Pigmented Lesions of the Oral Mucosa

  • Eric T. StooplerEmail author
  • Faizan Alawi
Reference work entry


Pigmented lesions of the oral mucosa are encountered on a routine basis in clinical practice. Oral health-care providers must assess several parameters associated with pigmented lesions, such as location, shape, color, and size. Etiology of pigmented lesions may be attributed to a local phenomenon and/or associated with an underlying systemic disorder. Diagnostic and therapeutic modalities must be carefully considered as these lesions encompass the spectrum of clinical pathology, ranging from benign to malignant. Clinicians should conduct a thorough medical history and relevant physical examination for patients with pigmented lesions to identify possible adrenal, gastrointestinal, or genetic disorders that are commonly associated with these types of lesions. If a systemic disorder is suspected, the patient should be promptly referred to the appropriate health-care provider for further evaluation and management. Multidisciplinary care is often necessary to effectively manage patients with these conditions. This chapter provides a contemporary perspective of pigmented lesions of the oral mucosa and is intended to serve as a practical clinical resource for oral health-care providers.


Oral mucosa Pigmentation Melanin Focal Multifocal Diffuse Systemic Genetic Exogenous 


  1. Alawi F. Pigmented lesions of the oral cavity: an update. Dent Clin N Am. 2013;57(4):699–710.PubMedCrossRefGoogle Scholar
  2. Anderson EJ, Cakir I, Carrington SJ, Cone RD, Ghamari-Langroudi M, Gillyard T, et al. 60 YEARS OF POMC: regulation of feeding and energy homeostasis by alpha-MSH. J Mol Endocrinol. 2016;56(4):T157–74.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Arava-Parastatidis M, Alawi F, Stoopler ET. Multifocal pigmentation of the oral cavity. Oral melanoacanthoma J Am Dent Assoc. 2011;142(1):53–6.PubMedCrossRefGoogle Scholar
  4. Bastiaens M, ter Huurne J, Gruis N, Bergman W, Westendorp R, Vermeer BJ, et al. The melanocortin-1-receptor gene is the major freckle gene. Hum Mol Genet. 2001;10(16):1701–8.PubMedCrossRefGoogle Scholar
  5. Berwick M, Buller DB, Cust A, Gallagher R, Lee TK, Meyskens F, et al. Melanoma epidemiology and prevention. Cancer Treat Res. 2016;167:17–49.PubMedCrossRefGoogle Scholar
  6. Bliss JM, Ford D, Swerdlow AJ, Armstrong BK, Cristofolini M, Elwood JM, et al. Risk of cutaneous melanoma associated with pigmentation characteristics and freckling: systematic overview of 10 case-control studies. Int J Cancer. 1995;62(4):367–72.PubMedCrossRefGoogle Scholar
  7. Bowen AR, McCalmont TH. The histopathology of subcutaneous minocycline pigmentation. J Am Acad Dermatol. 2007;57(5):836–9.PubMedCrossRefGoogle Scholar
  8. Bravo IM, Correnti M, Escalona L, Perrone M, Brito A, Tovar V, et al. Prevalence of oral lesions in HIV patients related to CD4 cell count and viral load in a Venezuelan population. Med Oral Patol Oral Cir Bucal. 2006;11(1):E33–9.PubMedGoogle Scholar
  9. Brooks JK, Reynolds MA. Ethnobotanical tattooing of the gingiva: literature review and report of a case. J Am Dent Assoc. 2007;138(8):1097–101.PubMedCrossRefGoogle Scholar
  10. Brown RJ, Kelly MH, Collins MT. Cushing syndrome in the McCune-Albright syndrome. J Clin Endocrinol Metab. 2010;95(4):1508–15.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Caito S, Aschner M. Neurotoxicity of metals. Handb Clin Neurol. 2015;131:169–89.PubMedCrossRefGoogle Scholar
  12. Campbell CM, Deas DE. Removal of an amalgam tattoo using a subepithelial connective tissue graft and laser deepithelialization. J Periodontol. 2009;80(5):860–4.PubMedCrossRefGoogle Scholar
