Pigmented Lesions of Oral Mucosa PDF

Pigmented Lesions of Oral Mucosa “Dr.Gillan El-Kimary” Mucosal Pigmentation Endogenous Hemoglobin, hemosiderin, and melanin represent the most common endogenous sources Exogenous Traumatically deposited Ingested / inhaled/ hematogenously spread Chromogenic bac...

Pigmented Lesions of Oral Mucosa “Dr.Gillan El-Kimary” Mucosal Pigmentation Endogenous Hemoglobin, hemosiderin, and melanin represent the most common endogenous sources Exogenous Traumatically deposited Ingested / inhaled/ hematogenously spread Chromogenic bacteria (tongue) Certain food, drinks (reversible) Classification of Endogenous Pigmentation - Focal - Multifocal /diffuse - Idiopathic - Associated with systemic/genetic diseases Classification of Exogenous Pigmentation Amalgam Tattoos Graphite Tattoos Heavy Metal Pigmentation Drug‐Induced Pigmentation Hairy Tongue Endogenous Pigmentation Melanin Melanin is the pigment derivative of tyrosine and is synthesized by melanocytes, which typically reside in the basal cell layer of the epithelium 1  Functions - Their presence in the skin is thought to protect against the damaging effects of actinic irradiation. - They also act as scavengers, protecting against cytotoxic intermediates. Melanin is synthesized within specialized structures known as melanosomes. Focal Melanotic Pigmentation Focal Melanotic Pigmentation Freckles/Ephelis Oral/Labial Melanotic Macule Oral Melanoacanthoma Melanocytic Nevus Malignant Melanoma 1- Freckles/Ephelis Asymptomatic, well‐circumscribed (1-2 mm), tan‐ or brown‐colored macules often seen on sun‐exposed regions of the skin. Blond individuals May be developmental in origin (genetic pleomorphism) more abundant in number and darker in intensity during childhood and adolescence. Seasonal : become darker during periods of prolonged sun exposure (e.g., spring, summer) and fade during the autumn and winter months. Etiology : the increase in pigmentation is solely related to an increase in melanin production without a concomitant increase in the number of melanocytes Rx : no therapeutic intervention is required 2- Oral/Labial Melanotic Macule unique, benign, pigmented lesion that has no known dermal counterpart the most common oral lesion of melanocytic origin (85% of all solitary melanocytic lesions) Cause: may be trauma / sun exposure has no role Females / lower lip & gingiva / adulthood When occurs on lower lip is named ”labial melanotic macule” 2  Doesn’t get darker with sun exposure Congenital melanotic macules have been described, occurring primarily in the dorsum of tongue It is distinguished by its appearance at birth 3- Oral Melanotic Macule Small (< 1mm), well circumscribed oval or irregular uniformly pigmented macule uniformly pigmented Grows till reaches a certain size then stops Histology : Abundance of melanin at basal cell layer at the tips of rete pegs without increase in the number of melanocytes ( no hyperplasia). Melanin spill outs….melanin incontinence into the submucosa. DDx melanocytic nevus, malignant melanoma, amalgam tattoo, focal ecchymosis (ruled out after 2 weeks) Rx Biopsy to confirm Dx and rule out malignancy (since oral mucosal malignant melanomas have no defining clinical characteristics) 4- Oral melanoacanthoma Oral melanoacanthoma is an innocuous melanocytic lesion that may spontaneously resolve, with or without surgical intervention Reactive not neoplastic rapid onset, with acute trauma or a history of chronic irritation preceding the development of the lesion rapidly enlarging, ill‐defined, darkly pigmented flat or slightly elevated lesion black females between the third and fourth decades commonly: solitary lesion generally asymptomatic 50% arise on the buccal mucosa Varying size/distribution/ Irregular borders 3  Uneven pigmentation Rx… Biopsy to confirm Dx (The biopsy procedure itself may lead to spontaneous regression of the lesion ) Eliminate underlying cause/ source of trauma Histo : Proliferation of benign dendritic melanocytes throughout the full thickness of epithelium DDx Pigmented nevus, melanotic macule, Malignant melanoma Rx A biopsy is warranted to obtain a definitive diagnosis. No further treatment is indicated 5- Melanocytic Nevus nevi arise as a consequence of melanocytic growth and proliferation Etiology: genetic and environmental factors play role in nevogenesis (eg. Sun exposure in cutaneous nevi) Acquired or congenital True benign neoplasms or developmental in nature (debatable due to proven role of oncogenes in cutaneous nevi) There are several examples of increased nevus susceptibility in various inherited diseases, thus confirming the role of genetics. Turner’s syndrome Noonan’s syndrome (autosomal dominant) Pathogenesis : There is still debate as to whether “nevus cells” are Distinct cell type derived from the neural crest OR if they are simply a unique or immature form of melanocyte. Additional differences include the tendency for nevus cells to closely approximate one another, if not aggregate in clusters, and their ability to migrate into and/or within the submucosal tissues. 