitzoid neoplasms: a review of potential markers of biological behavior including sentinel node biopsy. 2014

McCormack, Christopher J / Conyers, Rachel K / Scolyer, Richard A / Kirkwood, John / Speakman, David / Wong, Nick / Kelly, John W / Henderson, Michael A. ·aPeter Macallum Cancer Institute, East Melbourne bVictorian Melanoma Service, Alfred Hospital, Prahran cDepartment of Paediatrics, Murdoch Children's Research Institute, Royal Children's Hospital, The University of Melbourne, Parkville dThe Royal Children's Hospital, Flemington Road, Parkville, Victoria eMelanoma Institute Australia , Royal Prince Alfred Hospital, The University of Sydney, Sydney, New South Wales, Australia fDepartment of Medicine, Melanoma and Skin Cancer Program, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA. ·Melanoma Res · Pubmed #24892957.

ABSTRACT: Atypical cutaneous melanocytic lesions, including those with Spitzoid features, can be difficult to categorize as benign or malignant. This can lead to suboptimal management, with potential adverse patient outcomes. Recent studies have enhanced knowledge of the molecular and genetic biology of these lesions and, combined with clinicopathological findings, is further defining their biological spectrum, classification, and behavior. Sentinel node biopsy provides important prognostic information in patients with cutaneous melanoma, but its role in the management of melanocytic lesions of uncertain malignant potential (MELTUMP) is controversial. This paper examines the role of molecular testing and sentinel node biopsy in MELTUMPs, particularly atypical Spitzoid tumors.

5 Clinical Trial Efficacy of imiquimod cream, 5%, for lentigo maligna after complete excision: a study of 43 patients. 2011

Ly, Lena / Kelly, John William / O'Keefe, Rodney / Sutton, Tina / Dowling, John P / Swain, Sarah / Byrne, Marguerite / Curr, Nathan / Wolfe, Rory / Chamberlain, Alex / Haskett, Martin. ·Victorian Melanoma Service, Level 1, Alfred Center, Alfred Health, Commercial Road, Melbourne, Victoria, Australia. lenaly21@yahoo.com.au ·Arch Dermatol · Pubmed #22006136.

ABSTRACT: OBJECTIVE: To determine the efficacy of imiquimod cream, 5%, in the treatment of lentigo maligna (LM). DESIGN: Open-label before-and-after interventional study. SETTING: A multidisciplinary melanoma clinic at a major tertiary hospital. PATIENTS: Forty-three patients with biopsy-proven LM of greater than 5 mm in diameter completed this study. INTERVENTIONS: Imiquimod cream, 5%, was applied to the lesion 5 days a week for 12 weeks. The original lesion was excised with a 5-mm margin. MAIN OUTCOME MEASURES: The primary outcome was histopathologic evidence of LM in the excision specimen assessed independently by 2 of 3 dermatopathologists. Visible inflammation during treatment and macroscopic clearance were recorded. RESULTS: When 5 of the 43 patients with discordant histopathologic assessment of the excision specimen were excluded, 20 of 38 patients (53% [95% confidence interval, 36%-69%]) demonstrated histopathologic clearance of LM after imiquimod treatment. Visible inflammation was significantly associated with histopathologic clearance (P = .04), but the positive predictive value was low (62%). Macroscopic clearance showed some association with histopathologic clearance (P = .11). Dermatopathologist concordance for all 43 specimens was substantial (κ = 0.77; 95% confidence interval, 0.57-0.96). CONCLUSIONS: Imiquimod cream, 5%, has limited efficacy in the treatment of LM when determined by histopathologic assessment of the entire treated area. The clinical signs of visible inflammation during treatment and apparent lesion clearance cannot be relied on to assess efficacy.

6 Article Clinically amelanotic or hypomelanotic melanoma: Anatomic distribution, risk factors, and survival. 2018

Wee, Edmund / Wolfe, Rory / Mclean, Catriona / Kelly, John W / Pan, Yan. ·Victorian Melanoma Service, Alfred Health, Melbourne, Australia; Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia. Electronic address: edmundwee1@gmail.com. · Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia. · Victorian Melanoma Service, Alfred Health, Melbourne, Australia. ·J Am Acad Dermatol · Pubmed #30241625.

ABSTRACT: BACKGROUND: The recognition and diagnosis of clinically amelanotic or hypomelanotic melanoma is a challenge. OBJECTIVE: This study aimed to examine the anatomic distribution and risk factors associated with clinically amelanotic or hypomelanotic melanoma and compare the survival of patients with clinically amelanotic or hypomelanotic melanoma with that of patients with pigmented melanoma. METHODS: A prospective cohort study of all cases of primary invasive melanoma managed at a tertiary referral center was performed. RESULTS: There were a total of 3913 invasive melanomas, and 384 (9.8%) were clinically amelanotic or hypomelanotic. Skin phototype I; red as well as blonde hair color; actinic keratoses; nodular, desmoplastic, and lentigo maligna subtype; increased Breslow thickness; and mitoses were independently associated with amelanotic or hypomelanotic melanoma (P < .05). After adjustment for subtype and thickness, the face, ears, lateral aspect of the neck, upper portion of the arm, posterior aspect of the forearm, dorsal aspect of the hand, and anterior aspect of the lower portion of the leg were associated with increased odds of amelanotic or hypomelanotic melanoma when compared with the upper portion of the back (P < .05). Mortality risk from melanoma appeared greater for amelanotic or hypomelanotic melanoma than for pigmented melanoma (hazard ratio, 1.5; 95% confidence interval, 1.1-2.1) but was similar once Breslow thickness was taken into account. LIMITATIONS: Single tertiary referral center. CONCLUSION: Although clinically amelanotic or hypomelanotic melanoma can occur on all body sites, it is more common on chronically sun-exposed areas. Clinicians should have an increased index of suspicion in patients with a sun-sensitive skin phenotype, red hair, and associated actinic keratoses.

