Multiple primary melanomas among 16,570 patients with melanoma diagnosed at Kaiser Permanente Northern California, 1996 to 2011

doi:10.1016/j.jaad.2015.06.059

Journal of the American Academy of Dermatology

Volume 73, Issue 4, October 2015, Pages 630-636

https://doi.org/10.1016/j.jaad.2015.06.059 Get rights and content

Background

Published rates of cutaneous multiple primary melanoma (MPM) vary widely.

Objective

We examined incidence of and risk factors associated with MPMs among Kaiser Permanente Northern California members.

Methods

We estimated MPM incidence among 16,570 patients with melanoma from 1996 through 2011. We compared characteristics between patients with MPMs and single primary melanomas and estimated crude and adjusted hazard ratios of MPMs using Cox models.

Results

In all, 15,448 patients had a single melanoma and 1122 had MPMs. Patients with MPMs were older and more often male, non-Hispanic white, and partnered. Subsequent primary melanomas were diagnosed after a mean of 3.83 (SD 3.61, median 2.82) years and were more likely in situ and thinner than initial tumors. The risk of a subsequent melanoma decreased from 2% in the first year after diagnosis to a stable approximately 1% rate through 15 years of follow-up.

Limitations

We lacked data on some known melanoma risk factors and had small numbers of non-white patients and certain tumor subtypes.

Conclusions

The risk of MPMs, although highest in the first year after diagnosis, remains stable thereafter. Those at highest risk of MPMs are older, male, white, and partnered. Clinicians should be aware of the rate of MPMs and recognize high-risk subgroups.

Section snippets

Study population

The cohort consisted of all members of KPNC given a diagnosis of primary cutaneous in situ or invasive melanoma between January 1, 1996, and December 31, 2011. Melanoma diagnoses were identified through the KPNC Northern California Cancer Registry (NCCR), which reports information on all reportable cancers to the State of California and the Surveillance, Epidemiology, and End Results (SEER) program. The NCCR gathers data from all 20 KPNC medical centers, serving a population of nearly 3.3

Results

We identified 15,448 patients with single primary melanomas (SPMs) and 1122 patients with MPMs. Of the 1122 patients with MPMs, 172 developed a third melanoma, and 63 had 4 or more subsequent primary melanomas. Our mean total observation time was 5.66 (SD 4.30, median 4.44) years. For MPMs, the mean observation time was 8.05 (SD 4.42, median 7.68) years. For SPMs, the mean observation time was 5.48 (SD 4.24, median 4.25) years. The time between diagnosis of initial primary melanoma and

Discussion

In a cohort of 16,570 patients with melanoma, we identified 15,448 patients with SPMs and 1122 patients with MPMs. Older age, male sex, and white race were risk factors for MPMs. Second and third MPMs were more likely to be in situ, were thinner when invasive, and were less likely to have mitoses, ulceration, or associated positive lymph nodes compared with all initial tumors. In the first year after initial melanoma diagnosis, we found a 2% risk of a second primary melanoma, whereas in

References (14)

A. Jemal et al.
Recent trends in cutaneous melanoma incidence and death rates in the United States, 1992-2006
J Am Acad Dermatol
(2011)
M.R. Bower et al.
Second primary melanomas: incidence and outcome
Am Surg
(2010)
C. Hwa et al.
Single versus multiple primary melanomas: old questions and new answers
Cancer
(2012)
F. Levi et al.
High constant incidence rates of second cutaneous melanomas
Int J Cancer
(2005)
C.R. Ferrone et al.
Clinicopathological features of and risk factors for multiple primary melanomas
JAMA
(2005)
L. Titus-Ernstoff et al.
Multiple primary melanoma: two-year results from a population-based study
Arch Dermatol
(2006)
M. Buljan et al.
Multiple primary melanoma: epidemiological and prognostic implications; analysis of 36 cases
Coll Antropol
(2010)

There are more references available in the full text version of this article.

Cited by (48)

