CASE 1

           

Diagnosis: Oral Melanoma.

 

A 57-year-old woman without antecedents of interest and subjected to estrogen therapy presented with a black stain on the gums. The lesion had been present for the past year, and the patient associated it with endodontic treatment of tooth 2.5.

The intraoral examination revealed two grayish lesions measuring 2 and 4 mm in diameter on the vestibular gingival zone of 2.5, together with a black pigmented, ulcerated and painful lesion measuring some 10 mm in diameter, located in the palatal gingiva of 2.6.

Orthopantomography revealed no significant alterations. Following excision biopsy, the histopathological study revealed the presence of large-size, atypical melanocytes with an elongated nucleus, and an abundant pale cytoplasm containing variable amounts of melanin as fine granules, located within the connective tissue component. Melanoma of the oral mucosa was diagnosed.

 

Melanomas are the most aggressive forms of skin cancer, due to their great metastatic potential. These malignancies account for 3-5% of all skin tumors, 1% of all malignancies, and nearly 2% of all cancer deaths. Both sexes are affected equally, though a greater frequency is observed among Caucasians ¹. Melanomas of the oral mucosa are less common than their cutaneous counterparts ²; they represent 0.5-2% of all melanomas ³, and in 55% of all patients they are located in the region of the head and neck ⁴. Oral mucosal melanomas tend to develop in older individuals in the 50-70 years age range (as in our patient), and a 2:1 male predominance has been reported ⁴ – though our patient was a female. While no clear racial predilection is observed, the lesions do appear to be more common among Asians and Negroes ⁵. The preferential locations are the nasal cavity and paranasal sinuses. Lesions are less commonly seen within the oral cavity, where the palate and gingiva are the most frequently affected locations ⁶ (the latter being the affected zone in our case).

 

The risk factors underlying skin melanoma include prolonged solar exposure and the presence of precursor lesions such as congenital nevus and dysplastic lesions, while a natural dark skin pigmentation confers protection (lesser risk). At intraoral level, however, melanoma is believed to develop over pre-existing melanosis ⁷.

It is now known that some cutaneous and mucosal melanomas can exhibit a prolonged superficial or radial growth phase at the junction of the epithelium and underlying connective tissue before commencing vertical infiltration ⁸. The presence of radial and vertical growth phases in melanomas led to their classification in the form of several clinicopathological entities. Thus, the subtypes observed in the skin are malignant lentigo, acral lentiginous melanoma, superficial growth lesions and nodular presentations – the latter being considered invasive melanoma. Similar lesions can be identified in the oral cavity, though in this case they are preferentially classified as in situ melanoma, invasive melanoma, or combined lesions ^6,7. Nevertheless, some authors consider most oral melanomas to exhibit clinical characteristics of acral lentiginous melanoma ⁹.

 

The diagnosis is determined by the case history, with particular attention to the evolutive changes of the lesion and the time in which the changes have occurred, as well as the accompanying symptoms. The latter tend to be scarce, though in some cases they may be suggestive of locoregional or distant metastases, in view of the important metastatic potential of these malignancies. In these cases it is necessary to perform liver tests, X-rays and CT studies of the chest, abdomen and brain, in order to discard possible disease spread ¹⁰. Clinical examination of course also plays a fundamental role, with determination of the characteristics of the lesion, the presence or absence of satellite lesions, ulcerations, etc., that may provide clues to the type of process involved. Of note in our patients was the presence of two types of lesions: a grayish macula located in the vestibular gums, and a black and ulcerated lesion in the palatal region. Some authors mention the possibility of rubbing the melanic lesion with gauze to establish an early diagnosis. In this sense, a positive result (i.e., suggestive of melanoma) is when the gauze is stained – though a negative test does not rule out the disease, since an amelanic melanoma (found in 30% of cases) may be involved ⁶.

Regarding the differential diagnosis, in our case a required first consideration was amalgam tattooing, due to the presence of amalgam filling of 2.6.

 

The definitive diagnosis is established by histological study of the lesion. A biopsy of suspect pigmented lesions is thus required. As far as possible, the biopsy should be excisional and in depth ¹¹, and leaving a sufficient clinical margin. In 30% of cases an incision biopsy is unable to determine lesion depth, and in some series this is defined as a negative prognostic factor. For this reason incision biopsy is reserved for very large lesions, and in cases where a benign lesion is suspected, located in an esthetically sensitive area. The biopsy should always be performed at a margin of the lesion, including the interface between normal and abnormal tissue. The biopsy can help us determine the degree of invasion (Breslow levels) ¹², which is classified into four levels according to the thickness of invasion in millimeters: level I = thickness ≤ 0.75 mm; level IV = thickness ≥ 4 mm. The biopsy can also inform of lesion depth (Clark levels), which comprises 5 levels: level I = lesion confined to the epidermis; level II = limited to the papillary dermis; level III = protrusion from the papillary dermis, without infiltrating the reticular dermis; level IV = invasion of the reticular dermis; and level V = lesion reaching the subcutaneous cellular tissue. Both classifications are essential for establishing the prognosis. While these classifications are less applicable to mucosal melanomas, patient survival is inversely proportional to the degree of invasion.

As regards staging, the international classification may be applied, taking into account the clinical and paraclinical data. Accordingly, melanoma is classified into three stages as follows:

 

Stage I:             Primary tumor

Stage II:            A. Skin metastases located in contiguity or in the post-excision scar

                        B. Regional lymph node metastases

Stage III:           Distant metastases through blood or lymphatic spread.

 

In relation to treatment, practically full consensus exists that stage I and II melanomas are amenable to surgery, while the more advanced stages are only open to palliative management¹³. Surgical treatment implies radical resection, with removal of the lesion and leaving a safety margin of 2-3 cm ¹⁴, with or without neck surgery – depending on whether or not the neck lymph nodes are affected ¹⁵. In this sense, the sentinel lymph node technique has acquired great relevance in the identification of possible adenopathies. In turn, radiotherapy and chemo-immunotherapy are valid complementary techniques. In our case the patient was subjected to extensive resection of the lesion, accompanied by a left hemimandibular resection and right functional cervical dissection.

 

The course and prognosis tend to be poor, with a survival rate of 15% after 5 years ⁶. In this context, the principal problem is posed by locoregional control of the disease – an 85% relapse rate being observed within the first two years ¹⁵. Such relapses are difficult to control. Local relapse tends to precede lymph node metastases and distant spread. The prognosis is dependent on a series of factors relating both to the patient and to the tumor itself ¹⁷. Regarding the former, the evidence suggests a discretely greater survival among women under the age of 45 years, with lesser survival beyond phase II. In phase III disease the liver and brain metastases define a particularly virulent course. As regards the tumor itself, factors of poor prognosis comprise initially nodular lesions and malignancy developing over in situ presentations, with surface spread of acral lentiginous presentations. Also associated with poor prognosis are BANS locations of the disease (Back: upper back region; Arm: posterior portion of arm; Neck; and Scalp), Clark classification level III or higher, and a Breslow score of over 1.5 mm. Mucosal lesions tend to be clinically more silent, as a result of which the diagnosis is typically established in later stages – with the worsening of patient prognosis this implies. In addition, the identification of a high mitotic rate is indicative of poor prognosis.

 

REFERENCES

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