Open Access
Issue
J Oral Med Oral Surg
Volume 25, Number 4, September 2019
Article Number 35
Number of page(s) 4
Section Cas clinique et revue de la littérature / Up-to date review and case report
DOI https://doi.org/10.1051/mbcb/2019020
Published online 17 September 2019

© The authors, 2019

Licence Creative Commons
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Introduction

Mucosal melanoma (MM) is a rare malignancy, with an estimated incidence of 0.7 new cases per 100,000 individuals per year. MMs account for 0.2%–10% of all melanomas detected in the head and neck. MM is one of the most aggressive tumors of the head and neck, with a very high risk of local or distant recurrence [1].

Sinonasal melanomas are the most common form of MM (66%) followed by oral MM (25%), and they represent 4% of all sinonasal tumors [2]. Their peak incidence occurs around the age of 60.

Observation

A 67-year-old patient consulted in June 2016 for left cervical lymphadenopathy. Examination revealed a tumor of the left maxillary sinus. Tumor biopsies revealed melanocytic tumor proliferation, suggesting melanoma or a melanocytic nevus. Melanoma was diagnosed based on the infiltrative nature of the tumor.

The patient's family history included a cutaneous melanoma of the knee that affected her sister. In 2002, the patient benefited from the placement of an individualized stent for coronary artery disease and was treated with acetylsalicylic acid, acebutolol, and pantoprazole. She also presented phototype I according to the Fitzpatrick's classification.

Intraoral clinical examination revealed a melanotic tumor mass approximately 4-cm long, which had started to infiltrate the gingiva of the maxilla. The teeth in the area were loose. Tooth extracting was proposed (Fig. 1).

Extension examination revealed osteolysis of the adjacent bone structures and invasion of the nasal fossae and pterygoid muscles (Fig. 2). Jugular and carotid satellite lymphadenopathies under the chin as well as secondary bone and liver lesions were detected.

Genome analysis was performed, and no BRAF, CKIT, or NRAS mutations were detected. The patient's medical records were reviewed at a Multidisciplinary Consultation Meeting (MCP). Because of the local extension, inoperable nature, and distant metastases of the tumor, treatment with immunotherapy (pembrolizumab) was initiated in late September 2016. Irradiation of the primary lesion was proposed to improve local control and to limit local progressive risks (pain or eating disorders). The treatment was delivered as 60 Gy in 30 sessions over 6 weeks, allowing a clinical response estimated at 50% at 3 weeks after the end of the irradiation (Fig. 3). No unusual toxicity was noted because of the combination of pembrolizumab and radiotherapy.

The patient subsequently developed lymph node and lung metastases and received a second line of ipilimumab immunotherapy. Chemotherapy with deticene and then fotemustine was initiated for subcutaneous and bone metastases. Despite these treatments, the patient died from metastatic progression.

thumbnail Fig. 1

Intraoral photograph showing melanocyte infiltration in the gingival mucosa and the tissue loss around the second maxillary left molar.

thumbnail Fig. 2

Sagittal split showing the tumor, the osteolysis, and the relationship with the upper maxillary left molar.

thumbnail Fig. 3

Intraoral photography 3 weeks before initiating the radiotherapy, a diminution of the tumor volume can be noticed.

Comments

The sinonasal MM has a poor prognosis, because of its late management, which at the time of the diagnosis is usually accompanied by adenopathies. According to Ascierto et al., the 5-year survival rate for individuals over 65 years of age is 19% [3]. This rate is low because patients present late, with nonspecific clinical signs of the disease such as unilateral, permanent, or progressive nasal obstruction and epistaxis in the initial stages. Subsequently, the appearance of pain, tearing, rhinorrhea, and, in the most advanced stages, a junctional swelling, nasal deformity, and exophthalmia can be noted [3,4].

To date, there is no clear consensus regarding MM treatment. The treatment of choice for these tumors remains surgical excision leaving healthy margins [5]. However, the frequency of recurrence is very important in this type of pathology [3,69]. Complete surgical resection (R0) is difficult to perform due to the anatomical proximity of certain significant or vital structures.

The use of radiotherapy in MM treatment remains controversial: It is used as an adjuvant treatment, and in case of surgical contraindication, as analgesic or palliative treatment. Indeed, these tumors are categorized as not radiosensitive. In the literature, improvements in local and regional control, with no effect on overall survival after 5 years, has frequently been reported [3,5,9].

