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Melanocytes arise from neural crest cells and are frequently found in the skin. However, melanocytes are also found in mucosal membranes. Melanocytes in mucosal membranes are distributed to the oral cavity, nasal cavity, paranasal sinuses, esophagus, larynx, vagina, cervix, rectum, and anus. Melanoma results from a malignant change of melanocytes. Melanoma in the head and neck account for upward of 25% of all melanomas. Mucosal melanomas account for less than 1% of all melanoma. However, mucosal melanoma accounts for roughly 10% of melanoma of the head and neck. The most common sites for mucosal melanoma in order are nasal, paranasal sinuses, oral cavity, and nasopharynx. Of all mucosal melanomas, paranasal sinus has the worst prognosis. The best prognosis locations are the nasal and oral cavity. In 1885, the first case of oral melanoma was reported. Approximately 80% of oral malignant melanomas develop in the mucosa of the upper jaws (maxillary anterior gingiva). The majority of these lesions occur in the keratinizing mucosa of the palate and alveolar gingivae. Lesions are frequently asymptomatic until ulceration and hemorrhage are present. Compared with other melanomas, mucosal melanomas have the lowest percentage of 5-year survival. There is a poor 5-year survival at approximately 15% to 30% likely due to delayed detection.[rx][rx][rx][rx]
Causes
Etiology is mostly unclear in malignant melanoma of the mouth. Mucosal melanoma of the mouth is not related to sun exposure. Risk factors largely remain obscure. Denture irritation, alcohol, and cigarette smoking have been listed as possible risk factors, but a direct relation is not substantiated.
Pathophysiology
Melanoma develops from a malignant transformation of melanocytes. A number of pathways have been identified.
Mutations in c-KIT
Recent data indicates that c-KIT (CD117) is overexpressed in upward of 80% of mucosal melanoma cases. This pathway is important and common in acral and mucosal melanoma, melanomas unrelated to sun exposure. KIT is a transmembrane tyrosine kinase receptor that is expressed on hematopoietic progenitor cells, melanocytes, mast cells, primordial germ cells, and interstitial cells of Cajal. Activating mutations and amplifications cause activation of growth and proliferation pathways. New drugs, such as imatinib, work on this pathway.
Mutations in BRAF
Bioinformatics Resources and Applications Facility (BRAF) protein mutations are uncommon in mucosal melanoma and found at less than 10% of cases. However, in cutaneous melanoma, BRAF mutations are found in up to 80% of melanomas.
Diagnosis of
The mucosa of the mouth differs from the skin. Due to the lack of histological landmarks that are analogous to the papillary, reticular dermis, and muscle bundles, a pathological leveling system and description cannot be applied properly for mucosal melanomas. Therefore, the use of Clark’s levels, which are commonly used in cutaneous melanoma, are unable to be used. Many melanomas in the mouth have a histologic similarity with lentigo maligna melanoma in a radial growth phase.
The mucosal melanomas can show 2 principal patterns: an in situ pattern and an invasive pattern. Approximately 15% of cases of oral melanoma are in situ mucosal lesions, 30% of cases are invasive lesions, and 55% of cases have a combined pattern of invasive with in situ components. Most advanced lesions have a combination pattern of invasive melanoma with an in situ component.
Melanocytic Markers
S100
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A common marker for neural tissue; acidic protein in the nucleus and cytoplasm
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Used in the workup for desmoplastic melanoma
MART-1 (MELAN-A)
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Most sensitive melanocytic marker
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Can stain pseudo nests in lichenoid actinic keratosis in sun-damaged skin
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Note that in desmoplastic melanoma, MART-1 is usually negative and S100 must be performed.
MITF-1
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Nuclear stain, positive in melanocytes, mast cells, and osteoclasts
HMB-45
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Recognizes melanosomal glycoprotein gp100
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Blue nevi stain with HMB-45
History and Physical
The initial presentation of malignant melanoma of the mouth is often swelling which is usually with a brown, dark blue, or black macule. Satellite foci may surround the primary ulcer. সহজ বাংলা: শরীরের অস্বাভাবিক দাগ, ক্ষত বা ফোলা অংশ।" data-rx-term="lesion" data-rx-definition="A lesion is an abnormal area of tissue such as a spot, wound, patch, lump, or ulcer. সহজ বাংলা: শরীরের অস্বাভাবিক দাগ, ক্ষত বা ফোলা অংশ।">lesion. Just like cutaneous melanomas, melanoma in the mouth may be asymmetric with irregular borders. In amelanotic melanomas, pigmentation is not present. Amelanotic melanomas may simulate pyogenic granulomas. Many times, due to late diagnosis, allergy, infection, or inflammation. সহজ বাংলা: চামড়া লাল হয়ে যাওয়া।" data-rx-term="erythema" data-rx-definition="Erythema means skin redness, often from irritation, allergy, infection, or inflammation. সহজ বাংলা: চামড়া লাল হয়ে যাওয়া।">erythema and ulceration may be present.