7 Article Concordance of somatic mutational profile in multiple primary melanomas. 2018

Adler, Nikki R / McLean, Catriona A / Wolfe, Rory / Kelly, John W / McArthur, Grant A / Haydon, Andrew / Tra, Thien / Cummings, Nicholas / Mar, Victoria J. ·Victorian Melanoma Service, Alfred Hospital, Melbourne, Vic., Australia. · School of Public Health and Preventive Medicine, Monash University, Melbourne, Vic., Australia. · Department of Anatomical Pathology, Alfred Hospital, Melbourne, Vic., Australia. · Divisions of Research and Cancer Medicine, Peter MacCallum Cancer Centre, East Melbourne, Vic., Australia. · Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Vic., Australia. · Department of Medical Oncology, Alfred Hospital, Melbourne, Vic., Australia. · Skin and Cancer Foundation Inc., Carlton, Vic., Australia. ·Pigment Cell Melanoma Res · Pubmed #29603877.

ABSTRACT: This study aimed to determine the frequency and concordance of BRAF and NRAS mutation in tumours arising in patients with multiple primary melanoma (MPM). Patients with MPM managed at one of three tertiary referral centres in Melbourne, Australia, from 2010 to 2015 were included. Incident and subsequent melanomas underwent mutation testing. Cohen's kappa (κ) coefficient assessed agreement between incident and subsequent primary melanomas for both BRAF and NRAS mutation status (mutant versus wild-type). Mutation testing of at least two primary tumours from 64 patients was conducted. There was poor agreement for both BRAF and NRAS mutation status between incident and subsequent melanomas (κ = 0.10, 95% CI -0.10 to 0.42; κ = 0.06, 95% CI -0.10 to 0.57, respectively). In view of the low concordance in BRAF mutation status between incident and subsequent melanomas, mutational analysis of metastatic tissue, rather than of a primary melanoma, in patients with MPM should be used to guide targeted therapy.

8 Article Primary Tumor Thickness is a Prognostic Factor in Stage IV Melanoma: A Retrospective Study of Primary Tumor Characteristics. 2018

Luen, Stephen / Wong, Siew Wei / Mar, Victoria / Kelly, John W / McLean, Catriona / McArthur, Grant A / Haydon, Andrew. ·Departments of Medical Oncology. · Victorian Melanoma Service, The Alfred Hospital. · Anatomical Pathology. · Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Vic., Australia. ·Am J Clin Oncol · Pubmed #26325493.

ABSTRACT: INTRODUCTION: Stage IV melanoma exhibits a diverse range of tumor biology from indolent to aggressive disease. Many important prognostic factors have already been identified. Despite this, the behavior of metastatic melanoma remains difficult to predict. We sought to determine if any primary tumor characteristics affect survival following the diagnosis of stage IV melanoma. METHODS: All patients diagnosed with stage IV melanoma between January 2003 and December 2012 were identified from the Victorian Melanoma Service database. Retrospective chart review was performed to collect data on primary tumor characteristics (thickness, ulceration, mitotic rate, melanoma subtype, or occult primary). Known and suspected prognostic factors were additionally collected (time to diagnosis of stage IV disease, age, sex, stage, receipt of chemotherapy, and era of recurrence). The effect of primary tumor characteristics on overall survival from the date of diagnosis of stage IV disease was assessed. RESULTS: A total of 227 patients with a median follow-up of 5 years from diagnosis of stage IV disease were identified. Median overall survival of the cohort was 250 days.Of the primary tumor characteristics assessed, only tumor thickness affected survival from diagnosis of stage IV disease, hazard ratio=1.09 (1.02 to 1.16), P=0.008. This remained significant in multivariate analysis, P=0.007. Other primary tumor characteristics did not significantly influence survival. CONCLUSIONS: Primary tumor thickness is a significant prognostic factor in stage IV melanoma. Our data suggest that the biology of the primary melanoma may persist to influence the behavior of metastatic disease.

9 Article Nodular melanoma is less likely than superficial spreading melanoma to be histologically associated with a naevus. 2017

Pan, Yan / Adler, Nikki R / Wolfe, Rory / McLean, Catriona A / Kelly, John W. ·Victorian Melanoma Service, Alfred Hospital, Melbourne, VIC nikki.adler@monash.edu. · Victorian Melanoma Service, Alfred Hospital, Melbourne, VIC. · Monash University, Melbourne, VIC. · Alfred Health, Melbourne, VIC. ·Med J Aust · Pubmed #29020904.

ABSTRACT: OBJECTIVES: To determine the frequency of naevus-associated melanoma among superficial spreading and nodular subtypes; and to investigate associations between naevus-associated melanoma and other clinico-pathological characteristics. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional study of all patients with nodular and superficial spreading melanomas diagnosed between 1994 and 2015 at the Victorian Melanoma Service, Melbourne. METHODS AND MAIN OUTCOME MEASURES: Clinical and pathological characteristics of naevus-associated and de novo melanomas were assessed in univariable and multivariable logistic regression analyses. RESULTS: Of 3678 primary melanomas, 1360 (37.0%) were histologically associated with a naevus and 2318 (63.0%) were de novo melanomas; 71 of 621 nodular (11.4%) and 1289 of 3057 superficial spreading melanomas (42.2%) were histologically associated with a naevus. In multivariable analyses, the odds of being associated with a naevus were higher for melanomas located on the trunk (v head and neck: adjusted odds ratio [OR], 2.27; 95% CI, 1.73-2.96; P < 0.001), while the odds were lower for thicker tumours (adjusted OR, 0.75 per millimetre increase in Breslow thickness; 95% CI, 0.69-0.81; P < 0.001), amelanotic/hypomelanotic melanomas (adjusted OR, 0.68; 95% CI, 0.48-0.97; P = 0.035), and older age (patients 70 years or older v patients under 30 at diagnosis: adjusted OR, 0.28; 95% CI, 0.20-0.40; P < 0.001). After adjusting for confounders, the odds of an associated naevus was three times as high for superficial spreading melanomas as for nodular melanomas (adjusted OR, 3.05; 95% CI, 2.24-4.17; P < 0.001). CONCLUSION: Melanomas are most likely to arise in the absence of a pre-existing naevus, particularly nodular melanomas. Public health campaigns should therefore emphasise the detection of suspicious de novo lesions, as well as of changing lesions.