4  Junctional nevi Nevus cells nests maintain their localization to basal cell layer Macular / Tan to brown Compound nevi Clustered melanocytes proliferate into CT but some nests maintain their position at the basement membrane Dome shaped/ brown Intramucosal Nevi Nevus cells loose their association with basement membrane and become confined to CT Nodule/ tan to brown or same mucosal color Blue nevi Spindle shaped cells in CT of submucosa Histo: proliferation of spindle shaped cells deep into CT overlied by blood vessels Bluish brown Cutaneous nevi The total number of nevi occurring in males tends to be higher than that seen in females. In contrast, oral melanocytic nevi are rare solitary lesions that are more common in females Oral Melanocytic Nevi Oral melanocytic nevi have no distinguishing clinical characteristics. Lesions are usually asymptomatic and often present as a small (6mm, E=surface elevation Oral Melanoma. (less than 1% of all melanomas) Gender: Male predilection Etiollogy.. unknow Age: >50 yrs Site: palate & maxillary gingiva 6  High prevalence among black-skinned and Japanese people No distinctive clinical appearance Macular/ plaque-like/mass The development of nodularity in a previously macular lesion is an ominous sign Well-circumscribed / irregular Focal or diffuse areas of brown /blue/ black pigmentation May exhibit “amelanosis” Ulceration, pain, tooth mobility, root resorption, bone loss, paresthesia and anesthesia Or totally asymptomatic DDx melanocytic nevus, oral melanotic macule, amalgam tattoo Kaposi sarcoma biopsy of any persistent solitary pigmented lesion is always warranted Prognosis Microscopic findings such as surface ulceration, vascular or lymphatic invasion, neurotropism, high mitotic index, and absence of lymphocytes infiltrating the tumor are all associated with a poor prognosis Clinical parameters, including tumor site, age of the patient (>60 years), sex (male), and regional or distant metastasis Involvement of the palate is predictive of the worst prognosis compared to other intraoral sites Regional lymphatic metastases are frequently identified and contribute to the poor survival rate Histo: Pleomorphism, nuclear atypia, hyperchromatism, mitotic figures within basal cell region of epithelium Radial pattern of growth: Superficial spread (macular lesions) Vertical pattern of growth: Invasion of the CT, seen in nodular lesions Once vertical growth into the connective tissue is established, the lesions become clinically tumefactive 7 Challenges in Dx Determining whether the lesion is a primary neoplasm or a metastasis from a distant site A history of a previous melanoma, sparing of the palate and gingiva, amelanosis, and microscopic features such as a lack of junctional activity are findings that may be more suggestive of a metastatic tumor Rx Primary oral melanomas, ablative surgery with wide margins In case of metastasis…. Adjuvant radiation or chemo therapy may also be necessary CT and MRI are necessary to explore metastases to the regional lymph nodes. Multifocal/Diffuse Melanotic Pigmentation Physiologic Pigmentation Drug‐Induced Melanosis Smoker’s Melanosis Postinflammatory (Inflammatory) Hyperpigmentation Melasma (Chloasma) Physiologic Pigmentation It is the most common multifocal or diffuse oral mucosal pigmentation Common in dark skinned The pigment is restricted to the gingiva; however, melanosis of other mucosal surfaces may be evident The pigment is typically first observed during childhood and does not develop de novo in the adult. DDx drug‐induced smoking‐induced melanosis, endocrinopathy, syndromic condition 8 Microscopically, increased amounts of melanin within the basal cell layer. Rx Gingivectomy, laser therapy, and cryosurgery can all effectively remove oral pigmentation ( if causing esthetic problem, otherwise no Rx is required) (high risk of recurrence ) Drug‐Induced Melanosis Etiology unknown One theory: drug or drug