Background

The oral mucosa is often a window into many systemic disorders and skin diseases. The following tables illustrate the variety of changes that may be observed and the diseases associated with them.

OUTLINE

Differential Diagnosis	Ulcers in children and adolescents White surface thickening White surface material White subsurface material Dark Mucosal lesions, red-blue blanching Dark mucosal lesions, red-blue, nonblanching Pigmented lesions
Gross Appearance and Clinical Variants
Treatment
Commonly Used Terms
Internet Links

ULCERS IN CHILDREN AND ADOLESCENTS

Focal vesicles and ulcers of sudden onset and short duration, recurrent	Perioral impetigo Superficial mucocele Secondary herpes simplex infection Pericoronitis Angular cheilitis Aphthous minor Transient lingual papillitis Median lip fissure
Focal vesicles and ulcers of sudden onset and short duration, non-recurrent	Traumatic ulcer Anesthetic necrosis
Multifocal ulcers of sudden onset and short duration, recurrent	Erythema multiforme Contact allergy Herpetiform aphthae
Multifocal ulcers of sudden onset and short duration, nonrecurrent	Primary herpetic gingivostomatitis Primary herpetic pharyngitis Varicella-herpes zoster Herpangina Hand-foot-mouth disease Erythema multiforme Acute necrotizing ulcerative gingivitis (ANUG) Infectious mononucleosis Streptococcal stomatitis
Focal ulcers of variable onset and persistent duration	Electrical burn Necrotizing sialometaplasia Riga-Fede disease Bednar's disease Traumatic granuloma Factitical injury NOMA Chronic HSV infection Geometric herpectic glossitis Chancre Deep mycotic infection Ulcerated tumor Langerhans cell histiocytosis Squamous cell carcinoma
Multifocal ulcers of variable onset and persistent duration	Factitial injury Aphthous major Immunodeficiency disorders Agranulocytosis Cyclic neutropenia Congenital neutropenia Leukemia/lymphoma Aplastic anemia Crohn's disease Celiac disease Ulcerative colitis Periodic fevers, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) Epidermolysis bullosa Juvenile dermatitis herpetiformis Childhood pemphigus Childhood linear IgA disease Childhood pemphigoid

WHITE SURFACE THICKENING IN CHILDREN AND ADOLESCENTS

General Description	Translucent to opaque surface Rough, shredded or wrinkled Flat, stuck on appearance Red component may be present Plaque, linear or circinate pattern Usually asymptomatic but may burn Adherent, does not rub off Persistent or regresses, if cause eliminated Localized or multifocal distribution A cause or cofactors may be present
Focal plaque	Chronic irritation Frictional keratosis Leukoplakia, precancer
Focal nodular	Viral infection Squamous papilloma Verruca vulgaris
Diffuse or multifocal plaque, asymptomatic	Factitial biting habit Sucking calluses of the neonate Hairy tounge Smokeless tobacco keratosis Nicotine stomatitis Leukoedema White sponge nevus Hereditary benign intraepithelial dyskeratosis Hairy leukoplakia Syndrome related leukoplakia including: Dyskeratosis congenita Pachyonychia congenita Focal palmoplantar and gingival hyperkeratosis Leukoplakia, tylosis, and esophageal cancer
Diffuse or multifocal plaque, symptomatic	Hyperplastic candidiasis Endocrine-candidiasis syndrome Uremic stomatitis
Diffuse of multifocal, linear or circinate, asymptomatic	Linea alba
Diffuse of multifocal, linear or circinate, symptomatic, red and white component	Lichen planus Lichenoid reaction Exfoliative cheilitis Cheilocandidiasis Erythema migrans Lupus erythematosus Contact allergy (Toothpaste hypersensitivity reaction)

WHITE SURFACE MATERIAL IN CHILDREN AND ADOLESCENTS

General Description	Creamy to filmy surface Soft surface debris Usually symptomatic Semiadherent or nonadherent Rubs off leaving an irritated surface Plaque or papular pattern Usually diffuse or multifocal distribution Regresses (heals) No tissue enlargement A cause may be present
Focal slough/pseudomembrane	Ulcers Thermal or chemical irritation Mucosal burn Plugged tonsillar crypts
Diffuse or Multifocal slough/pseudomembrane	Koplik's spots (Rubeola) ANUG White strawberry tounge (Streptococcal infection) Exudative pharyngotonsillitis Mucous patches (Syphilis) Pseudomembranous candidiasis Mucosal sloughing from oral hygiene products Plaque, materia alba Coated tounge (inadequate oral hygeine)

WHITE SUBSURFACE MUCOSAL CHANGES
IN CHILDREN AND ADOLESCENTS

General Description	Yellow-pink to pearly white Smooth surface Soft to hard Usually asymptomatic Does not rub off Submucosal thickening or enlargement Plaque, papular or nodular pattern Localized or multifocal distribution Static, regresses or progresses A cause may be present
Focal, flat	Trauma Cicatrix Mucosal graft
Focal, elevated	Granular cell tumor Lipoma Oral-facial-digitial syndrome Epidermoid/dermoid cyst Lymphoepithelial cyst Soft tissue abscess Parulis Sialolith
Diffuse or multifocal, flat	Trauma Cicatrix Child abuse Resolved aphthous major Factitial injury Lesch-Nyhan syndrome Hereditary sensory syndromes with oral mutilation Seizure disorders
Diffuse or multifocal, elevated	Gingival cysts of the newborn Palatal cysts of the newborn Lymphoid aggregates Fordyce granules

