Focal, Flat Pigmentations of the Oral Mucosa: A Clinical Approach to the Differential Diagnosis

The purpose of this article is to assist the clinician in establishing a clinical approach to the diagnosis of focal, flat pigmentations of the oral mucosa. These pigmentations include lesions that may be blue, purple, red, black, or brown. The etiopathogenesis may be variable and the pigment may originate from an exogenous (extrinsic) or endogenous (intrinsic) source. Exogenous pigmentations are of a traumatic or iatrogenic origin. Intrinsic pigmentations are either vascular or melanocytic. Clinical approaches include a thorough history and physical exam coupled with diascopy (blanchability), radiographs, and tissue examination (biopsies). An algorithm is presented to clarify the diagnostic approach. The diagnosis may vary from pathologic entities that require no treatment to others that may involve malignancies and their associated management. It is therefore extremely important that these lesions are identified and properly managed in an expeditious manner.

Focal pigmentations of a flat (macular) nature are frequently encountered on the oral mucosa. A large number of lesions must be considered in the differential diagnosis, and the treatment may vary from observation to radical surgery. It is therefore crucial that the appropriate course of action be followed. These pigmentations may be due to many etiologic factors but basically can be considered of an exogenous (e.g., amalgam, root canal sealer) or endogenous (e.g., vascular, melanocytic) origin. The coloration of these pigmentations may be red, blue, purple, black, gray, or brown. The determination of the exact coloration may be helpful in beginning the differential workup (Figure 1) and several clinical aids (diascopy, radiographs, biopsy) may be useful to continue this diagnostic approach and arrive at a definitive diagnosis.^1-7

Vascular Lesions

Lesions that are red, blue, or purple are most frequently of a vascular origin; and the color is due to the hemoglobin in the blood. Oxygenated hemoglobin in the arterial system will usually appear reddish, while unoxygenated blood in the venous system will take on a blue-purple appearance. The first decision in diagnosing vascular lesions is to determine whether the blood is within the vessels (intravascular) or has been extravasated (extravascular) into the submucosal tissues (see Figure 1). A clinical test called diascopy may often be helpful in this regard. Diascopy is a clinical test of applying pressure with a transparent object to allow visualization of the blanchability of the underlying mucosa.⁸ A glass slide can be used but with caution, since the edges are sharp. A more suitable choice is a flat, clear plastic object with smooth, polished edges, such as a ruler. If a lesion is blanchable (see Figure 1), the lesion would represent vasodilation or vascular proliferation in which blood is extruded by pressure from within patent blood vessels. Vasodilation is found as an inflammatory response as in the erythema associated with gingivitis (Figure 2), post-trauma (Figure 3), hypersensitivity (Figure 4), a varix (varicose vessel) (Figure 5), or telangiectasia. Other inflammatory reactions may appear red but are usually more diffuse (e.g., erythematous candidiasis). A focal red or blue macule may also represent a vascular proliferation such as a hemangioma (port-wine stain) (Figures 6 and 7) or a malignant vascular proliferation (e.g., Kaposi’s sarcoma).

Lesions that are nonblanchable by diascopy may still represent intravascular blood that cannot be emptied due to a large number of feeder vessels or small vascular lumens. However, these nonblanchable lesions will mostly represent extravascular blood (purpura). This condition occurs spontaneously in several pathologic conditions or may be induced by trauma with submucosal hemorrhage (Figures 8 and 9). The exact coloration is determined by the length of the time the blood is in the submucosal tissue with the hemoglobin undergoing degradation to biliverdin and bilirubin. This extravascular blood can be seen in small pinpoint areas (petechiae), larger areas (ecchymosis) or swellings (hematomas) (Figure 10). History taking may be helpful in differentiating these etiologic possibilities, and further laboratory tests may be indicated to establish systemic conditions such as a thrombocytopenia (petechiae) or coagulopathies (ecchymosis). These may include platelet count, partial thromboplastin and prothrombin time (international normalized ratio). Palatal petechiae (Figure 11) may occur secondary to trauma or suction, infectious mononucleosis, or a platelet problem (thrombocytopenia or thrombocytopathia).

