Maksiller diş etinde primer malign melanoma: olgu sunumu

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Introduction
Malign melanoma is a rare, life threatening disease.
It constitutes only 3% to 5% of all cutaneous malignancies and oral malign melanoma accounts for about 0.2-8% of all melanomas (1-5).
Oral melanoma is seen as 11-14% of all cases of
melanomas among Japanese which is more than any
other population (6). Barker et al. have declared from
the Western Society of Teachers of Oral Pathology
(WESTOP) Banff workshop on primary oral mucosal melanomas that the average age for oral mucosal
melanoma is 56 years and the range is 22-83 years
in a large sample study (7). A predilection for male
has been reported in many studies (4,5,8). Up to 80%
of all cases, oral malignant melanomas occur on the
hard palate and maxillary gingival (7,9). Buccal mucosa, mandibular gingiva, lips, tongue and the base
of the oral cavity follow them in decreasing frequency (7). Mucosal melanoma has a relatively poor
prognosis in oral cavity, with 5-year survival rates of
12% (10). It has a distinct tendency for both regional
and distant metastasis to sites such as the lungs, liver,
brain and bones (4).
The clinical presentation of oral melanoma has a
wide range. It can be seen as pigmented maculae, pigmented nodule, a large pigmented exophytic lesion
or amelonotic with the varying colors of black, gray,
purple, or reddish. The melanomas mostly grow rapidly with or without ulceration or an erythematous
border. It may also appear as a swelling on a pigmented area several years later. Pain is an uncommon
symptom of malignant melanoma, generally found
in the advanced stages (1-5,7). Destruction of the underlying bone is present in 78% of cases (11).
The difficulty of applying cutaneous melanoma
classification (nodular, superficial spreading, lentigo maligna, acral lentiginous) to oral melanomas
has been noted by several investigators (8,12,13).
* Department of Periodontology, Dental Sciences Center, Gulhane Military
Medical Academy
** Private Practitioner, Konya
*** Department of Periodontology, Faculty of Dentistry, Ondokuz Mayıs
University, Samsun
**** Department of Pathology, Gulhane Military Medical Faculty, Ankara
This article was presented as poster at the Europerio 6 Congress (Stockholm,
Sweden, June 4-6, 2009)
Reprint request: Dr. Sermet Sahin, Department of Periodontology, Dental
Sciences Center, Gulhane Military Medical Academy, Etlik-06018, Ankara,
Turkey
E-mail: sermetsahin@superonline.com
Date submitted: March 31, 2010 • Date accepted: May 31, 2010Volume 52 • Issue 3 Primary malignant melanoma • 209
Whether oral melanomas are biologically different
from cutaneous melanomas is yet to be determined.
The differential diagnosis of oral mucosal melanomas can include melanotic macule, smokingassociated melanosis, pigmented and blue nevus, melanoacanthoma, hemangioma, amalgam tatoo, other
heavy metal deposits, thrombus or hematoma associated with trauma, Addison’s disease, Peutz-Jeghers
syndrome, and Kaposi’s sarcoma (4,7,14-16). The
surface architecture of mucosal melonomas ranged
from macular (in situ melanomas) to ulcerated and
nodular (invasive melanomas and invasive with in
situ component).
The aim of this paper is to present a life threatening
case of primary malignant melanoma affecting the
maxillary gingiva.
Case Report
A 64-year-old female patient was admitted to the
Department of Periodontology of Gulhane Military
Medicine Academy with a complaint of rapidly growing pigmented mass in the maxillary premolar region. The patient was aware of the lesions over the
past 3 to 4 months. There was no history of pain
associated with it. There was no significant finding
in the patient’s past medical history. A tender submandibular lymph node was palpated on the related
side.
Intraoral findings revealed an elastic, grey red
exophytic tumor (25×20 mm) with well-defined margins which was buccal to the first molar, premolars
and canine and bluish-black pigmentation surrounding the swelling on the labial attached gingiva was
extending to the central incisor and midline (Figure
1). The lesion showed no extension to palatal mucosa. On palpation, there was no tenderness or bleeding. Plaque control was not bad. The premolars had
Miller grade II mobility.
A panoramic radiograph showed smooth alveolar
bone adjacent to the gingival tumor and no obviously abnormal bone resorption. A computerized tomography scan on the neck, liver, and lungs revealed
no further evidence of disease and distant metastasis
was found. An incisional biopsy was performed under local anesthesia.
The diagnosis of primary malignant melanoma of
the gingiva was established with microscopic and immunohistochemical studies, which revealed the neoplastic cells to be positive for HMB-45. Histopathological
examination revealed mucosal ulceration and subepithelial malignant tumor infiltrations (Figures 2, 3).
Tumor was composed of islands of atypical polygonal
cells having large nucleol and frequent mitosis. There
was melanin pigmentation on tumor cells positively
stained with Fontana. Tumor cells show positive reaction with HMB-45 immunostaining (Figure 4).
