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Melanoma

Last updated: October 29, 2021

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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 biopsy of the primary tumor is usually the best initial diagnostic test and may be therapeutic for localized disease. Chemotherapy, biologics, and/or radiation therapy are recommended for recurrent or widespread disease. Tumor thickness is the most important prognostic factor.

Most common life-threatening dermatological disease

References:[1]

Epidemiological data refers to the US, unless otherwise specified.

Appearance

  • 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

Overview of melanoma types [5]
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, mucousmembranes
  • Irregularly shaped, brown-black pigmented macule
  • Ulceration may occur
  • Hutchinson sign of the nail in subungual type: dark linear patch, widens with time, arising from the nail
  • Slow horizontal growth

Genitourinary melanoma (GU melanoma)

Overview [6]

  • Rare (< 5%)
  • Approx. 45% of all mucosal melanomas
  • Most commonly affects female individuals (approx. 90%)
  • Cause remains unknown.
  • Expression of cell biomarkers such as PD-1 and PD-L1 in vulvar melanoma is significantly higher than in cutaneous melanomas.
  • Prognosis is generally poor.

Types of GU melanoma [6]

Overview of GU melanoma types
Characteristics Female genital melanoma Male genital melanoma Urological mucosal melanoma
Epidemiology
  • Rare: ∼ 1% of all melanomas, 5% of vaginal malignancies [7][8]
  • >
  • Peak age of onset: 7th decade
  • Peak age of onset: 6th decade
Classification
  • Vulvar melanoma
  • Vaginal melanoma
  • Renal melanoma
  • Ureteral melanoma
  • Bladder melanoma
  • Urethral melanoma
Clinical features
Diagnosis
  • Clinical presentation and histopathological confirmation
Treatment
  • Surgical resection with an adequate margin
  • Preferably organ-sparing surgery
  • Depending on the type of cancer, surgical management involves, TUR, wide local excision, cystectomy, and/or nephrectomy

Other

  • Amelanotic melanoma
    • Pink or skin-colored nodes ; may be difficult to recognize
    • Histological diagnosis is necessary
  • Uveal melanoma

  • A full-thickness excisional biopsy (best diagnostic test) with 1–3 mm margins is indicated in all suspicious lesions. [9]
    • An excisional biopsy procedure used to obtain a tissue sample of skin that includes every layer (i.e., healthy and abnormal tissue)
    • A second resection may be necessary if the melanoma is histologically confirmed.
    • Pathology shows s100-protein positive, epithelioid cells with fine granules in cytoplasm
  • Staging tests (e.g., ultrasound or MRI) once diagnosis confirmed: to determine tumor thickness, spread to lymph nodes, or distant metastasis [10]

Complete excisional biopsies are always preferred over incisional biopsies, as they allow tumor thickness to be properly estimated!

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
  • 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)

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.

  • Surgical excision: full-thickness excision with appropriate safety margins
    • 0.5–1 cm safety margin: melanoma in situ (T0)
    • Other margins according to Breslow depth: thickness from the granular layer to the lowest detectable tumor cell. The Breslow index correlates with the risk of metastasis.
Breslow classification of invasive melanoma
Breslow stage TNM stage Modified by AJCC Safety margin
I pT1 ≤ 1.0 mm 1 cm
II pT2 1.01–2 mm 1–2 cm
III pT3 2.01–4 mm 2 cm
IV pT4 ≥ 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.

Metastatic disease [13]

We list the most important complications. The selection is not exhaustive.

  • Negative prognostic factors
    • Epidemiological features: male sex
    • Clinical features: type , localization , and presence of ulcerations
    • Melanoma has a significant risk of metastasis, which is associated with a poorer prognosis.
    • Tumor thickness, as determined from the Breslow thickness, is the most important prognostic factor.
    • Regression

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