This document discusses endogenous pigmentation of the oral mucosa. It begins by classifying pigmentation as focal, diffuse, or associated with systemic diseases. Common causes of pigmentation include melanin, hemoglobin, carotene, and hemosiderin. Specific conditions addressed include freckles, oral melanotic macules, oral melanoacanthoma, melanocytic nevi, and malignant melanoma. Diffuse pigmentation can be due to physiologic pigmentation, drugs, smoking, or post-inflammatory changes. Systemic diseases like Addison's disease and Peutz-Jeghers syndrome can also cause oral pigmentation. Histopathology and differential diagnoses are provided for many of the conditions.

1. ENDOGENOUS MELANOCYTIC PIGMENTATION
FARAKATH KHAN.M
Guided by
Dr. Tatu Joy

2. MELANIN
CLASSIFICATION
FOCAL
DIFFUSE
MELANOSIS ASSOCIATED WITH SYSTEMIC OR GENETIC DISEASE
IDIOPATHIC PIGMENTATION

3. Oral mucosa

4. ORAL MUCOSA

5. ORAL MUCOSA

6. The normal color represents the combined effect of a
number of factors:
• The concentration and state of dilation of capillaries in the
underlying connective tissue,
• The thickness of the epithelium,
• The degree of keratinization,
• And the amount of melanin pigment in the epithelium.

7. BILIRUBIN, Β-
CAROTENE
HEMOGLOBIN,
HEMOSIDERIN,
MELANIN
ENDOGENOUS PIGMENTATION

8. Hemoglobin, hemosiderin, melanin represent
the most common endogenous source of
mucosal color change.

9. LYSIS OF RBC
SUB MUCOSAL COLLECTION
OF
HEMOGLOBIN/HEMOSIDERIN
RED, BLUE OR BROWN
COLOUR
HEMOGLOBIN
 HAEMOGLOBIN &
IRON ASSOCIATED
PIGMENTATION
a. Ecchymosis
b. Purpura /
Petechiae
c. Hemochromatosis

10. melanin
TYROSINE - DOPA
MELANOCYTES
(BASAL LAYER)
MELANOSOMES
MELANIN
EUMELANIN
PHEOMELANIN
TYROSINASE
BROWN, BLUE, BLACK

11. CLEAR CELLS

12. MELANIN

13. MELANIN

14. MELANIN

15. MELANOCYTES

16. MELANIN

18. MELANIN INCONTINENCE
Melanin is seen free or within melanophages in sub
epithelial connective tissue.

20. CLASSIFICATION
FOCAL MELANOCYTIC PIGMENTATION
DIFFUSE PIGMENTATIONFRECKLE/EPHELIS
ORAL MELANOTIC MACULE
ORAL MELANOACANTHOMA
MELANOCYTIC NEVUS
MALIGNANT MELANOMA
PHYSIOLOGIC PIGMENTATION
DRUG-INDUCED MELANOSIS
POST INFLAMMATORY
PIGMENTATION
MELASMA(CHLOASMA)

21. MELANOSIS ASSOCIATED WITH SYSTEMIC OR GENETIC DISEASE
HYPOADRENOCORTICISM (ADDISONS DISEASE)
CUSHINGS SYNDROME
HYPERTHYROIDISM
PRIMARY BILIARY CIRRHOSIS
VITAMIN B 12 DEFICIENCY
PEUTZ JEGHERS SYNDROME
CAFÉ AU LAIT PIGMENTATION
HIV/AIDS ASSOCIATED MELANOSIS
IDOPATHIC PIGMENTATION
LAUGIER-HUNZIKER PIGMENTATION

22. FRECKLE

23. FRECKLE
Asymptomatic, small (1-3 mm), well circumscribed, tan or brown
color macule.
Sun exposed facial and perioral skin
Light skinned, red or light blond haired individuals
ETIOLOGY
Developmental in origin
Polymorphism in MCIR gene.
Ch 4q32-q34.
( Increase melanin production without concomitant increase in
no of melanocytes)

24. ORAL/LABIAL MELANOTIC MACULE

25. ORAL/LABIAL MELANOTIC MACULE
Benign pigmented lesion that has no dermal counterpart.
Most common oral lesion - melanocytic origin
Etiology – trauma?
Females - lower lip – gingiva.
<1 cm, well circumscribed, oval or irregular in outline and
uniformly pigmented.
( Increase melanin production without concomitant increase in
no of melanocytes)
A macular lesion that, histologically, exhibits increased no of
melanocytes – melanocytic hyperplasia.

