Conditions: Mucosal Melanoma
(Melanoma of mucosal sufaces, such as mouth, nose, sinus)
what is melanoma?
Melanoma is a a cancer arising from pigment producing cells called melanocytes, and usually occurs on the skin, but may occur in the digestive tract, nose or sinuses, and eyes. Overall, melanoma is the most dangerous type of skin cancer owing mainly to its notable ability to spread to lymph nodes or other organs, but also because it does not respond especially well to radiation therapy. The risk to life of a given melanoma may be predicted by specific features. Early cutaneous (skin) melanoma without spread has a cure rate nearing 99%. When cutaneous melanoma has spread to surrounding lymph nodes, the cure rate drops to 65%, and when it has spread to other organs (distant spread), the cure rate is about 25%. Given the significant drop in survival based on extent of spread, physicians identify and use several characteristics from the initial evaluation and biopsy to predict spread, primarily the depth of the melanoma.
What is mucosal melanoma?
Mucosal melanoma is a rare and aggressive form of melanoma that originates in the mucosal membranes of the body. These membranes line various cavities and surfaces, including the respiratory tract, gastrointestinal tract, and genitourinary tract. Unlike cutaneous melanoma, which primarily occurs on the skin due to sun exposure, mucosal melanoma can arise in areas that are not directly exposed to sunlight.
Common sites for mucosal melanoma include the nasal cavity, oral cavity, vulva, vagina, and rectum. Symptoms can vary depending on the site of origin, but may include persistent pain, bleeding, changes in normal tissue, and other localized signs.
Diagnosis typically involves a biopsy followed by histopathological examination to confirm the presence of melanoma cells. Treatment options may include surgery, radiation therapy, and immunotherapy, depending on the stage of the disease and the specific location of the melanoma.
Due to its usually advanced stage at the time of detection and aggressive nature, mucosal melanoma often has a poorer prognosis compared to other types of melanoma. The aggressive nature of mucosal melanoma is partly due to the abundant lymph node drainage of mucosal surfaces.
What causes mucosal melanoma?
The exact causes of mucosal melanoma are not fully understood, but several factors have been identified that may contribute to its development:
Genetic Mutations: Similar to other forms of melanoma, mucosal melanoma may involve specific genetic mutations. Changes in genes such as BRAF, NRAS, and KIT have been associated with the occurrence of this type of cancer.
Sun Exposure: While mucosal melanoma is less directly linked to ultraviolet (UV) radiation exposure compared to cutaneous melanoma, certain areas like the nasal cavity may still be affected by UV, particularly in individuals with certain genetic predispositions.
Histological Features: Mucosal melanoma sometimes displays different histological characteristics than cutaneous melanoma. These differences may influence how the tumor develops and progresses.
Underlying Conditions: Individuals with immunosuppressed conditions, such as those with HIV/AIDS or transplant recipients, may have a higher risk of developing mucosal melanoma, potentially due to lowered immune surveillance.
Geographic and Ethnic Factors: Epidemiological studies suggest variations in the incidence of mucosal melanoma among different geographic regions and ethnic groups, indicating that environmental and genetic factors may play a role.
Local Irritation: Chronic irritation or injury to the mucous membranes could potentially lead to changes that precede a mucosal melanoma.
What does mucosal melanoma look like?
Mucosal melanoma is a rare form of melanoma that occurs on mucosal surfaces, such as the mouth, nasal passages, or genitals. Unlike skin (cutaneous) melanoma, which often presents as a pigmented skin lesion, mucosal melanoma may not have as many of the classic features described by the ABCDE criteria.
Characteristics of Mucosal Melanoma:
Asymmetry: Lesions may appear asymmetrical, but this may be less apparent than in typical skin melanomas.
Borders: Irregular and indistinct borders can be seen, although they may be less defined due to the mucosal context.
Color Variability: Mucosal melanomas can exhibit multiple colors, including shades of brown, but they can also appear flesh-colored, red, or ulcerated, making color variability less straightforward.
Diameter: Lesions may not conform to the 6 mm rule, as they can be smaller or larger and still represent a malignant process.