10 Article Tumour mutation status and sites of metastasis in patients with cutaneous melanoma. 2017

Adler, Nikki R / Wolfe, Rory / Kelly, John W / Haydon, Andrew / McArthur, Grant A / McLean, Catriona A / Mar, Victoria J. ·Victorian Melanoma Service, Alfred Hospital, Melbourne, Victoria 3004, Australia. · School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria 3004, Australia. · Department of Medical Oncology, Alfred Hospital, Melbourne, Victoria 3004, Australia. · Divisions of Research and Cancer Medicine, Peter MacCallum Cancer Centre, Melbourne, Victoria 3000, Australia. · Sir Peter MacCallum Department of Oncology, University of Melbourne, Victoria 3000, Australia. · Department of Anatomical Pathology, Alfred Hospital, Melbourne, Victoria 3004, Australia. · Skin and Cancer Foundation, Carlton, Victoria 3053, Australia. ·Br J Cancer · Pubmed #28787433.

ABSTRACT: BACKGROUND: Cutaneous melanoma can metastasise haematogenously and/or lymphogenously to form satellite/in-transit, lymph node or distant metastasis. This study aimed to determine if BRAF and NRAS mutant and wild-type tumours differ in their site of first tumour metastasis and anatomical metastatic pathway. METHODS: Prospective cohort of patients with a histologically confirmed primary cutaneous melanoma at three tertiary referral centres in Melbourne, Australia from 2010 to 2015. Multinomial regression determined clinical, histological and mutational factors associated with the site of first metastasis and metastatic pathway. RESULTS: Of 1048 patients, 306 (29%) developed metastasis over a median 4.7 year follow-up period. 73 (24%), 192 (63%) and 41 (13%) developed distant, regional lymph node and satellite/in-transit metastasis as the first site of metastasis, respectively. BRAF mutation was associated with lymph node metastasis (adjusted RRR 2.46 95% CI 1.07-5.69, P=0.04) and sentinel lymph node positivity (adjusted odds ratio [aOR] OR 1.55, 95% CI 1.14-2.10, P=0.005). BRAF mutation and NRAS mutation were associated with increased odds of developing liver metastasis (aOR 3.09, 95% CI 1.49-6.42, P=0.003; aOR 3.17, 95% CI 1.32-7.58, P=0.01) and central nervous system (CNS) metastasis (aOR 4.65, 95% CI 2.23-9.69, P<0.001; aOR 4.03, 95% CI 1.72-9.44, P=0.001). NRAS mutation was associated with lung metastasis (aOR 2.44, 95% CI 1.21-4.93, P=0.01). CONCLUSIONS: BRAF mutation was found to be associated with lymph node metastasis as first metastasis and sentinel lymph node positivity. BRAF and NRAS mutations were associated with CNS and liver metastasis and NRAS mutation with lung metastasis. If these findings are validated in additional prospective studies, a role for heightened visceral organ surveillance may be warranted in patients with tumours harbouring these somatic mutations.

11 Article Single institution experience of paediatric melanoma in Victoria, Australia. 2017

Le, Quynh / Norris, Diana / McClean, Catriona A / Mcguiness, Myra / Meani, Rowena / Kelly, John W / Pan, Yan. ·Victorian Melanoma Service, The Alfred Hospital, Melbourne, Victoria, Australia. · Department of Anatomical Pathology, The Alfred Hospital, Melbourne, Victoria, Australia. · Monash University, Melbourne, Victoria, Australia. · Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia. ·Australas J Dermatol · Pubmed #26821217.

ABSTRACT: BACKGROUND/OBJECTIVES: Paediatric melanoma is an uncommon presentation of melanoma that accounts for 3% of all paediatric cancers. The objective was to describe a series of paediatric melanoma cases presenting to a state-wide tertiary referral service over the past 19 years. METHODS: A search of the Victorian Melanoma Service database was performed to identify all patients under the age of 20 years diagnosed with melanoma from 1994 to 2013. Histological, demographic and phenotypical information for each patient was collected. Patients were matched against the Victorian Death Registry to identify those who had died. Fisher's exact test was used to examine associations. Melanoma-specific survival was estimated using the Kaplan-Meier method. RESULTS: A total of 65 paediatric melanoma patients were included for analysis, in whom 72.3% of melanomas were diagnosed when they were 16-19 years of age with a mean age at diagnosis of 16 years. The mean Breslow thickness was 1.4 mm. It was greatest (3.4 mm) in the youngest age group (< 12 years of age). Ten patients developed nodal metastatic disease, eight of which progressed to visceral metastatic disease. The 5-year melanoma-specific survival rate was 96.8%. CONCLUSION: This is the first descriptive epidemiological study of paediatric melanoma in Victoria. Further large, population-based, multi-institutional studies of paediatric melanoma are warranted to provide a clearer understanding of this group of melanoma patients.

12 Article Scalp melanoma: Distinctive high risk clinical and histological features. 2017

Xie, Charles / Pan, Yan / McLean, Catriona / Mar, Victoria / Wolfe, Rory / Kelly, John W. ·Victorian Melanoma Service, The Alfred Hospital, Melbourne, Victoria, Australia. · School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia. ·Australas J Dermatol · Pubmed #26768190.