  13. Cantudo-Sanagustín E, Gutiérrez-Corrales A, Vigo-Martínez M, Serrera-Figallo MÁ, Torres-Lagares D, Gutiérrez-Pérez JL. Pathogenesis and clinicohistopathological characteristics of melanoacanthoma: a systematic review. J Clin Exp Dent. 2016;8(3):e327–36.PubMedPubMedCentralGoogle Scholar
  14. Chandran R, Feller L, Lemmer J, Khammissa RA. HIV-associated oral mucosal melanin hyperpigmentation: a clinical study in a South African population sample. AIDS Res Treat. 2016;2016:8389214.PubMedPubMedCentralGoogle Scholar
  15. Charmandari E, Nicolaides NC, Chrousos GP. Adrenal insufficiency. Lancet. 2014;383(9935):2152–67.PubMedCrossRefGoogle Scholar
  16. Chatzistefanou I, Kolokythas A, Vahtsevanos K, Antoniades K. Primary mucosal melanoma of the oral cavity: current therapy and future directions. Oral Surg Oral Med Oral Pathol Oral Radiol. 2016;122(1):17–27.PubMedCrossRefGoogle Scholar
  17. De Leo M, Cozzolino A, Colao A, Pivonello R. Subclinical Cushing’s syndrome. Best Pract Res Clin Endocrinol Metab. 2012;26(4):497–505.PubMedCrossRefGoogle Scholar
  18. Dereure O. Drug-induced skin pigmentation. Epidemiology, diagnosis and treatment. Am J Clin Dermatol. 2001;2(4):253–62.PubMedCrossRefGoogle Scholar
  19. Felix DH, Luker J, Scully C. Oral medicine: 7. Red and pigmented lesions. Dent Update. 2013;40(3):231–4. 236–8.PubMedCrossRefGoogle Scholar
  20. Feller L, Chandran R, Kramer B, Khammissa RA, Altini M, Lemmer J. Melanocyte biology and function with reference to oral melanin hyperpigmentation in HIV-seropositive subjects. AIDS Res Hum Retrovir. 2014a;30(9):837–43.PubMedCrossRefGoogle Scholar
  21. Feller L, Masilana A, Khammissa RA, Altini M, Jadwat Y, Lemmer J. Melanin: the biophysiology of oral melanocytes and physiological oral pigmentation. Head Face Med. 2014b;10:8.PubMedPubMedCentralCrossRefGoogle Scholar
  22. Femiano F, Lanza A, Buonaiuto C, Gombos F, Di Spirito F, Cirillo N. Oral malignant melanoma: a review of the literature. J Oral Pathol Med. 2008;37(7):383–8.PubMedCrossRefGoogle Scholar
  23. Fernandes D, Ferrisse TM, Navarro CM, Massucato EM, Onofre MA, Bufalino A. Pigmented lesions on the mucosa: a wide range of diagnoses. Oral Surg Oral Med Oral Pathol Oral Radiol. 2015;119(4):374–8.PubMedCrossRefGoogle Scholar
  24. Gaeta GM, Satriano RA, Baroni A. Oral pigmented lesions. Clin Dermatol. 2002;20(3):286–8.PubMedCrossRefGoogle Scholar
  25. Gandhi SA, Kampp J. Skin cancer epidemiology, detection, and management. Med Clin North Am. 2015;99(6):1323–35.PubMedCrossRefGoogle Scholar
  26. Gondak RO, da Silva-Jorge R, Jorge J, Lopes MA, Vargas PA. Oral pigmented lesions: clinicopathologic features and review of the literature. Med Oral Patol Oral Cir Bucal. 2012;17(6):e919–24.PubMedPubMedCentralCrossRefGoogle Scholar
  27. Hashemi Pour MS. Malignant melanoma of the oral cavity: a review of the literature. Indian J Dent Res. 2008;19(1):47–51.PubMedCrossRefGoogle Scholar
  28. Hassona Y, Sawair F, Al-Karadsheh O, Scully C. Prevalence and clinical features of pigmented oral lesions. Int J Dermatol. 2016;55(9):1005–13.PubMedCrossRefGoogle Scholar
  29. Hatch CL. Pigmented lesions of the oral cavity. Dent Clin N Am. 2005;49(1):185–201. ix–x.PubMedCrossRefGoogle Scholar
  30. Hruz PW. HIV and endocrine disorders. Endocrinol Metab Clin N Am. 2014;43(3):xvii–xviii.CrossRefGoogle Scholar
  31. Jiang AJ, Rambhatla PV, Eide MJ. Socioeconomic and lifestyle factors and melanoma: a systematic review. Br J Dermatol. 2015;172(4):885–915.PubMedCrossRefGoogle Scholar
  32. Kaugars GE, Heise AP, Riley WT, Abbey LM, Svirsky JA. Oral melanotic macules: a review of 353 cases. Oral Surg Oral Med Oral Pathol. 1993;76(1):59–61.PubMedCrossRefGoogle Scholar
