Primary Amelanotic Malignant Melanoma of the Tongue

Background: Primary malignant melanoma rarely occurs in the oral cavity. The tongue is a particularly unusual primary site; lesions may be pigmented or amelanotic. Primary malignant melanoma is frequently mistaken for squamous cell carcinoma. Case Report: A 27-year-old male presented with a large, painless, ulceroproliferative mass on the dorsal surface of the tongue for 6 months. Squamous cell carcinoma was suspected, and the lesion was biopsied. Histopathology was compatible with primary amelanotic malignant melanoma. The patient had no cutaneous lesions consistent with malignant melanoma, and no definitive metastatic lesions were found. Ultrasound and computed tomography did not reveal any evidence of regional draining lymph node metastasis or suspicious lesions anywhere else in the body. The patient underwent composite resection of the tongue tumor and bilateral neck lymph node dissection, had an uneventful postoperative recovery, but was lost to follow-up. Conclusion: Primary oral amelanotic malignant melanoma is a highly aggressive, potentially fatal tumor and because of its rarity, presents a diagnostic challenge. The ideal treatment modality for primary malignant melanoma of the tongue is poorly defined, but surgery is regarded as the most effective course of therapy.


INTRODUCTION
In various studies, the incidence of oral mucosal malignant melanoma ranges from 2% to 10% of all melanomas. 1he nasal cavity and hard palate are the most frequent sites of occurrence of oronasal melanoma. 2Primary tongue malignant melanoma is uncommon, accounting for <2% of all oronasal melanoma. 2Mucosal melanomas often display invasive and aggressive clinicopathologic behavior and a dismal prognosis compared to cutaneous melanoma. 3,4The 5-year survival rate of oral melanoma is 6.6% to 20%. 5 The diagnosis of melanoma can typically be made with morphologic investigations when melanin is present, but immunohistochemistry analyses are crucial for amelanotic lesions.Because of the rarity of tongue malignant melanoma, definitive diagnostic tools and therapies have yet to be developed. 3e report the case of a 27-year-old male who presented with an ulceroproliferative mass on the dorsum of the tongue.The clinical diagnosis was squamous cell carcinoma, but primary amelanotic malignant melanoma was the final diagnosis on microscopy.

CASE REPORT
A 27-year-old male presented to the Department of Surgical Oncology with complaints of a painless, nonhealing ulcer of the tongue for 6 months.He had no history of trauma or systemic disease and denied smoking and drinking alcohol.
An ulceroproliferative mass measuring approximately 3.5 × 3.2 × 1.5 cm was seen on the dorsum of the tongue.Multiple enlarged lymph nodes were noted over bilateral level 1a, left level 4, and the supraclavicular region.No skin lesions were present on the patient's body, and no definitive metastatic lesions were found.No evidence of excision of melanomalike lesions or pigmented cutaneous lesions on the body, extremities, head, and neck was seen, and no pigmented lesions in the nasal cavity, pharynx, or larynx were seen.
Based on the physical examination, primary squamous cell carcinoma of the tongue was provisionally diagnosed.Punch biopsy of the lesion was taken and reported as a poorly differentiated malignant tumor.Magnetic resonance imaging showed an irregular, exophytic mass involving the dorsum of the tongue and a necrotic metastatic lymph node at level 4 on the left side (Figure 1).
The patient underwent subtotal glossectomy with bilateral neck lymph node dissection.The resected specimen histology revealed an unremarkable overlying epithelium.Subepithelium showed a malignant tumor arranged in diffuse sheets, composed of epithelioid to spindle cells displaying moderate nuclear pleomorphism, large prominent nucleoli, and moderate cytoplasm.A high level of mitotic activity with aberrant mitotic figures was seen.Neither pigmentation nor squamous differentiation was seen in the tumor (Figures 2A, 2B, and 2C).Also, the skeletal muscle underneath was invaded.Neither junctional activity nor epidermal migration was observed.The differential included rhabdomyosarcoma, poorly differentiated squamous cell carcinoma, and amelanotic malignant melanoma.Immunohistochemistry showed positivity for S100 and HMB-45 and negativity for pan cytokeratin (pan CK) and desmin (Figures 2D, 2E, and 2F).Three lymph nodes from the neck dissection showed evidence of metastasis.
The patient had an uneventful postoperative recovery but was lost to follow-up.

