cutaneous melanoma
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Classification
- melanoma in situ
- acral lentiginous melanoma
- balloon cell melanoma
- desmoplastic melanoma
- epithelioid cell melanoma
- lentigo maligna melanoma
- mucous membrane melanoma
- nodular melanoma
- superficial spreading melanoma
- blue nevus, malignant
- malignant melanoma in giant pigmented nevus
* classification by histology
Etiology
- 1/3 of melanomas arise from a pre-existing nevus
- precursors of cutaneous melanoma
- risk factors:
- > 50 nevi >= 2 mm in diameter
- family history of malignant melanoma
- blond or red hair
- freckles on upper back
- 3 or more blistering sunburns before age 20
- only early sun exposure associated with increased risk[32]
- 3 or more years of outdoor summer job
- actinic keratosis
- history of endometriosis (RR = 1.6)[11]
- history of uterine fibromas (RR = 1.3)[11]
- alcohol consumption
- airline pilots & cabin crew members wirh 2-fold increased risk & 42% increased mortality from melanoma[33]
- high citrus fruit consumption[38]
- RR=1.36 for orange juice & grapefruit only[38]*
* association possibly due to psoralen in citrus fruits; psoralen has photocarcinogenic properties in animals[38]
Epidemiology
- common
- less common
- acral lentiginous melanoma
- mucous membrane melanoma
- melanoma arising from congenital melanocytic nevus
- melanoma arising from dysplastic melanocytic nevus
- rare
- incidence of melanoma 2.4 fold in US from 1986-2001, 18/100,000, parallels increase in skin biopsies[9]
- 5% of all skin cancers
- 3-6% of patients with melanoma will develop a 2nd primary melanoma
- in USA, lifetime probability of developing melanoma
- incidence of invasive melanoma increasing in U.S.
- 22.2 (2009) vs 23.6 (2016) per 100,000 population
- melanoma mortality 2.8 (2009) vs 3.1 (2016) per 100,000
- In Australia which has the highest rate of skin cancer in the world, melanoma was 4th most common cause of cancer in men & 3rd most common cause of cancer in women in 2001[8]
- bulky melanomas occur most often on sun-damaged head & neck of older men[29]
- ulcerated melanomas more common in older men & associated with increased mortality[31]
Pathology
- excisional skin biopsy is diagnostic test of choice[3]
- essential components of a melanoma pathology report are:
- thickness
- depth of lesion (Breslow depth) is most important prognostic factor[3]
- depth of deep margin in cutaneous melanoma (Loinc)
- lymph node involvement uncommon if depth < 1 mm[3]
- ulceration
- dermal mitotic rate (mitoses/mm2)
- mitotic count > 1.0/mm2 upstages to Stage Ib
- peripheral & deep margins
- Clark level
- microsatellitosis
- upstages to Stage IIIb (even if thin)
- thickness
- metastases
- lymph nodes (58%)
- liver (63%)
- lung (60%)
- bone (48%)
- brain (48%)
- skin (44%)
- adrenal (48%)
- kidney (27%)
Genetics
- familial melanoma has been mapped to chromosome 9p
- point mutations in BRAF gene in 66% if patients[6]
- these are somatic (acquired mutations)
- V599E found in 80% of BRAF point mutations
- V600E: BRAF & MEK inhibitors approved to treat BRAF V600E
- expression of BAMBI, GPNMB, LLGL1 may be diminished or absent
- other implicated genes KAAG1, JARID1B, MIA3, SH3PXD2A, SPANXC, SPANXD, SPANXE, CSAG1, CSAG2, FMR1NB, BAGE1, BAGE2, BAGE3, BAGE4, BAGE5, RASEF, PHF19, ARMS, CDK4, GINS4, NOX5, c-MYC, TP73, C9orf14, CDKN2A, VDR, XRCC3, MCAM
Clinical manifestations
- classic clinical features (ABCDE)
- A: Asymmetry
- B: irregular Border
- C: irregular Color
- D: expanding Diameter (> 6 mm)
- E: Evolution (lateral expansion or vertical growth)
- pigmented lesions of different form depending upon type, i.e. superficial-spreading melanoma, nodular melanoma
- amelanoytic melanomas occur & resemble basal cell carcinoma
- in dark-skinned patients, melanomas may occur in non sun exposed areas, including palms, soles, mucous membranes