  33. Kauzman A, Pavone M, Blanas N, Bradley G. Pigmented lesions of the oral cavity: review, differential diagnosis, and case presentations. J Can Dent Assoc. 2004;70(10):682–3.PubMedGoogle Scholar
  34. Kim Y, Suh HS, Cha HJ, Kim SH, Jeong KS, Kim DH. A case of generalized argyria after ingestion of colloidal silver solution. Am J Ind Med. 2009;52(3):246–50.PubMedCrossRefGoogle Scholar
  35. Lacroix A, Feelders RA, Stratakis CA, Nieman LK. Cushing’s syndrome. Lancet. 2015;386(9996):913–27.PubMedCrossRefGoogle Scholar
  36. Lau D, Rutledge C, Aghi MK. Cushing’s disease: current medical therapies and molecular insights guiding future therapies. Neurosurg Focus. 2015;38(2):E11.PubMedCrossRefGoogle Scholar
  37. Lee CS, Thomas CM, Ng KE. An overview of the changing landscape of treatment for advanced melanoma. Pharmacotherapy. 2017;37(3):319–33.PubMedCrossRefGoogle Scholar
  38. Lim GF, Cusack CA, Kist JM. Perioral lesions and dermatoses. Dent Clin N Am. 2014;58(2):401–35.PubMedCrossRefGoogle Scholar
  39. Lloyd C, Grossman A. The AIP (aryl hydrocarbon receptor-interacting protein) gene and its relation to the pathogenesis of pituitary adenomas. Endocrine. 2014;46(3):387–96.PubMedCrossRefGoogle Scholar
  40. Lodish MB. Clinical review: kinase inhibitors: adverse effects related to the endocrine system. J Clin Endocrinol Metab. 2013;98(4):1333–42.PubMedPubMedCentralCrossRefGoogle Scholar
  41. Lonser RR, Nieman L, Oldfield EH. Cushing’s disease: pathobiology, diagnosis, and management. J Neurosurg. 2016:1–14.Google Scholar
  42. MacLennan R, Kelly JW, Rivers JK, Harrison SL. The eastern Australian childhood nevus study: site differences in density and size of melanocytic nevi in relation to latitude and phenotype. J Am Acad Dermatol. 2003;48(3):367–75.PubMedCrossRefGoogle Scholar
  43. Marangon Junior H, Souza PE, Soares RV, de Andrade BA, de Almeida OP, Horta MC. Oral congenital melanocytic nevus: a rare case report and review of the literature. Head and Neck Pathol. 2015;9(4):481–7.CrossRefGoogle Scholar
  44. Meleti M, Vescovi P, Mooi WJ, van der Waal I. Pigmented lesions of the oral mucosa and perioral tissues: a flow-chart for the diagnosis and some recommendations for the management. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008;105(5):606–16.CrossRefGoogle Scholar
  45. Meserve EE, Nucci MR. Peutz-Jeghers syndrome: pathobiology, pathologic manifestations, and suggestions for recommending genetic testing in pathology reports. Surg Pathol Clin. 2016;9(2):243–68.PubMedCrossRefGoogle Scholar
  46. Michels A, Michels N. Addison disease: early detection and treatment principles. Am Fam Physician. 2014;89(7):563–8.PubMedGoogle Scholar
  47. Mohan M, Sukhadia VY, Pai D, Bhat S. Oral malignant melanoma: systematic review of literature and report of two cases. Oral Surg Oral Med Oral Pathol Oral Radiol. 2013;116(4):e247–54.PubMedCrossRefGoogle Scholar
  48. Moraes PC, Noce CW, Thomaz LA, Cintra ML, Correa ME. Pigmented lichenoid drug eruption secondary to chloroquine therapy: an unusual presentation in lower lip. Minerva Stomatol. 2011;60(6):327–32.PubMedGoogle Scholar
  49. Muller S. Melanin-associated pigmented lesions of the oral mucosa: presentation, differential diagnosis, and treatment. Dermatol Ther. 2010;23(3):220–9.PubMedCrossRefGoogle Scholar
  50. Napier C, Pearce SH. Current and emerging therapies for Addison’s disease. Curr Opin Endocrinol Diabetes Obes. 2014;21(3):147–53.PubMedCrossRefGoogle Scholar
  51. Naziat A, Grossman A. Adrenal Insufficiency. In: De Groot LJ, Chrousos G, Dungan K, et al., editors. Endotext. South Dartmouth (MA):, Inc.; 2000-. Available from:
  52. Nikitakis NG, Koumaki D. Laugier-Hunziker syndrome: case report and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol. 2013;116(1):e52–8.PubMedCrossRefGoogle Scholar
