Diagnostic Phase

Box 3 identifies the steps usually required to establish an accurate diagnosis of oral diseases and disorders.

Box 3. Diagnostic Phase.4
  • Past History
  • Clinical appearance
  • Biopsy
    • Histology
    • Direct immunofluorescence
  • Indirect immunofluorescence
  • Candida culture/smear
  • Ancillary tools
    • Exfoliative cytology
    • “Brush” biopsy
    • Fluorescence lighting

Asking questions regarding the patient’s past medical and dental history of the onset, duration, previous treatment and response to previous treatment can often be of value in diagnosis.

  • Do the lesions come and go?
  • How long have you had the signs and symptoms?
  • Are lesions becoming progressively more painful?
  • Is there a family history of these types of lesions?
  • What medications do you take? Why? And for how long?
  • Does anything seem to trigger worsening of the lesions?
  • What treatment has been rendered at this point?
  • Was the treatment effective?

As the term mucocutaneous implies, the patient should be carefully examined for both intraoral and extraoral lesions. For example, mucous membrane pemphigoid and pemphigus vulgaris may exhibit oral, cutaneous, genital and ocular lesions (Figure 3), while oral lichen planus may be accompanied by cutaneous lesions 12-14% of the time.26

Figure 3. Early ocular lesion of mucous membrane pemphigoid.
Note the beginning scar attaching the eyelid to the cornea.

Genital lesions are common in oral lichen planus, especially among women (the so-called vulvovaginal-gingival lichen planus syndrome – Figure 4).24,26,61,62 Sites of involvement of mucocutaneous diseases may include the pharynx, esophagus, larynx, eye, anus and occasionally the internal organs.30

Figure 4. The vulvovaginal-gingival lichen planus syndrome.

On occasion the gingiva and/or other oral sites present with the classical appearance of specific mucocutaneous diseases that may support the tentative diagnosis. For example, the presence of reticular lesions in addition to the erosions associated with DG may strongly suggest a diagnosis of oral lichen planus. However, some other diseases may present with similar clinical appearance (lupus erythematosus, chronic ulcerative stomatitis, graft versus host disease, lichen planus pemphigoides) so further diagnostic steps are often indicated.30,34,49,59,75,90,95,103 Histopathology examination of biopsied tissue remains the gold standard for accurate diagnosis of most oral diseases and disorders although direct (DIF) and indirect (IIF) immunofluorescence is often considered diagnostic for classic autoimmune diseases such as mucous membrane pemphigoid and pemphigus vulgaris.13,30,77,95 Conversely, negative immunofluorescence findings should be anticipated in biopsies of hypersensitivity reactions, while DIF is only considered to be supportive but not diagnostic of oral lichen planus.30,75,82

Biopsy sites should be selected that appear to have an intact epithelial surface (Boxes 4 and 5). It is usually of little value to select an erosive lesion for biopsy since the epithelium is often missing.

Box 4. Biopsy Site Selection.
  • Choose an area of intact epithelium
  • Include perilesional and possibly distant tissue
  • Consider selecting normal appearing tissue for some DIF testing, when necessary
  • When possible, avoid gingival biopsies
Box 5. Biopsy Shipment.
  • Formaldehyde for routine histological evaluation
  • Ambient temperature transport media (Michel’s solution) for DIF
  • Obtain transport media from pathology facility and/or immunology lab, usually without charge

Consequently, perilesional sites or even normal appearing tissue sites may be more appropriate for biopsy, especially if DIF evaluation is to be used. Autoimmune diseases such as MMP and PPV will often present with positive DIF findings even in normal appearing tissue.56,93 Conversely, there is no benefit in obtaining a biopsy of normal tissue for histopathological evaluation in suspected non-autoimmune disorders. Figure 5 reveals an individual with DG for whom alternative biopsy sites are preferred.

Figure 5. Biopsy site selection.
ce481-fig05a-biopsy-site-selection ce481-fig05b-biopsy-site-selection ce481-fig05c-biopsy-site-selection
Due to risk of gingival desquamation, an alternate biopsy site should be selected when possible. Suitable alternative sites are present bilaterally in this patient.

Of all oral soft tissues, the gingiva is likely to be the site that is most often traumatized by normal functions such as chewing, toothbrushing, flossing, use of toothpicks, gingival massage, or ingestion of hot or caustic foods or liquids. This is likely to cause the epithelium to slough when a mucocutaneous condition is present, thereby interfering with biopsy diagnosis. This sloughing is also especially common when a gingival biopsy is performed. Consequently, lesions in other oral sites should probably be selected for biopsy.30,43,74 Data from the TAMUBCD Stomatology Center indicates 18.9% of oral lichen planus patients and 16.3% of pemphigus vulgaris patients had lesions confined only to the gingiva. This indicates accessible extragingival oral sites are usually available.74,77 In contrast, over 67% of patients with oral mucous membrane pemphigoid had lesions that were confined exclusively to the gingiva, indicating the type of mucocutaneous disease present can markedly influence the necessity for a gingival biopsy.74 Nonetheless, there is often no option to performing a gingival biopsy. In the past this factor has presented a major impediment to confirmation of the histopathological and immunofluorecence diagnosis.80 However, some newer developments in biopsy techniques may aid in retaining intact epithelium in gingival biopsies.31 In addition, studies are currently being conducted to evaluate the effectiveness of reflectance confocal microscopy in diagnosis of mucocutaneous diseases without requiring a biopsy.2