Guidelines

MALIGNANT CUTANEOUS MELANOMA (MM)

Malignant Melanoma is the most deadly form of skin cancer (Swetter, et al., 2019; Oakley, 2015). The rates of cutaneous melanoma doubled from 1982 to 2011 (Swetter, et al., 2019) and about 7,000 patients died as a result of MM in 2019.  Risk factors for melanoma include sun exposure, tanning bed use (particularly in women less than 45 years of age),  more than 50 moles or those with atypical moles, immediate family history of melanoma, fair skin, blue eyes and previous non melanoma skin cancer or other cancers such as breast or thyroid CA (Swetter, et al., 2019; Oakley, 2015).  About 75% of melanomas initiate from an existing nevus. Common locations for melanoma for men include the back and for women, it is found more often on the lower extremities.  Melanoma less commonly occurs on the genitals, lips, eyes, palms and soles. In situ melanoma (MMIS) occurs only within epidermis of the skin (Oakley, 2015). Invasive melanoma indicates that it has spread to the dermis. Metastatic melanoma indicates a spread to other organs or tissue.

The presentation of melanoma typically follows the ABCDE rules: asymmetry, border irregularity, color variation, diameter greater than 6 mm and/or evolving (Oakley, 2015). There are multiple types of cutaneous melanoma.  Superficial spreading type is the most common and typically originates from a pre-existing nevus. Nodular melanoma is typically dome shaped or ulcerated and occurs de novo. It is less common and represents about 15% of MMs. Lentigo Maligna Melanoma is a form of MMIS that develops over five to twenty years. It occurs in sun exposed areas, normally the face, neck or ears. Other examples of less common forms of melanoma include nail and acral melanomas, amelanotic melanoma, regressing melanoma and desmoplastic melanoma.

Below is a summary of the American Academy of Dermatology (AAD) guidelines for management of primary cutaneous melanoma that was published in 2019. 

Biopsy technique

  • Excisional biopsy is the standard of care with a goal of removing the entire lesion in question in order to provide a full evaluation including depth and type of MM as well as other pertinent prognostic factors.
  • Acceptable methods for an excisional biopsy include:
    • elliptical excision
    • deep sauceration/scoop shave (most common)
    • punch excision.
  • Narrow margins of 1-3mm are acceptable.
  • Incomplete or partial sampling will prevent accurate staging of the lesion.

Pathology

The AAD recommends that the pathologist provide the following in the pathology report for a melanoma:

  • Size of specimen
  • Thickness - Breslow depth to the nearest 0.1mm
  • Presence of ulceration +/-
  • Mitotic rate: No. of mitoses/mm2
  • Margins- e.g. clear, MMIS at margins, transected, etc.
  • Regression
  • Optional information that is recommended to be supplied by the pathologist include:
    • subtype, lymphovascular or perineural invasion, regression, tumor category for staging, Clark level, vertical growth phase.

Staging - The Basics

  • The most important factors are Breslow depth (thickness) and ulceration.
    • Mitotic rate is also important to understand because there is evidence that high mitoses indicate a poorer outcome.
  • Stage T1a is currently defined as less than 0.8mm Breslow Depth and no ulceration.
  • Stage T1b is currently defined as 0.8mm to 1mm Breslow depth with or without ulceration.
    • If a melanoma is >0.8mm or if less and ulcerated, it is recommended that the patient have a discussion and option for a sentinel lymph node (SNL) biopsy.  This type of offering is typically provided through a consultation with surgical oncology or a specialized melanoma surgeon.
    • If the melanoma is >1mm, there is more evidence in favor of performing a SNL biopsy and an SNL biopsy is generally recommended.

A description of melanoma staging was developed by the American Joint Committee on Cancer and a summary is found in the AAD guidelines (Swetter, et al., 2019, pg. 213).

Treatment of Melanoma

Wide Local Excision is the standard of care for melanoma. Surgical margin recommendations are based on the Breslow depth of the melanoma as follows:

  • Melanoma in situ (no Breslow depth) → 0.5cm to 1 cm surgical margins
    • Head and Neck MMIS and lentigo maligna are usually treated with a staged excision.
    • It is possible that Mohs may become a recommendation in the future but there is a need for more research.
  • 1 cm surgical margins are recommended for a Breslow Depth of < 1mm.
  • 1 to 2 cm surgical margins are recommended for a Breslow Depth of > 1mm to 2mm.
  • 2 cm surgical margins are recommended for a Breslow Depth of > 2mm.