26. MELANOTIC MACULE

27. MELANOTIC MACULE

28. DIFFERENTIAL
DIAGNOSIS
Melanocytic nevus
Malignant melanoma
Amalgam tattoo
Focal ecchymosis
hematoma
Brown/blue, macular/swollen…..2 weeks

29. ORAL MELANOACANTHOMA
Benign lesion unique to mucosal tissues
ETIOLOGY
Rapid Onset, Acute Trauma, Chronic Irritation
CLINICAL FEATURES
Rapidly enlarging, ill defined, darkly pigmented macular or
plaque like lesion, and most develop in black females.
Cutaneous melanoacanthoma represents a pigmented variant of
seborrheic keratosis.
(Proliferation of benign, dendritic melanocytes throughout the
full thickness of an acanthotic and spongiotic epithelial layer)

30. MELANOACANTHOMA

31. DIFFERENTIAL DIAGNOSIS

32. ACQUIRED MELANOCYTIC NEVUS
(NEVOCELLULAR NEVUS, MOLE)
Localized benign proliferation of cells from neural crest called nevus cells.
Intraoral lesions occur but not common.
CLINICAL FEATURES
Develop in skin during child hood
Sharply demarcated brown or black macule <6mm, adult – nevus cell
proliferate – slightly elevated soft papule with smooth surface.(Compound
nevus) more time – nevus loses pigmentation, surface papillomatous,
hairs seen growing from centre. (Intra dermal nevus) <6mm
Many acquired melanocytic nevi will involute and disappear.

33. INTRAORAL NEVI
Evolution and appearance similar to skin nevi
Mature lesion does not show papillary change
2/3 rd lesions found in female
Average age of diagnosis 35 yrs
CLINICAL FEATURES
Oral melanocytic nevi - small <1 cm, solitary, brown or blue, well
circumscribed nodule or macule
Hard palate, buccal mucosa, labial mucosa, gingiva.
Oral nevi common in black..

34. Pathogenesis
Nevus cells – neural crest or immature melanocytes.
Nevic melanocytes – round, ovoid or sprindle shaped.
Migrate into and within submucosal tissues.
Etiology
Genetic, sun exposure
Association with inherited diseases
Familial atypical multiple mole and melanoma syndrome
Carney complex
Turners syndrome and noonans syndrome
90% of dermal melanocytes – mutations in BRAF, HRAS, NRAS oncogenes

35. HISTOPATHOLOGY
Benign encapsulated proliferation of small ovoid cells (nevus
cells) cells have small uniform nuclei, moderate eosinophilic
cytoplasm with indistinct cell boundries.
Nevus cells lack dentritic process that melanocytes possess.

36. Relationship of nevus cells to epithelium and
connective tissue.
(most intraoral melanocytic nevi are classified
microscopically as intramucosal nevi)
JUNCTIONAL NEVUS
COMPOUND NEVUS
INTRADERMAL/INTRAMUCOSAL NEVUS

37. NEVUS

38. JUNCTIONAL NEVUS
INTRADERMAL NEVUS

39. NEVUS

40. INTRAMUCOSAL NEVI

41. Treatment /prognosis
• Risk of transformation to melanoma is approx
1 in 1 million.

42. VARIANTS OF MELANOCYTIC NEVUS
Congenital melanocytic nevus
Halo nevus
Spitz nevus
Blue nevus

43. CONGENITAL MELANOCYTIC NEVUS

44. CONGENITAL MELANOCYTIC NEVUS

45. HALO NEVUS

46. BLUE NEVUS
TYNDALL EFFECT

47. NEVUS OF OTA

48. MALIGNANT MELANOMA

49. • Least common, most deadly of all primary skin cancers.
RISK FACTORS
• Multiple episode of acute sun exposures,
immunosuppression, multiple cutaneous nevi, family history
of melanoma.
• Mutations in tumour suppressor genes- cdkna2/p16ink4a ,cdk4
• Mutation in BRAF, HRAS, and NRAS proto oncogenes (similar
to melanocytic nevi)

50. CLINICAL FEATURES
Common in white who live in sunbelt region of world.
Mortality rates high in blacks and hispanics.
Increased incidence in patients, especially males over 45.
On facial skin malar region affected (sun exposure)

51. MELANOMA OR MELANOCYTIC NEVUS ?

52. FOUR CLINIC PATHOLOGIC SUBTYPES

53. • Radial growth phase
• Vertical growth phase
Nodular melanoma –radial growth phase is very short or nonexistent and
vertical growth phase predominates

54. CLARKS LEVEL OF INVASION – CUTANEOUS MELANOMA

55. HISTOPATHOLOGY

56. KAPOSIS SARCOMA
DIFFERENTIAL DIAGNOSIS

57. MULTIFOCAL/DIFFUSE PIGMENTATION
PHYSIOLOGIC PIGMENTATION
DRUG-INDUCED MELANOSIS
POST INFLAMMATORY PIGMENTATION
MELASMA(CHLOASMA)

58. PHYSIOLOGIC PIGMENTATION
Most common
Dark complexioned indivudals, including blacks, asians, south
americans.
Microscopically-increased amount of melanin pigment within
the basal layer.
Differential diagnosis - idiopathic, drug induced, smoking
induced melanosis.

