Biology:Oral melanosis

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Oral melanosis is a benign pigmented lesion arising in the oral cavity.[1] Oral pigmentation is asymptomatic and does not usually cause any alteration to the texture or thickness of the affected area. The colour can be uniform or speckled and can appear solitary or as multiple lesions.[2] Depending on the site, depth, and quantity of pigment, the appearance can vary considerably.[3] Oral pigmentation is found in the following places:

  • Lower vermillion border  (the exposed pink or reddish margin of a lip[4])
  • Tongue
  • Oral mucosa
  • Gingivae
  • Palate[3]

Oral pigmentation affects about 3% of the population[5] and is most likely seen in those with dark skin[6]; however people with light skin have, on average, 30 local pigmented areas and in some circumstances will present intra-orally. They are more often found in females than males[1] and the typical age at presentation is 40 years although they can appear at any age[4].

Diagnosis of oral pigmentation is by a complete history taken by the clinican followed by a thorough clinical examination[2]. Management of such lesions is typically by close clinical monitoring, photographs and measuring tools. A biopsy may be indicated where the following features are present: large or new-pigmented lesions and those with a papular appearance or irregular colouration.[7]

Aetiology

Physiological Oral Melanosis

Oral pigmentation affects about 3% of the population[5] and is most likely seen in those with dark skin[8]; however people with light skin have, on average, 30 local pigmented areas and in some circumstances will present intra-orally. They are more often found in females than males[1] and the typical age at presentation is 40 years although they can appear at any age[4]

Systemic Causes of Oral Melanosis

Peutz- Jeghers Syndrome

The autosomal dominant disorder Peutz-Jeghers Syndrome is characterized by ‘intestinal hamartomatous polyps in association with mucocutaneous melanocytic macules’. These macules often vary in shades of brown, size and are confluent, Although any oral site can be affected, in almost all cases pigmented macules appear on the buccal mucosae, lips and around the mouth. Pigmented macules on the face are less common. The extent of oral involvement and degree of pigmentation varies between each individual case.

An individual who has this syndrome has a relative risk fifteen times greater of developing cancer in comparison to the general population.

In older patients, the main consequence of the syndrome is cancer. The sites mainly affected include the pancreas, stomach, lungs, colon, small intestine, uterus, breasts and the ovaries and breasts. Additionally, Peutz-Jeghers Syndrome can be associated with other reproductive site cancers including  sertoli cell tumours and adenoma malignum of the cervix.

In young patients, intussusception and obstruction of the small intestinal obstruction and are the main complications, these are caused by the small intestinal location of the polyps.

Addison's Disease

Systemically oral melanosis can also be associated with the following;

-       Pregnancy

-       Oral contraceptive intake

-       Exposure to sunlight

-       HIV [9]

-       Antimalarial drug therapy [10]

Pathological Oral Melanosis

Kaposi's Sarcoma

Iatrogenic oral pigmentation (eg, Smoker's melanosis).

Oral Melanoacanthoma

Melanocytic Nevi

Hyperplastic/Neoplasm

Melanotic Macules

Melanotic macules can be found on the buccal mucosa, lip, palate, alveolar ridge and gingiva.[11]

Oral Melanoma

Epidemiology

Oral Melanosis can also be classified as 2 categories, melanocytic or non-melanocytic. (Melanocytic being the genesis due to the increase in melanotic pigments and non-melanocytic origin being the genesis from non melanotic causes). The prevalence of melanocytic and non-melanocytic causes of oral melanosis was roughly 1:1.[12][11]

Physiological Oral Melanosis

Oral pigmentation affects about 3% of the population[5] and is most likely seen in those with dark skin[8]

Systemic Oral Melanosis

Peutz Jeghers syndrome

For Peutz Jeghers syndrome the frequency is approximately 1 case per 60,000-300,000 people in the USA. Equal occurrence in both sexes and all races. Average age of diagnosis being 23 years in men and 26 years in women.[13]

Pathological Oral Melanosis

Smokers melanosis

Smoker’s melanosis is present in all age groups, has no observed sex or race predilection.[11]

Hyperplastic/Neoplasm

Melanotic Macule

For hyperplastic or neoplastic processes, the mean age of oral melanotic macule (hyperplastic- increase in malanoticpigments without an increase in malanocytes)  is 43.1 years with the mean size of the lesion was about 6.8mm.  The female: male ratio is 2:1 and lower lip being the most common location. For oral melanoma (neoplastic) the mean age was 53.8 years with equal ratio of female:male and most common location being in the palate or gingiva.[13][14]

Oral Melanoma

For oral Melanoma (neoplastic lesion) ,the mean age was 53.8 years with equal ratio of female:male and most common location being in the palate or gingiva.[13][14]

Cumulative frequency

The occurrence of oral malanosis on the cheeks were (21%) ,alveolar mucosa (16.6%) , gingiva (11.8%). Amalgam tattoo being majority of the cases (46.3%) , malanotic macules (22.9%) and nevus (20.5%). [15]

Pathogenesis

Many different diseases can cause melanin pigmented lesions in the mouth through

  1. Increase in the number of melanocytes or melanocytosis
  2. Increased melanin production with or without melanocytosis