ABSTRACT: BACKGROUND/OBJECTIVES: Scalp melanoma has a worse prognosis than melanoma elsewhere, though the reasons for this are poorly understood. Current literature describing the clinicopathological associations of scalp melanoma is sparse. This study aims to compare clinical and histological features of scalp melanoma with other cutaneous head and neck melanomas (CHNM). METHODS: A cross-sectional study was performed of all primary CHNM cases seen by the Victorian Melanoma Service between 1994 and 2014, using prospectively recorded clinical data. Invasive and in situ melanomas were compared separately. RESULTS: Invasive scalp melanoma was associated with male sex (OR, 2.7; 95% CI, 1.9-3.9), increasing age (OR, 1.02 per year increase in age; 95% CI, 1.01-1.03), being first noticed by a person other than self, spouse/relative or doctor (OR, 2.9; 95% CI, 1.5-5.7), amelanosis (OR, 1.6; 95% CI, 1.1-2.3), and increased growth rate (OR, 1.14 per 1 mm/month growth rate increase; 95% CI, 1.04-1.26). Compared with other CHNM, scalp melanoma had greater median Breslow thickness (2.8  vs 1.2 mm) and was independently associated with satellite metastases (OR, 4.7; 95% CI, 1.9-11.5) and nodular subtype (OR, 1.8; 95% CI, 1.1-3.1). In situ scalp melanoma was associated with male sex, increasing age and solar keratoses. CONCLUSION: Scalp melanoma tends to occur in older men, is often rapidly growing and amelanotic, and is associated with high risk histological features. As it is likely to be overlooked, increased recognition of the atypical presentations of scalp melanoma is required.

13 Article Frequency of residual melanoma in wide local excision (WLE) specimens after complete excisional biopsy. 2016

Bolshinsky, Vladimir / Lin, Matthew J / Serpell, Jonathan / Leung, Michael / Wolfe, Rory / McLean, Catriona / Kelly, John W. ·Breast, Endocrine, and General Surgery Unit, Alfred Hospital, Melbourne, Victoria, Australia; General Surgery, Alfred Hospital, Melbourne, Australia. Electronic address: bolshinskyv@gmail.com. · Victorian Melanoma Service, Alfred Hospital, Melbourne, Victoria, Australia. · General Surgery, Alfred Hospital, Melbourne, Australia. · Plastics, Hand, Facio-Maxillary Surgery Unit, Alfred Hospital, Melbourne, Victoria, Australia. · Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia. · Department of Anatomical Pathology, Alfred Hospital, Melbourne, Victoria, Australia. ·J Am Acad Dermatol · Pubmed #26601566.

ABSTRACT: OBJECTIVE: We sought to better understand the role of wide local excision (WLE) in the treatment of cutaneous melanoma by analyzing residual or locally metastatic disease in WLE specimens of melanomas initially diagnosed with a complete excisional biopsy. METHODS: This was a retrospective review of 807 consecutive WLEs of melanomas diagnosed after complete excisional biopsy. All specimens were reviewed by a single dermatopathologist. Risk of residual or locally metastatic disease was analyzed using univariate and multivariate logistic regression models. RESULTS: In the 807 WLE specimens, further melanoma was found in 34 cases (4.2%; 95% confidence interval [CI] 2.9-5.8). Residual primary melanoma was found in 33 of these. On univariate analysis, features associated with residual or locally metastatic disease were histologic subtype (odds ratio 3.0; 95% CI 1.3-7.1, P = .01) and tumor location (odds ratio 7.3; 95% CI 2.0-26.6, P < .01). On multivariate analysis, lentigo maligna was independently associated with melanoma remaining in WLE specimens (odds ratio 2.7; 95% CI 1.0-7.3, P = .04). CONCLUSION: Residual melanoma in WLE specimens after histologically assessed complete excisional biopsy is not uncommon. Patients with lentigo maligna subtype melanomas are most at risk. Our findings indicate that the procedure of WLE is most important therapeutically for its role in controlling the primary tumor, rather than in preventing local metastatic recurrence.

14 Article An assessment of clinical pathways and missed opportunities for the diagnosis of nodular melanoma versus superficial spreading melanoma. 2016

Cicchiello, Mark / Lin, Matthew J / Pan, Yan / McLean, Catriona / Kelly, John W. ·Victorian Melanoma Service, Alfred Hospital, Melbourne, Victoria, Australia. · Department of Anatomical Pathology, Alfred Hospital, Melbourne, Victoria, Australia. ·Australas J Dermatol · Pubmed #26563931.

ABSTRACT: BACKGROUND: Missed opportunities in the diagnosis of nodular melanoma (NM) carry high prognostic penalties due to the rapid rate of NM growth. To date, an assessment of the pathways to diagnosis of NM versus superficial spreading melanoma (SSM) specifically comparing numbers of opportunities missed to undertake biopsy has not been performed. METHODS: A retrospective questionnaire of 120 patients (60 NM patients, age and sex matched to 60 SSM patients) from the Victorian Melanoma Service (VMS) database was undertaken to assess pathways to diagnosis. The numbers of opportunities missed to undertake a biopsy and doctor behaviour at such encounters were recorded. Diagnostic delay (overall, patient's and doctor's delay) in terms of time was assessed. RESULTS: Significant differences in opportunities missed to make a diagnosis of NM compared to SSM were found. In all, 43% of NM were biopsied at a first encounter compared to 70% of SSM. All SSM were diagnosed within three reviews. Overall, 33% of NM required at least three and up six reviews until biopsy. Patients with NM were more likely than those with SSM to be reassured that their lesions were benign. No significant differences in terms of time delay to diagnosis between NM and SSM were found. CONCLUSIONS: NM contributes disproportionately to melanoma mortality in Australia. Addressing earlier diagnosis of NM with renewed focus may make the biggest impact on the overall mortality of melanoma. The message that a period of observation is not appropriate for patients re-presenting with lesions of concern must be more effectively communicated.