metabolites stimulate melanogenesis Ex of drugs causing melanosis Antimalarials (eg.hydroxycholoroquine) Oral contraceptives Cytotoxic medication Gold Minocycline (Rx of acne) Tacrolimus Tyrosine kinase inhibitors used for the treatment of chronic myeloid leukemia Clinical features Intraorally, the pigment can be diffuse yet localized to one mucosal surface, often the hard palate, or it can be multifocal and involve multiple surfaces The lesions are flat and without any evidence of nodularity or swelling. Sun exposure may exacerbate cutaneous drug‐induced pigmentation Pathology: Microscopically, there is evidence of basilar hyperpigmentation and melanin incontinence without a concomitant increase in the number of melanocytes DDx: Other causes of multifocal pig. Laboratory tests may be necessary to rule out an underlying endocrinopathy Management: If the onset of the melanosis can be chronologically and accurately associated with the initial use of a specific medication (frequently within several weeks or months before development of the pigmentation), Then …… No further intervention is warranted fades within a few months after the drug is discontinued 9  Smoker’s Melanosis Diffuse melanosis of the anterior vestibular maxillary and mandibular gingivae, buccal mucosa, lateral tongue, palate, and floor of the mouth is occasionally seen among cigarette smokers Etiology : melanin synthesis may be stimulated by tobacco smoke products,OR heat of the smoke may stimulate oral pigmentation among dark‐skinned individuals who normally exhibit physiologic pigmentation, smoking can stimulate a further increase in oral pigmentation Clinically… present as brown, flat, and irregular, with some even geographic or map‐like in configuration Increases prominently during first year of smoking A reduction in smoking may lead to fading of the pigmentation Smokeless tobacco (snuff) does not appear to be associated with an increase in oral melanosis. Alcohol has also been associated with increased oral pigmentation of the posterior regions of the mouth, including the soft palate (higher risk of cancers of the upper aerodigestive tract) Histologically basilar melanosis and melanin incontinence are observed Postinflammatory/ Inflammatory Hyperpigmentation Focal or diffuse pigmentation in areas that were subjected to previous injury or inflammation more commonly in dark‐ complexioned individuals Most important example is “lichen planus pigmentosus” Upon resolution of lichenoid lesion, it may subside Spontaneous postsurgical healing pigmentation of palatal donor sites for free gingival grafts has been reported 10  Melasma (Chloasma) “mask of pregnancy” Melasma is a relatively common, acquired symmetric melanosis that typically develops on sun‐exposed areas of the skin and frequently on the face Most cases arise in darker‐skinned individuals (females) During pregnancy / intake of contraceptive pills (combination of both estrogen and progesterone) Evolves rapidly over a period of a few weeks Thyroid abnormalities, including hypothyroidism, also may play a role in the pathogenesis of pregnancy‐ and non‐pregnancy‐associated melasma Histo: basilar melanosis with no increase in the number of melanocytes Melasma may spontaneously resolve after parturition, cessation of the exogenous hormones Melanosis Associated with Systemic or Genetic Disease Hypoadrenocorticism (Adrenal Insufficiency, Addison’s Disease) Cushing’s Syndrome/Cushing’s Disease Hyperthyroidism (Graves’ Disease) Primary Biliary Cirrhosis Vitamin B12 (Cobalamin) Deficiency Peutz–Jeghers Syndrome Café au Lait Pigmentation HIV/AIDS‐Associated Melanosis Addison’s Disease Etiology (adrenal destruction or an impairment of endogenous steroid production) Autoimmune infectious agents, neoplasia, trauma, certain medications, iatrogenic decrease in endogenous corticosteroid levels Rx: exogenous steroid replacement therapy 11 Mechanism decrease in endogenous corticosteroid levels ,,,, increase in ACTH & MSH…. Stimulatory effects on melanocytes Clinical features Weakness, fatigue, and depression first sign of disease may be mucocutaneous hyperpigmentation Generalized bronzing of the skin diffuse/patchy melanosis of the oral mucosa Histo: melanin incontinence DDx : Include other causes of diffuse pigmentation, including physiologic and drug‐induced pigmentation Laboratory tests, Low serum cortisol and aldosterone Hyponatremia Hyperkalemia Peutz - Jeghers Syndrome PJS is an autosomal dominant disease that is associated with mutations