Lip Biopsy

Updated: Oct 24, 2022
Author: Johnathan D McGinn, MD, FACS; Chief Editor: Arlen D Meyers, MD, MBA 


Lip biopsy may be necessary to identify the histopathology of a visible oral lesion or to assist in the diagnosis of a systemic disorder.

If a lesion is noted on the lip or oral mucosa, incisional or excisional biopsy is clinically indicated if concern for malignancy exists. Findings such as red or white discoloration, induration or fixation to deeper tissues, rapid growth, friability, or ulceration should raise concerns for malignancy. Some advocate monitoring a lesion for 2 weeks after any irritants are eliminated, to allow for any inflammatory or irritative lesions to resolve. If a lesion does not respond to this conservative management, then biopsy is indicated.

Lip biopsy (specifically the minor salivary glands of the lip) may also be used to assist in the diagnosis of Sjogren syndrome, a chronic autoimmune disorder involving the destruction of glandular tissue. The glandular tissues involved include both minor and major salivary glands and the lacrimal gland. Other systemic disorders, such as sarcoidosis, amyloid polyneuropathy, and neonatal hemochromatosis may be confirmed with a lip biopsy.[1]

Punch biopsy and scalpel biopsy may also be of assistance.



See the list below:

  • Biopsy should be performed on any oral lesion that persists despite removal of an irritative stimulus.

  • Biopsy is indicated if mucosal lesion findings suggest malignancy (eg, erythroplakia, leukoplakia, induration or fixation to deeper tissues, rapid growth, friability, ulceration).

  • Submucosal minor salivary gland biopsy should be done if the diagnosis of Sjögren syndrome (SS) cannot be made by history and serologic testing (eg, SS-A/Ro and SS-B/La) or if, despite testing, the diagnosis remains in question.



Lip biopsy has few absolute contraindications. The decision to proceed with biopsy in the following circumstances must be individualized to the patient’s findings and the ability of the surgeon to minimize morbidity.

  • Bleeding diathesis secondary to anticoagulation, or significant coagulopathy.  However, the lip is very amenable to manual pressure and easy to access for cauterization.

  • Biopsy of tissue overlying irradiated bone or over bone in patients on bisphosphonates.  Mandibular osteonecrosis may occur in these patients. This is not typically a problem with true lip biopsies but can be with other oral cavity biopsies or if the lip biopsy extends to the gingiva.

  • Medical conditions that do not allow for the use of local anesthetics



Lip biopsy for mucosal lesions or minor salivary glands is typically done under local anesthesia, using 1% or 2% lidocaine with 1:100,000 epinephrine. Procedures in children may require sedation. For more information, see Procedural Sedation.

Topical anesthetic sprays are not usually sufficient for anesthesia in the case of biopsies, although some clinicians may use them prior to injection of the local anesthetic.

Spray benzocaine or apply viscous lidocaine to the lip mucosa, if desired. Benzocaine can be associated with methemoglobinemia and should be used cautiously.[2]

Inject the lip at the desired biopsy location (see image below), using a 27- or 30-ga needle and a 1- to 3-mL syringe. For more information, see Nerve Block, Oral.

Injection of local anesthesia into lip for biopsy. Injection of local anesthesia into lip for biopsy.


See the list below:

  • Local anesthesia and syringes as described in Anesthesia

  • Scalpel with No. 15 blade, chalazion clamp (see image below), or biopsy punch, per surgeon preference (see Technique)

    Chalazion clamp. Chalazion clamp.
  • Fine tissue forceps with teeth

  • Fine curved scissors (eg, Iris, Littler)

  • Needle holder

  • Gauze sponges

  • Retractors (Sharp skin-type may be helpful.)

  • Suture for closure

  • Cautery method (silver nitrate, electrocautery, or laser)

  • Carbon dioxide or Nd:YAG laser, if available and deemed advantageous by the surgeon[3]

  • Specimen bottle with 10% formalin (If direct immunofluorescence studies are needed, the specimen should be sent in Michel solution.)



An upright sitting position is preferable.

The patient may be seated in a otolaryngology or dental examination chair. A gurney or hospital bed placed in an upright position is also acceptable.




See the list below:

  • Explain the procedure, indications, and risks as part of the informed consent process.

  • Insure that adequate lighting is available. This may take the form of a head mirror, headlight, or surgical light.

  • Anesthetize the biopsy site via infiltration of the local anesthetic.

  • The surgeon should be familiar with the anatomy of the region (see image below). For a detailed discussion, see Medscape Reference article Lips and Perioral Region Anatomy.

    Cross-section of lip. Cross-section of lip.

Scalpel technique for mucosal lesion

An elliptical incision is typically used to obtain an incisional or excision biopsy of a visible mucosal lesion. Orientation of the ellipse should take into account the vascular and neural structures in the area, as well as any functional or cosmetic concerns. For the lip, most elliptical incisions should parallel the long axis of the lip, to most easily allow the recommended 3:1 length:width ratio. In large resections, the vermilion of the lip may be reduced or the white roll at the vermilion junction may be retracted. Incisions perpendicular to the long axis cause less of this distortion but may require extension beyond the vermilion border or onto gingival tissue to maintain the 3:1 ratio.