Evaluation
Oral melanomas are often silent with minimal symptoms until the advanced stage. On physical examination, the lesions can appear as pigmented dark brown to blue-black lesions, or pigmented mucosa-colored or white lesions. allergy, infection, or inflammation. সহজ বাংলা: চামড়া লাল হয়ে যাওয়া।" data-rx-term="erythema" data-rx-definition="Erythema means skin redness, often from irritation, allergy, infection, or inflammation. সহজ বাংলা: চামড়া লাল হয়ে যাওয়া।">Erythema may be present if infection, or irritation, often causing pain, swelling, heat, or redness. সহজ বাংলা: শরীরের প্রদাহ; ব্যথা, ফোলা বা লালভাব হতে পারে।" data-rx-term="inflammation" data-rx-definition="Inflammation is the body’s response to injury, infection, or irritation, often causing pain, swelling, heat, or redness. সহজ বাংলা: শরীরের প্রদাহ; ব্যথা, ফোলা বা লালভাব হতে পারে।">inflammation is present. The majority of the cases involve the palate and maxillary gingiva. Metastatic melanoma usually arises from the buccal mucosa, tongue, or the mandible. If an elevated ulcer. সহজ বাংলা: শরীরের অস্বাভাবিক দাগ, ক্ষত বা ফোলা অংশ।" data-rx-term="lesion" data-rx-definition="A lesion is an abnormal area of tissue such as a spot, wound, patch, lump, or ulcer. সহজ বাংলা: শরীরের অস্বাভাবিক দাগ, ক্ষত বা ফোলা অংশ।">lesion with a variety of color within the lesion is present, with surrounding satellite lesions and ulceration, a high grade advanced disease can be expected. Regional metastasis is rare.
Treatment of
Surgery is the mainstay of treatment in oral malignant melanoma. Radical excision with disease-free margins is the first goal in surgical management. A diagnostic excisional biopsy followed by wide local excision where the diagnosis is proven. Following complete surgical excision, relapse rates have been reported to be 10% to 20%.[rx][rx][rx][rx]
Neck Dissection
In a clinically positive neck, a neck dissection is mandatory in all cases of head and neck mucosal melanoma that is amenable to radical treatment.
Sentinel Lymph Node Biopsy/Lymphoscintigraphy
It has less value in staging and is less useful in predicting lymphatic drainage patterns in oral melanoma.
Radiotherapy
Radiotherapy is used to control local disease. This is in contrast to cutaneous melanoma. Radiotherapy is valuable in the goal of achieving relapse-free survival.
Medical Therapy
Due to the low incidence of oral melanoma, well-controlled trials with large participants have been limited. Chemotherapy and immunotherapy may have a role in the prevention of metastatic disease.
diagnosis: Differential diagnosis is a list of possible conditions that may explain symptoms. সহজ বাংলা: একই লক্ষণের সম্ভাব্য রোগের তালিকা।" data-rx-term="differential diagnosis" data-rx-definition="Differential diagnosis is a list of possible conditions that may explain symptoms. সহজ বাংলা: একই লক্ষণের সম্ভাব্য রোগের তালিকা।">Differential Diagnosis
The diagnosis: Differential diagnosis is a list of possible conditions that may explain symptoms. সহজ বাংলা: একই লক্ষণের সম্ভাব্য রোগের তালিকা।" data-rx-term="differential diagnosis" data-rx-definition="Differential diagnosis is a list of possible conditions that may explain symptoms. সহজ বাংলা: একই লক্ষণের সম্ভাব্য রোগের তালিকা।">differential diagnosis of oral melanoma involves anything that can cause pigmentation within the mouth:
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Oral melanotic macule
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Amalgam tattoo
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Labial lentigines
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Physiologic pigmentation
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Smoking associated melanosis
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Postinflammatory pigmentation
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Melanotic nevi of the oral mucosa
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Blue nevi
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Melanoacanthoma
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Melanoplakia
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Medication-induced melanosis (examples: minocycline and antimalarial drugs)
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Peutz-Jeghers syndrome
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Cushing syndrome
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Addison’s disease
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Kaposi sarcoma
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Malignant melanoma
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Amelanotic melanoma
Staging
Tumor, T
There is no T1 or T2 in mucosal melanoma.
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T3: Tumors limited to the mucosa and immediately underlying soft tissue, regardless of thickness or greatest dimension; for example, polypoid nasal disease, pigmented or non-pigmented lesions of the oral cavity, pharynx, or larynx
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T4: Moderately advanced or very advanced
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T4a: Moderately advanced disease. Tumor involving deep soft tissue, cartilage, bone, or overlying skin
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T4b: Very advanced disease. Tumor involving the brain, dura, skull base, lower cranial nerves (IX, X, XI, XII), masticator space, carotid artery, prevertebral space, or mediastinal structures
Lymph Nodes, N
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NX: Regional lymph nodes cannot be assessed
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N0: No regional lymph node metastases
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N1: Regional lymph node metastases present
Distant Metastases, M
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M0: No distance metastasis
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M1: Distant metastasis
