C LINICAL P RACTICE Pigmented Lesions of the Oral Cavity: Review, Differential Diagnosis, and Case Presentations • Adel Kauzman, BDS, DMD, MSc • • Marisa Pavone, DDS • • Nick Blanas, BSc, DDS, FRCD(C) • • Grace Bradley, DDS, MSc, FRCD(C) • Abstract Pigmented lesions are commonly found in the mouth. Such lesions represent a variety of clinical entities, ranging from physiologic changes to manifestations of systemic illnesses and malignant neoplasms. Evaluation of a patient presenting with a pigmented lesion should include a full medical and dental history, extraoral and intraoral examinations and, in some cases, biopsy and laboratory investigations. In this paper, an algorithm is proposed for the assessment of pigmented lesions of the oral cavity, and 3 patients with such lesions are described. MeSH Key Words: diagnosis, differential; mouth mucosa/pathology; pigmentation disorders/diagnosis © J Can Dent Assoc 2004; 70(10):682–3 This article has been peer reviewed. igmented lesions are commonly found in the mouth. extraoral and intraoral examinations, and laboratory tests.2 Such lesions represent a variety of clinical entities, The history should include the onset and duration of the P ranging from physiologic changes (e.g., racial lesion, the presence of associated skin hyperpigmentation, pigmentation) to manifestations of systemic illnesses the presence of systemic signs and symptoms (e.g., malaise, (e.g., Addison’s disease) and malignant neoplasms fatigue, weight loss), use of prescription and nonprescrip- (e.g., melanoma and Kaposi’s sarcoma). Therefore, an tion medications, and smoking habits. Pigmented lesions understanding of the causes of mucosal pigmentation and on the face, perioral skin and lips should be noted. The appropriate evaluation of the patient are essential. number, distribution, size, shape and colour of intraoral Oral pigmentation may be exogenous or endogenous in pigmented lesions should be assessed. In general, benign origin. Exogenous pigmentation is commonly due to pigmented lesions show regular borders and are small, foreign-body implantation in the oral mucosa. Endogenous symmetric and uniform in colour. They may be either flat pigments include melanin, hemoglobin, hemosiderin and or slightly elevated. In contrast, irregular borders, colour carotene. Melanin is produced by melanocytes in the basal variation, and surface ulceration suggest malignancy. layer of the epithelium and is transferred to adjacent Clinical tests such as diascopy and radiography and labo- keratinocytes via membrane-bound organelles called ratory investigations such as blood tests can be used to melanosomes. Melanin is also synthesized by nevus cells, confirm a clinical impression and reach a definitive diagno- which are derived from the neural crest and are found in sis. However, because it is not always possible to distinguish the skin and mucosa. Pigmented lesions caused by increased melanin deposition may be brown, blue, grey or between a benign pigmented lesion and an early melanoma black, depending on the amount and location of melanin on the basis of clinical features alone, biopsy is usually in the tissues.1 recommended for focal oral pigmented lesions that cannot be explained by local factors. In this paper, we present an Differential Diagnosis of Oral Pigmented algorithm to guide the assessment of pigmented lesions of Lesions the oral cavity on the basis of history, clinical examination Evaluation of a patient presenting with a pigmented and laboratory investigations (Fig. 1). The algorithm is lesion should include a full medical and dental history, based on the typical or predominant clinical presentation of 682 November 2004, Vol. 70, No. 10 Journal of the Canadian Dental Association Pigmented Lesions of the Oral Cavity Pigmented lesions Diffuse and bilateral Focal Early Predominantly Red-blue-purple Blue–grey Brown onset adult onset Amalgam Melanotic Physiologic Blanching Nonblanching tattoo macule pigmentation With systemic No systemic Other foreign- Pigmented signs and signs and Hemangioma Peutz- Thrombus body tattoos nevus symptoms symptoms Jeghers Varix Hematoma Blue nevus Melano- syndrome Addison’s Drug-induced acanthoma disease pigmentation Melanoma Heavy metal Postinflammatory pigmentation pigmentation Kaposi’s sarcoma Smoker’s melanosis Figure 1: An algorithm for evaluation of pigmented lesions of the oral cavity. first 2 decades of life but may not come to the patient’s attention until later. The colour ranges from light to dark brown. The attached gingiva is the most common intraoral site of such pigmentation, where it appears as a bilateral, well-demarcated, ribbon-like, dark brown band that usually spares the marginal gingiva1 (Fig. 2). Pigmentation of the buccal mucosa, hard palate, lips and