- the back is the most common site in men, the legs in women[3]
Laboratory
- excisional skin biopsy is diagnostic test of choice[3]
- complete removal with 1-3 mm margins[17]; 1-2 mm margins[69]
- partial sampling is acceptable for facial lesions, large pigmented lesions[17]
- sentinal lymph node biopsy for lesions > 1 mm thick
- do not shave, freeze, laser or otherwise destroy a pigmented lesion suspicious for melanoma
- lentigo maligna not suspicious for melanoma is exception[3]
- routine lab tests not helpful[3]
- BRAF V600E mutation all patients with metastatic melanoma[3][39][44]
- 50-70% positive[3]
- Loincs for pathology specimens
- see ARUP consult[20]
Radiology
- imaging studies (CT, MRI, PET scan) after surgical resection have low yield & fairly high rate of false-positives[3]
Staging
AJCC/TNM classification/staging[7]
primary tumor [T]
TX: primary tumor cannot be assessed. T0: no evidence of primary tumor. Tis: melanoma in situ T1: melanoma ~1 mm thickness with or without ulceration. T1a: melanoma ~1 mm thickness, level II or III, no ulceration. T1b: melanoma ~1 mm thickness, level IV or V or with ulceration. T2: melanoma 1.01 - 2 mm thickness with or without ulceration. T2a: melanoma 1.01 - 2 mm thickness, no ulceration. T2b: melanoma 1.01 - 2 mm thickness, with ulceration. T3: melanoma 2.01 - 4 mm thickness with or without ulceration. T3a: melanoma 2.01 - 4 mm thickness, no ulceration. T3b: melanoma 2.01 - 4 mm thickness, with ulceration. T4: melanoma > 4mm in thickness with or without ulceration. T4a: melanoma > 4mm in thickness, no ulceration. T4b: melanoma > 4mm in thickness with ulceration.
regional lymph nodes [N]
NX: regional lymph nodes cannot be assessed. N0: no regional lymph node metastases. N1: metastasis in one lymph node. N1a: clinically occult (microscopic) metastasis. N1b: clinically apparent (macroscopic) metastasis. N2: metastases in 2 - 3 regional lymph nodes or intralymphatic regional metastasis without nodal metastasis. N2a: clinically occult (microscopic) metastasis. N2b: clinically apparent (macroscopic) metastasis. N2c: satellite or in-transit metastasis without nodal metastasis. N3: metastasis in 4 or more regional nodes or matted metastatic nodes or in-transit metastasis or satellite(s) with metastasis in regional node(s).
distant metastasis [M]
MX: distant metastasis cannot be assessed. M0: no distant metastasis. M1: distant metastasis. M1a: metastasis to skin, subcutaneous tissues or distant lymph nodes. M1b: metastasis to lung. M1c: metastasis to all other visceral sites or distant metastasis at any site associated with elevated serum LDH
clinical & pathologic stage grouping
80% of newly diagnosed cutaneous melanomas are stage 1[14]
| stage | T | N | M | comment |
|---|---|---|---|---|
| stage 0: | Tis | N0 | M0 | (clinical & pathologic) |
| stage IA: | T1a | N0 | M0 | (clinical & pathologic) |
| stage IB: | T1b | N0 | M0 | (clinical & pathologic) |
| - | T2a | N0 | M0 | (clinical & pathologic) |
| stage IIA: T2b | N0 | M0 | (clinical & pathologic) | |
| - | T3a | N0 | M0 | (clinical & pathologic) |
| stage IIB: T3b | N0 | M0 | (clinical & pathologic) | |
| - | T4a | N0 | M0 | (clinical & pathologic) |
| stage IIC: T4b | N0 | M0 | (clinical & pathologic) | |
| stage III: any T | any N | M0 | (clinical) | |
| stage IIIA: T1 - 4a | N1a | M0 | (pathologic) | |
| - | T1 - 4a | N2a | M0 | (pathologic) |
| stage IIIB: T1 - 4b | N1a | M0 | (pathologic) | |
| - | T1 - 4b | N2a | M0 | (pathologic) |
| - | T1 - 4a | N1b | M0 | (pathologic) |
| - | T1 - 4a | N2b | M0 | (pathologic) |
| - | T1 - 4a/b | N2c | M0 | (pathologic) |
| stage IIIC: T1 - 4b | N1b | M0 | (pathologic) | |
| - | T1 - 4b | N2b | M0 | (pathologic) |
| - | any T | N3 | M0 | (pathologic) |
| stage IV: | any T | any N | M0 | (clinical & pathologic) |
| stage | T | N | M | comment |
|---|---|---|---|---|