DISCUSSION
Primary malignant melanoma rarely develops on mucosal membranes, and its occurrence in the respiratory, digestive, and urogenital systems is explained by the presence of melanocytes in the mucosal membranes of these tissues. 6][9] In a literature review, we retrieved 36 cases of tongue melanoma from 1939 to 2021 in the PubMed and Google Scholar databases, using the keywords "primary melanoma tongue," "amelanotic melanoma tongue," "oral melanoma," and "tongue cancer." [3][4][5] Baxter (1939) reported the first case of primary malignant melanoma of the tongue. 10In the cases retrieved from the literature, the mean patient age was 56.9 years (range, 7 to 90 years), and the highest incidence was seen in the seventh decade (Table ).
Motiee-Langroudi et al documented that the incidence of oral and tongue melanoma is more frequent in the fourth and seventh decades of life. 40Chikumaru et al found no sex difference, while Motiee-Langroudi et al and Chiu et al found that males were more frequently affected than females. 5,30,40Ethnic variation has been observed, with the Japanese being particularly more vulnerable to oral malignant melanoma, perhaps related to a genetic or unidentified environmental vulnerability. 5,29,40The clinical presentation of tongue malignant melanoma is nonspecific. 3Clinical signs typically include nodules or macules at the base of the tongue that are painless and dark brown or black in appearance. 3The absence of specific symptoms frequently  contributes to a delay in diagnosis; therefore, melanomas of the tongue often manifest in advanced stages before being recognized. 33Rowland and Schnetler described tongue malignant melanoma as a pale mass that grew out of a diffuse, faint pigmentation that had previously covered the whole dorsum of the tongue. 41Not all mucosal melanomas are pigmented; according to a study by Prasad et al, approximately 38.8% are amelanotic. 43n the retrieved studies, tumor size varied, ranging from 0.4 to 6.5 cm, with a mean of 3.08 cm (Table ).40,41 Only Leite et al documented malignant melanoma on the tip of the tongue. 39Lymph node metastasis was noted in 4 cases, including the present case. 4,38,3941,42 According to Takagi et al, mucosal melanosis was associated with 66% of oral melanoma: preexisting in 36.2% and concurrent in 29.8%. 22he therapeutic strategy and results will differ depending on whether the cancer is a primary oral malignant melanoma or a metastatic deposit from primary skin cancer. 4Billings et al observed on histopathology that all metastatic lesions lacked signs of junctional activity in the surrounding mucosa and did not exhibit epidermal migration. 44Junctional activity and epidermal migration were present in 44% and 38% of primary lesions, respectively. 44Also, extensions of the melanotic pigment into the small salivary glands favored a primary lesion, but these findings were inconsistent. 44nce, we validated the primary malignant melanoma diagnosis by comparing clinical and histologic data.However, a primary malignant melanoma of the tongue can only be diagnosed when all other possible cutaneous or mucosal melanomas have been ruled out. 4 Except for the absence of pan CK positivity, the immunohistochemical profile of oral malignant melanoma was comparable to that of cutaneous melanoma. 5HMB-45 is thought to be more melanomaspecific than the S100 protein. 5,34In our patient, the tumor was immunopositive for HMB-45 and the S100 protein, while negative for pan CK and desmin.
For melanoma, surgery is regarded as the most effective course of therapy. 3Oral malignant melanoma is difficult to treat because of anatomic constraints, but wide resection with a surgical margin of 2 cm to 5 cm is required for cutaneous melanoma. 3The role of radiotherapy is debatable because melanoma is a radioresistant tumor. 5In the primary management of unresectable tumors, however, radiotherapy and chemotherapy are crucial for palliation. 5Moya-Plana et al recommend neoadjuvant immunotherapy such as anti-PD-1 antibodies nivolumab as the initial step in treatment of head and neck mucosal malignant melanoma. 45atients with oral malignant melanoma typically have a worse prognosis than those with cutaneous tumors. 31The poor prognosis may be attributable to various factors, such as the absence of symptoms in the early stages of the disease, the difficulty of performing a wide radical excision because of anatomic restrictions, and a rich blood supply that may promote hematogenous spread. 31Recurrence and Ochsner Journal Kumar, T metastasis are frequent after surgical ablation; most patients die within 2 years. 34

CONCLUSION
Although rare, primary malignant melanoma of the tongue might appear as a nonpigmented lesion that resembles squamous cell carcinoma.The head and neck surgeon faces a diagnostic problem when dealing with amelanotic lesions of the oral cavity.A robust index of suspicion and applying a panel of immunohistochemical markers are critical for the correct diagnosis of amelanotic lesions.

Figure 1 .
Figure 1.Magnetic resonance imaging (A) T2-weighted axial and (B) short TI inversion recovery sagittal images show a hyperintense, irregular, partly exophytic mass involving the anterior tongue (arrow).(C) On T1-weighted image, the mass is hypointense.Postcontrast T1-weighted (D) axial and (E) sagittal images show heterogeneous contrast enhancement.(F) Postcontrast T1-weighted axial image shows a peripherally enhancing necrotic metastatic lymph node at level 4 on the left side (arrow).

Table . Summary of Studies Reporting Primary Malignant Melanoma of the Tongue Clinicopathologic Features of the Tumor
Note: Clinicopathologic data were not reported in many cases, and some cases lacked demographic information.Instances of missing/unavailable data are indicated with a dash (-).F, female; M, male.