Recently, the use of targeted therapies (tyrosine kinase receptor inhibitors) and advances in immunotherapy (PD1/PDL1 nivolumab or pembrolizumab) have led increased patient survival, particularly in cases of unresectable or metastatic tumors [3,10,11].

The diagnosis of pigmented lesions of the oral mucosa can be complex. In the present case, an extensive, diffuse, dark blue, slate lesion of the oral cavity was present. This type of lesion must be systematically biopsied (except in the case of suspicion of vascular lesion, which requires arteriographic or Doppler evaluation).

In some cases, MM may be in an achromic form. The diagnosis is often poorer because of the aggressive nature of the tumor and its more difficult diagnosis [3]. Several differential diagnoses of various etiological origins can be evoked when dealing with pigmented lesions of the oral mucosa.

Systemic disease-related colorations include Laugier–Hunziker syndrome, hemochromatosis, endocrine disorders, such as acromegaly and McCune–Albright syndrome, Cushing's disease or syndrome, hyperthyroidism, neurofibromatosis, and beta thalassemia [12,13]. Carney complex is characterized by pigmented macules on the lips in 50% of the cases. This is a potentially severe disease due to the presence of cardiac myxomas. Mucosal signs can sometimes be the first sign of this disease [12]. Peutz–Jeghers syndrome results in cutaneous and mucosal hyperpigmentation, with perioral pigmented macules on the oral mucosa as well as intestinal and gastric hamartomatous polyposis. These polyps are associated with a risk of malignant degeneration in 2%–3% of the cases. There is also an increased risk of breast, ovarian, and testicular tumors [12]. Finally, Addison's disease or primary adrenal insufficiency may cause a diffuse grayish discoloration of the mucous membranes [12].

Colorations may be related to a chronic inflammatory condition, such as lichen planus or sarcoidosis. Mucosal colorations may also have an extrinsic origin, as in the case of heavy metal poisoning (lead, mercury, or silver) and ethnic coloring (tattoos or amalgam tattoos), or an iatrogenic origin.

Some colorations can be of neoplastic origin. Oral melanoma is the most frequently found malignant tumor, accounting for ∼1% of all melanomas and 0.5% of all malignant tumors in the oral cavity [14]. Oral melanomas can be brown, black, gray, purplish, or depigmented [15]. In fact, in 35% of the cases, oral melanomas are achromic, making diagnosis more difficult [13]. The overlaying mucosa may be smooth, intact in appearance, or ulcerated. The presence of locoregional lymphadenopathy is possible and is a clear sign of a worse prognosis [15]. Benign nevi may look similar to oral melanomas.

Kaposi's sarcoma is frequently found on the palate of HIV Patients on SIDA stage. Finally, some coloration may have a vascular origin, such as hemangiomas that are common in the oral cavity. Table I presents a non-exhaustive list of the main causes of mucosal colorations sorted by their possible origins [12,13,16].

Table I

Causes of pigmented lesions of the oral mucosa according to their origin.

Conclusion

Pigmented lesions of the oral mucosa can be of various origins. Practitioners should always consider the possibility of a malignant melanoma when dealing with a suspicious, rapidly evolving lesion. Here, we have detailed the case of an oral manifestation of sinus melanoma in the form of a pigmented mucosal lesion. It is pathology with a poor prognosis and difficult treatment, and there is no treatment consensus. Surgery remains the best option to date, despite a high frequency of local or regional recurrence.

Conflicts of interests

The authors declare that they have no conflicts of interest in relation to this article.