| stage 0: | Tis | N0 | M0 | (clinical & pathologic) |
| stage IA: | T1a | N0 | M0 | (clinical & pathologic) |
| stage IB: | T1b | N0 | M0 | (clinical & pathologic) |
| - | T2a | N0 | M0 | (clinical & pathologic) |
| stage IIA: T2b | N0 | M0 | (clinical & pathologic) | |
| - | T3a | N0 | M0 | (clinical & pathologic) |
| stage IIB: T3b | N0 | M0 | (clinical & pathologic) | |
| - | T4a | N0 | M0 | (clinical & pathologic) |
| stage IIC: T4b | N0 | M0 | (clinical & pathologic) | |
| stage III: any T | any N | M0 | (clinical) | |
| stage IIIA: T1 - 4a | N1a | M0 | (pathologic) | |
| - | T1 - 4a | N2a | M0 | (pathologic) |
| stage IIIB: T1 - 4b | N1a | M0 | (pathologic) | |
| - | T1 - 4b | N2a | M0 | (pathologic) |
| - | T1 - 4a | N1b | M0 | (pathologic) |
| - | T1 - 4a | N2b | M0 | (pathologic) |
| - | T1 - 4a/b | N2c | M0 | (pathologic) |
| stage IIIC: T1 - 4b | N1b | M0 | (pathologic) | |
| - | T1 - 4b | N2b | M0 | (pathologic) |
| - | any T | N3 | M0 | (pathologic) |
| stage IV: | any T | any N | M0 | (clinical & pathologic) |
Complications
- metastases (see Pathology: above)
Differential diagnosis
- melanocytic nevus
- hemangioma
- lentigo
- juvenile lentigo
- solar lentigo
- basal cell carcinoma (pigmented or not)
- pigmented dermatofibroma
- seborrheic keratosis
- subungual hematoma
- tattoo (medical or medicinal)
- malignant melanoma (distinguishing features)*
- asymmetry
- border irregularity
- color variegation
- diameter > 6 mm
- enlargement & elevation of lesion
* pruritus in a pigmented lesion may suggest melanoma
Management
- excision (surgery) is the primary treatment
- biopsy & excision by dermatologists associated with the lowest likelihood of delay[37]
- Mohs micrographic surgery for T1a-T2a may be an option[61]
- depth of lesion is most important prognostic factor (< 0.8 mm low risk)
- other independent predictors of survival include:
- women have better prognosis than men
- age > 60 years is associated with poorer prognosis
- truncal lesions are associated with poor prognosis than lesions on extremities
- 95% can be surgically removed when < 0.76 mm in depth
- lesions > 4 mm are associated with a 40% surgical cure rate
- surgical margins determined by lesion depth/thickness (lesion thickness: surgical margin)
- in situ: 0.5-1 cm
- < 1 mm: 1 cm
- 1.0-2.0 mm: 1-2 cm
- > 2.0 mm: 2 cm
- surgical margins have become narrower over time[9][17]
- maximum margin at 2 cm[17]
- consider sentinal lymph node biopsy for melanomas > 0.8-1 mm thick[3][17][30][43]
- spread to regional lymph nodes (stage III)
- lymph node dissection[3]
- decreases 5 year survival to < 30%
- therapeutic lymph node dissection indicated
- interferon alpha-2b improves survival
- interferon therapy
- melanoma > 4 mm thick or
- lymph node positive melanoma
- pegylated interferon alfa-2b maginally effective for stage 3 melanoma[40]
- talimogene laherparepvec (Imlygic)
- distant metastases
- metastases renders melanoma incurable
- resection is still indicated if primary tumor is resectable & metastases are limited[3]
- surgical resection of isolated brain metastasis[3]
- postoperative radiosurgery to tumor bed[3]
- combination of BRAF inhibitor plus MEK inhibitor (BRAF V600 mutation-positive) for metastatic melanoma
- dabrafenib (Tafinalar) or vemurafenib[39] plus trametinib (Mekinist) or cobimetinib[34]
- useful for patients with poor performance status &/or advanced disease[3]
- vemurafenib induces clinical responses in > 1/2 of patients with previously treated BRAF V600 mutation-positive metastatic melanoma[44]
- ipilimumab (Yervoy) a checkpoint inhibitor (CTLA4 inhibitor)
- FDA-approved to treat metastatic melanoma
- improves survival 10 vs 6.5 months[24], not curative
- ipilimumab apparently decreases Bacteroidales species in stool[46]
- tremelimumab in phase 3 trials
- prior to approval of ipilimumab
- treatment did not prolong life, even if detected early when patient asymptomatic
