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Leukoplakia

Leukoplakia is a potentially malignant lesion affecting the squamous epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium: Histology usually within the oral cavity. Leukoplakia can be associated with a history of chronic tobacco and alcohol use, both of which can synergistically damage the epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium: Histology. Leukoplakia presents as a white plaque Plaque Primary Skin Lesions that cannot be scraped off. Diagnosis is confirmed with a biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma. The lesion can be surgically treated, but close observation is always recommended owing to the risk of malignant transformation Transformation Change brought about to an organism's genetic composition by unidirectional transfer (transfection; transduction, genetic; conjugation, genetic, etc.) and incorporation of foreign DNA into prokaryotic or eukaryotic cells by recombination of part or all of that DNA into the cell's genome. Bacteriology.

Last updated: 31 Jan, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Overview

Definition

Epidemiology

  • Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency:
  • 80% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship are > 40 years of age.
  • Affects more men than women
  • Annual malignant transformation Transformation Change brought about to an organism’s genetic composition by unidirectional transfer (transfection; transduction, genetic; conjugation, genetic, etc.) and incorporation of foreign DNA into prokaryotic or eukaryotic cells by recombination of part or all of that DNA into the cell’s genome. Bacteriology rate: 0.6%–20%

Risk factors

Risk factors are similar to those for squamous cell carcinoma Squamous cell carcinoma Cutaneous squamous cell carcinoma (cSCC) is caused by malignant proliferation of atypical keratinocytes. This condition is the 2nd most common skin malignancy and usually affects sun-exposed areas of fair-skinned patients. The cancer presents as a firm, erythematous, keratotic plaque or papule. Squamous Cell Carcinoma (SCC).

  • Tobacco use (most common risk factor)
  • Alcohol consumption 
  • Increasing age
  • Infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease
    • HPV HPV Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. Papillomavirus (HPV)
    • Chronic candidiasis Candidiasis Candida is a genus of dimorphic, opportunistic fungi. Candida albicans is part of the normal human flora and is the most common cause of candidiasis. The clinical presentation varies and can include localized mucocutaneous infections (e.g., oropharyngeal, esophageal, intertriginous, and vulvovaginal candidiasis) and invasive disease (e.g., candidemia, intraabdominal abscess, pericarditis, and meningitis). Candida/Candidiasis

Pathophysiology

Clinical Presentation

General findings

  • Patches Patches Vitiligo or plaques:
    • Affect Affect The feeling-tone accompaniment of an idea or mental representation. It is the most direct psychic derivative of instinct and the psychic representative of the various bodily changes by means of which instincts manifest themselves. Psychiatric Assessment mucosa
    • Tend to be bright white
    • Cannot be scraped off 
  • Lesions are asymptomatic.

Homogeneous Homogeneous Imaging of the Spleen leukoplakia

This form is less likely to be malignant and is characterized by:

  • Uniformly white plaques 
  • Well-defined margins

Nonhomogenous leukoplakia

Nonhomogenous leukoplakia presents a higher risk of malignant transformation Transformation Change brought about to an organism’s genetic composition by unidirectional transfer (transfection; transduction, genetic; conjugation, genetic, etc.) and incorporation of foreign DNA into prokaryotic or eukaryotic cells by recombination of part or all of that DNA into the cell’s genome. Bacteriology and may appear:

Locations

  • Oral cavity (most common):
    • Tongue Tongue The tongue, on the other hand, is a complex muscular structure that permits tasting and facilitates the process of mastication and communication. The blood supply of the tongue originates from the external carotid artery, and the innervation is through cranial nerves. Lips and Tongue: Anatomy
    • Buccal mucosa Buccal mucosa Oral Cancer
  • Genitalia 
  • Esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy 
  • Larynx Larynx The larynx, also commonly called the voice box, is a cylindrical space located in the neck at the level of the C3-C6 vertebrae. The major structures forming the framework of the larynx are the thyroid cartilage, cricoid cartilage, and epiglottis. The larynx serves to produce sound (phonation), conducts air to the trachea, and prevents large molecules from reaching the lungs. Larynx: Anatomy
  • Bladder Bladder A musculomembranous sac along the urinary tract. Urine flows from the kidneys into the bladder via the ureters, and is held there until urination. Pyelonephritis and Perinephric Abscess

