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Integumentary system ORGAN SYSTEMS

Melanoma

Melanoma, also known as malignant melanoma, is a type of cancer that develops from the pigment-containing cells known as melanocytes.

Melanoma, also known as malignant melanoma, is a type of cancer that develops from the pigment-containing cells known as melanocytes.

  • Benign formNevus/mole
  • Skin cancer: Basal (BCC) > Squamous (SCC) >> melanoma

Etiology

Extrinsic factors:

  • UV-light exposure
    • UV-B (short UV rays) > UV-A
    • (↓ duration, ↑ intensity) > (↑ duration, ↓ intensity) exposure
Melanoma pathogenesis
Melanoma pathogenesis

Intrinsic (genetic) factors:

  • Fair skin
  • Other diseases: Xeroderma pigmentosum
  • Mutations:
    • BRAF (proto-oncogene, somatic mutation): Also found in non-Hodgkin lymphoma, papillary thyroid carcinoma
    • CDKN2A (Tumour suppressor gene, germline mutation): Also found in pancreatic cancer
The Calgary Guide | http://calgaryguide.ucalgary.ca/

Presentation

ABCDE rule:

ABCDE rule, encompasses several clinical features of melanoma, including Asymmetry, Border irregularity, Color variation (both intralesional color variation as well as a color that is different from the patient’s other nevi), Diameter > 6mm, and Evolving (a new or changing lesion).
  • Asymmetry
  • Border: Irregular
  • Colour: Multiple
  • Diameter: > 6 mm
  • Enlarging or evolving
ABCD rule illustration
ABCD rule illustration: On the left side from top to bottom: melanomas showing (A) Asymmetry, (B) a border that is uneven, ragged, or notched, (C) coloring of different shades of brown, black, or tan and (D) diameter that had changed in size. The normal moles on the right side do not have abnormal characteristics (no asymmetry, even border, even color, no change in diameter). | By Unknown creator; six images merged by User:Stevenfruitsmaak – National Cancer Institute via Skin Cancer Foundation, Public Domain, https://commons.wikimedia.org/w/index.php?curid=5582818

Ugly duckling sign:

Ugly Duckling Sign
The Ugly Duckling Sign – SkinCancer.org. (2017). Skincancer.org. Retrieved 4 September 2017, from http://www.skincancer.org/skin-cancer-information/melanoma/melanoma-warning-signs-and-images/the-ugly-duckling-sign

Little Red Riding Hood sign:

Melanoma is observed to differ from naevi only when seen close-up – the sharp teeth of the wolf
  • Indicator for patients with fair skin and light-colored hair that are likely to suffer from amelanotic melanomas, which can be difficult to see and, therefore, diagnose
Numerous neurofibromas and one café au lait spot on the trunk. The black arrow indicates a light brown nodule with a pinkish halo.
Numerous neurofibromas and one café au lait spot on the trunk. The black arrow indicates a light brown nodule with a pinkish halo. | Giuffrida, R., Uranitsch, M., Schmid, K., Deinlein, T., Favero, F., & Zalaudek, I. (2017). Hypomelanotic melanoma detected by the “little red riding hood sign” in a patient with neurofibromatosis type 1. Dermatology practical & conceptual, 7(4), 71–73. https://doi.org/10.5826/dpc.0704a14

Morphological types:

  • Superficial spreading
  • Nodular
  • Lentigo maligna
  • Acral lentiginous (highest prevalence in African-Americans and Asians)
Clinical spectrum of cutaneous melanoma morphology
Clinical spectrum of cutaneous melanoma morphology | Klebanov, N., Gunasekera, N. S., Lin, W. M., Hawryluk, E. B., Miller, D. M., Reddy, B. Y., Christman, M. P., Beaulieu, D., Rajadurai, S., Duncan, L. M., Sober, A. J., & Tsao, H. (2019). Clinical spectrum of cutaneous melanoma morphology. Journal of the American Academy of Dermatology, 80(1), 178-188.e3. https://doi.org/10.1016/j.jaad.2018.08.028

Common sites:

Case study:


Diagnosis

Punch biopsy:

  • Cellular atypia
  • Mitosis
  • Melanocyte cyst
  • Dermal invasion
Morphology of melanocytic lesions in situ
a) Picture of a nevus presenting regular border. b) Picture of a dysplastic nevus presenting irregular border and microstructures. c) Histopathological cut of a melanoma presenting melanoma nests. d) Picture of a nodular melanoma. Figures a), b) and d) were kindly given by Dr. Pascale Guitera. Figure c) was taken from the work of Viros | Balois, T., Amar, M. Morphology of melanocytic lesions in situ. Sci Rep 4, 3622 (2014). https://doi.org/10.1038/srep03622

Breslow thickness:

Depth of tumor (Breslow thickness) correlates with risk of metastasis:
  • Tis: Melanoma only in epidermis
  • T1: Melanoma is ≤ 1 mm thick
  • T2: Melanoma is 1.1-2 mm thick
  • T3: Melanoma is 2.1-4 mm thick
  • T4: Melanoma is > 4 mm thick
Staging of melanoma
Staging of melanoma—TNM staging and Breslow thickness. (n.d.). Retrieved July 26, 2022, from https://www.macmillan.org.uk/cancer-information-and-support/melanoma/staging-of-melanoma

Management

Primary treatment:

  • Excision with appropriately wide margins

Metastatic or unresectable melanoma (BRAF V600E mutation):

  • Vemurafenib (BRAF kinase inhibitor)

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