References

  1. Lombardi D, Bottazzoli M, Turri-Zanoni M, Raffetti E, Villaret AB, Morassi ML, et al. Sinonasal mucosal melanoma: A 12-year experience of 58 cases. Head Neck 2016;38 Suppl 1:E1737–E1745. [CrossRef] [PubMed] [Google Scholar]
  2. Williams MD. Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Mucosal Melanomas. Head Neck Pathol 2017;11:110–117. [CrossRef] [PubMed] [Google Scholar]
  3. Ascierto PA, Accorona R, Botti G, Farina D, Fossati P, Gatta G, et al. Mucosal melanoma of the head and neck. Crit Rev Oncol Hematol 2017;112:136–152. [CrossRef] [PubMed] [Google Scholar]
  4. Gilain L, Houette A, Montalban A, Mom T, Saroul N. Mucosal melanoma of the nasal cavity and paranasal sinuses. Eur Ann Otorhinolaryngol Head Neck Dis 2014;131:365–369. [CrossRef] [PubMed] [Google Scholar]
  5. Papaspyrou G, Garbe C, Schadendorf D, Werner JA, Hauschild A, Egberts F. Mucosal melanomas of the head and neck: new aspects of the clinical outcome, molecular pathology, and treatment with c-kit inhibitors. Melanoma Res 2011;21:475–482. [CrossRef] [PubMed] [Google Scholar]
  6. Guzzo M, Grandi C, Licitra L, Podrecca S, Cascinelli N, Molinari R. Mucosal malignant melanoma of head and neck: forty-eight cases treated at Istituto Nazionale Tumori of Milan. Eur J Surg Oncol J Eur Soc Surg Oncol Br Assoc Surg Oncol 1993;19:316–319. [Google Scholar]
  7. Lee SP, Shimizu KT, Tran LM, Juillard G, Calcaterra TC. Mucosal melanoma of the head and neck: the impact of local control on survival. Laryngoscope 1994;104:121–126. [PubMed] [Google Scholar]
  8. Bradley PJ. Primary malignant mucosal melanoma of the head and neck. Curr Opin Otolaryngol Head Neck Surg 2006;14:100–104. [PubMed] [Google Scholar]
  9. Amit M, Tam S, Abdelmeguid AS, Kupferman ME, Su SY, Raza SM, et al. Patterns of treatment failure in patients with sinonasal mucosal melanoma. Ann Surg Oncol 2018;25:1723–1729. [CrossRef] [PubMed] [Google Scholar]
  10. Ribas A, Puzanov I, Dummer R, Schadendorf D, Hamid O, Robert C, et al. Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial. Lancet Oncol 2015;16:908–918. [CrossRef] [PubMed] [Google Scholar]
  11. Mignard C, Deschamps Huvier A, Gillibert A, Duval Modeste AB, Dutriaux C, Khammari A, et al. Efficacy of Immunotherapy in Patients with Metastatic Mucosal or Uveal Melanoma. J Oncol 2018. [PubMed] [Google Scholar]
  12. Eisen D. Disorders of pigmentation in the oral cavity. Clin Dermatol 2000;18:579–587. [CrossRef] [PubMed] [Google Scholar]
  13. Hatch CL. Pigmented lesions of the oral cavity. Dent Clin North Am. 2005;49:185–201. [CrossRef] [PubMed] [Google Scholar]
  14. Meleti M, Leemans CR, Mooi WJ, van der Waal I. Oral malignant melanoma: the Amsterdam experience. J Oral Maxillofac Surg 2007;65:2181–2186. [CrossRef] [PubMed] [Google Scholar]
  15. Meleti M, Leemans CR, Mooi WJ, Vescovi P, van der Waal I. Oral malignant melanoma: a review of the literature. Oral Oncol 2007;43:116–121. [CrossRef] [PubMed] [Google Scholar]
  16. Gaeta GM, Satriano RA, Baroni A. Oral pigmented lesions. Clin Dermatol 2002;20:286–288. [CrossRef] [PubMed] [Google Scholar]

All Tables

Table I

Causes of pigmented lesions of the oral mucosa according to their origin.

All Figures

thumbnail Fig. 1

Intraoral photograph showing melanocyte infiltration in the gingival mucosa and the tissue loss around the second maxillary left molar.

In the text
thumbnail Fig. 2

Sagittal split showing the tumor, the osteolysis, and the relationship with the upper maxillary left molar.

In the text
thumbnail Fig. 3

Intraoral photography 3 weeks before initiating the radiotherapy, a diminution of the tumor volume can be noticed.

In the text

Current usage metrics show cumulative count of Article Views (full-text article views including HTML views, PDF and ePub downloads, according to the available data) and Abstracts Views on Vision4Press platform.

Data correspond to usage on the plateform after 2015. The current usage metrics is available 48-96 hours after online publication and is updated daily on week days.

Initial download of the metrics may take a while.