Association of multiple primary melanomas with malignancy risk: A population-based analysis of entries from the Surveillance, Epidemiology, and End Results program database during 1973-2014
2023, Journal of the American Academy of Dermatology
Genetic and environmental risk factors have been associated with the development of multiple primary melanomas (MPMs). We hypothesized that individuals with MPMs might have an increased incidence of internal malignancies.
To identify the risk for subsequent malignancies in MPM patients.
Multiple primary standardized incidence ratios were analyzed for individuals with ≥1, ≥2 and ≥3 primary melanomas (PMs) recorded in the Surveillance, Epidemiology, and End Results database during 1973-2014.
We identified 223,799 individuals with ≥1 PM, 19,709 with ≥2 PMs, and 3,995 with ≥3 PMs. Risks of subsequent internal malignancy increased with number of PMs, with observed:expected ratios of 0.99, 1.14, and 1.23 (P < .05) for patients with ≥1 PM, ≥2 PMs, and ≥3 PMs, respectively. Internal malignancy was higher in younger MPM patients and those with superficial spreading melanoma. The most common malignancies among MPM patients included breast, prostate, thyroid, soft tissue, brain, kidney, non-Hodgkin lymphoma, and chronic lymphocytic leukemia. Risk for subsequent cutaneous melanoma increased with observed:expected ratios of 8.09, 22.52, 41.03 (P < .05) for patients with ≥1 PM, ≥2 PMs, and ≥3 PMs, respectively.
Surveillance, Epidemiology, and End Results records limited information about pigmentation phenotypes, histology, and treatments.
Patients with MPMs have an increased risk for subsequent internal and cutaneous malignancies and might benefit from tight adherence to age-specific cancer screening.
European consensus-based interdisciplinary guideline for melanoma. Part 1: Diagnostics: Update 2022
2022, European Journal of Cancer
Citation Excerpt :
Subsequent primary melanomas are diagnosed at a median of 3 years and are more often in situ and thinner than the initial tumors. The risk of subsequent melanoma decreased from 2% in the first year after diagnosis to a stable rate of approximately 1% during the 15-year follow-up period [136,137]. A German study analyzed a cohort of 2253 patients from the German Central Malignant Melanoma Registry with prospectively documented follow-up found that 146 patients (6.5%) developed multiple primary melanomas, of whom 39 had synchronous melanoma within the first 30 days after initial diagnosis and 107 developed multiple primary melanomas later.
Cutaneous melanoma (CM) is potentially the most dangerous form of skin tumor and causes 90% of skin cancer mortality. A unique collaboration of multi-disciplinary experts from the European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO) and the European Organization for Research and Treatment of Cancer (EORTC) was formed to make recommendations on CM diagnosis and treatment, based on systematic literature reviews and the experts' experience. The diagnosis of melanoma can be made clinically and shall always be confirmed with dermatoscopy. If a melanoma is suspected, a histopathological examination is always required. Sequential digital dermatoscopy and full body photography can be used in high-risk patients to improve the detection of early melanoma. Where available, confocal reflectance microscopy can also improve clinical diagnosis in special cases. Melanoma shall be classified according to the 8th version of the American Joint Committee on Cancer classification. Thin melanomas up to 0.8 mm tumor thickness do not require further imaging diagnostics. From stage IB onwards, examinations with lymph node sonography are recommended, but no further imaging examinations. From stage IIC onwards whole-body examinations with computed tomography (CT) or positron emission tomography CT (PET-CT) in combination with brain magnetic resonance imaging are recommended. From stage III and higher, mutation testing is recommended, particularly for BRAF V600 mutation. It is important to provide a structured follow-up to detect relapses and secondary primary melanomas as early as possible. There is no evidence to define the frequency and extent of examinations. A stage-based follow-up scheme is proposed which, according to the experience of the guideline group, covers the optimal requirements, but further studies may be considered. This guideline is valid until the end of 2024.
Clinical and Histologic Features of Multiple Primary Melanoma in a Series of 31 Patients
2021, Actas Dermo-Sifiliograficas
Realizamos una revisión de los melanomas múltiples primarios que se han diagnosticado en nuestro servicio a lo largo de los últimos 32 años (1987-2019) con el objetivo de tener mejor caracterizada nuestra población de pacientes con melanoma y poder ofrecerles un seguimiento más estrecho mediante la elaboración de un protocolo de seguimiento personalizado.
Estudio observacional, descriptivo y retrospectivo de los melanomas primarios múltiples diagnosticados en un hospital de tercer nivel entre enero de 1987 y marzo de 2019. Se recogieron las características clínicas, epidemiológicas e histológicas de los melanomas primarios, así como de los subsecuentes melanomas, y se realizó un análisis descriptivo de las mismas.
Se incluyeron 31 pacientes (15 hombres y 16 mujeres), con una media de edad de 67 años (intervalo: 36-85 años). La mediana de tiempo transcurrido desde el diagnóstico del primer melanoma primario y el del segundo melanoma fue de 2 años (intervalo 0-4 años). La mediana del número de melanomas por paciente fue de 2 (entre 2 y 6). Del total de 31 pacientes, 25 padecieron 2 melanomas (80%), 4 de ellos 3 melanomas (13%), y 2 pacientes presentaron 5 y 6 melanomas primarios, respectivamente. Los segundos melanomas primarios o subsecuentes eran menos invasivos comparados con los primeros. La mediana de índices de Breslow fue de 1 mm en los primeros (entre 0,67 y 4 mm) y de 0,5 mm (0,32-2,42 mm) en los segundos.
Los melanomas subsecuentes son más finos que los primeros melanomas diagnosticados. Se encontró un aumento de la frecuencia en los dos últimos años de melanomas múltiples primarios. Estos datos resaltan la importancia del seguimiento estrecho y a largo plazo de estos pacientes.
We reviewed all cases of multiple primary melanoma diagnosed at our department over a 32-year period (1987-2019) to better characterize this subgroup of patients and develop a tailored protocol to offer them closer follow-up.
Retrospective, observational, descriptive study of patients diagnosed with multiple primary melanoma at a tertiary care hospital between January 1987 and March 2019. We collected clinical, epidemiologic, and histologic characteristics of primary and subsequent melanomas and performed a descriptive analysis.
Thirty-one patients (15 men and 16 women) with a median age of 67 years (range, 36-85 years) were included. Second primary melanomas were diagnosed after a median of 2 years (range, 0-4 years). The median number of melanomas per patient was 2 (range, 2-6). Twenty-three of the 31 patients, 25 had 2 primary melanomas (80%), 4 had 3 melanomas (13%), and 2 patients each had 5 and 6 primary melanomas. Subsequent melanomas were less invasive than the initial primary melanomas. Median Breslow thickness was 1 mm (range, 0.67-4 mm) for the first primary melanoma and 0.5 mm (range, 0.32-2.42 mm) for subsequent melanomas.
Subsequent melanomas are thinner than primary melanomas. We observed an increase in the number of cases of multiple primary melanoma diagnosed in the last 2 years of our study. Our findings highlight the importance of close, long-term follow-up of patients.
Survival in patients with multiple primary melanomas: Systematic review and meta-analysis
2020, Journal of the American Academy of Dermatology
The literature surrounding survival of patients with multiple primary melanomas (MPM) yields variable and opposing findings, constrained by statistical challenges.
To critically examine the available literature regarding survival of patients with MPM compared with a single primary melanoma and detail statistical methods used.
Electronic searches were performed of PubMed, Embase, Web of Science, and Scopus, with cross-checking of references, for the period January 1956 to June 2019. Studies published in English examining survival in patients with multiple melanomas were included. Case studies and small case series were excluded.
There were 14 studies eligible for inclusion. Conclusions on survival varied markedly depending on the statistical method used. Four studies that accounted for survival bias by partitioning the survival time were included in the quantitative review, with 3 of these reporting a survival disadvantage for MPM, whereas the fourth showed no difference in survival. The pooled hazard ratio was 1.39 (95% confidence interval, 1.07-1.81) but with significant heterogeneity (I² = 96.8%, P_het < .001).
Studies showed significant heterogeneity in methodology.
When data were analyzed with robust statistical methods, patients with MPM had a survival disadvantage compared with patients with a single primary melanoma.
Simultaneous melanomas in the setting of multiple primary melanomas
2024, Melanoma Research
Risk factors for subsequent primary melanoma in patients with previous melanoma: a systematic review and meta-analysis
2024, British Journal of Dermatology