15 Article The Victorian Melanoma Service: A 20-year review of an Australian multidisciplinary cancer service. 2016

Meani, Rowena E / Pan, Yan / McLean, Catriona / Haydon, Andrew / Leung, Michael / Kelly, John W. ·Victorian Melanoma Service, Alfred Hospital, Victoria, Australia. · Department of Anatomical Pathology, Alfred Hospital, Victoria, Australia. · Department of Plastic, Reconstructive and Faciomaxillary Surgery, Alfred Hospital, Victoria, Australia. · Department of Medical Oncology, Alfred Hospital, Victoria, Australia. ·Australas J Dermatol · Pubmed #26559638.

ABSTRACT: Australia has the highest incidence and mortality rates for melanoma in the world. The Victorian Melanoma Service began operation in 1994 as one of the first multidisciplinary melanoma clinics in Victoria. We conducted a review of the Victorian Melanoma Service database of 6721 patients and present the trends observed in a statewide referral centre in Australia. Our results highlight the importance of multidisciplinary care of melanoma patients and emphasise the significance of histological reviews and dermatological skin assessments for the detection of synchronous melanoma.

16 Article The role of BRAF mutations in primary melanoma growth rate and survival. 2015

Mar, V J / Liu, W / Devitt, B / Wong, S Q / Dobrovic, A / McArthur, G A / Wolfe, R / Kelly, J W. ·Victorian Melanoma Service, Alfred Hospital, Melbourne, Vic., 3181, Australia. · Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Vic., 3181, Australia. · Division of Cancer Research, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Vic., 3002, Australia. · Department of Oncology, St Vincent's Hospital, Fitzroy, Vic., 3065, Australia. · Translational Genomics and Epigenomics Laboratory, Ludwig Institute for Cancer Research, Olivia Newton-John Cancer and Wellness Centre, Heidelberg, Vic., 3084, Australia. ·Br J Dermatol · Pubmed #25752325.

ABSTRACT: BACKGROUND: The clinical behaviour and prognosis of primary melanomas harbouring BRAF mutations is not fully understood. OBJECTIVES: To investigate the effect of mutation status on primary melanoma growth rate and melanoma-specific survival (MSS). METHODS: A prospective cohort of 196 patients with stage I-III primary cutaneous melanoma were followed for a median of 92 months, pre-dating the institution of BRAF inhibitor therapy. Clinicopathological variables were correlated with mutation status and hazard ratios (HRs) estimated for MSS. RESULTS: Of 196 tumours, 77 (39.2%) were BRAF V600E, 10 (5.1%) BRAF V600K and 33 (16.8%) were NRAS mutant. BRAF V600E mutant melanomas were associated with favourable clinical characteristics and tended to be slower growing compared with BRAF V600K, NRAS mutant or BRAF/NRAS wild-type tumours (0.12 mm per month, 0.61 mm per month, 0.36 mm per month and 0.23 mm per month, respectively; P = 0.05). There were 39 melanoma deaths, and BRAF mutant melanomas were associated with poorer MSS in stage I-III disease [HR 2.60, 95% confidence interval (CI) 1.20-5.63; P = 0.02] and stage I-II disease (HR 3.39, 95% CI 1.12-10.22; P = 0.03) after adjusting for other prognostic variables. Considered separately, BRAF V600E mutant melanomas were strongly associated with MSS independently of thickness and nodal status (HR 3.89, 95% CI 1.67-9.09; P < 0.01) but BRAF V600K mutant tumours were not (HR 1.19, 95% CI 0.36-3.92; P = 0.77). CONCLUSIONS: The presence of a BRAF mutation does not necessarily 'drive' more rapid tumour growth but is associated with poorer MSS in patients with early-stage disease.

17 Article Prognosis associated with cutaneous melanoma metastases. 2015

Pan, Yan / Haydon, Andrew M / McLean, Catriona A / McDonald, Priska B B / Kelly, John W. ·Victorian Melanoma Service, The Alfred, Melbourne, Victoria, Australia. ·Australas J Dermatol · Pubmed #25688698.

ABSTRACT: BACKGROUND/OBJECTIVE: Information on the prognosis for patients with regional cutaneous melanoma metastases has been sparse and difficult to establish. In 2009 the American Joint Committee on Cancer (AJCC) melanoma staging has for the first time provided survival rates for patients who manifest intralymphatic metastases. We sought to validate the new staging system in this contemporary, prospectively collected cohort of patients following the development of cutaneous metastases as the first evidence of metastatic disease and explored the factors that influenced their prognosis. METHODS: The Victorian Melanoma Service database was searched to identify all patients with cutaneous melanoma metastases. Patients who were found to have lymph node or visceral metastases at the time they were diagnosed with cutaneous metastatic disease were excluded. Survival curves were generated and univariate and multivariate assessments of prognostic factors associated with survival were performed. RESULTS: In total, 72 patients presented with cutaneous metastases as the first evidence of metastatic disease. The median melanoma-specific survival of patients with only regional cutaneous metastases (n = 56) was 5.07 years and their 5-year survival rate was 52%. Distant cutaneous metastases and thickness of the primary melanoma were found to be significant negative predictors of survival. CONCLUSION: We were able to validate the new AJCC melanoma staging system survival for patients with cutaneous metastatic disease. Patients presenting with regional cutaneous metastases have a much better prognosis than those with distant cutaneous metastases.

