Oropharynx Biopsy
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The oropharynx occupies the area of the aerodigestive tract between the oral cavity, the nasopharynx, and the hypopharynx. The anterior border is defined as the glossopalatal arch (also known as the anterior tonsillar pillar); the superior border is the plane of the soft palate; and the inferior border is the plane of the epiglottic tip. Major structures within the oropharynx include the tonsillar (faucial) arches, tonsils, vallecula, base of the tongue, soft palate, uvula, and posterior and lateral pharyngeal wall (within the confines of the axial planes outlined above).
The muscles that form the posterior wall of the oropharynx are the overlapping superior and middle pharyngeal constrictors and their overlying mucous membrane. The glossopharyngeal nerve and the stylopharyngeus muscle enter the pharynx at the border between the superior and middle constrictors. For more information about the relevant anatomy, see Throat Anatomy.
Oropharyngeal biopsy may take several forms, all sharing the purpose of identifying the histopathology of lesions. Biopsies may be performed in the setting of an outpatient office, or may require formal operative settings with general anesthesia. The setting of the biopsy is determined by patient factors (eg, age, gag reflex), the extent of the biopsy (eg, small mucosal sample vs tonsillectomy), and accessibility of the lesion’s location (eg, base of the tongue, vallecula).
Biopsy should be performed on any oral lesion that persists despite removal of any irritative stimulus.
Biopsy is indicated if mucosal lesion findings suggest malignancy as follows: erythroplakia, leukoplakia, induration or fixation to deeper tissues, rapid growth, friability, or ulceration. [1, 2, 3]
Biopsy samples of tonsillar lesions may be best obtained through formal tonsillectomy, particularly if neoplasm is the concern.
In adults, tonsil ulcerations, friability, or induration are concerning findings and should be biopsied.
In adult patients, particularly those exposed to tobacco or alcohol, tonsillectomy is advised. However, tonsil extranodal non-Hodgkin lymphoma does not have the same association with these exposures. Evidence of a role for human papillomavirus (HPV; particularly HPV-16) in tonsillar squamous cell carcinoma has grown. [1, 4, 5, 6, 7] Some series indicate greater than 50% of tonsillar carcinoma contain HPV-16 genetic material and do not have the strong association with tobacco that many other head and neck squamous cell carcinomas do. HPV-associated squamous cell carcinoma of the tonsil and base on tongue is more prevalent in men than women, adn presenting at an earlier age than those tumors associated with tobacco use. Many of these tumors are occult, and are found during the investigation of a new neck mass (metastatic disease)
Asymmetry of the tonsils has traditionally been considered an indication for tonsillectomy in order to pathologically evaluate for potential neoplasm as the source of the asymmetry. However, some studies have shown that most visualized tonsillar asymmetry is an optical illusion caused by tonsillar fossa depth. [8] When tonsillectomy is performed for asymptomatic tonsillar asymmetry, only 5% of patients will have malignant findings on pathology results. [9] Others have noted even lower rates. [10] Therefore, some have advocated a period of conservative management and observation in patients with no risk factors for malignancy and no other abnormal head and neck examination findings. [11]
In patients with cervical squamous cell carcinoma metastasis with unknown primary tumor (Neck Cancer, Unknown Primary Site), biopsies of the oropharynx are included in the evaluation. [12] Most unknown primary cancers reside within the Waldeyer ring, and biopsies of the base of the tongue and tonsils are recommended. Within the new era of HPV-related oropharyngeal carcinoma, the majority of these “unknown primaries” are metastatic HPV-positive orpharyngeal cancers. Some controversy exists as to the necessary extent of this biopsy, ranging from focal biopsy of abnormal findings to unilateral or bilateral tonsillectomy and base of tongue resection. “Blind” focal biopsy of the tonsils is not recommended, with a positive rate of only 13% vs 39% found on formal tonsillectomy. [13] Some authors advocate bilateral tonsillectomy, given a 10% chance of the primary cancer being contralateral to the neck disease, [14, 15] whereas others recommend it only in bilateral neck disease. [16] The nasopharynx should be inspected for abnormalities and biopsy as appropriate, although the historic blind biopsy is not recommened.
