Pigmented Oral Mucosal Lesions - Finals PDF

Pigmented oral mucosal lesions - melanin and other pigments - discolorations due to drug ingestion, metal implantation, heavy-metal intoxication, extravascular blood (trauma, blood dyscrasias) - ranges in trivial to serious -> careful evaluation and biopsy Melanocytic Lesions - br...

Pigmented oral mucosal lesions - melanin and other pigments - discolorations due to drug ingestion, metal implantation, heavy-metal intoxication, extravascular blood (trauma, blood dyscrasias) - ranges in trivial to serious -> careful evaluation and biopsy Melanocytic Lesions - brown to black to blue, depends on melanin produced and depth of pigment - Darkening preexisting lesion -> pigment cells produces more melanin or invading deeper tissue Melanocytes - melanin-producing cells from neural crest -> migrate to epithelial surfaces - found in oral mucosa - unnoticed due to low pigment production - produces melanosomes - granules of pigment - Light, hormones, genetic constitution = amount of pigment produced - responsible for melanoma (relative of melanocytes) Nevus cell - responsible for melanocytic nevi or "moles." - same enzyme, tyrosinase, responsible for converting tyrosine to melanin in the melanosome organelle Physiologic (Ethnic) Pigmentation - symmetric, persistent, doesn’t alter normal tissue architecture (gingival stippling) - seen in any age and not gender-specific - degree of intraoral pigmentation is not the degree of cutaneous coloration - found in any location, gingiva is common - primary cause: melanin production (basal keratinocytes & subjacent connective tissue macrophages) Postinflammatory pigmentation - seen after mucosal inflammation (mucosal injury or lichen planus) -> hyperpigmentation around the lesion Differential Diagnosis - smoking-associated melanosis - Peutz-Jeghers syndrome - Addison's disease - physiologic pigmentation w/ melanoma = diagnostic - atypical clinical features = biopsy Smoking-Associated Melanosis (Smoker’s Melanosis) - abnormal melanin pigmentation - caused by tobacco, female sex hormones, stimulating melanocytes - women are more affected than men - Smoking 9 cigars/day -> gingival melanin deposition Clinical Features - anterior labial gingiva -> most affected region - brownish color -> subtle to obvious - Palate & buccal mucosal pigmentation -> pipe smoking - smokeless tobacco (India) -> oral melanosis, esp to alcoholics Histopathology - increased melanin production - adjacent basal keratinocyte pigmentation - microscopic appearance similar to physiologic pigmentation and melanotic macules Differential Diagnosis - physiologic pigmentation - diffuse melanoac-anthoma - Peutz-Jeghers syndrome - Addison's disease - other systemic drugs, and melanoma Treatment - Quitting -> improvement over months to years - Smoker's melanosis -> mask other lesions/cosmetically objectionable - Biopay -> for surface irregularity or focally intense pigment deposits are noted Oral Melanotic Macule Clinical Features - focal pigmented lesions - represent intraoral freckles, postinflammatory pigmentation, macules with Peutz-Jeghers syndrome, Bandler syndrome, or Addison's disease - asymptomatic & no malignant potential - melanotic macules seen in oral and perioral distribution Peutz-Jeghers syndrome - Mutation in STK11/LKB1 gene - inherited in an autosomal-dominant manner - risk of developing several cancers - small intestine - Breast - Colon - Pancreatic - Stomach - ovarian cancer Addison's disease (Primary Adrenocortical Insufficiency) - adrenal gland infection, autoimmune disease, or idiopathic causes - Overproduction of pituitary adrenocorticotropic hormone (ACTH) - G2 melanocyte-stimulating hormone (MSH) -> stimulation of melanocytes -> diffuse pigmentation of the skin - Oral flares and larger melanotic macules - generalized pigmentation - Weakness - weight loss - Nausea - vomiting, and hypotension Pigmented macules Carney's complex -> endocrinopathies Laugier-Hunziker syndrome -> lip, oral, or finger maculars & subungual melanocytic streaks Bandler syndrome -> melanotic macules of oral mucosa, perioral region w/ hemangiomas of small intestine Lentigo - melanotic macule for sun-damaged skin - seen in older patients - brown patches larger & darker than ephelides (freckles) Histopathology - accumulation in basal keratinocytes - Normal melanocyte numbers -> observed in melanotic macules - melano phagocytosis (connective tissue macrophages) -> observed in lamina propria Differential Diagnosis - Early superficial melanomas - mistaken for blue nevi or amalgam tattoos - If numerous -> Peutz-Jeghers syndrome, Addison's disease, Carney's complex, Bandler syndrome, and Laugier-Hunziker syndrome. Treatment - biopsy -> definitive diagnosis - no treatment Café-au-Lait Macules - melanin-pigmented patches of skin - irregular margins - uniform brown coloration - normal children or be part of a syndrome - Six+ large café-au-lait -> neurofibromatosis (NF) - autosomal-dominant disorder - Associated with Albright's syndrome, Noonan syndrome, Watson syndrome, Bloom syndrome, ring chromosome syndromes, and other sporadic disorders - Not remarkable