  53. Pasquali E, Garcia-Borron JC, Fargnoli MC, Gandini S, Maisonneuve P, Bagnardi V, et al. MC1R variants increased the risk of sporadic cutaneous melanoma in darker-pigmented Caucasians: a pooled-analysis from the M-SKIP project. Int J Cancer. 2015;136(3):618–31.PubMedGoogle Scholar
  54. Pearce JM. Burton’s line in lead poisoning. Eur Neurol. 2007;57(2):118–9.PubMedCrossRefGoogle Scholar
  55. Pinto A, Raghavendra S, Lee R, DeRossi S, Alawi F. Epithelioid blue nevus of the oral mucosa: a rare histologic variant. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2003;96(4):429–36.PubMedCrossRefGoogle Scholar
  56. Ponti G, Tomasi A, Manfredini M, Pellacani G. Oral mucosal stigmata in hereditary-cancer syndromes: from germline mutations to distinctive clinical phenotypes and tailored therapies. Gene. 2016;582(1):23–32.PubMedCrossRefGoogle Scholar
  57. Rangwala S, Doherty CB, Katta R. Laugier-Hunziker syndrome: a case report and review of the literature. Dermatol Online J. 2010;16(12):9.PubMedGoogle Scholar
  58. Rawal SY, Burrell R, Hamidi CS, Kalmar JR, Tatakis DN. Diffuse pigmentation of maxillary attached gingiva: four cases of the cultural practice of gingival tattoo. J Periodontol. 2007;78(1):170–6.PubMedCrossRefGoogle Scholar
  59. Riegert-Johnson D, Gleeson FC, Westra W, Hefferon T, Wong Kee Song LM, Spurck L, et al. Peutz-Jeghers syndrome. In: Riegert-Johnson DL, Boardman LA, Hefferon T, Roberts M, editors. Cancer syndromes. Bethesda: National Center for Biotechnology Information (US); 2009.Google Scholar
  60. Schernthaner-Reiter MH, Trivellin G, Stratakis CA. MEN1, MEN4, and carney complex: pathology and molecular genetics. Neuroendocrinology. 2016;103(1):18–31.PubMedCrossRefGoogle Scholar
  61. Sharma ST, Nieman LK, Feelders RA. Cushing’s syndrome: epidemiology and developments in disease management. Clin Epidemiol. 2015;7:281–93.PubMedPubMedCentralGoogle Scholar
  62. Shen ZY, Liu W, Bao ZX, Zhou ZT, Wang LZ. Oral melanotic macule and primary oral malignant melanoma: epidemiology, location involved, and clinical implications. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011;112(1):e21–5.PubMedCrossRefGoogle Scholar
  63. Shorning BY, Clarke AR. Energy sensing and cancer: LKB1 function and lessons learnt from Peutz-Jeghers syndrome. Semin Cell Dev Biol. 2016;52:21–9.PubMedCrossRefGoogle Scholar
  64. Tarakji B, Umair A, Prasad D, Alsakran AM. Diagnosis of oral pigmentations and malignant transformations. Singap Dent J. 2014;35C:39–46.CrossRefGoogle Scholar
  65. Thumbigere-Math V, Johnson DK. Treatment of amalgam tattoo with a subepithelial connective tissue graft and acellular dermal matrix. J Int Acad Periodontol. 2014;16(2):50–4.PubMedGoogle Scholar
  66. Wood BR, Lacy JM, Johnston C, Weigle DS, Dhanireddy S. Adrenal insufficiency as a result of ritonavir and exogenous steroid exposure: report of 6 cases and recommendation for management. J Int Assoc Provid AIDS Care. 2015;14(4):300–5.PubMedCrossRefGoogle Scholar
  67. Yago K, Tanaka Y, Asanami S. Laugier-Hunziker-Baran syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008;106(2):e20–5.PubMedCrossRefGoogle Scholar
  68. Yilmaz HG, Bayindir H, Kusakci-Seker B, Tasar S, Kurtulmus-Yilmaz S. Treatment of amalgam tattoo with an Er, Cr:YSGG laser. J Investig Clin Dent. 2010;1(1):50–4.PubMedCrossRefGoogle Scholar
  69. Yuan A, Woo SB. Adverse drug events in the oral cavity. Oral Surg Oral Med Oral Pathol Oral Radiol. 2015;119(1):35–47.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Oral MedicineUniversity of Pennsylvania School of Dental MedicinePhiladelphiaUSA
  2. 2.Department of PathologyUniversity of Pennsylvania School of Dental MedicinePhiladelphiaUSA

Personalised recommendations