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. The following may be contraindications to biopsy, or they may alter the circumstances of the biopsy (office vs operating room):
Bleeding diathesis secondary to anticoagulation, or significant coagulopathy
Airway issues that could be exacerbated by the biopsy (If concerns regarding airway control exist [eg, bleeding, edema], biopsy may be better performed in the operating room with the airway secured.)
Lesion located near vital structures that could be injured by biopsy (eg, lateral pharynx near carotid artery)
Medical conditions that do not allow for the use of local anesthetics (These patients may require general anesthesia in the operating room.)
Oropharyngeal biopsy for mucosal lesions may be performed under local anesthesia, using 1% or 2% lidocaine, with 1:100,000 epinephrine. For more information, see Nerve Block, Oral.
The use of topical anesthetic sprays is not usually sufficient for anesthesia in the case of biopsies, although some clinicians may use them prior to injection of the local anesthetic. Topical anesthetics may also be beneficial in reducing the gag reflex. For more information, see Anesthesia, Topical.
Spray benzocaine may be used, if desired. The use of benzocaine can be associated with methemoglobinemia and should be used cautiously. Follow the manufacturer’s recommendations closely. Spray bursts should be limited to less than 2 seconds. [17]
Inject the site at the desired biopsy location, using a 27- or 30-gauge needle and a 1- to 3-mL syringe. Posterior sites may require the use of a small-gauge spinal needle.
Equipment includes the following:
Local anesthesia and syringes as described in Anesthesia section
Scalpel with No. 15 blade
Through-cut/true-cut/Tru-cut endoscopic forceps (shown below), as used in sinus procedures
Fine tissue forceps with teeth
Fine curved scissors, such as Iris or Littler
Needle holder
Gauze sponges
Tongue retractor, such as sweetheart retractor, or tongue depressor (see below)
Sutures (Most biopsies do not require suture closure, but it may be appropriate per the surgeon’s discretion.)
Cautery method (silver nitrate, electrocautery, or laser)
Carbon dioxide or Nd:YAG laser, if available and deemed advantageous to the surgeon
Specimen bottle with 10% formalin (If direct immunofluorescence studies are needed, the specimen should be sent in Michel’s solution.)
Mouth prop, such as McIvor, Crowe-Davis, or Dingman (if performed in the operating room)
Positioning in the office Having the patient in an upright seated position is preferable. This may be accomplished in an otolaryngology or dental examination chair. A gurney or hospital bed placed in an upright position is also acceptable.
After induction of anesthesia, the patient is placed in the Rose position with a shoulder roll in place.
See the list below:
Preparation
Explain the procedure, indications, and risks as part of the informed consent process.
Ensure 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.
Through-cut forceps technique for mucosal lesion
This technique is best for easily seen and exophytic lesions.
After anesthetizing the patient, depress the tongue with a retractor.
Use the cutting forceps to sample or remove the exophytic lesion, depending on its size.
Take care not to drop the biopsy sample from the forceps and lose it or create a potential airway foreign body.
Cautery is not likely necessary if local anesthesia with epinephrine is used. No sutures are necessary.
Crush artifact can be one concern with this technique; take care to minimize this issue.
Other techniques for mucosal lesions
A scalpel and forceps may be used instead of the through-cut endoscopic forceps. However, the surgeon may find that manipulation of the scalpel in the oropharynx is more difficult, particularly if an assistant is not available.
Punch biopsies of the oropharynx are best used on areas of limited mucosal mobility (eg, hard palate), but they may be used in certain areas of the oropharynx. As a whole, they likely do not provide any significant advantage over scalpel excision.
See the list below:
Preparation
Explain the procedure, indications, and risks as part of the informed consent process.
Discuss the operative plan with the anesthesiologist. If laser is to be used, a laser safe tube should be used. If the oropharyngeal lesion interferes with the airway and traditional transoral intubation techniques, a difficult airway plan should be made with the anesthesiologist.
After induction of anesthesia, place the patient in the Rose position with a shoulder roll in place.
As in tonsillectomy, use a mouth prop for exposure.
Use a headlight for illumination of the oropharynx.
Injection of local anesthesia with epinephrine may be helpful to reduce bleeding and possibly allow for some postoperative analgesia.