Figure 1. Intraoral photograph showing an elastic, grey red exophytic
tumor bluish-black pigmentation surrounding the swelling on the labial
attached gingiva was extending to the central incisor and midline
Figure 2. Photomicrographs showing infiltration of malignant melanocytes
into the connective tissue (Hematoxylin and eosin stain, x 200)
Figure 3. Atypical melanocyte groups with big vesicular nucleus
and prominent nucleolus are seen with high magnification. Dark
brown colored melanin pigment exists in the melanocyte cytoplasms
(Hematoxylin and eosin stain, X 400)210 • September 2010 • Gulhane Med J Şahin et al.
A partial right maxillectomy with radical neck dissection was planned. In spite of our all informative persuasion efforts, the patient refused further treatment.
The patient died after four months of her refusal.
Discussion
Mucosal melanoma may be primary or metastatic
from other locations of the body (3). Accor ding to
Greene et al. the criteria for the diagnosis of a primary
oral melanoma are the following: 1) demonstration
of clinical and microscopic tumor in the oral mucosa,
2) presence of junctional activity in the lesion, and 3)
inability to show any other primary site. Our patient
fulfilled all these criteria (14).
The etiology of oral melanoma is unknown. Several
risk factors have been proposed including human papillomavirus, denture irritation as a chronic irritant,
carcinogenic compounds, tobacco smoking, and chewing (8,17,18). In addition, it was speculated in the
WESTOP Banff workshop that oral melanomas could
be due to genetic abnormalities occurring in a clone
of melanocytes, or to the effects of an abnormal regional production of cytokines and growth factors on
melanocytes (7). However, there has been no evidence to support these risk factors (10,19).
Oral melanomas are usually diagnosed later in the
course of the disease than the ones presenting on the
skin, mainly due to anatomic reasons (19). At the time
of diagnosis, most oral melanomas have already progressed to the vertical growth phase (vertical invasion
of the tumor cells into the underlying tissues) and
have invaded the underlying submucosal tissues (20).
Differential diagnosis includes oral melanotic macule, smoking-associated melanosis,
medication-induced melanosis (antimalarial drugs
and Minocycline), melanoplakia, pituitary-based
Cushing’s syndrome, postinflammatory pigmentation, melanoacanthoma, melanocyctic nevi of the oral
mucosa, blue nevi, nevi of Spitz, Addison’s disease,
Peutz-Jeghers syndrome, amalgam tattoo, Kaposi’s
sarcoma, physiologic pigmentation, pigmentation
related with the use of heavy metals, and many other
conditions sharing some macroscopic characteristics
(21,22,23).
Morover, it is necessary that oral malignant melanoma should be under differential diagnosis than other malignant entities, such as poorly differentiated
carcinoma and large cell anaplastic lymphoma (21).
Immunohistochemical studies may help distinguish mucosal melanomas from other malignancies.
They are likely to stain positively for S-100, vimentin, and HMB-45 (20). Diagnostic evaluation should
include computerized tomography to evaluate the
primary tumor and cervical lymph nodes, as well as
a chest radiogram to screen for lung metastasis and
additional studies to detect distant metastasis include
bone scan, and positron emission tomography (18).
Treatment modalities for oral melanoma include surgical resection with or without neck dissection, immunochemotherapy, and radiation therapy
(7,19,24). It has been reported that vascular invasion,
clinical stage, gender, postoperative radiotherapy and
response to treatment are significant prognostic factors (25-27).
The reported prognosis of oral melanoma is quite
poor. While Rapidis et al. found the survival range of
five primer oral melonama patients under treatment
with vertical invasion as 14 months to 38 months
(mean 25.6 months), Ardekian et al. declared the
survival of two treated patients with primer gingival
malign melanoma as 2 and 3 years. Meleti et al. reported the survival rate as 30% in a 5-year follow up,
however, all the patients died at the end of 10 years
(4,19,28).
According to Batsakis, “there is no evidence that
a preliminary biopsy of the primary lesion increases
the risk of metastatic dissemination or unfavorably
affects the prognosis” (29). However, Liversedge reported that patients with oral melanoma frequently
had pigmented areas for a long time before melanoma developed (30). The natural history of some oral
mucosal in situ melanomas may include interface or
intraepithelial spread that is particularly prolonged
(as long as 10 years) (7). In situ oral mucosal melanomas may be microscopically subtle and deceptive.
These lesions may be misinterpreted as benign proliferations. It is generally agreed that the clinician
should be suspicious of irregular or heterogeneous
macules (even those less than 1 cm in greatest dimension) occurring in high risk sites (palate and gingiva)
Figure 4. With immunohistochemical examination, strong HMB-45
positivity in tumor cells is seen (Avidin-biotin peroxidase, X 400)Volume 52 • Issue 3 Primary malignant melanoma • 211
as potentially representing in situ melanomas (7). In
malignant melanoma of the gingiva, survival rates
may be increased by early diagnosis and treatment.
Dentists must carefully examine oral cavity, and pigmented lesions should be biopsied.