Melanoma

Basics

Description

  • Tumor arising from malignant degeneration of cells from the melanocytic system:
    • Most arise in the skin, but may also present as a primary lesion in any tissue: Ocular, GI, GU, lymph node, and leptomeninges
    • Metastatic spread to any site in body
  • 4 main types of melanoma:
    • Superficial spreading melanoma: 50–80% cases, occurs in sun-exposed areas, most ~ 6 mm diameter at diagnosis
    • Nodular: 20–30%, most commonly thick and pigmented
    • Acral lentiginous: <5% of all melanomas; however, most common melanoma in African Americans, found in palmar, plantar, and subungual areas:
      • Subungual melanoma: Dark longitudinal band in nail bed, Hutchinson sign when proximal nail fold involved
    • Lentigo maligna: Slowest growing, least likely to metastasize, older population, occurs in sun-exposed areas (1)
  • System(s) affected: Skin/Exocrine

Geriatric Considerations
Lentigo maligna, with slowly enlarging pigmented lesion, is most common in elderly patients. This type usually found on face, beginning as a circumscribed macular patch of mottled pigmentation showing shades of dark brown, tan, or black.

Pediatric Considerations
Congenital large nevi (>5 cm) are risk factors and have a >2% lifetime risk of malignant conversion. Blistering sunburns in childhood significantly increase risk.

Pregnancy Considerations
No increased risk of melanoma in pregnancy. However, its suggested waiting 1–2 years if further pregnancy desired in case of recent melanoma. Melanomas can spread to the placenta (2).

Epidemiology


Incidence
  • In 2010, an estimated 68,000 Americans were diagnosed with melanoma.
  • 5th most common cancer in men, 7th most common cancer in women
  • Predominant age: Median age: 55 years, >50% of all individuals with melanoma are between 20 and 40 years of age.
  • Predominant sex: Male > Female (1.5×)
  • Incidence among whites greater than that among blacks or Hispanics
  • Low socioeconomic status associated with high incidence of melanoma
Prevalence
  • Lifetime risk: Men: 1/37; Female: 1/56
  • 2% of all cancer deaths

Risk Factors

  • UV-A and UV-B exposure
  • History of >5 sunburns during lifetime
  • Previous pigmented lesions (especially, dysplastic/melanocytic nevi)
  • Fair complexion, freckling, blue eyes, and blond/red hair
  • Highest predictor of risk is increased number of nevi (>100).
  • Family/personal history of melanoma
  • Tanning bed use: 75% increased risk if 1st exposure before age 35
  • Changing nevus
  • Large (>5 cm) congenital nevi
  • Other skin cancers
  • Immunosuppression
  • Blistering sunburns in childhood
  • Living at high altitude (>700 m or 2,300 ft above sea level)
  • Occupational exposure to ionizing radiation
Genetics
  • Dysplastic nevus syndrome is a controversial risk factor for development of melanoma. Close surveillance warranted.
  • 8–12% of patients with melanoma have a family history of disease.
  • Mutation in CDKN2A found in 1/3 of patients with family incidence of melanoma (3).

General Prevention

  • Avoidance of sunburns, especially in childhood
  • Use of sunscreen with at least SPF 15 to all skin exposed to sunlight
  • Avoid tanning beds; class 1 carcinogen by WHO (3)
  • Screening of high risk individuals.

Pathophysiology

DNA damage by UV-A/UV-B exposure

Etiology

Tumor progression: Initially may be confined to epidermis with lateral growth, may then grow into dermis with vertical growth

Commonly Associated Conditions

  • Dysplastic nevus syndrome
  • Heavy mole formers: >50 nevi. These individuals have higher lifetime risk of melanoma than the general population as 50–75% of all melanoma arise in pre-existing nevi.
  • Giant congenital nevus syndrome: 6% lifetime incidence of melanoma
  • Xeroderma pigmentosum rare condition associated with an extremely high risk of skin cancers, including melanoma
  • Psoriasis after psoralen-UV-A (PUVA) therapy

Diagnosis

History

Change in a pigmented lesion: Hypo- or hyperpigmentation, bleeding, scaling, size change, texture change

Physical Exam

  • “ABCDE”: Asymmetry, Border irregularity, Color variegation (especially red, white, black, blue), Diameter >6 mm, Elevation above skin surface
  • Any new and/or changing nevus, bleeding/ulcerated.
  • Location on Caucasians is primarily back and lower leg, on African Americans is the hands, feet and nails
  • Individuals at high risk for melanoma should have careful ocular exam to assess for presence of melanoma in the iris and retina.

Diagnostic Tests and Interpretation

Lab
Lactate dehydrogenase (LDH) may be helpful in metastatic disease.

Imaging

Initial Imaging Approach
Imaging studies only helpful in detecting metastatic disease.