tongue may also be seen as brown patches with less well-defined borders. The pigmentation is asymptomatic, and no treatment is required. Peutz-Jeghers Syndrome Peutz-Jeghers syndrome is a rare genetic disorder associ- ated with mutation of the LKB1 gene on chromosome Figure 2: Physiologic (racial) pigmentation in an African boy 19.4,5 It is characterized by pigmented mucocutaneous presenting as a well-demarcated dark brown band on the attached gingiva. The marginal gingiva is unaffected. macules, intestinal hamartomatous polyposis and an increased risk of cancer in many organs, including the small intestine, colon, stomach, pancreas, breast and genital 6 the various lesions and should not be taken as absolute tract. The melanotic spots of Peutz-Jeghers syndrome are indicator of diagnosis. Moreover, although differences in characteristically small and multiple, and are very obvious colour can help to differentiate among pigmented lesions, around the lips. Pigmented spots also occur inside the the interpretation of colour can be subjective and is influ- mouth, in the mucosa of the nose, conjunctiva and rectum, and on the skin of the extremities.7 The melanotic spots do enced by the amount and location of the pigment within not require treatment and are not associated with increased the mucosa. risk of melanoma. However, the patient should be moni- Diffuse and Bilateral Pigmentation tored for the development of internal malignancies. Physiologic (Racial) Pigmentation Addison’s Disease Physiologic pigmentation, which is common in African, Addison’s disease, or primary hypoadrenalism, is due to Asian and Mediterranean populations,3 is due to greater progressive bilateral destruction of the adrenal cortex by melanocyte activity rather than a greater number of autoimmune disease, infection or malignancy.8 The lack melanocytes. Physiologic pigmentation develops during the of adrenocortical hormones in the blood stimulates Journal of the Canadian Dental Association November 2004, Vol. 70, No. 10 683 Kauzman, Pavone, Blanas, Bradley Table 1 Drugs associated with oral mucosal pigmentation9,10 Antimalarials: quinacrine, chloroquine, hydroxychloroquine Quinidine Zidovudine (AZT) Tetracycline Minocycline Chlorpromazine Oral contraceptives Clofazimine Ketoconazole Amiodarone Busulfan Doxorubicin Bleomycin Cyclophosphamide Figure 3: Diffuse macular pigmentation of the gingiva in a patient with 5-Fluorouracil Addison’s disease. Pigmented lesions were also present on the buccal and labial mucosa (not shown). In contrast to the situation for physiologic pigmentation (Fig. 2), the marginal gingiva is involved in this case. production of adrenocorticotropic hormone (ACTH) by the recognition and treatment of the underlying cause to the anterior pituitary gland. The increased production of avoid severe systemic toxic effects. ACTH induces melanocyte-stimulating hormone, which Kaposi’s Sarcoma results in diffuse pigmentation of the skin and oral mucosa. Oral involvement presents as diffuse brown patches on the Kaposi’s sarcoma (KS) is a multifocal vascular malig- gingiva, buccal mucosa, palate and tongue, which may nancy seen predominantly in HIV-infected individuals. resemble physiologic pigmentation9 (Fig. 3). However, oral The development of this tumour is considered diagnostic of mucosal pigmentation associated with Addison’s disease AIDS progression. A human herpesvirus (HHV-8, also develops and progresses during adult life and is usually called Kaposi’s sarcoma-associated herpesvirus) has been accompanied by systemic manifestations including weak- implicated as the cause. KS in the oral mucosa most ness, nausea and vomiting, abdominal pain, constipation or commonly affects the hard palate, gingiva and tongue. diarrhea, weight loss and hypotension. Patients presenting Early lesions appear as flat or slightly elevated brown to with these features should be sent for medical evaluation purple lesions that are often bilateral. Advanced lesions and laboratory tests to assess levels of ACTH, plasma corti- appear as dark red to purple plaques or nodules that may sol and serum electrolytes. Addison’s disease can be fatal if exhibit ulceration, bleeding and necrosis. Definitive diag- left untreated. Management involves treatment of the nosis requires biopsy, which shows a proliferation of spin- underlying cause and corticosteroid replacement therapy. dle-shaped cells surrounding poorly formed vascular spaces or slits with numerous extravasated red blood cells.9,10 Heavy Metal Pigmentation Increased levels of heavy metals (e.g., lead, bismuth, Drug-Induced Pigmentation mercury, silver, arsenic and gold) in the blood represent a A number of medications may cause oral mucosal known cause of oral mucosal discolouration. In adults, the pigmentation