• Clinical science

Melanoma

Summary

Melanoma, a highly malignant tumor arising from melanocytes, is the most common life-threatening dermatological disease. Risk factors include UV radiation exposure, particularly in light-skinned individuals that are easily sunburned, increasing age, family history, and immunosuppression. The superficial spreading melanoma is the most common subtype. Other subtypes, such as nodular melanoma, have a significantly worse prognosis because they tend to metastasize more rapidly. Invasive melanoma is particular in its propensity to metastasize to unusual locations that are not commonly affected by other malignancies. Immediate full-thickness surgical excision of the primary tumor is usually the best initial diagnostic test and may be therapeutic for localized disease. Chemotherapy, biologics, and/or radiation therapy is recommended for recurrent or widespread disease. Tumor thickness is the most important prognostic factor.

Epidemiology

Most common life-threatening dermatological disease

References:[1]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

References:[2][3][4]

Clinical features

  • Pruritic, persistently bleeding skin lesion
  • Dermoscopy should be used to examine lesions for ABCDE criteria:
    • A = Asymmetry
    • B = Border (irregular border with indistinct margins)
    • C = Color (new changes in pigmentation or variations in pigmentation within the same lesion)
    • D = Diameter > 6 mm
    • E = Evolving (new lesion or a lesion that changes in size, shape, or color over time)

Types of melanoma

Frequency and characteristic features Predilection sites Clinical appearance Growth

Superficial spreading melanoma

  • ∼ 60%
  • Back or chest (common in men)
  • Extremities (common in women)
  • Flat irregular tumor; sometimes with nodular segments
  • Variable pigmentation
  • Relatively prolonged horizontal growth .

Nodular melanoma

  • ∼ 20%
  • Reddish-brown-black, smooth nodules
  • Verrucous surface or ulceration with bleeding
  • Fast growth in depth

Lentigo maligna melanoma

  • Sun-exposed skin areas (esp. face)
  • Large and irregularly shaped patch
  • Irregular pigmentation
  • Relatively slow horizontal growth

Acral lentiginous melanoma

  • ∼ 5%
  • More common in dark-skinned and Asian populations
  • Palms, soles, nailbed, mucous membranes
  • Irregularly shaped, brown-black pigmented macule
  • Ulceration may occur
  • Hutchinson's sign in subungual type: dark linear patch, widens with time, arising from the nail
  • Slow horizontal growth

Superficial spreading melanoma

Nodular melanoma

Lentigo maligna melanoma

Acral lentiginous melanoma

  • Epidemiology: more common in African-American and Asian populations
  • Predilection sites:
  • Prognosis: Generally good because of relatively slow horizontal growth pattern. Late diagnosis often occurs, however, due to poorly visible predilection sites (e.g., sole of the foot)

Special types

Metastatic disease

References:[3][5][6][7][8]

Diagnostics

  • A full-thickness excisional biopsy (best diagnostic test) is indicated in all suspicious lesions.
  • Staging tests (e.g., ultrasound or MRI) once diagnosis confirmed: to determine tumor thickness, spread to lymph nodes, or distant metastasis

Complete excisional biopsies are always preferred over incisional biopsies, as they allow tumor thickness to be properly estimated!
References:[9]

Differential diagnoses

Differential diagnosis of common skin cancers
Color Morphology Location Other characteristic features
Melanoma
  • Brown, black (variable pigmentation)
  • Irregular macule, nodule, or patch
  • Anywhere
  • Commonly on trunk or extremities
  • Slow growth (rapid growth possible)
Cutaneous squamous cell carcinoma
  • Red
  • Scaly, plaque-like, nodular, papillomatous, and/or verrucous lesion
  • Sun exposed areas (e.g., typically lower lip)
  • “Rough” texture
  • Slow growth
  • All eventually ulcerate (everted edges, friable, inflamed)
Basal cell carcinoma
  • Pink
  • Pearly, nodular lesion
  • Sun exposed areas (e.g., typically upper lip, eyelid, nose)
  • Superficial veins
  • Central dimpling
  • Slow growth

Benign lesions commonly resemble melanomas and should be biopsied to rule out cancer (see Benign skin lesions)!

The differential diagnoses listed here are not exhaustive.

Treatment

Surgical excision

Full-thickness incision with appropriate safety margins

  • 0.5 cm safety margin
    • Suspicious lesion without proven melanoma →
    • Melanoma in situ (T0) 0.5 cm safety margin
  • Other margins: according to Breslow's depth: thickness from the granular layer to the lowest detectable tumor cell
Breslow stage Modified by AJCC (valid since 2001) Safety margin
I ≤ 1.0 mm 1 cm
II 1.01–2 mm 1–2 cm
III 2.01–4 mm 2 cm
IV ≥ 4 mm
If tumor thickness > 1 mm (Breslow stage ≥ II): perform sentinel lymph node biopsy

The gold standard is immediate, complete excision of the tumor!

Chemotherapy, biologic therapy (e.g., intravenous interferon therapy), and radiation therapy are recommended for recurrent or widespread disease!
References:[10][11]

Prognosis

  • Survival rate is highly unpredictable
TNM classification and Breslow thickness Estimated 5-year survival rate
T1 (< 1mm), no nodular involvement, no metastases
(without ulcerations)
> 90%
Up to T4 (> 4 mm), no nodular involvement, no metastases ≈ 70 %
N1, regional skin metastases
(no distant metastases)
≈ 20–40 %
M1, distant metastases < 5 %
  • Negative prognostic factors
    • Epidemiological features: male sex
    • Clinical features: type , localization , and presence of ulcerations
    • Tumor thickness is the most important prognostic factor.

References:[12]