Diagnostic Procedures/Surgery
  • Surgical biopsy is the only appropriate diagnostic procedure. Any suspicious nevus should be excised. Any irregularly pigmented lesion >2 cm in a preadolescent should be considered for excision.
  • Punch biopsies are not recommended and may lead to misdiagnosis.
  • Sentinel lymph node biopsies often recommended for lesions >1 mm deep for staging purposes.
Pathological Findings
  • Nodular melanoma is primarily vertical growth, whereas the other 3 types are horizontal.
  • Estimated that 1/10,000 dysplastic nevi become melanoma annually.
  • Immunohistochemical testing on melanoma cells increases sensitivity of lymph node biopsies (2)
  • Staging based on the tumor-node-metastasis (TNM) criteria.

Differential Diagnosis

  • Dysplastic and blue nevi
  • Vascular skin tumor
  • Actinic keratosis
  • Traumatic hematoma
  • Lentigo
  • Pigmented squamous cell and basal cell carcinomas, seborrheic keratoses, other changing nevi

Treatment

Medication (Drugs)

  • Early stages surgical excision is curative in most cases; patients with stage IV disease, systemic treatment with chemotherapy is recommended (e.g., DTIC, temozolomide, paclitaxel, BCNU, cisplatin, carboplatin, vinblastine).
  • Combination chemotherapy has not shown an increase in survival and does not appear to have any advantage over a single agent regimen. Consultation with oncologist strongly recommended.
  • Biochemotherapy is advocated by some (i.e., chemo- + immunotherapy combination).
  • Ipilimumab, monoclonal antibody against CTLA-4, is FDA approved for treatment of advanced melanoma, increasing patient survival by 4 months in stage III and IV.
  • Interferon-α is FDA approved to treat advanced melanoma; shown to slightly increase survival rates.
  • Interleukin-2 is FDA approved to treat metastatic melanoma and may induce remission in some patients; however, due to its toxicity, not all patients will be able to tolerate, or be candidates for, treatment (1).
  • Melanoma is relatively radiotherapy resistant.
  • Vitamin D and E supplements may reduce the severity of disease.

Additional Treatment

General Measures
Fully excise lesion with a 2-mm rim of normal skin is the primary treatment for melanoma.

Issue for Referral
  • Consultation with oncology highly recommended for consideration of chemotherapeutic options.
  • Cosmetic surgery often needed after final excision

Additional Therapies
Early benefit with vaccines has not stood the test of time (2).

Complementary and Alternative Therapies

Many have been tried with no proven benefits

Surgery/Other Procedures

  • Appropriate treatment for melanoma is early surgical excision.
  • Sentinel lymph node biopsy for lesions 1–4 mm deep has become standard of care in many locations, without proven increase in survival.
  • Lesions <1 mm thick, 1 cm margin recommended. Lesions 1–4 mm thick, 2 cm margin recommended. Lesions >4 mm, margin of at least 2 cm. For melanoma in situ, margin of 5 mm recommended; however, some studies suggest 9 mm (1,6).
  • Mohs surgery often used for lesions with ill-defined borders, or lesions of head and neck (6).
  • Radiotherapy can be used to treat lentigo maligna.

In-Patient Considerations

Initial Stabilization
Most surgeries are done as outpatients with no stabilization needed.

Ongoing Care

Follow-Up Recommendations

Once diagnosed, close follow-up and skin protection (i.e., sunblock, UV protective clothing) are highly advised.

Patient Monitoring
  • Skin exams every 3–6 months in patients with history of melanoma
  • Physician skin exams annually for all persons over the age of 40 is controversial and without proven benefit.
  • Total body photography used for surveillance of skin lesions, most commonly used for patients with >5 atypical nevi

Diet

No data suggesting the benefit/risk of dietary manipulations

Patient Education

  • Teach patients who are at risk or have had melanoma the principles of ABCDE examinations.
  • Patients with a history of melanoma or dysplastic nevus syndrome must have frequent total-body examinations.

Prognosis

  • Median age at death 68 years
  • Highest survival seen in women <45 years of age at diagnosis
  • Metastatic melanoma with average survival of 6–9 months
  • Palliative radiation therapy used with metastatic melanoma

Complications

  • Metastatic spread
  • Unsatisfactory cosmetic results following the primary surgery

Additional Reading

Riker AI, Zea N, Trinh T. The epidemiology, prevention, and detection of melanoma. Ochsner J. 2010;10(2):56–65.

