Cutaneous Melanoma

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Contents

More Specific Terms

Classification

Etiology

  • 1/3 of melanomas arise from a pre-existing nevus
  • precursors of cutaneous melanoma

Epidemiology

  • common
  • less common
  • rare
  • 2.8% men
  • 1.8% women [18]
  • In Australia which has the highest rate of skin cancer in the world, melanoma was 4th most common cause of cancer in men and 3rd most common cause of cancer in women in 2001 [8].

Pathology

  • mitotic count > 1.0/mm2 upstages to Stage Ib
  • peripheral & deep margins
  • Clark level
  • microsatellitosis
  • upstages to Stage IIIb (even if thin)

Genetics

Physical-examination

  • examine for (ABCDE)
  • A: Asymmetry
  • B: irregular Border
  • C: irregular Color
  • D: expanding Diameter
  • E: Evolution

Clinical-manifestations

Laboratory

  • complete removal with 1-3 mm margins [17]
  • partial sampling is acceptable fot facial lesions, large pigmented lesions [17]

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] 
<br>  
*  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). 



<br>  
*  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] 
<br>  
*  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

Differential-diagnosis

  • asymmetry
  • border irregularity
  • color variegation
  • diameter > 6 mm
  • enlargement & elevation of lesion

Management

  • excision ( surgery) is the primary treatment
  • depth of lesion is most important prognostic factor
  • 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 (lesion thickness: surgical margin)
  • FDA-approved to treat metastatic melanoma
  • improves survival 10 vs 6.5 months
  • not curative
  • 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%
  • investigational
  • prognosis: survival by stage [18]
  • localized: 98%
  • regional: 61%
  • distant: 15%
  • prevention:
  • suncreen has not been shown to provide protection [3]
  • daily sunscreen uses reduces risk 50-75% [15]

