Diagnosis (Swetter & Geller, 2023)

Dermoscopy
Dermoscopic examination can be performed on suspicious, pigmented lesions as a first-line diagnostic and may reduce the number of unnecessary biopsies. A dermoscope is a handheld light magnifier (10-fold magnification) used to assess the general appearance, pigmentation pattern, color, globules, dots, depigmentation, and margins. Proper training is necessary to use this specialized instrument that helps distinguish benign and malignant pigmented lesions.

Biopsy
All suspicious lesions should be biopsied for a definitive diagnosis.

• Excisional/complete biopsy: preferred biopsy technique with removal of entire growth with a margin of normal surrounding skin (1- to 3- mm margins), to a depth below the plane of the lesion; should be performed whenever possible; includes full-thickness elliptical, punch excision and deep shave removal ("scoop" biopsy)

• Incisional biopsy (partial sampling) or core biopsy: removes only a sample of the lesion;  acceptable in select cases (i.e., face, palm, sole, ear, distal digit, subungual lesions, or very large lesions)
• Fine-needle aspiration biopsy: removes a small sample of tissue; not performed on a suspicious mole, but on deeper tissue (i.e., lymph node or internal organ) to check for metastasis
• Narrow-margin excisional biopsy: may be performed if an initial partial biopsy is inadequate for diagnosis or microstaging, but it should not generally be performed if the initial specimen meets criteria for sentinel lymph node biopsy
• Punch biopsy (different from punch excision): removes a small, cylindrical sample of the skin, including epidermis and dermis
• Shave biopsy (different from deep shave excision): removes a small, upper layer of dermis; limit use to lesions with low suspicion of melanoma as there is a high risk for sampling error 

Pathology Report

• The clinician must provide the following data to the pathologist: patient identification, type of biopsy, size of specimen, ABCDE criteria, dermoscopic features or photos (if available), age and sex of patient, and precise anatomic location (i.e. forearm, hand) of the biopsy site, including laterality, to reduce chances of subsequent wrong-site surgery.
• An essential element of the report is the status of the peripheral and deep margins (positive and negative) of the specimen.

Tumor Staging and Treatment (Buzaid & Gershenwald, 2023)

Staging and prognosis of cutaneous melanoma are based on the eighth edition American Joint Committee on Cancer (AJCC) tumor, node, metastasis (TNM) system. This system includes:

• Information about the primary tumor (T): presence, thickness (Breslow depth), ulceration status
• Regional lymphatics (N): metastasis to the proximal lymph nodes
• Distant metastatic sites (M), and for patients with stage IV disease only, serum lactate dehydrogenase (LDH).

For complete staging information, please refer to this poster, AJCC Melanoma of the Skin Staging. Other prognostic factors include age, sex, sentinel lymph node tumor burden, mitotic rate, and circulating tumor DNA (ctDNA) or melanoma cells.

Treatment (Buzaid & Gershenwald, 2023)

Melanoma Stage and Treatment
Stage	Tumor Depth and Metastasis	Treatment
Stage 0 (melanoma in situ)	Tumor is limited to the epidermis (melanoma in situ); no regional or distant metastases	Surgical removal with a margin of normal skin surrounding the melanoma
Stage I	Low-risk primary melanoma; localized tumor, 1-2 mm thick with or without ulceration and involves epidermis, dermis, or subcutaneous tissue; no spread to the lymph nodes or distant metastases.	Surgical removal with a margin of normal skin; sentinel lymph node (SLN) biopsy may be performed prior to excision to check for metastasis; SLN biopsy is recommended for tumor thickness greater than 0.75 mm
Stage II	Primary tumors are at higher risk of recurrence; localized tumor may be greater than 2 mm thick and involve muscle	SLN biopsy and surgical excision with wide margin of normal skin; immunotherapy may be prescribed
Stage III	Invasion of the regional lymph nodes, but no metastasis to other parts of the body	Surgical removal with wide margin of normal skin and removal of regional lymph nodes to help prevent spread of disease; adjuvant therapy like immunotherapy, chemotherapy, and radiation may be utilized to prevent spread
Stage IV	Presence of metastases, spread to lymph nodes that are distant from the original tumor or spread to internal organs (i.e., lung, liver, brain, bone, and GI tract)	Difficult to treat; surgical excision of lesions or lymph nodes in addition to aggressive immunotherapy, chemotherapy, and radiation therapy

Imiquimod and Radiation Therapy (Swetter et al., 2019)

• Topical imiquimod 5% cream may be used as second-line treatment for melonoma in situ, lentigo maligna type, when surgery is not possible; carefully discuss the risks and benefits with the patient and family.
• For nonsurgical candidates, radiation therapy may be utilized as a second-line therapy for melonoma in situ, lentigo maligna type; consultation with a radiation oncologist is recommended to review the risks and benefits of radiation therapy.
• Management of advanced cutaneous melanoma will include (Sosman, 2023):
  • Checkpoint immunotherapy inhibition with programmed cell death 1 (PD-1) inhibitor (pembrolizumab, nivolumab) in addition to ipilimumab.
  • Targeted therapy for specific gene mutations
  • Cytotoxic chemotherapy

Tumor Surveillance (Swetter et al., 2019)

• Schedule regular clinical follow-ups for full skin exam and assessment of lymph nodes.
• Collaboration with medical oncology is recommended for patients with high-risk cutaneous melanoma and those with a positive sentinel lymph node biopsy result.
• Educate patients and family members to perform regular skin self-exams and to look for:
  • New moles
  • Moles that look abnormal
  • Change in size, shape, color, or texture of mole or birthmark
  • Wound that doesn’t heal
  • Recurrent disease or new primary cutaenous melanoma
  • Regional lymph node enlargement

Genetic Counseling (Swetter et al., 2019)

Cancer risk counseling by a qualified genetic counselor is recommended for patients who have:

• A family history of invasive cutaneous melanoma or pancreatic cancer (3 or more affected members on 1 side of the family)
• Multiple primary invasive cutaneous melanoma (3 or more), including 1 early-onset tumor (at age less than 45 years)
• 1 or more melanocytic BAP1-mutated atypical intradermal tumors and a family history of mesothelioma, meningioma, and/or uveal melanoma
• 2 or more melanocytic BAP1-mutated atypical intradermal tumors