Recognition of coagulopathic and hemostatic disorders is extremely important. The platelet defects usually culminate in the appearance of petechiae rather than ecchymoses. Thrombocytopenia may be ideopathic (autoimmune), HIV-associated, leukemia-associated or drug-induced. Thrombocytopathia is a defect in platelet function and may be a hereditary disorder of platelet adhesion molecules, such as the von Willibrand group of diseases, or the defect may be drug-induced as is seen in patients taking high doses of aspirin. The coagulopathies are deficiencies in clotting factors that may involve either the intrinsic or extrinsic pathways of coagulation and typically result in ecchymosis. The hereditary types include hemophilia A and B, among others; although the most common is coagulopathy induced by coumadin among patients with thromboembolic disease. It must be recalled that most of the clotting factors are made in the liver; and, therefore, patients with liver disease may be bleeders. Clotting factor deficiencies are also encountered in late-stage renal disease and among patients with steatorrhea.

Epithelial Thinning

Other nonblanchable red macules are inflammatory reactions including burns or erosions with partial loss of the epithelium. This thinning of the oral mucosa (epithelial atrophy) will allow a reddish appearance due to the underlying vasculature as in this thermal injury (Figure 12). This same histologic finding of epithelial thinning can occur in a neoplastic condition such as erythroplakia with a diagnosis of epithelial dysplasia, carcinoma-in-situ or microinvasive squamous cell carcinoma (Figure 13). Any lesion that fails to show signs of healing should be subjected to cellular analysis.

Exogenous Pigmentation

Other discolorations of the oral mucosa may appear as black or gray (Figure 14), and these often represent an exogenous pigmentation from iatrogenic sources.^9,10 A radiograph (Figure 15) of the area will commonly reveal a metallic source responsible for the pigmentation, usually amalgam (focal argyosis) (Figure 14) or root canal sealer that has been embedded in the submucosa or periapical tissue. If these metals are not large enough to be detected radiographically (Figure 16), further history taking and evaluation are necessary. Lesions that are on the gingiva or alveolar mucosa in close proximity to amalgam restorations or at the apices of endodontically treated teeth are often clinically diagnosed. Other cases are more problematic, and a decision must be made to evaluate these lesions periodically. Since these lesions can slowly enlarge as they are absorbed by the tissue, it may be necessary to perform a biopsy for definitive diagnosis. Another exogenous source occurs as a result of children falling with pencils in their mouths and creating a graphite tattoo, most commonly seen on the palate (Figure 17).

Endogenous Pigmentation -- Melanin

Other pigmented lesions of a blackish, bluish or more frequently brownish coloration may be of melanocytic origin. The color is dependent on the amount and location of the melanin. Melanocytic lesions may represent a basilar melanosis or a melanocytic proliferation. The basilar melanosis or ephelis (freckle) on the skin is actinically induced. In the oral cavity, the etiology is unknown, although a history of antecedent trauma may be noted.¹¹ Frequently they are solitary, and the appellation oral melanotic macule is applied (Figure 18). The diffuse or multifocal lesions are most commonly seen in racial pigmentations that are genetically controlled. They also may be associated with several systemic conditions, including Addison’s disease or intestinal disorders (Peutz-Jeghers syndrome). There are other systemic conditions, particularly palatal melanosis, that can occur as a result of several medications (e.g. antimalarials and minocycline), smoking or pulmonary disease¹² (Figure 19).

Melanocytic proliferations are very common on the skin and are known as a pigmented nevi, lesions that progress through histologic stages and ultimately enter a final period of growth arrest (Figure 20). Nevi are fairly uncommon in the oral mucosa and are of four histologic types, depending on the location of the nevus cells (junctional, compound, intradermal intramucosal and blue).¹³ These lesions may frequently be nodular. Nevi should be excised for a definitive diagnosis. The main concern with pigmented lesions is that they may represent a malignant melanocytic proliferation or melanoma (Figure 21). Melanomas of the oral mucosa are rare and usually begin de novo but may occur as a progression of a nevus (junctional type). Any changes in a lesion with regard to irregular borders, enlargement, and/or color changes are ominous signs. A rapid referral for a biopsy is crucial to allow expeditious and proper management. Oral melanomas are most frequently seen on the anterior maxillary gingiva and palate.¹⁴ The early lesions may be macular, representing superficial spreading melanomas that have not invaded into the submucosal connective tissues. When invasion occurs, a nodular mass will appear. In most oral melanomas, there is a mixture of macular and nodular pigmentation. Whereas oral mucosal melanomas are very rare, those arising on the facial skin, particularly the malar region, are common.¹⁵ These facial skin melanomas are typically superficial spreading types referred to as lentigo maligna melanoma. They are multicolored with foci of hypopigmentation and classically have irregular, jagged boundaries.

This paper has presented a practical, clinical approach to the diagnosis of focal, flat oral mucosal pigmentations that will allow dentists to be confident in their initial recognition and management. Biopsy is always recommended in cases that are not readily recognized as traumatic vascular lesions or amalgam tattoos.

