eMedicine Specialties > Dermatology > Diseases of the Oral Mucosa

Oral Submucous Fibrosis: Differential Diagnoses & Workup

Author: Nektarios I Lountzis, MD, Staff Physician, Department of Dermatology, Geisinger Medical Center
Coauthor(s): Tammie Ferringer, MD, Teaching Staff, Departments of Dermatology and Pathology, Geisinger Medical Center; Nada MacAron, MD, Staff Physician, Department of Pathology, Emory University School of Medicine; Amy Howard, MD, Fellow, Department of Dermatopathology, Emory University
Contributor Information and Disclosures

Updated: Mar 25, 2009

Differential Diagnoses

Other Problems to Be Considered

Amyloidosis: Hyalinized stroma can be distinguished from amyloid infiltration by using Congo red and thioflavine T staining under polarized and immunofluorescent light, respectively.

Generalized fibromatosis: Although soft tissue masses are not produced in the usual sense, the fibrosis of oral submucous fibrosis may be confused with generalized fibromatosis.

Oral manifestations of scleroderma: Scleroderma can be distinguished by other cutaneous, systemic, and characteristic laboratory findings. A case of localized plaque-type morphea was seen in a patient with long-standing oral submucous fibrosis.40

Oral lichen planus: Wickham striae can mimic atrophy and fibrosis.

Anemia: Pale oral mucosa can mimic atrophy and fibrosis.

Workup

Laboratory Studies

  • No specific laboratory tests are available for oral submucous fibrosis, and abnormalities may be related to secondary nutritional deficiencies. Some oral submucous fibrosis studies have reported the following laboratory findings: 
    • Decreased hemoglobin levels
    • Decreased iron levels
    • Decreased protein levels
    • Increased erythrocyte sedimentation rate
    • Decreased vitamin B complex levels

Other Tests

  • Cytologic smears may be performed.
  • A neural network–based oral precancer stage detection method has been proposed.34 This new technique uses wavelet coefficients from transmission electron micrography images of subepithelial fibrillar collagen in healthy oral submucosa and in oral submucous fibrosis tissues. These wavelet coefficients are used to choose the feature vector, which, in turn, can be used to train an artificial neural network. This trained network is able to classify normal and oral precancer stages (less advanced and advanced) after obtaining the image as an input. This technology is not readily available but could theoretically be used as an adjunct to hematoxylin and eosin histologic evaluations.

Procedures

  • Currently, oral biopsy for hematoxylin and eosin provides the most definitive diagnosis and is crucial because of the association of oral submucous fibrosis with oral cancer.4
  • Some authorities have reported benefit with immunohistochemical techniques such as Masson trichrome staining when pathology involved muscle.41 Alteration of cytokeratin expression, as is seen in leukoplakia and oral cancer, has also been noted in oral submucous fibrosis. Increased intensity of staining for pancytokeratin and high molecular weight cytokeratin, aberrant expression of cytokeratin 8, and decreased expression of cytokeratins 5 and 14 suggest their potential as surrogate markers for malignant transformation.42

Histologic Findings

Histologic findings vary according to the stage of the disease.

Very early stage

Fine fibrillar collagen, marked edema, large fibroblasts, dilated and congested blood vessels, and inflammatory infiltrates (primarily polymorphonuclear leukocytes and eosinophils) are found.

Early stage

Early hyalinization is characterized by thickened collagen bundles, moderate numbers of fibroblasts, and inflammatory cells (primarily lymphocytes, eosinophils, and plasma cells).

Moderately advanced and advanced stages

Dense bundles and sheets of collagen, thick bands of subepithelial hyalinization extending into the submucosal tissues (replacing fat or fibrovascular tissue), decreased vascularity, no edema, and inflammatory cells (lymphocytes and plasma cells) are found.