Sentinel Lymph Node Biopsy Summary

A blue dye is injected around the primary melanoma. The surgeon uses a gamma probe to identify the afferent lymph node reservoirs that light up from the blue dye and sample those nodes.  A positive SNL biopsy has an established poorer prognosis and negative SNL biopsies typically have better prognosis. The SNL biopsy should be performed at the same time or prior to the excision of the primary melanoma, which allows the correct lymphatic channels to be identified and produces a more accurate SNL biopsy.

  • Complete Lymph Node Dissections (CLND) after a positive SNL biopsy has been NOT shown to improve melanoma survival rate compared to monitoring with nodal based ultrasounds.
    • The AAD recommends collaboration of medical providers and the surgical oncologist before performing a CLND.
  • Patients with a positive SNL biopsy will be offered immunotherapies by oncology.    

Monitoring

  • Imaging and labs is NOT recommended for asymptomatic patients without nodal involvement.
    • CT/PET or CT is performed on patients with positive SNL biopsies and is usually ordered and monitored by oncology.
  • History and physical exams are key. It is important to inquire about weight loss, night sweats, fatigue/malaise, SOB, new onset headaches, GI symptoms, etc. 
  • Regular skin exams are recommended and detailed below.

Second Line Treatments

  • Imiquimod 5% has been shown to effectively treat LM or MMIS for non-surgical candidates
    • Range: 64-94% clearance from studies performed
    • Generally five times/weeks for at least 12 weeks.
    • This is OFF LABEL and  is recommended as second line treatment by AAD and only for non-surgical candidates.
    • This should be prescribed and monitored by a dermatology provider who has experience with this method.
  • Non-surgical patients also can be treated with radiation but this approach is not common in the US.
  • Radiation adjuvant therapy can be offered for high-risk desmoplastic types of melanoma.

Follow up

  • Always screen for signs and symptoms of metastatic melanoma as discussed above.
  • Educate the patient in performing self skin checks.
  • Total body exams are recommended with a dermatology provider per AAD guidelines as follows:
    • MMIS: Every 6-12 months for 1-2 years, then annually
    • Stage IA-IIA: Every 6-12mos for 2-5 years, then annually
    • Stage IIB and higher: Every 3-6mos for 2 years, then every 6mos from year 3-5, then annually
    • In practice, skin exams are often performed more frequently than the AAD minimum recommendations above.
  • There is a higher risk of a second MM in males as well as those with fair skin, multiple nevi, a family history of MM and history of atypical nevi.

Pregnancy and Melanoma

There is not enough evidence to support that pregnancy is a risk factor for MM.  Women in general have a higher rate of melanoma, and especially young women in their reproductive years.  Melanoma is the most common cancer to occur during pregnancy. However, several studies have found no causal link between MM and pregnancy, and results are conflicting. Currently, melanoma that does occur in pregnant women is thought to be more likely related to tanning bed use or sun exposure habits.

There is no recommendation for a woman with a history of melanoma to postpone conception after treatment. There is no contraindication for biopsying a suspicious nevus in a pregnant woman. There are also no contraindications for oral contraceptive therapy, hormone replacement therapy, in-vitro fertilization or other hormonal treatments for women with a history of MM.

References

Oakley, A. (2015). Melanoma. DermNet NZ. https://dermnetnz.org/topics/melanoma/. 

Swetter, S., Tsao, H.,  Bichakjian, C.,  Curiel-Lewandrowski, C.,  Elder, D., Gershenwald, J., Guild, V., Grant-Kels, J., Halpern, A., Johnson,T.,  Sober, A., Thompson, J., Wisco, O., Wyatt, S., Hu, S. & Lamina, T. (2019). Guidelines of care for the management of primary cutaneous melanoma. Journal of the American Academy of Dermatology, 80(1), 208–250. https://doi.org/10.1016/j.jaad.2018.08.055.