- chemotherapy was not indicated
- workup for metastases was not indicated
- 5 year survival < 5%
- pembrolizumab (PD-1 inhibitor) superior to ipilimumab[36]
- 6 month survival 47% vs 25%[36]
- treatment of cutaneous melanoma BRAF V600 mutation positive (NICE, NGC)
- adjuvant chemotherapy after surgical resection of stage 3 cutaneous melanoma[53]
- lenvatinib plus pembrolizumab[63]
- pembrolizumab for patients with brain metastases[56]
- nivolumab (PD-1 inhibitor) + ipilimumab (CTLA4 inhibitor) superior to ipilimumab alone[36]
- objective response rates of 61%, versus 11%[36]
- > 50% response rates in brain metastases[54]
- 53% response rate[62]
- standard of care for immunotherapy in most patients[62]
- investigational
- IL-2 plus gp100:209-217(210 M) peptide vaccine[16]
- anti-PDCD1 &/or anti-CD274 antibody may induce tumor regression & prolonged stabilization in patients with advanced cutaneous melanoma, renal cell carcinoma, or non-small-cell lung cancer[19]
- RNA vaccine elicits response in 17 of 42 patients with late-stage melanoma[59]
- non-responders to immunotherapy may respond after fecal transplantation from patients who had responded to that immunotherapy.[60]
- positive association between a Mediterranean diet & response to treatment with immune checkpoint inhibitors[67]
- metastases renders melanoma incurable
- prognosis: survival by stage[18][42]
- localized: 98%
- regional: 61%
- distant: 15%
- checkpoint inhibitors have improved melanoma mortality rates[64]
- follow-up[41]
- observation alone is an acceptable option for asymptomatic patients with surgically resected cutaneous melanoma[3]
- annual skin examinations for life
- monthly self examination[3]
- low risk cutaneous melanoma (< 0.8 mm thickness) may be followed by physical examination & dermatologic evaluation every 6 months[3]
- imaging studies have low yield with fairly high false-positives[3]
- observation alone is an acceptable option for asymptomatic patients with surgically resected cutaneous melanoma[3]
- prevention:
- suncreen has not been shown to provide protection[3]
- daily sunscreen uses reduces risk 50-75%[15]
- aspirin may reduce risk of melanoma in postmenopausal white women[22]
- vitamin D supplementation may reduce risk of cutaneous melanoma[66]
- a diagnosis of melanoma does not change long-term behavior regarding unsafe sun exposure[25]
Comparative biology
- fecal transplantation from mice with anti-melanoma immunity augments responses to anti-PDL1 immunotherapy[45]
- augmented response apparently conferred by Bifidobacterium
- fecal transplantation into mice from patients treated with ipilimumab enhances responses of mice to anti-CTLA4 therapy[46]
Notes
- classification of melanoma in situ & early-stage invasive melanoma can vary among pathologists[52]
- 8% of biopsies are over-interpreted & 9% are under- interpreted by the initial pathologist[52]
More general terms
More specific terms
- acral lentiginous melanoma
- anal melanoma
- desmoplastic melanoma
- external ear melanoma
- eyelid melanoma
- face melanoma
- lentigo maligna melanoma
- lip melanoma
- lower extremity melanoma
- nodular melanoma
- scalp/neck melanoma
- superficial spreading melanoma
- trunk melanoma
- upper extremity melanoma
Additional terms
- chromosomal translocation t(12;22)(q13;q12) (MMSP)
- clinical features distinguishing atypical from benign nevi
- melanocytic nevus (mole)
References
- ↑ DeGowin & DeGowin's Diagnostic Examination, 6th edition, RL DeGowin (ed), McGraw Hill, NY 1994, pg 62
- ↑ Color Atlas and Synopsis of Clinical Dermatology, Common and Serious Diseases, 3rd ed, Fitzpatrick et al, McGraw Hill, NY, 1997, pg 180-207
- ↑ 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 3.12 3.13 3.14 3.15 3.16 3.17 3.18 3.19 3.20 3.21 3.22 Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2006, 2009, 2012, 2015, 2018, 2021.
Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022 - ↑ Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 673-674
- ↑ Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 521, 543-47
- ↑ 6.0 6.1 Journal Watch 22(16):128, 2002 Davies H et al Mutations of the BRAF gene in human cancer. Nature 417:949, 2002 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12068308
Pollock PM & Meltzer PS Lucky draw in the gene raffle. Nature 417:906, 2002 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12087387 - ↑ 7.0 7.1 AJCC Cancer Staging Manual. 6th ed. Springer 2002
- ↑ 8.0 8.1 http://www.cancersa.org.au/aspx/home.aspx
- ↑ 9.0 9.1 9.2 Journal Watch 24(7):59, 2004 Thomas JM et al, Excision margins in high-risk malignant melanoma. N Engl J Med 350:757, 2004 PMID: https://www.ncbi.nlm.nih.gov/pubmed/14973217 Krown SE & Chapman PB Defining adequate surgery for primary melanoma. N Engl J Med 350:823, 2004 PMID: https://www.ncbi.nlm.nih.gov/pubmed/14973210
- ↑ Welch HG, Woloshin S, Schwartz LM. Skin biopsy rates and incidence of melanoma: population based ecological study. BMJ. 2005 Sep 3;331(7515):481. Epub 2005 Aug 4. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16081427
- ↑ 11.0 11.1 11.2 Kvaskoff M et al, Personal history of endometriosis and risk of cutaneous melanoma in a large prospective cohort of French women. Arch Intern Med 2007, 167:2061 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17954799
- ↑ Quintana E et al. Efficient tumour formation by single human melanoma cells. Nature 2008 Dec 4; 456:593. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19052619
- ↑ Petrella T et al and the and the Melanoma Disease Site Group Systemic Adjuvant Therapy for Patients at High Risk for Recurrent Melanoma: Updated Guideline Recommendations 2009 A Quality Initiative of the Program in Evidence-based Care (PEBC), Cancer Care Ontario (CCO) EVIDENCE-BASED SERIES #8-1 VERSION 3.2009 http://www.cancercare.on.ca/common/pages/UserFile.aspx?fileId=34373
- ↑ 14.0 14.1 Santillan AA Pathology review of thin melanoma and melanoma in situ in a multidisciplinary melanoma clinic: Impact on treatment decisions. J Clin Oncol 2010 Jan 20; 28:481. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20008627
- ↑ 15.0 15.1 Green AC et al. Reduced melanoma after regular sunscreen use: Randomized trial follow-up. J Clin Oncol 2011 Jan 20; 29:257. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21135266
Gimotty PA and Glanz K. Sunscreen and melanoma: What is the evidence? J Clin Oncol 2011 Jan 20; 29:249. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21135278 - ↑ 16.0 16.1 Schwartzentruber DJ et al. gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma. N Engl J Med 2011 Jun 2; 364:2119 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21631324
- ↑ 17.0 17.1 17.2 17.3 17.4 17.5 Bichakjian CK et al. Guidelines of care for the management of primary cutaneous melanoma. J Am Acad Dermatol 2011 Nov; 65:1032. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21868127 (corresponding NGC guideline withdrawn Nov 2016)
- ↑ 18.0 18.1 18.2 Journal Watch, Massachusetts Medical Society, March 12, 2012 Siegel R et al. Cancer Statistics, 2012. CA Cancer J Clin 2012 Jan/Feb; 62:10. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22237781
- ↑ 19.0 19.1 Topalian SL et al Safety, Activity, and Immune Correlates of Anti-PD-1 Antibody in Cancer N Engl J Med, June 2, 2012 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22658127 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1200690
Brahmer JR et al Safety and Activity of Anti-PD-L1 Antibody in Patients with Advanced Cancer N Engl J Med, June 2, 2012 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22658128 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1200694 - ↑ 20.0 20.1 ARUP Consult: Melanoma The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/melanoma
- ↑ Bilimoria KY Importance of Quality Metrics for Providing High Quality Melanoma Care deprecated reference - National Guideline Clearinghouse. November 5, 2012
- ↑ 22.0 22.1 Gamba CA et al Aspirin is associated with lower melanoma risk among postmenopausal Caucasian women. Cancer 2013 Mar 11 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23483536 <Internet> http://onlinelibrary.wiley.com/doi/10.1002/cncr.27817/abstract
- ↑ Tsao H, Atkins MB, Sober AJ. Management of cutaneous melanoma. N Engl J Med. 2004 Sep 2;351(10):998-1012. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15342808