Oral submucous fibrosis is generally characterized by diffuse hyalinization of the subepithelial stroma with pigment incontinence from the overlying epithelial melanin.43 Other histologic findings include an atrophic epithelium and intercellular edema, with or without hyperkeratosis, parakeratosis, or orthokeratosis; epithelial dysplasia (25% of patients who underwent biopsy); squamous cell carcinoma histologically identical to typical squamous cell carcinomas; chronic inflammation and fibrosis in the minor salivary glands in the area of quid placement; and atrophy of the underlying muscle.29

Ultrastructural changes in oral submucous fibrosis include an increase in collagen type I; however, fibrils retain the normal structure.44

Staging

In addition to the above clinical staging, in 1995 Khanna and Andrade40 developed a group classification system for the surgical management of trismus.

  • Group I: This is the earliest stage and is not associated with mouth opening limitations. It refers to patients with an interincisal distance of greater than 35 mm.
  • Group II: This refers to patients with an interincisal distance of 26-35 mm.
  • Group III: These are moderately advanced cases. This stage refers to patients with an interincisal distance of 15-26 mm. Fibrotic bands are visible at the soft palate, and pterygomandibular raphe and anterior pillars of fauces are present.
  • Group IVA: Trismus is severe, with an interincisal distance of less than 15 mm and extensive fibrosis of all the oral mucosa.
  • Group IVB: Disease is most advanced, with premalignant and malignant changes throughout the mucosa.

More on Oral Submucous Fibrosis

Overview: Oral Submucous Fibrosis
Differential Diagnoses & Workup: Oral Submucous Fibrosis
Treatment & Medication: Oral Submucous Fibrosis
Follow-up: Oral Submucous Fibrosis
References
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Further Reading

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Keywords

oral submucous fibrosis, OSF, Asian sideropenic dysphagia, atrophica idiopathica mucosa oris, oral disease, oral cancer, oral fibrosis, oral mucosal disease, oral soft tissue disease, sub-mucous fibrosis, betel nut chewing, Areca catechu, pan parag, gutka, gutkha, guttkha, guthka, betel nut, pan, betel quid, areca nut, mawa, mainpuri

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Contributor Information and Disclosures

Author

Nektarios I Lountzis, MD, Staff Physician, Department of Dermatology, Geisinger Medical Center
Nektarios I Lountzis, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

Coauthor(s)

Tammie Ferringer, MD, Teaching Staff, Departments of Dermatology and Pathology, Geisinger Medical Center
Tammie Ferringer, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, and American Society of Dermatopathology
Disclosure: Nothing to disclose.

Nada MacAron, MD, Staff Physician, Department of Pathology, Emory University School of Medicine
Nada MacAron, MD is a member of the following medical societies: College of American Pathologists and United States and Canadian Academy of Pathology
Disclosure: Nothing to disclose.

Amy Howard, MD, Fellow, Department of Dermatopathology, Emory University
Disclosure: Nothing to disclose.

Medical Editor

Alexa F Boer Kimball, MD, MPH, Associate Professor of Dermatology, Harvard University School of Medicine; Vice Chair, Department of Dermatology, Massachusetts General Hospital; Director of Clinical Unit for Research Trials in Skin (CURTIS), Department of Dermatology, Massachusetts General Hospital
Alexa F Boer Kimball, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

Pharmacy Editor

David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic
David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Managing Editor

Drore Eisen, MD, DDS, Consulting Staff, Department of Dermatology, Dermatology Research Associates of Cincinnati
Drore Eisen, MD, DDS is a member of the following medical societies: American Academy of Dermatology, American Academy of Oral Medicine, and American Dental Association
Disclosure: Nothing to disclose.

CME Editor

Joel M Gelfand, MD, MSCE, Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania
Joel M Gelfand, MD, MSCE is a member of the following medical societies: Society for Investigative Dermatology
Disclosure: AMGEN Consulting fee Consulting; AMGEN Grant/research funds None; Genentech Consulting fee Consulting; Centocor Consulting fee Consulting; Centocor Grant/research funds None; Covance Consulting fee Consulting; Shire  Consulting

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
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