Evolution: Change over time can be observed, such as increased size, bleeding, or crusting, but mucosal melanomas may evolve more subtly than their cutaneous counterparts.
How is mucosal melanoma diagnosed?
Mucosal melanoma diagnosis involves several steps to accurately identify the presence of cancerous cells in mucosal tissues, such as those found in the mouth, nose, or gastrointestinal tract. Key diagnostic methods include:
History: Suspicion for a mucosal melanoma may be generated when any of the following symptoms have been persistent or recurrent for greater than about three weeks:
one sided nosebleed
one sided nasal blockage
a non-healing mouth ulcer
persistent hoarseness
enlarged lymph node in the neck
a pigmented lesion in the mouth, especially on the palate or gums
a rapidly progressing and/or bleeding non-pigmented lesion of the head and neck mucosa
Physical Examination: A physical exam to look for unusual lesions or changes in the mucosal membranes and check an area causing symptoms and to evaluate for signs of metastatic disease, including palpation of lymph nodes and an assessment of other organ systems. This may involve endoscopy.
Biopsy: A definitive diagnosis is usually made through a biopsy, where a sample of the suspicious tissue is removed and examined under a microscope. There are different types of biopsies, including excisional (removal of the entire lesion), incisional (removal of a portion of the lesion), and punch biopsies (removal of a small cylindrical section).
Histopathological Analysis: The biopsy sample is subjected to histological analysis to evaluate the cellular structure. Features indicating melanoma include atypical melanocytes and irregular patterns of growth. Histopathological analysis may be supplemented with the following:
Immunohistochemistry: Specialized staining techniques may be used to identify specific markers associated with melanoma cells, aiding in the confirmation of the diagnosis.
Genetic Testing: In some cases, testing for certain genetic mutations or alterations can provide additional information about the tumor and its potential behavior.
After diagnosis of mucosal melanoma, what evaluation is performed next?
After a diagnosis of mucosal melanoma, the next evaluation typically involves staging the disease to determine its extent. This may include the following assessments:
Endoscopy: If the melanoma is suspected to involve the gastrointestinal or respiratory tract, endoscopic evaluation may be warranted.
Imaging Studies:
Biopsy of Regional Lymph Nodes: If there is suspicion of lymphatic spread, a biopsy may be performed to assess for melanoma cells. This may take the form of sentinel lymph node biopsy.
Laboratory Tests: Blood tests to evaluate overall health and organ function, and possibly tumor markers such as LDH, which can provide additional prognostic information.
What are the predictors of a more aggressive mucosal melanoma from a tissue sample?
Several pathologic findings can serve as poor prognostic indicators for this condition:
Increased Tumor Thickness: Greater tumor thickness is associated with a more advanced disease stage and poorer survival rates. Depth of invasion is a critical factor in determining prognosis.
Mitotic Activity: High mitotic activity indicates a more aggressive tumor. Increased mitotic counts correlate with a higher likelihood of metastasis and reduced patient survival.
Lymphovascular Invasion: The presence of lymphovascular invasion suggests that the tumor has breached local barriers and may spread to regional lymph nodes or distant sites, adversely affecting prognosis.
Ulceration: Tumors exhibiting ulceration are often linked to a worse prognosis. Ulceration is associated with the aggressive behavior of melanoma and increased risk of metastasis.
Presence of Tumor Infiltrating Lymphocytes (TILs): While some lymphocytic infiltration is associated with a better prognosis, a lack of TILs or a predominance of T-regulatory cells can indicate an immune escape mechanism, which may hinder response to therapy.
Non-Nodal Metastasis: Initial metastasis to sites other than lymph nodes (such as liver, lung, or bone) typically signifies a more advanced stage and is associated with a poorer outcome.
Histological Subtypes: Certain histological variants of mucosal melanoma, particularly those with epithelioid or pleomorphic cells, may be associated with less favorable prognoses compared to more common spindle cell variants.
Genetic Alterations: Specific mutations, such as those in the KIT gene or altered expression of key tumor suppressor genes, can correlate with a more aggressive disease course and poorer overall survival.
When is imaging used?