59. PHYSIOLOGIC PIGMENTATION

60. DRUG INDUCED MELANOSIS
ANTIMALARIALS
CHLOROQUINE
QUINE
PHENOTHIAZINES
CHLORPROMAZINE
ORALCONCRACEPTIVE
CYTOTOXIC
CYCLOPHOSPHAMIDE
BLEOMYCIN
GOLD
KETOCONAZOLE
METHYLDOPA
MINOCYCLINE
TACROLIMUS

61. MINOCYCLINE INDUCED PIGMENTATION CYCLOPHOSPHAMIDE
CLOFAZIMINEORAL CONTRACEPTIVES

62. Smoker’s melanosis
• Patchy brown macular pigmentations are sometimes present
in the buccal mucosa among heavy cigarette smokers.
• These macules are 0.5 to 1.0 cm spots that are multiple and
bilateral. Microscopically they are forms of basilar melanosis
without melanocyte proliferation.
• The mechanism for this association is unknown.

63. SMOKERS MELANOSIS

64. • The pathogenesis is believed to be related to a component in
tobacco smoke that stimulates melanocytes.
• Smoking up to nine cigarettes per day has been sufficient to
produce gingival melanin deposition

65. POST INFLAMMATORY PIGMENTATION

66. LICHENOID REACTION

67. OSMF

68. MELASMA

69. • These basilar melanosis of the skin may also involve the lips,
indeed, perioral and periorbital diffuse brown macular
pigmentation
• Their genesis is probably related to hormonal changes that
affect melanosome stimulation
• Following delivery and upon cessation of birth control
administration, the Cutaneous lesions slowly in volute.

70. MELANOSIS ASSOCIATED WITH SYSTEMIC OR GENETIC DISEASE
HYPOADRENOCORTICISM (ADDISONS DISEASE)
CUSHINGS SYNDROME
HYPERTHYROIDISM
PRIMARY BILIARY CIRRHOSIS
VITAMIN B 12 DEFICIENCY
PEUTZ JEGHERS SYNDROME
CAFÉ AU LAIT PIGMENTATION
HIV/AIDS ASSOCIATED MELANOSIS

71. HYPOADRENOCORTICISM (ADRENAL INSUFFICIENCY)
ENDOGENOUS CORTICOSTEROID
COMPENSATORY ACTIVATION OF ACTH
ADRENAL CORTEX
SERUM MELANOCYTE
STIMULATING HARMONE

72. HYPOADRENOCORTICISM

73. • Generalized bronzing of skin and diffuse but patchy melanosis
of oral mucosa.
• Increased melanin in basal layer with melanin incontinence.
• Hyperpigmentation, hyponatremia, hyperkalemia.

74. Café au lait pigmentation
Bronze and tan diffuse and multifocal macular pigmentations
appear on the skin in neurofibromatosis, an autosomal
dominantly inherited disease characterized by multiple skin
nodules or even pendulous tumors.
These pale brown macules may be several centimeters wide.
They can occur anywhere, including the face and neck, and
occasionally, oral mucosa pigmentations arise. Owing to their
pale brown color, they are referred to as café au lait spots.

75. • Café-au-lait macules may be associated with albright’s syndrome
(polyostotic fibrous dysplasia, endocrine dysfunction, precocious puberty,
café-au-lait macules), noonan syndrome, watson syndrome, bloom
syndrome, ring chromosome syndromes, and others. The café-au-lait
macules of albright’s syndrome tend to be large and unilateral and have
irregular borders.
• Microscopically, café-au-lait macules are not particularly remarkable. They
generally show excess amounts of melanin in basal keratinocytes and
subjacent macrophages. Melanocytes are normal in appearance and may
be slightly increased in number.

76. • Albright syndrome – The borders of pigmented macules are
irregularly outlined.
• Neurofibromatosis – Borders smooth.

77. Café au lait pigmentation

78. • Pathogenesis
• Unclear.
• Gene mutation that give rise to various
genetic disease stimulate melanin production.

79. PEUTZ JEGHERS SYNDROME
Peutz-Jeghers Syndrome
Bluish black macules
Skin pigment but not oral tends fade with age
Intestinal
polyp

80. HIV/AIDS ASSOCIATED MELANOSIS
Diffuse mucocutaneous pigmentation.
Antifungal, antiretroviral.
IMMUNE DYSREGULATION associated with AIDS leads to
increased secretion of MSH.
Basilar melanosis, melanin incontinence.

81. “THE EYE DOSENT SEE WHAT THE MIND DOSENT KNOW”

82. THANK YOU

83. REFERENCE:
Greenberg, Glick, Ship. Burket`s Oral Medicine.
Neville, Allen, Bouquot. Oral And Maxillofacial
Pathology.
Jean M. Bruch. Clinical Oral Medicine And Pathology.
Lewis R. Eversole. Clinical Outline Of Oral Pathology..
Silverman, Eversole. Essentials Of Oral medicine.