morphologically but shows excess melanin in basal keratinocytes and subjacent macrophages. neurofibromatosis 1 (NF1) - common disorder, 1 in 3000 - 50% of cases inherited, remainder has new mutations - multiple neurofibromas in skin, oral mucosa, nerves, CNS, and jaw - Axillary freckling/six+ of NF1 -> pathognomonic for the disorder - genetic abnormality -> tumor suppressor gene on chromosome 17q11.2 - Encodes neurofibromin protein that downregulates p21ras protein neurofibromatosis 2 (NF2) - bilateral acoustic neuromas, plexiform neurofibromas, and Lisch nodules (iris nodules). Pigmented Neuroectodermal Tumor of Infancy Etiology - rare, fast-growing biphasic tumor from neural crest - composed of melanin-containing and neuroblast-like cells - AKA melanotic progonoma or retinal anlage tumor -> related to melanin Clinical Features - 90% of cases of adenocarcinoma in children (-1 YO) - maxilla, mandible, epididymis, brain, and skull - presents as a nonulcerated, darkly pigmented mass -> melanin production by tumor cells Histopathology - alveolar pattern - tumor cells nesting in well-defined connective tissue margin - Centrally dense and compact cells resemble neuroendocrine cells - peripheral cells -> larger, contain melanin -> well-defined connective tissue margin Differential Diagnosis - early childhood malignancies -> neuroblastoma, rhabdomyosarcoma, and "histio-cytic" tumors - odontogenic cysts and tumors -> not considered Treatment and Prognosis - wide local surgical excision - few cases has local recurrence (10-20%) -> close clinical follow-up - rare malignant variant -> metastasis following local excision Melanocytic Nevus Nevus - congenital lesion of cell types or tissue type - Referred as pigmented lesion w/ nevus or melanocytic cells Melanocytic nevi  - round or polygonal collections of nevus cells - seen in nested pattern - found in epithelium or supporting connective tissue - originates from cells migrating from the neural crest to the epithelium and dermis or from altered resident melanocytes Clinical Features - common skin papular lesions - appear after birth & throughout childhood Intraoral melanocytic nevi most common affected site - buccal mucosa and labial -> Less common sites Histopathology Junctional nevi - Found in epithelium-connective tissue junction intradermal/intramucosal nevus - Found in connective tissue - Most common compound nevus - combination of these zones blue nevus - Spindle-shaped, deep in connective tissue - 2nd most common Malignant transformation -> highly improbable - Due to absence of malignant features - rare presence of preexisting nevi in oral melanomas - lack of cases in malignant counterpart of the common oral blue nevus undiagnosed pigmented lesions -> biopsy, potential to mimic melanoma Differential Diagnosis - melanotic macule, amalgam tattoo, and melanom Palatal lesions - challenging to diagnose -> pigmented nevi and mucosal melanoma Vascular lesions -> Diascopy to rule out - hematoma, Kaposi's sarcoma, varix, and hemoma may also be considered. Treatment - excised due to mimicry - excisional biopsy -> less than 1 cm Melanoacanthoma - rare, benign pigmented lesion - dendritic melanocyte proliferation in acanthotic epithelium with hyperkeratotic surface features. - hyperpigmented lesions -> solitary, but multifocal ones have been described. - usually focal - found in buccal mucosa, sometimes palate or gingiva - Trauma -> etiologic role - Lesions -> disappear or after incisional biopsy - No Malignant transformation Melanoma Cutaneous Melanoma in skin - increasing in frequency, 2% of all cancers - age at diagnosis -> 60 years, with cutaneous melanoma being more common in locations closer to the Equator and whites. - Predisposing factors: - extensive sun exposure - fair natural pigmentation - tanning bed abuse - precursor lesions radial or horizontal growth phase - malignant melanocytes spread laterally along the epidermal-dermal interface vertical growth phase - penetration of dermis and subcutaneous tissues by malignant melanocytes Treatment - Surgery -> primary treatment - chemotherapy, immunotherapy, or radiation -> advanced disease patient - 5-year survival rate -> localized disease over 98%, regional disease is 60%, advanced disease is 15% - Newer therapies -> targeted biological immunotherapy with the monoclonal antibody ipilimumab - Blocks suppressive antigen (CTLA-4) on cytotoxic T lymphocytes, for T cells to attack and destroy tumor cells Oral Melanoma - Rare, no racial predilection - Japan -> oral melanoma is high than cutaneous melanoma (low in this population) - Preexisting melanosis -> appear before some melanomas -> early radial growth phase - 40% of mucosal melanomas of head and neck, found in adults, most cases are under 40 YO - strong predilection for palate and gingiva, 70% of cases are found - average time to diagnosis is 9 months -> third of oral melanomas are amelanotic invasive melanoma - invasive or vertical growth pattern, no significant lateral spread in situ melanoma - junctional growth phase, last months to years before entering a vertical growth phase Atypical melanocytic proliferation - oral