- ↑ 24.0 24.1 Hodi FS, O'Day SJ, McDermott DF et al Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010 Aug 19;363(8):711-23. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20525992
- ↑ 25.0 25.1 Idorn LW et al A 3-Year Follow-up of Sun Behavior in Patients With Cutaneous Malignant Melanoma. JAMA Dermatol. Published online September 30, 2013 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24080851 <Internet> http://archderm.jamanetwork.com/article.aspx?articleid=1745116
- ↑ 26.0 26.1 Kubo JT et al. Alcohol consumption and risk of melanoma and non-melanoma skin cancer in the Women's Health Initiative. Cancer Causes Control 2013 Oct 31 PMID: https://www.ncbi.nlm.nih.gov/pubmed/24173533
- ↑ Balch CM, Gershenwald JE, Soong SJ et al Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol. 2009 Dec 20;27(36):6199-206 PMID: https://www.ncbi.nlm.nih.gov/pubmed/19917835
- ↑ Garbe C, Peris K, Hauschild A Diagnosis and treatment of melanoma: European consensus-based interdisciplinary guideline. Eur J Cancer. 2010 Jan;46(2):270-83 PMID: https://www.ncbi.nlm.nih.gov/pubmed/19959353
- ↑ 29.0 29.1 29.2 Geller AC et al. Melanoma epidemic: An analysis of six decades of data from the Connecticut Tumor Registry. J Clin Oncol 2013 Nov 20; 31:4172 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24043747 <Internet> http://jco.ascopubs.org/content/31/33/4172
- ↑ 30.0 30.1 Morton DL et al. Final trial report of sentinel-node biopsy versus nodal observation in melanoma. N Engl J Med 2014 Feb 13; 370:599. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24521106 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1310460
Balch CM and Gershenwald JE. Clinical value of the sentinel-node biopsy in primary cutaneous melanoma. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24521113 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMe1313690 - ↑ 31.0 31.1 Richardson BS et al. The age-specific effect modification of male sex for ulcerated cutaneous melanoma. JAMA Dermatol 2014 Mar 5 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24599332 <Internet> http://archderm.jamanetwork.com/article.aspx?articleid=1833957
- ↑ 32.0 32.1 Wu S et al. Long-term ultraviolet flux, other potential risk factors, and skin cancer risk: A cohort study. Cancer Epidemiol Biomarkers Prev 2014 Jun; 23:1080 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24876226 <Internet> http://cebp.aacrjournals.org/content/23/6/1080
- ↑ 33.0 33.1 Sanlorenzo M et al The Risk of Melanoma in Airline Pilots and Cabin Crew. A Meta-analysis. JAMA Dermatol. Published online September 03, 2014 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25188246 <Internet> http://archderm.jamanetwork.com/article.aspx?articleid=1899248
- ↑ 34.0 34.1 Mescape Oncology. Sept 30, 2014 New Standard in Melanoma: Combo of BRAF and MEK Inhibitors. http://www.medscape.com/viewarticle/832566?nlid=66983_2202
- ↑ Dabrafenib for treating unresectable or metastatic BRAF V600 mutation-positive melanoma. National Institute for Health and Care Excellence (NICE) ngc-guideline: http://www.guideline.gov/content.aspx?id=48755
- ↑ 36.0 36.1 36.2 36.3 36.4 Robert C, Schachter J, Long GV et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med 2015 Apr 19; [e-pub] <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25891173 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1503093
Postow MA et al. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N Engl J Med 2015 Apr 20 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25891304 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1414428 - ↑ 37.0 37.1 Lott JP et al. Delay of surgery for melanoma among Medicare beneficiaries. JAMA Dermatol 2015 Apr 8 PMID: https://www.ncbi.nlm.nih.gov/pubmed/25853865
- ↑ 38.0 38.1 38.2 38.3 Wu S, Han J, Feskanich D et al Citrus Consumption and Risk of Cutaneous Malignant Melanoma. JCO published online on June 29, 2015 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26124488 <Internet> http://jco.ascopubs.org/content/early/2015/06/24/JCO.2014.57.4111.abstract
Berwick M Dietary Advice for Melanoma: Not Ready for Prime Time. JCO published online on June 29, 2015 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26124491 <Internet> http://jco.ascopubs.org/content/early/2015/06/24/JCO.2015.61.8116.full - ↑ 39.0 39.1 39.2 Chapman PB, Hauschild A, Robert C et al Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011 Jun 30;364(26):2507-16 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21639808