18 Article Characteristics and associations of high-mitotic-rate melanoma. 2014

Shen, Sarah / Wolfe, Rory / McLean, Catriona A / Haskett, Martin / Kelly, John W. ·Victorian Melanoma Service, Alfred Hospital, Victoria, Australia2Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia. · Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia. · Department of Anatomical Pathology, Alfred Hospital, Victoria, Australia. · Victorian Melanoma Service, Alfred Hospital, Victoria, Australia. ·JAMA Dermatol · Pubmed #25142970.

ABSTRACT: IMPORTANCE: Mitotic rate is now recognized as having independent prognostic significance in melanoma survival. However, its clinicopathologic associations have not been the focus of any previous study. OBJECTIVE: To identify a set of patient and tumor characteristics associated with high-mitotic-rate melanoma with the aim of facilitating the earlier detection of aggressive primary invasive melanoma. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study of patients from a multidisciplinary melanoma clinic based in a public hospital. A total of 2397 cases from January 2006 to December 2011 were reviewed by the Victorian Melanoma Service, and 1441 patients with 1500 primary invasive melanomas were included in the study. MAIN OUTCOMES AND MEASURES: Mitotic rate was measured as number of mitoses per mm2 and analyzed as ordered categories (0, <1, 1 and <2, 2, 3-4, 5-9, and ≥10) according to patient demographics, phenotypic markers, historical data, tumor presentation, and histopathologic features. RESULTS: Melanomas with higher mitotic rates were more likely to occur in men (odds ratio [OR], 1.5; 95% CI, 1.3-1.8), patients 70 years or older (OR, 2.1; 95% CI, 1.7-2.8), and those with a history of solar keratosis (OR, 1.3; 95% CI, 1.1-1.6). These melanomas occurred more frequently on the head and neck (OR, 1.4; 95% CI, 1.0-1.9) and presented more often as amelanotic (OR, 1.9; 95% CI, 1.4-2.5) and rapidly growing (≥2 mm/mo) lesions (OR, 12.5; 95% CI, 8.4-18.5). An association was seen with the nodular melanoma subtype (vs superficial spreading [reference]) (OR, 2.5; 95% CI, 1.8-3.4), greater tumor thickness (vs ≤1 mm [reference]) (>1-4 mm: OR, 4.5; 95% CI, 3.2-6.1; >4 mm: OR, 12.6; 95% CI, 7.5-21.1), and ulceration (OR, 2.0; 95% CI, 1.5-2.7). These histopathologic features, along with amelanosis and rate of growth, remained as significant associations with high mitotic rate in the overall multivariate analysis. CONCLUSIONS AND RELEVANCE: High-mitotic-rate primary cutaneous melanoma is associated with aggressive histologic features and atypical clinical presentation. It has a predilection for the head and neck region and is more likely to be seen in elderly men with a history of cumulative solar damage who present clinically with rapidly developing disease.

19 Article Clinical and pathological associations of the activating RAC1 P29S mutation in primary cutaneous melanoma. 2014

Mar, Victoria J / Wong, Stephen Q / Logan, Aleksandra / Nguyen, Trung / Cebon, Jonathan / Kelly, John W / Wolfe, Rory / Dobrovic, Alexander / McLean, Catriona / McArthur, Grant A. ·Victorian Melanoma Service, Alfred Hospital, Melbourne, Vic., Australia; Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Vic., Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Vic., Australia. ·Pigment Cell Melanoma Res · Pubmed #25043693.

ABSTRACT: Activating mutations in the GTPase RAC1 are a recurrent event in cutaneous melanoma. We investigated the clinical and pathological associations of RAC1(P29S) in a cohort of 814 primary cutaneous melanomas with known BRAF and NRAS mutation status. The RAC1(P29S) mutation had a prevalence of 3.3% and was associated with increased thickness (OR=1.6 P = 0.001), increased mitotic rate (OR=1.3 P = 0.03), ulceration (OR=2.4 P = 0.04), nodular subtype (OR=3.4 P = 0.004), and nodal disease at diagnosis (OR=3.3 P = 0.006). BRAF mutant tumors were also associated with nodal metastases (OR=1.9 P = 0.004), despite being thinner at diagnosis than BRAF WT (median 1.2 mm versus 1.6 mm, P < 0.001). Immunohistochemical analysis of 51 melanomas revealed that 47% were immunoreactive for RAC1. Melanomas were more likely to show RAC1 immunoreactivity if they were BRAF mutant (OR=5.2 P = 0.01). RAC1 may therefore be important in regulating the early migration of BRAF mutant tumors. RAC1 mutations are infrequent in primary melanomas but may accelerate disease progression.

20 Article An objective measure of growth rate using partial biopsy specimens of melanomas that were initially misdiagnosed. 2014

Lin, Matthew J / Mar, Victoria / McLean, Catriona / Kelly, John W. ·Victorian Melanoma Service, Alfred Hospital, Melbourne, Australia. Electronic address: drmatthewlin@gmail.com. · Victorian Melanoma Service, Alfred Hospital, Melbourne, Australia; Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia. · Victorian Melanoma Service, Alfred Hospital, Melbourne, Australia; Department of Anatomical Pathology, Alfred Hospital, Melbourne, Australia. · Victorian Melanoma Service, Alfred Hospital, Melbourne, Australia. ·J Am Acad Dermatol · Pubmed #24976443.