Melanin is an endogenous pigment synthesized by melanocytes that are located in the basal layer of epithelium. Melanin is then transferred to keratinocytes in melanosomes. Nevus cells in the skin and oral mucosa also produce melanin. Oral melanosis can present as black, gray, blue or brown lesions depending on the site and amount of melanin deposition in tissues[16]

Physiological Oral Melanosis

Increased melanin production without increase in melanocytes[17]

Systemic Oral Melanosis

Peutz-Jeghers syndrome

Increased production of melanin without increase in number of melanocytes[18]

Addison’s disease

Decrease in blood adrenocortical hormone level causes increased levels of adrenocorticotropic hormone secreted by anterior pituitary gland. As a result, melanocyte-stimulating hormone is induced which causes oral melanosis[17]

Pathological Oral Melanosis

Smoker’s melanosis

Increased melanin production to defend against damage from tobacco smoke[17]

Oral Melanoacanthoma

Increased number of dendritic melanocytes [17]

Melanocytic nevi

Accumulation of nevus cells at the basal layer of the epithelium or in the connective tissue or both[17]

Hyperplastic/Neoplasm

Oral Melanoma

Increased number of malignant melanocytes[17]

Management

Pathological Oral Melanosis

Kaposi's Sarcoma

There is a variety of different treatment options for Kaposi sarcoma. The appropriate therapy options may vary depending on the variation of disease and the patients immune status[19].  If the lesion is localised, usually found in classical Kaposi sarcoma, and not systemic treatments can be any from lasers, cryotherapy, non-intervention, chemotherapy and immune upregulation[20] . For generalized and systemic cases chemotherapeutic drugs are used[21]. HAART is also a recognised treatment if the patient is known to suffer from AIDS-related Kaposi sarcoma. For cases of iatrogenic Kaposi sarcoma any immunosuppressive medication should be stopped or reduced if able.

Smoker's Melanosis

Smokers melanosis may resolve over several years following smoking cessation[22].

Hyperplastic/Neoplasm

An initial biopsy of the lesion may be carried out first to determine correct diagnosis. Following this there is a number of different treatment options available. The combination used will be based on the individual patient and presenting melanoma. Surgical resection[23] is most commonly carried out. This involves cutting out the lesion and ensuring complete removal from the oral cavity. Chemotherapy and Radiotherapy  are considered first line management[24] and they may be used in conjunction with surgery. Another option available is Immunotherapy. The aim of this is to target cells or molecules in the immune system in an effort to destroy tumours[25]. This can be done by suppressing or stimulating the patients immune system. After treatment has been carried out patients should be seen for regular follow ups[26] to manage any reoccurrence early and ensure complete healing following surgeries. If the melanoma has progressed extensively and metastasised, treatment, for example surgery, would be carried out in a palliative nature only[27].

