Dark pigmentation in the oral cavity


  • Amalgam Tattoo_0314 Derm Look 1

  • Oral Melanoma_0314 Derm Look 2

Case #1

A woman, aged 53 years, presented complaining of a dark spot of unknown duration inside her mouth. Examination of the right posterior gingiva and buccal mucosa revealed a darkly pigmented macule. A large amalgam restoration was also noted on her first upper-right molar. A large fracture was noted within the amalgam restoration. The patient reported that the amalgam had been placed more than 35 years ago. She was also experiencing hypersensitivity involving that tooth and had made an appointment with her dentist to have it checked.

Case #2

A man, aged 67 years, presented with pigmentation in his oral cavity of unknown duration. He had recently seen an oral surgeon for implant placement in his upper left quadrant to restore an edentulous area, and the lesion was discovered at that time. X-ray revealed an irregular, moth-eaten appearance of the bone and showed no evidence of any radiopaque material. A cone beam scan revealed a large subgingival growth. Subsequent clinical examination showed a diffuse dark-pigmented area on the left maxillary gingiva.

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Case #1Amalgam tattoos often present as a solitary area of discoloration caused by dental amalgam becoming embedded under the mucosal surface within the oral cavity. These lesions arose concurrently with the use of amalgam as a restorative dental material. Analysis...

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Case #1

Amalgam tattoos often present as a solitary area of discoloration caused by dental amalgam becoming embedded under the mucosal surface within the oral cavity. These lesions arose concurrently with the use of amalgam as a restorative dental material.

Analysis of cadaver teeth from the T’ang dynasty in China estimates dental amalgam was used around 618 a.d.-907 a.d. for restorations. Amalgam’s first documented use was presented by Strockerus in Germany in approximately 1528. It was not until 1830 that use of amalgam as a dental material became widespread.1

In its earliest form, amalgam was made out of a mixture of mercury and silver derived from commonly used coins. Today, amalgam alloy is a powder comprised primarily of silver, zinc, tin, and copper.2 Dental amalgam consists of the amalgam alloy (50%) mixed with mercury (50%). The mercury is needed for a surface reaction to take place within the alloy powder, leading to the formation of a crystallized structure.

Amalgam materials are not bonded to the tooth structure but are retained mechanically using various features in tooth preparation and design.

Amalgam tattoos appear to affect all races, sexes, and ages equally and occur when dental amalgam becomes embedded in the oral mucosa. Amalgam may become embedded due to rubber-dam perforation during restorative procedures, through amalgam dust created by high-speed turbines used during polishing and occlusal adjustments, and even as a result of flossing newly placed interproximal amalgam restorations.

Larger particles of amalgam may become implanted into an open wound during a concomitant surgical procedure. Amalgam is also used for endodontic treatments in apical retrofill procedures, which may cause apical discoloration of the mucosa. Intentional intraoral tattooing is also prevalent in various cultures around the world.

Clinically, an individual with an amalgam tattoo will present with persistent multiple or single gray, black, or blue lesions in the oral cavity. The border may be well defined or irregular. Overall, amalgam tattoos remain stable in size, but they may grow laterally in the initial few months.

The lesions are generally painless, but local inflammation and peripheral nerve injury may cause some pain in rare instances in which large particles have been implanted. The most commonly affected areas are the buccal mucosa, the alveolar mucosa, and the gingiva. However, lesions can be found on any area on the mucosa that is in close proximity to an amalgam restoration.

Histologically, brown and/or black granules of varying sizes are seen within the connective tissue. Silver salts, which are found as a corrosion component of amalgam, preferentially stain the reticulin fibers that surround nerves and vascular channels.

Smaller particles often cause a more significant inflammatory response, which may consist of lymphocytes and plasma cells, or a granulomatous reaction with macrophages and foreign-body giant cells. Larger particles often become surrounded by dense fibrous connective tissue with minimal inflammation.

The differential diagnosis of an amalgam tattoo includes malignant oral melanoma, melanocytic nevus, melanotic macule, Kaposi sarcoma, hyperestrogenemia, smoker’s melanosis, and physiologic pigmentation. An easy way to distinguish amalgam tattoo from other entities is to obtain a radiograph of the discolored region with a high-resolution film. If amalgam is present, it will easily be identified as a radiopaque anomaly.