Authors

William M. Carpenter, DDS, MS, is professor and chairman in the Department of Pathology and Medicine at the University of the Pacific School of Dentistry.

Mitchell Rudd, DDS, is a dental resident with Pocatello Family Dentistry Clinic at Idaho State University.

References

1. Regezi JA and Sciubba J, Oral Pathology Clinical Pathologic Correlations, 2nd ed. WB Saunders Co, Philadelphia, 1993.

2. Eversole LR, Clinical Outline of Oral Pathology: Diagnosis and Treatment, 3rd ed. Lea & Febiger, Philadelphia, 1992.

3. Neville BW, Damm DD, et al, Oral & Maxillofacial Pathology. WB Saunders Co, Philadelphia, 1995.

4. Wood NK and Goaz PW, Differential Diagnosis of Oral Lesions, 4th ed. Mosby-Year Book, St. Louis, 1991.

5. Eversole LR, Oral Medicine: A Pocket Guide. WB Saunders Co, Philadelphia, 1996.

6. Coleman GC and Nelson FN, Principles of Oral Diagnosis. Mosby-Year Book, St. Louis, 1993.

7. Bhaskar SN, Synopsis of Oral Pathology, 7th ed. Mosby Co, St. Louis, 1973.

8. Rudd MG, Eversole LR, and Carpenter WM, Diascopy. Academy of General Dentistry, Submitted for publication June 2000.

9. Seward GR, Amalgam tattoo. Br Dent J 184:470, 1998.

10. Owens BM, Johnson WW, Schuman NJ, Oral amalgam pigmentations (tattoos): a retrospective study. Quintessence Int 23(12):805-10, 1992.

11. Kaugars GE, Heise AP, et al, Oral melanotic macules. A review of 353 cases. Oral Surg Oral Med Oral Pathol 76:59-61, 1993.

12. Meyerson MA, Cohen PR, Hymes SR, Lingual hyperpigmentation associated with minocycline therapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 79:180-4, 1995.

13. Buchner A, Leider AS, et al, Melanocytic nevi of the oral mucosa: a clinicopathologic study of 130 cases from northern California. J Oral Pathol Med 19:197-201, 1990.

14. Gorsky M, Epstein JB, Melanoma arising from the mucosal surfaces of the head and neck. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 86:715-9, 1998.

15. Massi D, Nardini P, et al, Simultaneous occurrence of multiple melanoma in situ on sun damaged skin (lentigo maligna), solar lentigo and labial melanosis: the value of dermoscopy in diagnosis. J Eur Acad Dermatol Venereol 13:193-7, 1999.

To request a printed copy of this article, please contact/ William M. Carpenter, DDS, MS, UOP School of Dentistry, 2155 Webster St., San Francisco, CA 94115 or e-mail the author at wcarpent@sf.uop.edu.

Legends

Figure 1. The differential workup.

Figure 2. Focal zone of gingival erythema associated with a severe periodontal defect.

Figure 3. A palatal erythema secondary to a traumatic event.

Figure 4. A contact mucositis as a result of gold hypersensitivity.

Figure 5. Several blue, purplish varices in the anterior floor mouth.

Figure 6. A port-wine stain (capillary hemangioma) of the right lower lip and skin.

Figure 7. Blanching of the hemangioma following diascopy.

Figure 8. Hematoma of the left lower lip.

Figure 9. Diascopy revealing extravascular blood and nonblanchability.

Figure 10. A focal hematoma following a traumatic incident.

Figure 11. Palatal petechiae that have coalesced in areas, representing extravascular blood.

Figure 12. A mucosal burn following pizza ingestion.

Figure 13. Erythroplakia of the anterior floor of mouth which represents an early squamous cell carcinoma.

Figure 14. Two focal areas of a grayish black pigmentation of the alveolar ridge.

Figure 15. A radiographic view of this exogenous pigmentation (amalgam).

Figure 16. An amalgam tattoo that was not visible radiographically.

Figure 17. Two black pigmentations of the palate representing graphite tattoos.

Figure 18. A brownish, focal pigmentation in which the biopsy revealed an oral melanotic macule.

Figure 19. A palatal melanotic macule associated with an antimalarial medication.

Figure 20. Blackish pigmentation of the mid-hard palate representing an intramucosal nevus.

Figure 21. A brownish black pigmentation of the left lower lip that was rapidly enlarging and represented an early malignant melanoma.