Techniques
The biopsy of mucosal lesions may be performed using a multitude of techniques. Scalpel and forceps may be used to excise the lesion elliptically or to take a representative sample. If a laser or cautery is used, the surgeon must be aware of the endotracheal tube position to avoid a potential ignition of the tube and subsequent airway fire. [18] Additionally, cautery-effect should be accounted for in the biopsy and wider margins included. Care should be taken if the lesion is ulcerative to not sample only the base of the ulcer but rather the leading edge of the ulcer to avoid nondiagnostic findings (eg, necrosis, acute and chronic inflammation).
Submucosal lesions may be biopsied via a simple incision and absorbable suture closure. The location of the lesion should determine if transoral biopsy is prudent, as lesions in the lateral oropharynx may be near the great vessels. Biopsy in these circumstances could yield a vascular injury, which would be very difficult to manage rapidly, as the surgeon would not have vascular control. Vascular injuries may be more likely with certain anatomic variants (eg, retropharyngeal course of the carotid artery) or anomalies (eg, carotid aneurysm, pseudoaneurysm) that are not recognized. See image below.
If the area of concern is the tonsil itself, tonsillectomy may be the best form of biopsy. See the Indications section above as well as Medscape Reference’s Tonsillectomy article.
The images below depict the procedure.
Biopsies may be performed in the office or operating room setting, depending on the patient’s tolerance, medical factors, extent of necessary biopsy, and location of the lesion.
Asymmetric tonsils may or may not mandate tonsillectomy, depending on risk factors, physical findings, and the comfort of the physician and patient with a watch and wait approach.
In unknown primary cervical squamous cell metastasis, bilateral tonsillectomy is recommended in combination with other areas of the oropharynx and Waldeyer ring.
Conservative use of benzocaine sprays is warranted, secondary to the risk of methemoglobinemia.
Complications include the following:
Bleeding
Pain: This is usually minimal but typically increases with increased surface area of the mucosal defect created by the biopsy. This is more notable in tonsillectomy.
Damage to nearby structures such as teeth, lips, tongue, glossopharyngeal nerve, greater palatine neurovascular bundle, and carotid artery
Lack of diagnosis secondary to nondefinitive biopsy
St Guily JL, Clavel C, Okaïs C, Prétet JL, Beby-Defaux A, Agius G, et al. Human papillomavirus genotype distribution in tonsil cancers. Head Neck Oncol. 2011 Feb 7. 3(1):6. [Medline]. [Full Text].
Sinha P, Kallogjeri D, Gay H, Thorstad WL, Lewis JS Jr, Chernock R, et al. High metastatic node number, not extracapsular spread or N-classification is a node-related prognosticator in transorally-resected, neck-dissected p16-positive oropharynx cancer. Oral Oncol. 2015 Mar 11. [Medline].
Bishop JA, Lewis JS Jr, Rocco JW, Faquin WC. HPV-related squamous cell carcinoma of the head and neck: An update on testing in routine pathology practice. Semin Diagn Pathol. 2015 Feb 4. [Medline].
Luginbuhl A, Sanders M, Spiro JD. Prevalence, morphology, and prognosis of human papillomavirus in tonsillar cancer. Ann Otol Rhinol Laryngol. 2009 Oct. 118(10):742-9. [Medline].
Nasman A, Attner P, Hammarstedt L, Du J, Eriksson M, Giraud G. Incidence of human papillomavirus (HPV) positive tonsillar carcinoma in Stockholm, Sweden: an epidemic of viral-induced carcinoma?. Int J Cancer. 2009 Jul 15. 125(2):362-6. [Medline].
Schneider K, Marbaix E, Bouzin C, Hamoir M, Mahy P, Bol V, et al. Immune cell infiltration in head and neck squamous cell carcinoma and patient outcome: a retrospective study. Acta Oncol. 2018 Mar 1. 1-8. [Medline].
Dang J, Feng Q. HPV16 infection in oral cavity and oropharyngeal cancer patients. J Oral Sci. 2016. 58 (2):265-9. [Medline].
Harley EH. Asymmetric tonsil size in children. Arch Otolaryngol Head Neck Surg. 2002 Jul. 128(7):767-9. [Medline].
Syms MJ, Birkmire-Peters DP, Holtel MR. Incidence of carcinoma in incidental tonsil asymmetry. Laryngoscope. 2000 Nov. 110(11):1807-10. [Medline].