Clinicians must also obtain a dental history, including any previous amalgam restorations. If the patient has had an amalgam restoration present for years or has recently had a long standing amalgam restoration removed, it is highly probably that the lesion is an amalgam tattoo. If needed, a biopsy can be done for a definitive diagnosis.

Amalgam tattoos are often asymptomatic and thus require no treatment. However, some lesions may occur in aesthetic areas and patients may prefer elective removal. Removal may be accomplished by conservative surgical excision or by laser therapy utilizing the Q-switched ruby or alexandrite laser.

The goal of laser surgery is to break up the pigmented particles into small enough pieces to be removed via phagocytes. The number of treatments needed is highly dependent on the density and composition of the amalgam.3

A radiograph performed on the woman in this case revealed a radiopaque anomaly in the area of the discoloration. A biopsy confirmed the diagnosis of amalgam tattoo, and no treatment was sought.


Melanoma is a malignant tumor derived from melanocytes, cells that are responsible for skin complexion. The tumor may arise from a benign melanocytic lesion or from melanocytes of normally healthy skin or mucosa. Although most melanomas arise on the skin, they may develop anywhere on the body that contains melanocytes (e.g., the oral cavity, eyes, nails).

Melanoma was originally discovered in the 1780s by an English surgeon named John Hunter. Malignant melanoma of the oral mucosa was first described by Weber in 1859.4 Today, oral melanoma falls under a rare subtype of melanoma called mucosal lentiginous melanoma. Only 1 of every 2 million persons in the United States will develop mucosal lentiginous melanoma. In fact, mucosal melanomas account for only 1.4% of all melanomas, and 25% to 50% occur in the head-and-neck region.5

The exact etiology of oral melanoma remains unknown. Melanoma arises from melanocytes, which originate from our neural crest cells. These cells migrate through cellular spaces (during the early fetal period) to the basal cell layer.

It is clear that melanocytes within the oral cavity are metabolically inactive and do not produce any melanin; hence, there is no pigmentation in the mouth. Because most mucosal melanomas are located in highly vascularized and hidden areas, they are often not found until they are in advanced stages. This unfortunately accounts for the high mortality rate associated with these cancers.

New advances have been made with gene expression models. The proto-oncogene c-kit is known to be a key regulator of proliferation, migration, growth, and differentiation of melanocytes. One study noted that c-kit expression was found in 88% of oral melanomas, and 22% of those tumors actually harbored activating mutations.6

Two out of every three patients with oral melanoma are males, and affected persons typically are in their sixth or seventh decade of life. It should be noted that 50% of all oral melanomas are found on the hard palate, and 20% on the maxillary gingiva.7

It is very rare for oral melanomas to be found on the buccal mucosa, floor of the mouth, or tongue. Most lesions are soft to palpation. Radiograph examinations may show underlying bone or adjacent bone with an irregular appearance or moth-eaten destruction.

Oral melanoma lesions typically begin as brown to black macules with irregular borders. The macule extends laterally and can vary in size from millimeters to centimeters. As the lesion progresses, vertical growth is initiated and a lobulated exophytic mass develops. It is at this stage that the cancer is typically diagnosed.

Early ulceration and pain may develop but is uncommon. Lesions are usually painless, which partially explains why patients are oblivious to the growing cancer. Another feature that adds to the cancer’s elusiveness is that more than 20% of oral melanomas contain so little pigment that they have an essentially normal mucosal tint.8

Histologically, atypical melanocytes are seen at the dermal-epidermal junction. Early lesions will show either nests or single scattered melanocytes among the basal epithelial cells. Atypical cells tend to be larger and have varying degrees of hyperchromatism and nuclear pleomorphism. As the cancer progresses, it will undergo a radial-growth phase that includes a lateral spread of the atypical melanocytes along the basal cell layer.