- ↑ 40.0 40.1 Eggermont AM, Suciu S, Testori A et al Long-term results of the randomized phase III trial EORTC 18991 of adjuvant therapy with pegylated interferon alfa-2b versus observation in resected stage III melanoma. J Clin Oncol. 2012 Nov 1;30(31):3810-8 PMID: https://www.ncbi.nlm.nih.gov/pubmed/23008300
- ↑ 41.0 41.1 Francken AB, Bastiaannet E, Hoekstra HJ. Follow-up in patients with localised primary cutaneous melanoma. Lancet Oncol. 2005 Aug;6(8):608-21. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16054572
- ↑ 42.0 42.1 Soong SJ, Ding S, Coit D et al Predicting survival outcome of localized melanoma: an electronic prediction tool based on the AJCC Melanoma Database. Ann Surg Oncol. 2010 Aug;17(8):2006-14. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20379784
- ↑ 43.0 43.1 Wong SL, Balch CM, Hurley P et al Sentinel lymph node biopsy for melanoma: American Society of Clinical Oncology and Society of Surgical Oncology joint clinical practice guideline. J Clin Oncol. 2012 Aug 10;30(23):2912-8 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22778321 (corresponding NGC guideline withdrawn Dec 2017)
- ↑ 44.0 44.1 44.2 Sosman JA, Kim KB, Schuchter L et al Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib. N Engl J Med. 2012 Feb 23;366(8):707-14 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22356324
- ↑ 45.0 45.1 Sivan A, Corrales L, Hubert N et al Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science. 2015 Nov 27;350(6264):1084-9 PMID: https://www.ncbi.nlm.nih.gov/pubmed/26541606
- ↑ 46.0 46.1 46.2 Vetizou M, Pitt JM, Daillere R et al Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science. 2015 Nov 27;350(6264):1079-84 PMID: https://www.ncbi.nlm.nih.gov/pubmed/26541610
Snyder A et al Could microbial therapy boost cancer immunotherapy? Science 27 November 2015. 350(6264):1031-1032 http://www.sciencemag.org/content/350/6264/1031 - ↑ 47.0 47.1 Swetter SM, Elston DM (images) Medscape: Cutaneous Melanoma http://emedicine.medscape.com/article/1100753-overview
- ↑ 48.0 48.1 DermNet NZ. Melanoma (images) http://www.dermnetnz.org/lesions/melanoma.html
- ↑ Marchalik RJ, Venna S (images) Eyelid Melanoma N Engl J Med 2016; 375:75. July 7, 2016 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27406350 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMicm1506399
- ↑ Glazer AM, Winkelmann RR, Farberg AS et al Analysis of Trends in US Melanoma Incidence and Mortality. JAMA Dermatol. Published online December 21, 2016 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28002545 <Internet> http://jamanetwork.com/journals/jamadermatology/fullarticle/2593033
- ↑ Elmore JG et al Pathologists' diagnosis of invasive melanoma and melanocytic proliferations: observer accuracy and reproducibility study. BMJ 2017;357:j2813 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28659278 Free PMC Article <Internet> http://www.bmj.com/content/357/bmj.j2813
- ↑ 52.0 52.1 52.2 Wong SL, Faries MB, Kennedy EB, et al. Sentinel Lymph Node Biopsy and Management of Regional Lymph Nodes in Melanoma: American Society of Clinical Oncology and Society of Surgical Oncology Clinical Practice Guideline Update. Ann Surg Oncol. 2018 Feb;25(2):356-377. PMID: https://www.ncbi.nlm.nih.gov/pubmed/29236202 https://www.ncbi.nlm.nih.gov/pubmed/29236202
- ↑ 53.0 53.1 Eggermont AMM, Blank CU, Mandala M et al Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma. N Engl J Med 2018; 378:1789-1801. May 10, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29658430 Free full text https://www.nejm.org/doi/full/10.1056/NEJMoa1802357
- ↑ 54.0 54.1 Tawbi HA, Forsyth PA, Algaz A et al Combined Nivolumab and Ipilimumab in Melanoma Metastatic to the Brain. N Engl J Med 2018; 379:722-730. Aug 23, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30134131 https://www.nejm.org/doi/full/10.1056/NEJMoa1805453
Turajlic S, Larkin J Immunotherapy for Melanoma Metastatic to the Brain. N Engl J Med 2018; 379:789-790 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30134137 https://www.nejm.org/doi/full/10.1056/NEJMe1807752 - ↑ Deutsch GB, Kirchoff DD, Faries MB. Metastasectomy for stage IV melanoma. Surg Oncol Clin N Am. 2015 Apr;24(2):279-98. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/25769712
- ↑ 56.0 56.1 Furst ML with expert commentary by Klil-Drori AJ Melanoma Brain Metastases Respond to Pembrolizumab. Patients who are healthy enough should receive dual checkpoint inhibitors, researchers say. MedPage Today. ASCO Reading Room 12.06.2018