Codes

ICD-9

  • 172.3 Malignant melanoma of skin of other and unspecified parts of face
  • 172.4 Malignant melanoma of skin of scalp and neck
  • 172.9 Melanoma of skin, site unspecified
  • 172.8 Malignant melanoma of other specified sites of skin
  • 172.0 Malignant melanoma of skin of lip
  • 172.1 Malignant melanoma of skin of eyelid, including canthus
  • 172.2 Malignant melanoma of skin of ear and external auditory canal
  • 172.5 Malignant melanoma of skin of trunk, except scrotum
  • 172.6 Malignant melanoma of skin of upper limb, including shoulder
  • 172.7 Malignant melanoma of skin of lower limb, including hip

ICD-10

  • C43.9 Malignant melanoma of skin, unspecified
  • C43.30 Malignant melanoma of unspecified part of face
  • C43.4 Malignant melanoma of scalp and neck
  • C43.39 Malignant melanoma of other parts of face
  • C43.0 Malignant melanoma of lip
  • C43.10 Malignant melanoma of unspecified eyelid, including canthus
  • C43.11 Malignant melanoma of right eyelid, including canthus
  • C43.12 Malignant melanoma of left eyelid, including canthus
  • C43.20 Malignant melanoma of unsp ear and external auricular canal
  • C43.21 Malignant melanoma of right ear and external auricular canal
  • C43.22 Malignant melanoma of left ear and external auricular canal
  • C43.31 Malignant melanoma of nose
  • C43.51 Malignant melanoma of anal skin
  • C43.52 Malignant melanoma of skin of breast
  • C43.59 Malignant melanoma of other part of trunk
  • C43.60 Malignant melanoma of unsp upper limb, including shoulder
  • C43.61 Malignant melanoma of right upper limb, including shoulder
  • C43.62 Malignant melanoma of left upper limb, including shoulder
  • C43.70 Malignant melanoma of unspecified lower limb, including hip
  • C43.71 Malignant melanoma of right lower limb, including hip
  • C43.72 Malignant melanoma of left lower limb, including hip
  • C43.8 Malignant melanoma of overlapping sites of skin

SNOMED

  • 372244006 Malignant melanoma (disorder)
  • 93655004 malignant melanoma of skin (disorder)
  • 93225001 Malignant melanoma of skin of face
  • 188044004 Malignant melanoma of scalp and/or neck
  • 188032002 Malignant melanoma of ear and/or external auditory canal
  • 269581007 Malignant melanoma of lower limb
  • 423425006 malignant neoplasm of skin of eyelid (disorder)
  • 93640008 Malignant melanoma of skin of lip
  • 93651008 Malignant melanoma of skin of trunk
  • 93653006 Malignant melanoma of skin of upper limb

Clinical Pearls

  • Always consider melanoma if a regional lymph node is enlarged and nontender.
  • Do not forget that amelanotic melanomas exist; the physician should biopsy new sites of no pigment/loss of pigment.
  • 80% of cutaneous melanomas arise in existing nevi. Any changing nevi should be considered for full-thickness biopsy.

Authors


Haley Newton, DO
Nitin Budhwar, MD

Figures

Figure 22-25

In situ melanoma. Note jetblack coloration of the lesion. Compare with surrounding seborrheic keratoses.
Figure 22-26

Acral lentiginous melanoma. Note the pronounced variegation pigmentation of this lesion. (Courtesy of Charles Miller, M.D., San Diego Naval Hospital.)
Figure 22-27

Superficial spreading melanoma. Note the "ABCD" features: asymmetry, notched border, varied colors, and diameter of more than 6 mm.
Figure 22-28

Superficial spreading melanoma. Note the central area (whitish gray) of regression.
Figure 22-31

Nodular melanoma. This is a nodule with surrounding satellite lesions that represent local "in transit" metastases.
Figure 22-32

Nodular amelanotic melanoma. This lesion arose de novo; it has a great probability of metastasizing.
Figure 22-33

Lentigo maligna. Note the irregular color and irregular border of this malignant melanoma in situ.
Figure 22-34

Lentigo maligna melanoma. Biopsy of this lesion demonstrated invasion into the dermis.
Figure 22-38

Acral lentiginous melanoma. Hutchinson's sign shows uneven pigmentation spreading beyond the nail into surrounding skin.

Bibliography

  1. Tuong W, Cheng LS, Armstrong AW, et al. Melanoma: epidemiology, diagnosis, treatment, and outcomes. Dermatol Clin. 2012;30:113–124, ix.  [PMID:22117873]
  2. Markovic SN, Erickson LA, Rao RD, et al. Malignant melanoma in the 21st century, part 1: Epidemiology, risk factors, screening, prevention and diagnosis. Mayo Clin Proc. 2007;82:364–380.  [PMID:17352373]
  3. Riker AI, Zea N, Trinh T. The epidemiology, prevention and detection of melanoma. Ochsner. 2010;10(2):56–65.
  4. Lane JE, Dalton RR, Sanguqza OP. Cutaneous melanoma. J Fam Prac. 2007;56(1):18–28.
  5. Markovic SN, Erickson LA, Rao RD, et al. Malignant melanoma in the 21st century, part 2: Staging, prognosis, and treatment. Mayo Clin Proc. 2007;82:490–513.  [PMID:17418079]
  6. Erickson C, Miller SJ. Treatment options in melanoma in situ: topical and radiation therapy, excisino and Mohs surgery. Int J Dermatol. 2010;49:482–491.  [PMID:20534080]


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