ABSTRACT: BACKGROUND: To calculate melanoma rate of growth (ROG), previous studies have relied on subjective patient recall to estimate time delay to diagnosis. OBJECTIVE: To objectively calculate ROG by measuring the rate of increase in melanoma thickness between 2 sequential biopsy specimens over time. METHODS: This was a retrospective review of 51 melanomas in which pathologic misdiagnosis of a partial biopsy specimen caused a delay before referral and excisional biopsy between January 1998 and January 2013. ROG was calculated as rate of increase in tumor thickness between biopsy specimens. RESULTS: The median delay between the 2 biopsy specimens was 27 months (range, 3-89 months). Biopsy specimens of melanomas that were obtained initially in their in situ phase were thinner at excision compared to those that were first obtained as invasive tumors (median, 0.7 vs. 3.2 mm; P<.01) and had a lower ROG (median, 0.04 vs. 0.11 mm/month; P=.05). Faster growth was associated with increased tumor thickness, higher mitotic rate, symptoms, elevation, and amelanosis. LIMITATIONS: Partial biopsy specimens may not be representative of deepest tumor thickness. CONCLUSION: We have demonstrated an objective measure of melanoma growth rate using sequential biopsy specimens. The correlation between faster growth and aggressive tumor features supports what others have found and validates the historical measure of growth rate as a reliable clinical marker.

21 Article Liability in the context of misdiagnosis of melanoma in Australia. 2014

Abikhair, Melody R / Mahar, Patrick D / Cachia, Adrian R / Kelly, John W. ·Department of Dermatology, Monash Medical Centre, Monash Health, Melbourne, VIC, Australia. pmahar@student.unimelb.edu.au. · Department of Medicine, St Vincent's Hospital, University of Melbourne, Melbourne, VIC, Australia. · Skin and Cancer Foundation Australia, Sydney, NSW, Australia. · Victorian Melanoma Service, The Alfred Hospital, Alfred Health, Melbourne, VIC, Australia. ·Med J Aust · Pubmed #24484118.

ABSTRACT: Malignant melanoma is a serious and relatively common condition, the diagnosis of which may be difficult. In a recent Supreme Court of New South Wales case, misdiagnosis of melanoma occurred, but there was failure to establish causation of the patient's poor prognosis. Aggressive melanomas may grow quickly, fail to conform to standard and commonly taught diagnostic criteria, and frequently escape early detection. In the event of uncertain diagnosis or failed treatment of a lesion, an appropriate standard of care is full excisional biopsy if not previously performed, or referral of the case to an appropriate specialist or melanoma centre. Clinicians should remain aware of the existence of higher-risk, easily misdiagnosed melanomas with a high mortality rate. Therefore, they should aim to identify these at the earliest opportunity.

22 Article Diagnostic accuracy of malignant melanoma according to subtype. 2014

Lin, Matthew J / Mar, Victoria / McLean, Catriona / Wolfe, Rory / Kelly, John W. ·Victorian Melanoma Service, The Alfred, Melbourne, Victoria, Australia. ·Australas J Dermatol · Pubmed #24283461.

ABSTRACT: BACKGROUND/OBJECTIVE: Although there has been improvement in clinical diagnosis of pigmented superficial spreading melanomas (SSM), less common melanoma subtypes have different clinical features and may be more difficult to diagnose. The objective was to assess diagnostic accuracy for different melanoma subtypes. METHODS: A retrospective review was made of a random selection of SSM, nodular melanomas (NM), desmoplastic melanomas (DM) and acral lentiginous melanomas (ALM) biopsied between February 2001 and May 2012 and referred to the Victorian Melanoma Service. Clinical differential diagnoses listed on pre-operative biopsy pathology request forms were recorded. Sensitivity for the diagnosis of melanoma was used as a marker of diagnostic accuracy. RESULTS: In total 111 SSM, 121 NM, 43 DM and 30 ALM were biopsied by 222 clinicians. Whereas diagnostic sensitivity for SSM and ALM were similar (77%, 95% CI 69-85% and 73%, 95% CI 58-89%, respectively) diagnostic sensitivity was lower for NM (41%, 95% CI 33-50%) and DM (21%, 95% CI 9-33%). Both NM and DM were diagnosed at greater tumour thickness (median 3.0 mm and 4.0 mm) than SSM and ALM (both median 1.0 mm). Amelanosis was associated with lower diagnostic sensitivity for SSM (0 vs 82%, P < 0.01), NM (19 vs 51%, P < 0.01) andDM (10 vs 32%, P = 0.07). Dermatologists were more accurate than non-dermatologists for NM (diagnostic sensitivity 57 vs 32%, P < 0.01) and ALM (diagnostic sensitivity 94 vs 43%, P = 0.02). CONCLUSIONS: Misdiagnosis of melanoma varies according to subtype and is particularly problematic for NM, DM and hypopigmented melanomas. Greater awareness of the different criteria required to diagnose these melanomas is needed.

23 Article BRAF/NRAS wild-type melanomas have a high mutation load correlating with histologic and molecular signatures of UV damage. 2013

Mar, Victoria J / Wong, Stephen Q / Li, Jason / Scolyer, Richard A / McLean, Catriona / Papenfuss, Anthony T / Tothill, Richard W / Kakavand, Hojabr / Mann, Graham J / Thompson, John F / Behren, Andreas / Cebon, Jonathan S / Wolfe, Rory / Kelly, John W / Dobrovic, Alexander / McArthur, Grant A. ·Molecular Oncology Laboratory, Oncogenic Signaling and Growth Control Program, Peter MacCallum Cancer Centre, East Melbourne, Australia. ·Clin Cancer Res · Pubmed #23833303.