Advanced oral melanoma shows atypical melanocytes advancing into the dermis; this is considered the vertical-growth phase. The invading cells are either spindle-shaped or epithelioid. As they infiltrate the connective tissue, the invading cells are loosely aggregated in cords or sheets of pleomorphic cells. Oral melanomas also tend to invade the lymphatic and blood vessels more frequently than do their cutaneous counterparts.

The oral cavity may pose diagnostic challenges for the clinician, as many lesions appear similar. The differential diagnosis of oral melanoma includes amalgam tattoo, melanotic macule, Kaposi sarcoma, hyperestrogenemia, smoker’s melanosis, physiologic pigmentation, and melanocytic nevus. Because all have similar clinical features, histopathologic confirmation is often necessary to differentiate between the disorders.

Surgical resection with or without sentinel lymph node biopsy (depending on depth at presentation) remains the treatment of choice for primary oral melanoma. Prognosis is typically poor if the depth is greater than 0.5 mm. Lymph node dissection is usually performed on patients with clinically evident regional metastasis in the absence of distant metastasis. If distant metastasis is confirmed, systemic chemotherapy is usually initiated.

Historically, dacarbazine (DTIC-Dome) has been the mainstay of treatment. Temozolomide (Temodar), a cytotoxic alkylating agent, has demonstrated results similar to those of dacarbazine. More recent advances and understanding of genetic mutations in melanomas have opened new doors for targeted therapy. For example, imatinib (Gleevec), a new tyrosine kinase inhibitor, is more specific for the c-kit domain that is often found in mucosal melanomas.9

Unfortunately, the prognosis for many patients with oral melanoma is extremely poor, with five-year survival studies ranging between 13% and 22%.10 Early metastasis and late detection are to blame for the high mortality rate.

The patient in this case was diagnosed with a mucosal melanoma with a depth of 0.9 mm and palpable lymph nodes on clinical examination. He was referred for surgical excision and oncology consultation.

Kerri Robbins, MD, is an instructor in the Department of Dermatology at Baylor College of Medicine in Houston.
Damjan Jutric is a third-year dental student at The University of Texas School of Dentistry, also in Houston.


  1. Bjørklund G. [The history of dental amalgam]. Tidsskr Nor Laegeforen. 1989;109:3582-3585.
  2. Lundin K, Schmidt G, Bonde C. Amalgam tattoo mimicking mucosal melanoma: a diagnostic dilemma revisited. Case Rep Dent. 2013;2013:787294. Available at www.ncbi.nlm.nih.gov/pmc/articles/PMC3606745/.
  3. Gojkov-Vukelic M, Hadzic S, Pasic E. Laser treatment of oral mucosa tattoo. Acta Inform Med. 2011;19:244-246. Available at www.ncbi.nlm.nih.gov/pmc/articles/PMC3564178/.
  4. Nehse G, Mensing H, Maerker R. [Differential diagnosis and therapy of malignant melanomas of the oral cavity]. Fortschr Kiefer Gesichtschir. 1988;33:127-129.
  5. Seetharamu N, Ott PA, Pavlick AC. Mucosal melanomas: a case-based review of the literature. Oncologist. 2010;15:772-781. Available at www.ncbi.nlm.nih.gov/pmc/articles/PMC3228004/.
  6. Rivera RS, Nagatsuka H, Gunduz M, et al. C-kit protein expression correlated with activating mutations in KIT gene in oral mucosal melanoma. Virchows Arch. 2008;452:27-32.
  7. Tucci R, Aburad De Carvalhosa A, Anunciação G, et al. Late diagnosis of a primary oral malignant melanoma: a case report. Minerva Stomatol. 2010;59:55-59.
  8. Neville BW, Damm DD, Allen CM, Bouquot J. Oral and Maxillofacial Pathology, 3rd ed. St. Louis, Mo.: Saunders/Elsevier; 2009:435.
  9. Carvajal RD, Antonescu CR, Wolchok JD, et al. KIT as a therapeutic target in metastatic melanoma. JAMA. 2011;305:2327-2334.
  10. Gorsky M, Epstein JB. Melanoma arising from the mucosal surfaces of the head and neck. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1998;86:715-719.

All electronic documents accessed March 10, 2014.

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