pigmentations, difficult to categorize - changes are not severe enough to justify diagnosis Etiology - abnormal expression of adhesion molecules -> invasion - Overexpression of cell cycle proteins p21 and cyclin D1 -> melanoma development familial melanoma syndromes - germline mutations, defined in highly penetrant gene products: - p16, p14ARF, and cyclin-dependent kinase 4 melanocortin 1 receptor gene (MC1R) - increase melanoma risk - genetic modifier in co segregating with mutant p16 gene wild-type BRAF or N-RAS melanomas - increases in copy numbers of genes for CDK4 and cyclin D1 - downstream components of the RAS-BRAF pathway Comparative genomic hybridization analysis - mucosal melanomas are genetically distinct from melanomas occurring on non-sun-exposed surfaces, such as acral lentiginous melanoma. Immunohistochemistry Melanoma (amelanotic) - mimic other malignancies - used in differential diagnosis of poorly differentiated neoplasms reliable antibodies: help locate occult tumor cells, evaluate invasion depth, and detect metastasis HMB45  - reacts with intracellular antigen, 90% of melanomas, some nevi may be reactive melan-A (MART-1) - antibody to transmembrane protein on melanoma cells recognized by T cells - useful in melanoma diagnosis anti–S-100 protein - react with proteins expressed by melanoma non melanoma tumors (lymphoma, adenocarcinoma, angiomyolipoma) - react to HMB45 Differential Diagnosis - intraorally differentiated lesions: melanocytic nevus, amalgam tattoo, physiologic pigmentation, melanocytic macule, and Kaposi's sarcoma - history, symmetry, and uniformity of pigmentation are crucial - biopsy -> for questionable pigmentation area Treatment and Prognosis - Surgery -> primary treatment for melanomas - chemotherapy, kinase inhibitors, and immunotherapy as adjuncts. - Radiotherapy -> not primary treatment method - supportive role in disease management - Treatment failures -> incomplete excision -> local recurrence and distant metastasis Regional lymph node metastases - detected by sentinel node biopsy - affects the choice and extent of therapy. - wide surgical excision of in situ melanomas w/ radial growth pattern Prognosis - histologic subtype and the depth of tumor invasion - Oral melanomas has greater thickness, more advanced than skin lesions - survival rate -> decline after 5-year measure -> late recognition - biologically more aggressive than skin lesions - distinct genomic profiles compared to cutaneous melanomas Nonmelanocytic Lesions Amalgam Tattoo (Focal Argyrosis) Etiology - iatrogenic lesion by traumatic soft tissue implantation of amalgam particles or passive transfer by chronic mucosa friction against an amalgam restoration. - occurs after tooth extraction, gold-casting restoration preparation, or polishing of old restorations - formation of soluble silver compounds -> soft tissue deposits. Clinical Features - affecting soft tissues like gingiva, buccal mucosa, palate, and tongue - benign and gray - rarely seen due to amalgam's well-tolerance - detected on soft tissue radiographs - inflammation are rare -> well-tolerated nature of amalgam Histopathology Silver in amalgam - stains collagen and elastic fibers -> black or golden brown color. - Few lymphocytes and macrophages are found, except in large particles - Multinucleated foreign body giant cells containing amalgam particles may be seen. Drug-Induced Pigmentations Tetracycline-associated pigmentation - after prolonged high doses of minocycline treatment for acne - Diffuse skin pigmentation -> sun-exposed areas, increased melanin production - focal pigment deposits -> legs and periorbital skin, drug complexes in melanocytes - Pigmentation in gingiva and palate -> + melanin levels, drug deposits in bone and tooth roots - Oral pigmentation - Seen in hormone replacement therapy AZT(azidothymidine - nail pigmentation and mucosal pigmentation Heavy-Metal Pigmentations Etiology - heavy metals like arsenic, bismuth, platinum, lead, and mercury - primarily through occupational exposure - used to treat diseases (syphilis, lichen planus, parasitic infections, and dermatoses) Cisplatinum - salt of these metals, - has antineoplastic activity - used to treat some malignancies Clinical Features - gingiva, skin and oral mucosa - gray to black color - linear distribution in gingival margin Bismuth & lead - staining of gingival tissues - Proportional to gingival inflammation -> reaction of heavy metal with bacterial hydrogen sulfide in inflammatory zones. Significance - Metallic deposits -> insignificant - cause must be investigated -> detrimental effects of systemic toxicity Chronic mercury vapor exposure - occupational hazard -> dental amalgam handled carelessly - Dental patients -> no risk, short exposure - elevated mercury vapor levels -> elevated body levels of mercury in the hair, nails, saliva, and urine Chronic mercury intoxication - Tremors - loss of appetite - Nausea - Depression - Headache - Fatigue - Weakness and insomnia Precautions for amalgam - storage of mercury in sealed container - Cover mercury spills with sulfur dust - well-ventilated spaces - water spray and suction when grinding amalgam