ABSTRACT: PURPOSE: The mutation load in melanoma is generally high compared with other tumor types due to extensive UV damage. Translation of exome sequencing data into clinically relevant information is therefore challenging. This study sought to characterize mutations identified in primary cutaneous melanomas and correlate these with clinicopathologic features. EXPERIMENTAL DESIGN: DNA was extracted from 34 fresh-frozen primary cutaneous melanomas and matched peripheral blood. Tumor histopathology was reviewed by two dermatopathologists. Exome sequencing was conducted and mutation rates were correlated with age, sex, tumor site, and histopathologic variables. Differences in mutations between categories of solar elastosis, pigmentation, and BRAF/NRAS mutational status were investigated. RESULTS: The average mutation rate was 12 per megabase, similar to published results in metastases. The average mutation rate in severely sun damaged (SSD) skin was 21 per Mb compared with 3.8 per Mb in non-SSD skin (P=0.001). BRAF/NRAS wild-type (WT) tumors had a higher average mutation rate compared with BRAF/NRAS-mutant tumors (27 vs. 5.6 mutations per Mb; P=0.0001). Tandem CC>TT/GG>AA mutations comprised 70% of all dinucleotide substitutions and were more common in tumors arising in SSD skin (P=0.0008) and in BRAF/NRAS WT tumors (P=0.0007). Targetable and potentially targetable mutations in WT tumors, including NF1, KIT, and NOTCH1, were spread over various signaling pathways. CONCLUSION: Melanomas arising in SSD skin have higher mutation loads and contain a spectrum of molecular subtypes compared with BRAF- and NRAS-mutant tumors indicating multigene screening approaches and combination therapies may be required for management of these patients.

24 Article Clinical and dermoscopic characteristics of desmoplastic melanomas. 2013

Jaimes, Natalia / Chen, Lucy / Dusza, Stephen W / Carrera, Cristina / Puig, Susana / Thomas, Luc / Kelly, John W / Dang, Lucy / Zalaudek, Iris / Braun, Ralph P / Menzies, Scott W / Busam, Klaus J / Marghoob, Ashfaq A. ·Dermatology Service, Memorial Sloan-Kettering Cancer Center, New York, New York 10022, USA. ·JAMA Dermatol · Pubmed #23325288.

ABSTRACT: OBJECTIVE: To describe and analyze the clinical and dermoscopic characteristics of desmoplastic melanoma (DM) as a function of pathologic subtype and phenotypic traits. DESIGN: Retrospective case series. SETTING: Eight high-risk dermatology clinics. PATIENTS: Patients with DM confirmed by histopathologic analysis whose records included a high-quality dermoscopic image. MAIN OUTCOME MEASURES: Clinical, dermoscopic, and histopathologic features of DM. RESULTS: A total of 37 DM cases were identified. The majority of patients had fair skin, few nevi, and no history of melanoma. Lentigo maligna was the most frequent subtype of melanoma associated with DM. The most frequent clinical presentation of DM was a palpable and/or indurated lesion located on sun-exposed skin. Forty-three percent of cases were classified as pure DM, and 57% as mixed DM. Pure DM lesions were thicker than mixed DM lesions (4.10 vs 2.83 mm) (P = .22) and were less likely to have an associated epidermal non-DM component (63% vs 100%) (P = .004). Dermoscopically, DMs had at least 1 melanoma-specific structure, the most frequent being atypical vascular structures. Peppering was more frequently seen in pure DM (44% in pure DM vs 24% in mixed DM) (P = .29). In contrast, crystalline structures, polymorphous vessels, and vascular blush were more commonly seen in mixed DM. CONCLUSIONS: Though DM can be difficult to diagnose based on clinical morphologic characteristics alone, dermoscopy has proved to be a useful aid during the evaluation of clinically equivocal lesions or those lesions with a benign appearance. The most common dermoscopic clues observed in DMs included atypical vascular structures, peppering, and occasionally other melanoma-specific structures.

25 Article Nodular melanoma: a distinct clinical entity and the largest contributor to melanoma deaths in Victoria, Australia. 2013

Mar, Victoria / Roberts, Hugh / Wolfe, Rory / English, Dallas R / Kelly, John W. ·Victorian Melanoma Service, Alfred Hospital, Melbourne, Australia; Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia; Peter MacCallum Cancer Center, Melbourne, Australia. Electronic address: torimar@ymail.com. · Victorian Melanoma Service, Alfred Hospital, Melbourne, Australia. · Victorian Melanoma Service, Alfred Hospital, Melbourne, Australia; Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia. · Cancer Council Victoria, Melbourne, Australia; Melbourne School of Population Health, University of Melbourne, Melbourne, Australia. ·J Am Acad Dermatol · Pubmed #23182058.

ABSTRACT: BACKGROUND: There is a growing body of evidence that nodular melanoma (NM), because of its association with increased growth rate and thickness at diagnosis, accounts for a substantial proportion of melanoma deaths. OBJECTIVE: We sought to assess the contribution of NM to melanoma deaths in comparison with other tumor subtypes. METHODS: Four cohorts were established comprising 5775 cases of invasive primary cutaneous melanoma reported to the Victorian Cancer Registry during 1989, 1994, 1999, and 2004. Original pathology reports were reviewed. Age-standardized melanoma incidence rates were compared from 1989 to 2004 with annual percentage change using Poisson regression. RESULTS: The incidence of thick tumors (>4 mm) increased by 3.8% (95% confidence interval 1.4 to 6.2) and 2.5% (95% confidence interval -0.5 to 5.5) per year for male and female patients, respectively. The median thickness of NM at diagnosis was 2.6 mm compared with 0.6 mm for superficial spreading melanoma. A third of patients who died from melanoma during the follow-up period had thick tumors (>4 mm), most of which were nodular subtype (61%). NM accounted for 14% of invasive melanomas, but was responsible for 43% of melanoma deaths in a total of 57,461 person-years of follow-up. By comparison, superficial spreading melanoma contributed 56% of invasive melanoma but only 30% of deaths. LIMITATIONS: Pathology review was limited to reports only. Mortality information relied mostly on death certificate information. CONCLUSION: The incidence of thick melanomas continues to increase. Nodular melanoma is clinically distinct and the predominant contributor to melanoma-related deaths, representing a public health challenge in reducing skin cancer mortality.

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