Oral Submucous Fibrosis Workup

Updated: Jun 18, 2018
  • Author: Nektarios I Lountzis, MD; Chief Editor: William D James, MD  more...
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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. [40] 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.



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. [54] 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. [55]


Histologic Findings

Histologic findings vary according to the stage of the disease. [56]

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). [57]

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. [57]

Oral submucous fibrosis is generally characterized by diffuse hyalinization of the subepithelial stroma with pigment incontinence from the overlying epithelial melanin. [58] 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. [34]

Ultrastructural changes in oral submucous fibrosis include an increase in collagen type I; however, fibrils retain the normal structure. [59]



In addition to the above clinical staging, in 1995 Khanna and Andrade [53] developed the following 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.