in the STK11/LKB1 tumor suppressor gene Clinical manifestations intestinal polyposis (bleeding , abdominal pain) , cancer susceptibility, and multiple, small, pigmented macules of the lips, perioral skin (freckling), hands, and feet the intensity of the macular pigment is not influenced by sun exposure Intraorally: anterior tongue and buccal and labial mucosae. The lip and perioral pigmentation is highly distinctive, although not pathognomonic for this disease Histologically increased basilar melanin without an increase in the number of melanocytes DDx: Cowden syndrome ( triad of gastrointestinal disorder, cancer susceptibility, and mucocutaneous pigmented macules) 12  Café au Lait Pigmentation DDx 1- Neurofibromatosis type I (genetic autosomal dominant) 2- McCune–Albright syndrome (fibrous dysplasia) 3- Noonan’s syndrome Idiopathic Melanosis Laugier–Hunziker Pigmentation ( “Acquired dermal melanocytosis”) Acquired, idiopathic, (may be genetic) macular hyperpigmentation of the oral mucosal tissues, specifically involving the lips and buccal mucosae Increased melanin pigmentation in the basal cell layer without an increase in the number of melanocytes Clinical presentation 60% of affected patients may also have nail involvement, usually in the form of longitudinal melanotic streaks and without any evidence of dystrophic change light‐skinned individuals Multiple discrete, brown or dark brown oral macules Dx: by exclusion ( PJS) Hemoglobin and Iron‐associated Pigmentation Ecchymosis. Extravascular Purpura/Petechiae Hemochromatosis Trauma….. Erythrocyte extravasation into submucosal tissues (Bright red macule) ,,,,,, Degradation of hemoglobin to hemosiderin (bluish/brown discoloration) 13 Ecchymosis Extravasation of blood at dermal and mucosal layer superficial Flat More common on face and lips less common intraorally ( may be caused by blunt trauma eg. Oral intubation / leukemia) Size: Larger than 1 cm Doesn’t blanch on diascopy (extravascular) It resolves within 2 weeks (otherwise, raises suspicion of bleeding disorders Eg. Anticoagulant therapy, leukemia) DDx : focal pigmented lesions Lab investigations (normal bleeding profile) Bleeding time. ( N : 1- 9 mins) PT (N: 12-13 secs ) PTT (N: 28-45 secs) INR (N: 1) Hematoma Extravasation of blood in tissues, organs or spaces deep elevated Purpura/ Petechiae Collection of extravasated RBC’s due to capillary hemorrhages diff based mainly on the size (petechiae pinpoint (1-2mm) Purpura: larger(2-4 mm) Etiology: mainly trauma Viral infections (itching of the throat so patient, performs suction between tongue and soft palate traumatizing this area) Systemic causes( platelet disorders) Most common site intraorally: soft palate Initially red then turn brown in few days Resolves after 2 weeks 14  Exogenous Pigmentation Amalgam Tattoos Graphite Tattoos Heavy Metal Pigmentation Drug‐Induced Pigmentation Hairy Tongue Amalgam Tattoos The most common pigmented lesion in the oral mucosa is the amalgam tattoo. Etiology: iatrogenic in origin; due to deposition of amalgam restorative material into submucosal tissue Clinical features Small, asymptomatic, bluish gray or black macular lesion Site: gingiva , alveolar mucosa most common sites Key feature: found close to teeth with large amalgam restorations or crowned teeth If large enough can be apparent on radiographs DDx: melanotic macule, nevus, melanoma. Rx: In some patients, surgical removal may be warranted due to esthetic considerations ( laser ) However, since amalgam tattoos are innocuous, their removal is not always necessary, particularly when they can be documented radiographically. In the absence of radiographic evidence of amalgam, or in the event that the lesion appears suddenly or is not in proximity to a restored tooth, a biopsy is warranted. 15  Graphite Tattoos Due to traumatic implantation of graphite particles from a pencil Similar appearance of amalgam tattoo Most common site: palate and gingiva Since trauma usually in childhood, no Hx can be retrieved thus biopsy is usually required Drug‐Induced Pigmentation Minocycline (a tetracycline derivative frequently used in the treatment of acne) … oral/ skin/ nails pig. subsides within months after discontinuation of the medication Depigmentation Vitiligo Acquired, autoimmune disease that is associated with hypomelanosis. Etiology (unknown) autoimmunity, cytotoxicity, genetics, oxidative stress where (end result is the destruction of )melanocytes rarely affects the intraoral mucosal tissues Thank You 16