Table 1.  The American Joint Committee on Cancer (AJCC) staging system,T:Tumor (8^th edition,2018)

Prasal et al and Patal et al proposed classification for mucosal melanoma with negative cervical lymph node involvement based on micro invasion as follows: Stage I is melanoma in situ (non-invasive), Stage II is the one invading the lamina propria and Stage III is the one invading deeper tissues. ^12.19.The Clark and Breslow classifications have not been accepted as prognostic predictors in oral malignant melanoma due to architectural differences between oral mucosa and skin.^10.12 The oral mucosa is thinner than skin and lacks histological points of reference similar to the papillary and reticular dermis.²¹ Most authors use the classification of the Western Society of Teachers of Oral Pathology (WESTOP), which divides them into a relatively simple system in relation to its histopathological pattern as (a) melanoma in situ, delineated to the epidermis and its junction with the connective tissue; (b) invasive melanomas, in which the neoplasia pervades into the connective tissue and (c) melanomas with a merged pattern between invasive and in situ.^12.13.22.23

In the case of a suspected tumor, CT and MRI can be used for evaluation of the loco regional extent of the lesion that is fundamental for defining resectability of the tumor, MRI is the modality of choice for more accurate investigation.^10.19 According to current German guidelines, a clinical examination is enough for in situ melanoma staging. Head MRI, whole-body imaging like PET-CT, CT, or skeletal scintigraphy combined with LDH and tumor marker S100B are used in advanced stages .¹

Optimal therapeutic management of OMM is still controversial. Multimodality management may be more beneficial in the treatment of mucosal melanoma.²³   Radical surgery with negative margins of the primary lesion is the cornerstone of treatment.^15.19.24.25 The safe margin of the OMM is at least 1.5 cm according to the National Comprehensive Cancer Network (NCCN) like SSC of the oral cavity, and 2.5 cm for lesions larger than 3 cm.^2.13 Although complete excision of the tumor is essential, the extent of safety margins has not been clearly clarified. ²⁶

If wide free margins (like 3 cm) are leading to serious morbidity, the surgeon can decrease it to just negative margin (like 5 mm) because there is no survival difference considering the size of safety margin.^22.26.27

Neck dissection should be added in cases with preoperatively confirmed lymph node metastasis. Prophylactic lymph node dissection is not recommended due to lack of effect on survival .^{12 .19.26.28.29.30}

Sentinel Lymph Node Biopsy(SLNB) that is currently used in cutaneous melanoma, and early-stage head and neck squamous cell cancer (T1, T2), is not usually performed at OMM however it is technically possible.^31.32.33 SLNB can be used to investigate the neck of patients with OMM and may create another option to define patients who would-be candidates for elective neck dissection.^.30.34.35.36The presence of a microscopic metastatic focus in the sentinel lymph node was associated with early hematogenous dissemination according to Starek et al study.^23..37 SLNB is not standard of care and can be used as a prognostic factor and a potentially efficient staging tool in mucosal melanoma, albeit few studies applied SLNB in OMM and further investigation is warranted.^{12.30.38.39.40}

Radiotherapy, chemotherapy, immunotherapy can be added to surgery, although their effectiveness is unknown.^2.23 Poor prognostic pathologic features like multiple positive nodes, or extra nodal extension of metastatic melanoma are indicators for post-operative radiotherapy;^2.19.25 however, OMM is considered as radio resistance, it can help to achieve local control despite not improving overall survival. ^12.41 A tumor thickness greater than 5 mm, presence of vascular invasion, necrosis, polymorphous tumor cell morphology, positive margins, primary site, bony invasion, and systemic metastasis have been associated with poor survival in patients with primary OMM.^2.11

The lesions that are discovered early and eliminated before the occurrence of metastases will have a better prognosis and are correlated with higher survival rates.⁴ Independent predictors of recurrence were the head or neck site of the primary tumor, ulceration, thickness, and mitotic rate greater than 3/mm², SLNB positivity, and signs of rapid tumor growth.³¹

After the individual mutation status has been determined, targeted systemic therapy using BRAF, MEK, KIT, or checkpoint inhibitors can be carried out to extend overall survival with an acceptable rate of side effects.^1.19 C-KIT is a key regulator of growth, differentiation, migration, and proliferation of melanocytes. Activating mutations in the c-KIT  gene are detected in a significant number of about 80% of patients with mucosal melanoma. ²¹The mitogen-activated protein kinase (MAPK) pathway (RAS/MEK/ERK) is a critical growth cascade in oral mucosal melanoma.¹² Immunotherapy is useful in the treatment of malignant melanoma at high risk for recurrence and metastatic melanoma.^23.34

In patients with recurrent diseases and without distant metastasis like our patient, the second surgical resection seems to be the best option if the lesion can be completely resected without considerable morbidity. Surgical procedures can salvage up to 25% of patients with local recurrence.³⁴

Oral melanomas are more aggressive and have a higher tendency for metastasis than other oral cancers or cutaneous melanomas.^8.12 The more aggressive behavior of OMM has been related to angioinvasion, anatomic relation that prevents sufficient surgical removal, and delay in diagnosis, the tendency to early ulceration due to repeated trauma, which in turn can cause pathways for metastasis and a higher rate of regional and systemic spread. ^13.26 About 25% of patients with OMM present with lymph node metastasis.^2.10.12.34

Late diagnosis often coincides with an extensive metastatic tumor.⁷ After surgical ablation, recurrence and metastasis are frequent events, and most patients die of the disease in 2 years. A review of the literature indicates that the 5-year survival rate is within a broad range of 4.5%–48.0%, but most are within the range of 10.0%–25.0%.⁴

The absence of early signs and symptoms, the lack of evidence-based treatment, the early development of metastases, and high rates of local recurrence contribute to the overall poor prognosis of these melanomas.¹⁵

In this article, we report a case of primary malignant melanoma of the tongue that underwent adequate surgery and adjuvant immunotherapy. During her close follow-up care, an early recurrence was detected, and she underwent standard surgery with adjuvant radiation therapy.