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: Dr Asgari is currently affiliated with the Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.

: Funded by Kaiser Permanente Community Benefit Grant.

: Disclosure: Dr Asgari received institutional research funding from Pfizer and Valeant that is not relevant to this manuscript. Dr Moore, Mr Geller, Ms Warton, and Ms Schwalbe have no conflicts of interest to declare.

: Reprints not available from the authors.

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Original articleMultiple primary melanomas among 16,570 patients with melanoma diagnosed at Kaiser Permanente Northern California, 1996 to 2011

Background

Objective

Methods

Results

Limitations

Conclusions

Section snippets

Study population

Results

Discussion

Recent trends in cutaneous melanoma incidence and death rates in the United States, 1992-2006

J Am Acad Dermatol

Second primary melanomas: incidence and outcome

Am Surg

Single versus multiple primary melanomas: old questions and new answers

Cancer

High constant incidence rates of second cutaneous melanomas

Int J Cancer

Clinicopathological features of and risk factors for multiple primary melanomas

JAMA

Multiple primary melanoma: two-year results from a population-based study

Arch Dermatol

Multiple primary melanoma: epidemiological and prognostic implications; analysis of 36 cases

Coll Antropol

Original article
Multiple primary melanomas among 16,570 patients with melanoma diagnosed at Kaiser Permanente Northern California, 1996 to 2011