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