DARK MUCOSAL LESIONS-RED BLUE BLANCHING
IN CHILDREN AND ADOLESCENTS

General Description	Flat or elevated Vascular anomaly Smooth surface Significant bleeding complication Often congenital or syndrome related Blanches with pressure Asymptomatic Spontaneous regression or persistent May cause facial asymmetry
Focal	Varicosity Hemangioma Caliber persistent labial artery
Multifocal	Syndromes with vascular anomalies: Ataxia-telangiectasia Beckwith-Wiedemann syndrome Hereditary hemorrhagic telangiectasia Klippel-Trenaunay-Weber syndrome Maffucci syndrome Sturge-Weber angiomatosis

DARK MUCOSAL LESIONS-RED BLUE NON-BLANCHING
IN CHILDREN AND ADOLESCENTS

General Description	Flat or elevated Extravasation of blood or increased vascularity Smooth or granular surface Bleeds with manipulation No significant blanching with pressure Often history of trauma or irritation Most regress, when cause removed May be mildly symptomatic Widespread distribution may indicate syndrome or systemic disease
Focal	Fungal infection Median rhomboid glossitis Trauma Ecchymoses, petechiae Precancer-erythroplakia Trauma and traumatic erosion Lymphangioma Neonatal alveolar lymphangioma Salivary gland tumor Metastatic disease Pyogenic granuloma Peripheral giant cell granuloma Eruption cyst/hematoma Lymphoid hyperplasia Mucocele-ranula Hematoma
Multifocal	Infectious mononucleosis (palate) Pharyngitis Erythematous candidiasis Kawasaki's disease Scarlet fever Contact mucositis Atrophic lichen planus Lupus erythematosus Mucoepithelial dysplasia syndrome Hemophilia Thrombocytopenia von Willebrand's disease Leukemia Linear gingival erythema Chronic hyperplastic gingivitis Puberty/pregnancy gingivitis Plasma cell gingivitis Leukemic infiltrates Amyloidaceous ulcerated gingival hyperplasia

PIGMENTED (BROWN, GRAY, AND BLACK)
MUCOSAL LESIONS IN CHILDREN AND ADOLESCENTS

General Description	Flat or slightly elevated Melanin pigmentation or tattoo Smooth surface No blanching with pressure Often oral and skin involvement Lesions of early or recent onset Usually persistent lesions Widespread distribution may indicate syndrome or systemic disease
Focal flat	Amalgam/lead tattoo Melanotic macule Melanocytic nevus Ephelis Post-inflammatory pigmentation
Focal elevated	Melanocytic nevus Melanoacanthoma
Diffuse or multifocal, flat, early onset	Physiologic pigmentation Nevus of Ota Melanotic macules and cafe-au-lait macules McCune-Albright syndrome Melanotic macules and perioral freckling Peutz-Jeghers syndrome Laugier-Hunziker syndrome Carney syndrome
Diffuse or multifocal, flat, recent onset	Heavy metal toxicosis Lead poisoning Medication melanosis Post-inflammatory pigmentation Smoker's melanosis Addison's disease

 