Puttasiddaiah P, Kumar M, Gopalan P, Browning ST. Tonsillectomy and biopsy for asymptomatic asymmetric tonsillar enlargement: are we right?. J Otolaryngol. 2007 Jun. 36(3):161-3. [Medline].
Sunkaraneni VS, Jones SE, Prasai A, Fish BM. Is unilateral tonsillar enlargement alone an indication for tonsillectomy?. J Laryngol Otol. 2006 Jul. 120(7):E21. [Medline].
Gilde J, Song B, Masroor F, Darbinian JA, Ritterman Weintraub ML, Salazar J, et al. The diagnostic pathway of oropharyngeal squamous cell carcinoma in a large U.S. healthcare system. Laryngoscope. 2017 Dec 15. [Medline].
McQuone SJ, Eisele DW, Lee DJ, Westra WH, Koch WM. Occult tonsillar carcinoma in the unknown primary. Laryngoscope. 1998 Nov. 108(11 Pt 1):1605-10. [Medline].
Koch WM, Bhatti N, Williams MF, Eisele DW. Oncologic rationale for bilateral tonsillectomy in head and neck squamous cell carcinoma of unknown primary source. Otolaryngol Head Neck Surg. 2001 Mar. 124(3):331-3. [Medline].
Goldenberg D, Sciubba J, Koch WM. Cystic metastasis from head and neck squamous cell cancer: a distinct disease variant?. Head Neck. 2006 Jul. 28(7):633-8. [Medline].
Randall DA, Johnstone PA, Foss RD, Martin PJ. Tonsillectomy in diagnosis of the unknown primary tumor of the head and neck. Otolaryngol Head Neck Surg. 2000 Jan. 122(1):52-5. [Medline].
Ash-Bernal R, Wise R, Wright SM. Acquired methemoglobinemia: a retrospective series of 138 cases at 2 teaching hospitals. Medicine (Baltimore). 2004 Sep. 83(5):265-73. [Medline].
Villarroya Gonzalez A, Longas Valien J, Vicente Armijo JJ, Cuartero Lobera J. [Orotracheal tube ignited by an electrocautery device during tracheostomy]. Rev Esp Anestesiol Reanim. 2009 Jan. 56(1):47-9. [Medline].
El-Mofty SK. Human papillomavirus-related head and neck squamous cell carcinoma variants. Semin Diagn Pathol. 2015 Jan. 32(1):23-31. [Medline].
Johnathan D McGinn, MD, FACS Associate Professor, Residency Program Director, Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, Milton S Hershey Medical Center, Pennsylvania State University College of Medicine
Johnathan D McGinn, MD, FACS is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery, American College of Surgeons, American Rhinologic Society, Pennsylvania Medical Society, Society of University Otolaryngologists-Head and Neck Surgeons
Disclosure: Nothing to disclose.
Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Nothing to disclose.
Arlen D Meyers, MD, MBA Professor of Otolaryngology, Dentistry, and Engineering, University of Colorado School of Medicine
Arlen D Meyers, MD, MBA is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, American Head and Neck Society
Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cerescan;RxRevu;Cliexa;Preacute Population Health Management;The Physicians Edge<br/>Received income in an amount equal to or greater than $250 from: The Physicians Edge, Cliexa<br/> Received stock from RxRevu; Received ownership interest from Cerescan for consulting; for: Rxblockchain;Bridge Health.
Arlen D Meyers, MD, MBA Professor of Otolaryngology, Dentistry, and Engineering, University of Colorado School of Medicine
Arlen D Meyers, MD, MBA is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, American Head and Neck Society
Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cerescan;RxRevu;Cliexa;Preacute Population Health Management;The Physicians Edge<br/>Received income in an amount equal to or greater than $250 from: The Physicians Edge, Cliexa<br/> Received stock from RxRevu; Received ownership interest from Cerescan for consulting; for: Rxblockchain;Bridge Health.
Medscape Reference thanks Dr. Brian Reilly, MD, Assistant Professor of Otolaryngology and Pediatrics, Department of Otolaryngology, Children’s National Medical Center, George Washington University School of Medicine, for images 5-9 and the video in this article.
Oropharynx Biopsy
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