Diagnosis and Management

Diagnosis

Biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma is required for a definitive diagnosis, to evaluate for dysplasia Dysplasia Cellular Adaptation, and to rule out other conditions. Findings include:

Histologic images of oral leukoplakia

Histological images of oral leukoplakia Oral leukoplakia A white patch seen on the oral mucosa. It is considered a premalignant condition and is often tobacco-induced. When evidence of Epstein-Barr virus is present, the condition is called hairy leukoplakia. Oral Cancer demonstrating progressive dysplasia Dysplasia Cellular Adaptation and malignant transformation Transformation Change brought about to an organism’s genetic composition by unidirectional transfer (transfection; transduction, genetic; conjugation, genetic, etc.) and incorporation of foreign DNA into prokaryotic or eukaryotic cells by recombination of part or all of that DNA into the cell’s genome. Bacteriology:
A: Hyperkeratosis Hyperkeratosis Ichthyosis Vulgaris with low-grade dysplasia Dysplasia Cellular Adaptation present
B: Moderate dysplasia Dysplasia Cellular Adaptation
C: High-grade dysplasia Dysplasia Cellular Adaptation
D: Leukoplakia in the state of becoming invasive carcinoma
E: Invasive carcinoma

Image: “Representative histological pictures of OPLs and OSCCs” by Yang Yi et al AL Amyloidosis. License: CC BY 2.0

Management

  • Close surveillance Surveillance Developmental Milestones and Normal Growth is indicated.
  • Elimination Elimination The initial damage and destruction of tumor cells by innate and adaptive immunity. Completion of the phase means no cancer growth. Cancer Immunotherapy of risk factors for all patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship, including smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases and alcohol use
  • Medical therapy:
    • Vitamin A Vitamin A Retinol and derivatives of retinol that play an essential role in metabolic functioning of the retina, the growth of and differentiation of epithelial tissue, the growth of bone, reproduction, and the immune response. Dietary vitamin A is derived from a variety of carotenoids found in plants. It is enriched in the liver, egg yolks, and the fat component of dairy products. Fat-soluble Vitamins and their Deficiencies
    • Retinoids Retinoids Retinol and derivatives of retinol that play an essential role in metabolic functioning of the retina, the growth of and differentiation of epithelial tissue, the growth of bone, reproduction, and the immune response. Dietary vitamin A is derived from a variety of carotenoids found in plants. It is enriched in the liver, egg yolks, and the fat component of dairy products. Fat-soluble Vitamins and their Deficiencies
    • Carotenoids
    • NSAIDs NSAIDS Primary vs Secondary Headaches
  • Surgical management:
    • Options:
      • Surgical excision 
      • Laser ablation
      • Cryosurgery
    • Recommended for:

Differential Diagnosis

  • Candidiasis Candidiasis Candida is a genus of dimorphic, opportunistic fungi. Candida albicans is part of the normal human flora and is the most common cause of candidiasis. The clinical presentation varies and can include localized mucocutaneous infections (e.g., oropharyngeal, esophageal, intertriginous, and vulvovaginal candidiasis) and invasive disease (e.g., candidemia, intraabdominal abscess, pericarditis, and meningitis). Candida/Candidiasis: a superficial fungal infection caused by Candida Candida Candida is a genus of dimorphic, opportunistic fungi. Candida albicans is part of the normal human flora and is the most common cause of candidiasis. The clinical presentation varies and can include localized mucocutaneous infections (e.g., oropharyngeal, esophageal, intertriginous, and vulvovaginal candidiasis) and invasive disease (e.g., candidemia, intraabdominal abscess, pericarditis, and meningitis). Candida/Candidiasis species. Candidiasis Candidiasis Candida is a genus of dimorphic, opportunistic fungi. Candida albicans is part of the normal human flora and is the most common cause of candidiasis. The clinical presentation varies and can include localized mucocutaneous infections (e.g., oropharyngeal, esophageal, intertriginous, and vulvovaginal candidiasis) and invasive disease (e.g., candidemia, intraabdominal abscess, pericarditis, and meningitis). Candida/Candidiasis can commonly occur on the oral mucosa Oral mucosa Lining of the oral cavity, including mucosa on the gums; the palate; the lip; the cheek; floor of the mouth; and other structures. The mucosa is generally a nonkeratinized stratified squamous epithelium covering muscle, bone, or glands but can show varying degree of keratinization at specific locations. Stomatitis, genitals, and skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions folds. Infection of the oral mucosa Oral mucosa Lining of the oral cavity, including mucosa on the gums; the palate; the lip; the cheek; floor of the mouth; and other structures. The mucosa is generally a nonkeratinized stratified squamous epithelium covering muscle, bone, or glands but can show varying degree of keratinization at specific locations. Stomatitis presents as white plaques that bleed when scraped. The diagnosis is based on a clinical exam and can be confirmed by the identification Identification Defense Mechanisms of yeast Yeast A general term for single-celled rounded fungi that reproduce by budding. Brewers’ and bakers’ yeasts are saccharomyces cerevisiae; therapeutic dried yeast is yeast, dried. Mycology on a KOH wet mount. Candidiasis Candidiasis Candida is a genus of dimorphic, opportunistic fungi. Candida albicans is part of the normal human flora and is the most common cause of candidiasis. The clinical presentation varies and can include localized mucocutaneous infections (e.g., oropharyngeal, esophageal, intertriginous, and vulvovaginal candidiasis) and invasive disease (e.g., candidemia, intraabdominal abscess, pericarditis, and meningitis). Candida/Candidiasis can be treated with oral antifungal Antifungal Azoles medications.
  • Squamous cell carcinoma Squamous cell carcinoma Cutaneous squamous cell carcinoma (cSCC) is caused by malignant proliferation of atypical keratinocytes. This condition is the 2nd most common skin malignancy and usually affects sun-exposed areas of fair-skinned patients. The cancer presents as a firm, erythematous, keratotic plaque or papule. Squamous Cell Carcinoma (SCC): a condition caused by the malignant proliferation of atypical keratinocytes Keratinocytes Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. Skin: Structure and Functions. Squamous cell carcinoma Squamous cell carcinoma Cutaneous squamous cell carcinoma (cSCC) is caused by malignant proliferation of atypical keratinocytes. This condition is the 2nd most common skin malignancy and usually affects sun-exposed areas of fair-skinned patients. The cancer presents as a firm, erythematous, keratotic plaque or papule. Squamous Cell Carcinoma (SCC) is the 2nd most common skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions malignancy Malignancy Hemothorax and usually affects the sun-exposed areas of light-skinned patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship. Squamous cell carcinoma Squamous cell carcinoma Cutaneous squamous cell carcinoma (cSCC) is caused by malignant proliferation of atypical keratinocytes. This condition is the 2nd most common skin malignancy and usually affects sun-exposed areas of fair-skinned patients. The cancer presents as a firm, erythematous, keratotic plaque or papule. Squamous Cell Carcinoma (SCC) presents as a firm, erythematous, keratotic plaque Plaque Primary Skin Lesions or papule Papule Elevated lesion < 1 cm in diameter Generalized and Localized Rashes. A biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma is used to confirm the diagnosis. Surgical excision is the mainstay of management.