Imaging plays a crucial role in the workup and monitoring of mucosal melanoma, particularly for staging and treatment planning. The indications for imaging in this context include:
Local Staging: Imaging is essential to assess the depth of invasion and the extent of the primary tumor. Techniques such as MRI or CT scans can be used to visualize the mucosal site and surrounding structures.
Regional Staging: Evaluation of regional lymph nodes is critical, as mucosal melanoma can exhibit varying patterns of lymphatic spread. Ultrasound, MRI, CT, or PET-CT scans may be utilized to identify lymphadenopathy.
Distant Metastasis: To assess for distant metastasis, especially in advanced cases, CT or PET-CT of the chest, abdomen, and pelvis is often recommended. This helps identify distant spread to organs such as the liver, lungs, and bones. In some cases, ultrasound or MRI may be used. This helps identify distant spread to organs such as the liver, lungs, and bones.
Preoperative Evaluation: Prior to surgical intervention, imaging can help provide a comprehensive overview of disease extent, aiding in surgical planning and ensuring complete resection. When sentinel node biopsy is undertaken, nuclear medicine lymphatic mapping is used.
Response Assessment: Imaging is also indicated to monitor the response to treatment, particularly during and after systemic therapies or radiation.
Symptomatic Evaluation: If a patient exhibits symptoms suggestive of progression or metastasis, physical exam may be augmented with imaging to clarify the diagnosis and guide further management.
What is sentinel node biopsy? When and why is it performed?
Gamma probe and scintigrapher used in sentinel lymph node biopsy.
For mucosal melanoma of the head and neck, sentinel lymph node biopsy may be undertaken when the primary tumor is accessible for injection with a radio tracer and when a positive result from a sentinel lymph node biopsy would change treatment. Sentinel lymph node biopsy is the surgical removal of one or a few targeted lymph nodes, which can be very informative. This technique is based on the observation that a given patch of mucosa drains to one or a few specific nearby lymph nodes. Identifying and removing the lymph node(s) that a certain skin area drains is called sentinel lymph node biopsy. This procedure is minimally invasive and provides the most accurate assessment of whether a melanoma has spread. If the sentinel lymph node biopsy is negative (meaning no melanoma is found in the removed lymph node or nodes), this strongly suggests (but does not prove) that no spread has yet occurred. Alternatively, if the sentinel lymph node biopsy is positive (meaning melanoma is found in a removed lymph node), spread has occurred at least to one lymph node. While removing one or more sentinel lymph nodes can, in some cases, remove the only area of spread that has occurred, a positive sentinel lymph node biopsy indicates that spread to other lymph nodes or organs is fairly likely. This situation informs the patient and physician of increased risk (including the risk for death from the melanoma) and therefore may indicate need for additional treatment in an effort to improve outcome.
TNM staging classification of mucosal melanoma of the head and neck
A cancer is given a TNM classification based on the size and characteristics of the primary tumor, where the cancer began, presence or absence of regional lymph nodes, and the presence or absence of distant metastatic spread. For the head and neck mucosal melanoma, regional lymph nodes are those in the head and neck, and distant metastatic spread is spread anywhere below the neck or to the brain.
Primary tumor (T)
T3: Tumors limited to the mucosa and immediately underlying soft tissue, regardless of thickness or greatest dimension; for example, polypoid nasal disease, pigmented or nonpigmented lesions of the oral cavity, pharynx, or larynx. Note that all head and neck mucosal melanoma is at least T3, as there is no T1 or T2 for this condition.
T4a: Tumor involving deep soft tissue, cartilage, bone, or overlying skin
T4b: Tumor involving brain, dura, skull base, lower cranial nerves (IX, X, XI, XII), masticator space, carotid artery, prevertebral space, or mediastinal structures
Regional lymph nodes (N)
NX: Regional lymph nodes cannot be assessed
N0: Absence of regional lymph node metastases
N1: Regional lymph node metastatic disease present
Distant metastasis (M)
cM0: Absence of clinical evidence of distant metastasis
cM1: Clinical evidence of the presence of distant metastatic disease
pM1: Presence of distant metastasis, confirmed by pathologic analysis of tissue
The T, N, and M scores are then plugged into the following table for the staging:
The stage and presence of any indicators of aggressive disease (see above) provide an estimate of death from this disease.
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