ADDITIONAL GROSS OR CLINICAL DISEASE VARIANTS	CHARACTERIZATION
Potential pitfalls in diagnostic oral pathology: a review for the general surgical pathologist. Massey D. From the Division of Anatomic Pathology, Virginia Commonwealth University School of Medicine, Richmond, VA.	Adv Anat Pathol. 2005 Nov;12(6):332-49. Abstract quote   Oral developmental, reactive, benign neoplastic and malignant neoplastic conditions, many odontogenic in origin, may not be seen routinely by the general surgical pathologist and therefore may present a diagnostic dilemma. This article describes odontogenic and nonodontogenic conditions with little or no destructive potential along with the more aggressive conditions that resemble them clinically and histologically. The importance of clinical and radiographic correlation as an adjunct to tissue diagnosis is highlighted. Additionally, a brief summary of odontogenesis is presented with attention given to odontogenic embryologic remnants and the developmental and pathologic processes that may arise from them.
FOCAL EPITHELIAL HYPERPLASIA
Association of HLA-DR4 (DRB1*0404) With Human Papillomavirus Infection in Patients With Focal Epithelial Hyperplasia Cristina García-Corona, MD Elisa Vega-Memije, MD; Adalberto Mosqueda-Taylor, DDS, MSc Jesús K. Yamamoto-Furusho, MD, MSc Alma A. Rodríguez-Carreón, MD; Jorge A. Ruiz-Morales, MD; Norma Salgado, PhD; Julio Granados, MD	Arch Dermatol. 2004;140:1227-1231. Abstract quote Objectives  To determine gene frequencies of HLA-DR alleles in 22 Mexican patients with focal epithelial hyperplasia and compare them with those present in ethnically matched healthy subjects, as well as to determine the types of human papillomavirus present in the lesions. Design  Prospective and retrospective observational study. Setting  Dermatology outpatient clinic in a general hospital. Patients  Twenty-two patients with clinically and histologically confirmed focal epithelial hyperplasia seen within a 10-year period. Interventions  None. Main Outcome Measures  Results of high-resolution DNA typing for HLA-DR alleles and biopsy for viral typing. Results  HLA-DR4 (DRB1*0404) was significantly increased (P<.001; odds ratio, 3.9; 95% confidence interval, 1.86-8.03). Seventeen (85%) of 20 patients had human papillomavirus subtype 13. The data on human papillomavirus differed from reports elsewhere that described association with human papillomavirus type 32. Conclusions  The HLA-DRB1*0404 allele suggests that Amerindian populations are at risk, and in this group, the Mexican population studied was affected only by human papillomavirus type 13.
GINGIVAL ENLARGEMENT
Diffuse gingival enlargement. Khera P, Zirwas MJ, English JC 3rd. Department of Dermatology, University of Pittsburgh, USA.	J Am Acad Dermatol. 2005 Mar;52(3 Pt 1):491-9. Abstract quote   Diffuse gingival enlargement is defined as an excessive growth of periodontal tissue. It can be considered a relatively common finding, as thousands of patients have been described in the literature. Patients may seek medical attention because of pain, tenderness, interference with speech and/or mastication, halitosis, or unsightly appearance, or gingival enlargement may be an unexpected finding on routine physical examination. Diffuse gingival enlargement has numerous causes, including poor dental hygiene, medications, serious systemic illnesses, genetic conditions, other specific physiologic states, or it may be idiopathic. Given the large number of possible underlying conditions, the work-up of a patient presenting with diffuse gingival enlargement may seem daunting. We present a systemic review of diffuse gingival enlargement, including an algorithm that can be used to direct the work-up of patients presenting with this condition.
HEREDITARY BENIGN INTRAEPITHELIAL DYSERKATOSIS
Hereditary benign intraepithelial dyskeratosis: Report of two cases with prominent oral lesions Camille A. Haisley-Royster, MD R. Rand Allingham, MD Gordon K. Klintworth, MD, PhD Neil S. Prose, MD Durham, North Carolina	J Am Acad Dermatol 2001;45:634-6 Abstract quote Hereditary benign intraepithelial dyskeratosis is a rare autosomal dominant disorder of the oral and ocular mucosa initially described in the Haliwa-Saponi Native American tribe of North Carolina. We describe 2 sisters with the characteristic oral and ocular findings. This entity should be distinguished from several other diseases that cause white lesions in the mouth including white sponge nevus.

 

TREATMENT

CHARACTERIZATION

Topical bleomycin treatment of oral leukoplakia: a randomized double-blind clinical trial. Epstein JB, Wong FL, Millner A, Le ND. Department of Dentistry, University of British Columbia, Vancouver, Canada.

Head Neck 1994 Nov-Dec;16(6):539-44 Abstract quote BACKGROUND. Oral leukoplakia and oral erythroplakia may be associated with benign and dysplastic cellular changes, and are at risk of malignant transformation. Additional means of management of these lesions is needed. The results of nonblinded trials using topical bleomycin in oral leukoplakia indicated the need for phase III study. METHODS. A prospective, double-blind, randomized trial of topical bleomycin versus placebo was conducted. Bleomycin 1% in dimethylsulphoxide (DMSO) or the carrier was applied for 5 minutes for 14 consecutive days. Clinical assessment and pre-application and post-treatment biopsies were conducted. RESULTS. Twenty-two patients were randomized. Of the patients who received bleomycin, decrease in clinical size of the lesion was achieved (p = 0.001), and histological reduction in dysplasia was seen (p = 0.094). CONCLUSIONS. The topical application of bleomycin in DMSO may represent an additional approach to management of oral leukoplakia. The treatment is well-tolerated, and may be considered when the location or extent of the lesion may make surgical excision difficult.

Adv Dermatol 2000;16:39-79.
Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.

Basic Principles of Disease
Learn the basic disease classifications of cancers, infections, and inflammation

Commonly Used Terms
This is a glossary of terms often found in a pathology report.

Diagnostic Process
Learn how a pathologist makes a diagnosis using a microscope

Surgical Pathology Report
Examine an actual biopsy report to understand what each section means

Special Stains
Understand the tools the pathologist utilizes to aid in the diagnosis

How Accurate is My Report?
Pathologists actively oversee every area of the laboratory to ensure your report is accurate

Got Path?
Recent teaching cases and lectures presented in conferences

Pathologists Who Make A Difference
Search for a Physician Specialist

Last Updated December 21, 2005

Send mail to The Doctor's Doctor with questions or comments about this web site.
Read the Medical Disclaimer.

Copyright © The Doctor's Doctor