  • Erythroplakia Erythroplakia A condition of the mucous membrane characterized by erythematous papular lesions. Oral Cancer: a precancerous Precancerous Pathological conditions that tend eventually to become malignant. Barrett’s Esophagus lesion that is similar to leukoplakia, which develops from chronic tobacco and alcohol use. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship usually present with granular, red, sharply demarcated lesions. A biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma can show dysplastic keratinocytes Keratinocytes Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. Skin: Structure and Functions that can progress to invasive carcinoma. Erythroplakia Erythroplakia A condition of the mucous membrane characterized by erythematous papular lesions. Oral Cancer is commonly treated with surgical excision.
  • Hairy leukoplakia Hairy leukoplakia Epithelial hyperplasia of the oral mucosa associated with epstein-barr virus and found almost exclusively in persons with HIV infection. The lesion consists of a white patch that is often corrugated or hairy. Epstein-Barr Virus: a lesion caused by EBV EBV Epstein-barr virus (EBV) is a linear, double-stranded DNA virus belonging to the herpesviridae family. This highly prevalent virus is mostly transmitted through contact with oropharyngeal secretions from an infected individual. The virus can infect epithelial cells and B lymphocytes, where it can undergo lytic replication or latency. Epstein-Barr Virus mostly in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship who are HIV HIV Anti-HIV Drugs positive. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship develop a white patch Patch Nonpalpable lesion > 1 cm in diameter Generalized and Localized Rashes on the oral mucosa Oral mucosa Lining of the oral cavity, including mucosa on the gums; the palate; the lip; the cheek; floor of the mouth; and other structures. The mucosa is generally a nonkeratinized stratified squamous epithelium covering muscle, bone, or glands but can show varying degree of keratinization at specific locations. Stomatitis. The patch Patch Nonpalpable lesion > 1 cm in diameter Generalized and Localized Rashes is often found on the lateral portion of the tongue Tongue The tongue, on the other hand, is a complex muscular structure that permits tasting and facilitates the process of mastication and communication. The blood supply of the tongue originates from the external carotid artery, and the innervation is through cranial nerves. Lips and Tongue: Anatomy. Some patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may experience mild pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, dysesthesia Dysesthesia Complex Regional Pain Syndrome (CRPS), and altered taste. Diagnosis is usually clinical, but biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma and immunocytopathology may be performed. Management includes antiviral Antiviral Antivirals for Hepatitis B medications, topical retinoids Retinoids Retinol and derivatives of retinol that play an essential role in metabolic functioning of the retina, the growth of and differentiation of epithelial tissue, the growth of bone, reproduction, and the immune response. Dietary vitamin A is derived from a variety of carotenoids found in plants. It is enriched in the liver, egg yolks, and the fat component of dairy products. Fat-soluble Vitamins and their Deficiencies, and cryotherapy Cryotherapy A form of therapy consisting in the local or general use of cold. The selective destruction of tissue by extreme cold or freezing is cryosurgery. Chondrosarcoma. Hairy leukoplakia Hairy leukoplakia Epithelial hyperplasia of the oral mucosa associated with epstein-barr virus and found almost exclusively in persons with HIV infection. The lesion consists of a white patch that is often corrugated or hairy. Epstein-Barr Virus may resolve spontaneously.

References

  1. Bishop, J.A., Sciubba, J.J., Taube, J.M. (2017). Leukoplakia and erythroplakia – premalignant squamous lesions of the oral cavity. In Anton, R. (Ed.). Medscape. Retrieved April 14, 2021, from https://emedicine.medscape.com/article/1840467-overview
  2. Sciubba, J.J., Narendan, A.R. (2017). Dermatologic manifestations of oral leukoplakia. In James, W.D. (Ed.). Medscape. Retrieved April 14, 2021, from https://emedicine.medscape.com/article/1075448-overview
  3. Harris, C.M. (2021). Oral leukoplakia. In Meyers, A.D. (Ed.). Medscape. Retrieved April 14, 2021, from https://emedicine.medscape.com/article/853864-overview
  4. Lodi, G. (2018). Oral leukoplakia. In Corona, R. (Ed.). UpToDate. Retrieved April 14, 2021, from https://www.uptodate.com/contents/oral-leukoplakia
  5. Mohammed, F., Fairozekhan, A.T. (2020). Oral leukoplakia. [online] StatPearls. Retrieved April 14, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK442013/

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