Many experts recommend excisional biopsies that include the visible lesion as well as a portion of neighboring normal mucosa. This recommendation is based on the concept that the junction of normal and abnormal tissue is the point of interest and allows for better pathologic evaluation of the lesion. While necessary in ulcerative lesions in which mucosa is absent, this consideration is likely not essential. More critical is obtaining a representative specimen of the entire lesion.[3]

  • Plan the elliptical incision.

  • After allowing for hemostatic properties of 1:100,000 epinephrine in local anesthetic, incise the mucosa with 2 curvilinear lines, forming the ellipse.

  • Delicately grasp the edge of the ellipse with fine forceps.

  • Dissect beneath the ellipse with fine sharp scissors. The depth of dissection should be determined by the lesion characteristics. In most mucosal lesions, the plane of dissection is in the layer that contains the minor salivary glands, leaving the orbicularis oris muscle intact. Sharp skin hook retractors may be helpful, if an assistant is available.

  • Deliver the elliptical specimen and send to the pathology laboratory in the appropriate tissue media.

  • Obtain hemostasis via manual pressure, silver nitrate cautery, or electrocautery.

  • Closure of the wound may be aided by circumferential undermining, depending on the size of the resultant defect.

  • Suture the mucosa to reapproximate the edges. Suture type is based on surgeon preference, from silk to chromic gut to polyglactin.

Other techniques for mucosal lesions

See the list below:

  • Biopsies may be performed with instruments other than a scalpel. Lasers may be used, if available, but care must be taken to include an additional rim of tissue around the lesion to compensate for tissue loss from the thermal device. Laser safety precautions for staff and patient must be used. Although immediate hemostasis is improved with the laser, the benefits may not outweigh the added issues.

  • Punch biopsies of oral and lip lesion likely do not provide any significant advantage over scalpel excision. On mucosa that is more attached to underlying tissues (eg, hard palate), the punch biopsy technique may offer some benefit.[3]

  • Cup biopsy forceps may also be used but have little advantage on the lip. They are better designed for oropharyngeal biopsy sites. Additionally, they offer the potential risk of crush artifact.

Scalpel technique for minor salivary gland biopsy

See the list below:

  • The goal of minor salivary gland biopsy is to provide the pathologist 3-5 glands for examination. Excision of mucosa is not necessary.[3, 1, 4, 5]

  • Make a linear 1.5-cm incision on the lip mucosa, oriented parallel to the lip’s long axis. The lower lip is used for convenience of positioning. This incision should be placed lateral to the midline, as the minor salivary gland density is greater than on the midline. Placing the lip on stretch may allow for visualization of the submucosal minor salivary glands. See image below.

    Minor salivary glands seen through the mucosa. Minor salivary glands seen through the mucosa.
  • The minor salivary glands are readily identifiable by their lobular nature, superficial to the muscle. Remove several individual glands for pathologic evaluation and place them in formalin. Take care during dissection to avoid injury to nearby branches of the mental nerve. See images below.

    Minor salivary glands seen in situ. A branch of th Minor salivary glands seen in situ. A branch of the mental nerve is also visible within the surgical site.
    Excised minor salivary glands. Excised minor salivary glands.
  • Achieve hemostasis via manual pressure, silver nitrate cautery, or electrocautery.

  • Close the incision with suture (silk, chromic gut, or polyglactin) to reapproximate the mucosal edges. See image below.

    Closure of lip biopsy site. Closure of lip biopsy site.

Alternative techniques for minor salivary biopsy

See the list below:

  • A chalazion clamp may be used to fixate the lower lip mucosa, allow for manipulation of the lip during the procedure, and permit the minor salivary glands to be more easily seen through the stretched mucosa. Additionally, bleeding is minimized by use of this clamp. See image below.

    Chalazion clamp in position for biopsy. Chalazion clamp in position for biopsy.
  • Some surgeons advocate a technique using several small stab incisions. If the lip is stabilized and then stretched, the underlying minor salivary glands may be visible. If their location is then marked, and a small stab incision placed over each, the glands can be individually delivered from the incision. No sutures are necessary for closure.[1]

  • Some literature supports the idea that alternative sites may provide some advantages in attempting to confirm Sjögren syndrome via biopsy. Both the parotid gland[6] and the sublingual gland[7] have been considered as alternative sites with similar sensitivity and specificity and reduced morbidity.



The decision to perform a biopsy on a lip lesion is based on clinical index of suspicion or lack of resolution within 2 weeks of removal of any irritants.

Minor salivary gland biopsy is done transorally and should include at least 3–4 glands.

Minor salivary gland biopsy has 38–82% sensitivity and approximately 85–94% specificity for Sjögren syndrome.[7, 6]

Minor salivary gland biopsy may assist in making other systemic disease diagnoses, such as sarcoidosis, amyloid polyneuropathy, or neonatal hemochromatosis.



Hypesthesia of the lower lip occurs in 1–6% of cases.[5, 8]

Pain is usually minimal and lasts 1–2 days.

Lip biopsy may not be sufficient for diagnosis. Given the sensitivity of these biopsies for Sjögren disease, additional biopsies may be needed. Some authors have recommended sublingual gland biopsy and parotid gland tail biopsies as alternatives with higher sensitivity and minimal complications.

One study found that minimally invasive lip biopsy technique for diagnosis of Sjögren disease induces fewer permanent neurological complications than conventional approaches with large linear incisions in the lower lip.[9]