Kluger HM, Chiang V, Mahajan A et al Long-Term Survival of Patients with Melanoma With Active Brain Metastases Treated with Pembrolizumab on a Phase II Trial. J Clin Oncol 2018; Nov 8, PMID: https://www.ncbi.nlm.nih.gov/pubmed/30407895 - ↑ Longo C, Pellacani G. Melanomas. Dermatol Clin. 2016 Oct;34(4):411-419. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/27692447
- ↑ Nelson R 'Truly Amazing': Huge Change in Melanoma Prognosis. Medscape - Oct 24, 2019. https://www.medscape.com/viewarticle/920362
- ↑ 59.0 59.1 Sahin U et al. An RNA vaccine drives immunity in checkpoint-inhibitor-treated melanoma. Nature 2020 Sep; 585:107. PMID: https://www.ncbi.nlm.nih.gov/pubmed/32728218 https://www.nature.com/articles/s41586-020-2537-9
- ↑ 60.0 60.1 Davar D et al Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients. Science 2021. Feb 5 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33542131 https://science.sciencemag.org/content/371/6529/595
- ↑ 61.0 61.1 Cheraghlou S, Christensen SR, Leffell DJ et al Association of Treatment Facility Characteristics With Overall Survival After Mohs Micrographic Surgery for T1a-T2a Invasive Melanoma. JAMA Dermatol. Published online March 31, 2021 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33787836 https://jamanetwork.com/journals/jamadermatology/fullarticle/2778025
Miller CJ, Bichakjian CK. Mohs Micrographic Surgery for Melanoma - Do Outcomes Vary Among Treatment Facilities? JAMA Dermatol. Published online March 31, 2021 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33787822 https://jamanetwork.com/journals/jamadermatology/fullarticle/2778027 - ↑ 62.0 62.1 62.2 Curti BD, Faries MB. Recent Advances in the Treatment of Melanoma. N Engl J Med 2021; 384:2229-2240.June 10 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34107182 https://www.nejm.org/doi/full/10.1056/NEJMra2034861
- ↑ 63.0 63.1 Alexander W LEAP-004: Durable Responses in Advanced Melanoma Achieved With Lenvatinib Plus Pembrolizumab. Cancer Therapy Advisor. June 11, 2021 https://www.cancertherapyadvisor.com/home/news/conference-coverage/asco-2021/melanoma-lenvatinib-leap004-durable-response-risk-treatment/
- ↑ 64.0 64.1 Kahlon N, Doddi S, Yousif R et al Melanoma Treatments and Mortality Rate Trends in the US, 1975 to 2019. JAMA Netw Open. 2022;5(12):e2245269. PMID: https://www.ncbi.nlm.nih.gov/pubmed/36472871 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2799216
- ↑ Tan WW, Marienberg ES Fast Five Quiz: Precision Medicine in Cancer Medscape. January 06, 2023 https://reference.medscape.com/viewarticle/954083
Porcelli L, Di Fonte R, Pierri CL et al BRAFV600E;K601Q metastatic melanoma patient-derived organoids and docking analysis to predict the response to targeted therapy. Pharmacol Res. 2022 Aug;182:106323 PMID: https://www.ncbi.nlm.nih.gov/pubmed/35752358 Free article - ↑ 66.0 66.1 Davenport L Regular Vitamin D Supplements May Lower Melanoma Risk. Medscape. Jan 12, 2023 https://www.medscape.com/viewarticle/986867
Kanasuo E et al Regular use of vitamin D supplement is associated with fewer melanoma cases compared to non-use: a cross-sectional study in 498 adult subjects at risk of skin cancers. Melanoma Research 2022. December 28. PMID: https://www.ncbi.nlm.nih.gov/pubmed/36580363 https://journals.lww.com/melanomaresearch/Abstract/9900/Regular_use_of_vitamin_D_supplement_is_associated.51.aspx - ↑ 67.0 67.1 Bolte LA, Lee KA, Bjork JR et al Association of a Mediterranean Diet With Outcomes for Patients Treated With Immune Checkpoint Blockade for Advanced Melanoma. JAMA Oncol. Published online February 16, 2023 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36795408 https://jamanetwork.com/journals/jamaoncology/fullarticle/2801594
- ↑ 68.0 68.1 68.2 NEJM Knowledge+ Dermatology
Schadendorf D, van Akkooi ACJ, Berking C et al Melanoma. Lancet. 2018 Sep 15;392(10151):971-984. PMID: https://www.ncbi.nlm.nih.gov/pubmed/30238891 Review. - ↑ 69.0 69.1 Swetter SM, Tsao H, Bichakjian CK, et al. Guidelines of care for the management of primary cutaneous melanoma. J Am Acad Dermatol. 2019;80:208-50. PMID: https://www.ncbi.nlm.nih.gov/pubmed/30392755
- ↑ Mar VJ, Chamberlain AJ, Kelly JW, et al. Clinical practice guidelines for the diagnosis and management of melanoma: melanomas that lack classical clinical features. Med J Aust. 2017;207:348-50. PMID: https://www.ncbi.nlm.nih.gov/pubmed/29020893
- ↑ Rashid S, Tsao H. Recognition, staging, and management of melanoma. Med Clin North Am. 2021;105:643-661. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34059243
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