More General Terms

Additional Terms

Internet Database

OMIM: 123829
OMIM: 155601

References

  1. DeGowin & DeGowin's Diagnostic Examination, 6th edition, RL DeGowin (ed), McGraw Hill, NY 1994, pg 62
  2. Color Atlas and Synopsis of Clinical Dermatology, Common and Serious Diseases, 3rd ed, Fitzpatrick et al, McGraw Hill, NY, 1997, pg 180-207
  3. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15 American College of Physicians, Philadelphia 1998, 2006, 2009
  4. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 673-674
  5. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 521, 543-47
  6. Journal Watch 22(16):128, 2002 Davies H et al Mutations of the BRAF gene in human cancer. Nature 417:949, 2002 PMID: [1] Pollock PM & Meltzer PS Lucky draw in the gene raffle. Nature 417:906, 2002 PMID: [2]
  7. AJCC Cancer Staging Manual. 6th ed. Springer 2002
  8. url>http://www.cancersa.org.au/aspx/home.aspx</url>
  9. 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: [3] Krown SE & Chapman PB Defining adequate surgery for primary melanoma. N Engl J Med 350:823, 2004 PMID: [4]
  10. 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: [5]
  11. 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: [6]
  12. Quintana E et al. Efficient tumour formation by single human melanoma cells. Nature 2008 Dec 4; 456:593. PMID: [7]
  13. 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 [8]
  14. 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: [9]
  15. Green AC et al. Reduced melanoma after regular sunscreen use: Randomized trial follow-up. J Clin Oncol 2011 Jan 20; 29:257. PMID: [10]
    - Gimotty PA and Glanz K. Sunscreen and melanoma: What is the evidence? J Clin Oncol 2011 Jan 20; 29:249. PMID: [11]
  16. 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: [12]
  17. Bichakjian CK et al. Guidelines of care for the management of primary cutaneous melanoma. J Am Acad Dermatol 2011 Nov; 65:1032. PMID: [13]
  18. 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: [14]
  19. Melanoma: NIH Institute and Center Resources [15]
  20. National Guideline Clearinghouse
    - Systemic adjuvant therapy for patients at high risk for recurrent melanoma (Program in Evidence-based Care) ngc-guideline: [16]
    - U.K. guidelines for the management of cutaneous melanoma. (British Association of Dermatologists) ngc-guideline: [17]
    - Single-agent interleukin-2 in the treatment of metastatic melanoma: a clinical practice guideline. (Program in Evidence-based Care) ngc-guideline: [18]
    - Temozolomide for the treatment of metastatic melanoma: a clinical practice guideline. (Program in Evidence-based Care) ngc-guideline: [19]
    - Treatment of cutaneous melanoma American Society of Plastic Surgeons ngc-guideline: [20]
    - Skin melanoma Association of Comprehensive Cancer Centres ngc-guideline: [21]
    - Adjuvant systemic therapy of melanoma. In: Clinical practice guidelines for the management of melanoma in Australia and New Zealand. ngc-guideline: [22]
    - Appropriate investigations. In: Clinical practice guidelines for the management of melanoma in Australia and New Zealand. ngc-guideline: [23]
    - Biopsy. In: Clinical practice guidelines for the management of melanoma in Australia and New Zealand. ngc-guideline: [24]
    - Classification and staging of melanoma. In: Clinical practice guidelines for the management of melanoma in Australia and New Zealand. ngc-guideline: [25]
    - Clinical diagnosis. In: Clinical practice guidelines for the management of melanoma in Australia and New Zealand. ngc-guideline: [26]
    - Clinical trials. In: Clinical practice guidelines for the management of melanoma in Australia and New Zealand. ngc-guideline: [27]
    - Complementary and alternative medicine. In: Clinical practice guidelines for the management of melanoma in Australia and New Zealand. ngc-guideline: [28]
    - Follow-up. In: Clinical practice guidelines for the management of melanoma in Australia and New Zealand. ngc-guideline: [29]
    - Histopathological reporting of cutaneous melanoma. In: Clinical practice guidelines for the management of melanoma in Australia and New Zealand. ngc-guideline: [30]
    - Identification and management of high-risk individuals. In: Clinical practice guidelines for the management of melanoma in Australia and New Zealand. ngc-guideline: [31]
    - Management of locoregionally recurrent melanoma. In: Clinical practice guidelines for the management of melanoma in Australia and New Zealand. ngc-guideline: [32]
    - Management of regional lymph nodes in melanoma. In: Clinical practice guidelines for the management of melanoma in Australia and New Zealand. ngc-guideline: [33]
    - Melanoma in children. In: Clinical practice guidelines for the management of melanoma in Australia and New Zealand. ngc-guideline: [34]
    - Melanoma in Maori and melanoma in Pacific peoples in New Zealand. In: Clinical practice guidelines for the management of melanoma in Australia and New Zealand. ngc-guideline: [35]
    - Melanoma in specific populations in Australia. In: Clinical practice guidelines for the management of melanoma in Australia and New Zealand. ngc-guideline: [36]
    - Mucosal melanoma. In: Clinical practice guidelines for the management of melanoma in Australia and New Zealand. ngc-guideline: [37]
    - Multidisciplinary care of melanoma. In: Clinical practice guidelines for the management of melanoma in Australia and New Zealand. ngc-guideline: [38]
    - Occult melanoma. In: Clinical practice guidelines for the management of melanoma in Australia and New Zealand. ngc-guideline: [39]
    - Palliative care in melanoma. In: Clinical practice guidelines for the management of melanoma in Australia and New Zealand. ngc-guideline: [40]
    - Population-based whole-body skin screening for melanoma. In: Clinical practice guidelines for the management of melanoma in Australia and New Zealand. ngc-guideline: [41]
    - Pregnancy and melanoma (including hormone replacement therapy and oral contraceptives) In: Clinical practice guidelines for the management of melanoma in Australia and New Zealand. ngc-guideline: [42]
    - Prevention. In: Clinical practice guidelines for the management of melanoma in Australia and New Zealand. ngc-guideline: [43]
    - Prognostic factors and survival outcomes in cutaneous melanoma. In: Clinical practice guidelines for the management of melanoma in Australia and New Zealand. ngc-guideline: [44]
    - Psychosocial issues in melanoma. In: Clinical practice guidelines for the management of melanoma in Australia and New Zealand. ngc-guideline: [45]
    - Treatment of desmoplastic melanoma. In: Clinical practice guidelines for the management of melanoma in Australia and New Zealand. ngc-guideline: [46]
    - Treatment of disseminated melanoma In: Clinical practice guidelines for the management of melanoma in Australia and New Zealand. ngc-guideline: [47]
    - Treatment of primary melanoma. In: Clinical practice guidelines for the management of melanoma in Australia and New Zealand. ngc-guideline: [48]
    - PET imaging in melanoma: recommendations. Program in Evidence-based Care ngc-guideline: [49]
    - Primary excision margins and sentinel lymph node biopsy in clinically node-negative cutaneous melanoma of the trunk or extremities: guideline recommendations. Program in Evidence-based Care ngc-guideline: [50]
    - Melanoma. (Finnish Medical Society Duodecim) ngc-guideline: [51]
    - Optimal excision margins for primary cutaneous melanoma. Alberta Health Services, Cancer Care ngc-guideline: [52]
    - Regional node dissection in primary cutaneous melanoma. Alberta Health Services, Cancer Care ngc-guideline: [53]

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