See also

References

  1. ↑ 1.0 1.1 1.2 "Melanotic neuroectodermal tumour of infancy: a case report". Journal of the Indian Society of Pedodontics and Preventive Dentistry 25 (3): 148–51. 2007. doi:10.4103/0970-4388.36568. PMID 17951934. 
  2. ↑ 2.0 2.1 "[Subconjunctival autohemotherapy of eye burns in our cases]" (in Polish). Klinika Oczna 94 (4): 113–4. April 1992. PMID 1405409. 
  3. ↑ 3.0 3.1 "Oral pigmented lesions: Clinicopathologic features and review of the literature". Medicina Oral, Patologia Oral Y Cirugia Bucal 17 (6): e919-24. November 2012. doi:10.4317/medoral.17679. PMID 22549672. 
  4. ↑ 4.0 4.1 4.2 Carol Culpepper, Jetta (January 2000). "Merriam‐Webster Online: The Language Center0011The Staff of Merriam‐Webster. Merriam‐Webster Online: The Language Center. 47 Federal Street, PO Box 281, Springfield, MA 01102; Tel: (413) 734‐3134; Fax: (413) 731‐5979;: Merriam‐Webster, Inc c1999. Free". Electronic Resources Review 4 (1/2): 9–11. doi:10.1108/err.2000.4.1_2.9.11. ISSN 1364-5137. 
  5. ↑ 5.0 5.1 5.2 "Giant volar melanotic macule". Skin Cancer 4 (1): 68–71. 1989. doi:10.5227/skincancer.4.68. 
  6. ↑ "Cawson, R. A.: Aids to Oral Pathology and Diagnosis. VII, 126 pages. Churchill Livingstone, Edinburgh - London - Melbourne - New York, 1981. Price: £ 3.50.". Pathology - Research and Practice 175 (4): 412. December 1982. doi:10.1016/s0344-0338(82)80057-5. ISSN 0344-0338. 
  7. ↑ "The treatment of hypopigmentation in children". Clinics in Dermatology 21 (4): 296–310. July 2003. doi:10.1016/s0738-081x(03)00045-2. PMID 14572700. 
  8. ↑ 8.0 8.1 "Cawson, R. A.: Aids to Oral Pathology and Diagnosis. VII, 126 pages. Churchill Livingstone, Edinburgh - London - Melbourne - New York, 1981. Price: £ 3.50.". Pathology - Research and Practice 175 (4): 412. December 1982. doi:10.1016/s0344-0338(82)80057-5. ISSN 0344-0338. 
  9. ↑ Langford, A.; Pohle, H.-D.; Gelderblom, H.; Zhang, X.; Reichart, P.A. (March 1989). "Oral hyperpigmentation in HIV-infected patients" (in English). Oral Surgery, Oral Medicine, Oral Pathology 67 (3): 301–307. doi:10.1016/0030-4220(89)90360-5. ISSN 0030-4220. 
  10. ↑ "Oral mucosal hyperpigmentation secondary to antimalarial drug therapy" (in English). Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics 90 (2): 189–94. August 2000. doi:10.1067/moe.2000.106340. PMID 10936838. 
  11. ↑ 11.0 11.1 11.2 Disorders of Oral Pigmentation: Background, Pathophysiology, Epidemiology. August 2018. https://emedicine.medscape.com/article/1078143-overview#a6. 
  12. ↑ "Pigmented lesions of the oral mucosa: A cross-sectional study of 458 histopathological specimens". Oral Diseases 24 (8): 1484–1491. November 2018. doi:10.1111/odi.12924. PMID 29945290. 
  13. ↑ 13.0 13.1 13.2 "Probiotic caries intervention…!!". Journal of the Indian Society of Pedodontics and Preventive Dentistry 32 (4): 271–2. 2014. doi:10.4103/0970-4388.140934. PMID 25231032. 
  14. ↑ 14.0 14.1 "Oral melanotic macule and primary oral malignant melanoma: epidemiology, location involved, and clinical implications". Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics 112 (1): e21-5. July 2011. doi:10.1016/j.tripleo.2011.02.040. PMID 21669356. 
  15. ↑ "Pigmented lesions of the oral mucosa: A cross-sectional study of 458 histopathological specimens". Oral Diseases 24 (8): 1484–1491. November 2018. doi:10.1111/odi.12924. PMID 29945290. 
  16. ↑ "Oral pigmentation: A review". Journal of Pharmacy & Bioallied Sciences 7 (Suppl 2): S403-8. August 2015. doi:10.4103/0975-7406.163471. PMID 26538887. 
  17. ↑ 17.0 17.1 17.2 17.3 17.4 17.5 "Diagnosis of oral pigmentations and malignant transformations". Singapore Dental Journal 35C: 39–46. December 2014. doi:10.1016/j.sdj.2014.03.001. PMID 25496584. 
  18. ↑ "Oral pigmented lesions: Clinicopathologic features and review of the literature". Medicina Oral, Patologia Oral Y Cirugia Bucal 17 (6): e919-24. November 2012. doi:10.4317/medoral.17679. PMID 22549672. 
  19. ↑ COLEMAN III, WILLIAM P. (December 2008). "Skin Cancer: Recognition and Management, 2nd Edition by ROBERT A. SCHWARTZ" (in en). Dermatologic Surgery 34 (12): 1702–1702. doi:10.1111/j.1524-4725.2008.34351.x. 
  20. ↑ Managing skin cancer. Stockfleth, Eggert., Rosen, Ted., Schumack, Stephen.. Berlin: Springer. 2010. ISBN 9783540793472. OCLC 663097085. https://www.worldcat.org/oclc/663097085. 
  21. ↑ COLEMAN III, WILLIAM P. (October 2008). "Skin Cancer: Recognition and Management, 2nd Edition by ROBERT A. SCHWARTZ" (in en). Dermatologic Surgery 34 (12): 1702–1702. doi:10.1111/j.1524-4725.2008.34351.x. 
  22. ↑ "Oral pigmented lesions: Clinicopathologic features and review of the literature". Medicina Oral, Patologia Oral Y Cirugia Bucal 17 (6): e919-24. November 2012. doi:10.4317/medoral.17679. PMID 22549672. 
  23. ↑ "Treatment and prognosis of malignant melanoma of the oral cavity: preoperative surgical procedure increases risk of distant metastasis". Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics 106 (1): 51–7. July 2008. doi:10.1016/j.tripleo.2008.03.003. PMID 18504155. 
  24. ↑ "Combination therapy improves immune response and prognosis in patients with advanced oral mucosal melanoma: A clinical treatment success". Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology 126 (4): 307–316. May 2018. doi:10.1016/j.oooo.2018.05.004. PMID 29958936. 
  25. ↑ Yamaguchi, Yoshiyuki, ed (2016). Immunotherapy of Cancer. doi:10.1007/978-4-431-55031-0. 
  26. ↑ "Oral malignant melanoma: systematic review of literature and report of two cases". Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology 116 (4): e247-54. October 2013. doi:10.1016/j.oooo.2011.11.034. PMID 22771409. 
  27. ↑ "Oral malignant melanoma: A silent killer?". Journal of Indian Society of Periodontology 15 (4): 425–8. October 2011. doi:10.4103/0972-124x.92587. PMID 22368374. 




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