Oral Biopsies: Methods and Applications

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IN BRIEF ● Biopsies of different tissue types and sites require specific techniques. ● Correct handling of biopsy specimens is crucial. VERIFIABLE ● The chosen site for a mucosal biopsy is dependent upon the disease/lesion. CPD PAPER ● Written consent is advised for all biopsies.

Oral biopsies: methods and applications

R. J. Oliver1 P. Sloan2 and M. N. Pemberton3

Biopsies are an important diagnostic tool for the diagnosis of lesions ranging from simple periapical lesions to malignancies. Planning prior to performing a biopsy is essential. It will be beneficial to the receiving pathologist in reaching a helpful and meaningful diagnosis, and therefore ultimately and more importantly, to the patient. This paper presents an updated view of biopsies and discusses some of the potential problems with biopsy technique and specimens and how to overcome them.

A biopsy is often the only way to diagnose avoid them. The authors feel it will be of of submitting material; one respondent4 oral lesions and diseases and as with most value to both general dental practitioners cited that the non-submission of material procedures there is often more than one and junior hospital staff. Problems related often leads to a failure to diagnose and the method of undertaking the surgery suc- to specific areas will be covered including situation regarding periapical lesions is no cessfully. Whatever the method used, how- apical lesions and those associated with the different, no matter how rare such ever, the aim is to provide a suitably repre- dental hard tissues. Mucosal and soft tissue instances occur. sentative sample for the pathologist to biopsies together with general points For diagnosis, the excised material interpret, while minimising perioperative regarding techniques and fixation will also needs to be fixed to stop tissue autolysis discomfort for the patient. An unsuitable, be discussed. prior to the sample reaching the pathology unrepresentative sample is of no use to the laboratory. The solution of choice to do this pathologist, clinician or most importantly SPECIFIC TISSUES is 10% neutral buffered formalin fixative (a the patient who would be ill served by an 4% solution of formaldehyde). This can unnecessary repeat procedure. Although Apical lesions and those associated with easily be obtained on request from most most biopsies are performed in hospitals, a the dental hard tissues pathology laboratories together with a sup- recent study has shown that many general Many apical lesions are submitted routine- ply of request forms and specimen pots. In dental practitioners felt able to perform ly from general dental practice as well as a recent survey,1 many practitioners biopsies but lacked some of the necessary hospitals following periradicular surgery. appeared unaware of these facilities and as skills.1 The purpose of this article is to The majority of the lesions are inflammato- such pathology laboratories may need to review those skills, to discuss new develop- ry in origin, most commonly periapical consider advertising their services more ments in this area, and to highlight some of granulomas or radicular cysts. Less com- widely. It should be noted that some labo- the potential pitfalls that may occur in tak- monly, other odontogenic cysts present at ratories might levy a nominal charge for ing a biopsy and methods available to the apex, namely nasopalatine duct cyst or such services. of greater significance the odontogenic Some clinicians submit apical lesions on keratocyst. Less frequently still, odonto- gauze which has been placed in formalin 1Lecturer in Oral Surgery, 2Professor of Oral Pathology, 3Consultant in Oral Medicine, Oral and Maxillofacial genic tumours may present at such a site. solution. However, if the volume of forma- Sciences, University Dental Hospital of Manchester, Higher Bone lesions such as Langerhans cell histi- lin in the container is not great enough, the Cambridge Street, Manchester M15 6FH ocytosis, giant cell granuloma and myelo- gauze tends to absorb most of the formalin Correspondence to: Dr. Richard Oliver, University Dental ma may also present in this way. Rarely, leaving the specimen dry and unfixed. Hospital of Manchester, Higher Cambridge Street, Manchester, M15 6FH malignant metastatic deposits or even Although not essential, it is desirable to E-mail: [email protected] intraosseous squamous cell carcinoma can inform the pathologist if bone is included occur at this site.2 The value of routinely in the specimen. Refereed Paper doi:10.1038/sj.bdj.4811075 examining apical lesions has recently been Occasionally, it is necessary to examine Received 05.12.02; Accepted 07.07.03 questioned,3 however, the resulting corre- the dental hard tissues, most often to rule © British Dental Journal 2004; 196: 329–333 spondence has all been strongly in support out an abnormality of dentine or enamel.

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As with most other tissues submitted for allows confirmation that it is arising from intact area of mucosa which is often the routine examination, teeth should also be the overlying epithelium rather than from a attached gingiva; an elliptical area of submitted in 10% neutral buffered formalin deeper structure or from a metastasis from mucosa is incised and carefully dissected fixative. A mineralised sample, such as a different site. It also allows the invasive from the underlying periosteum with a bone or tooth may require decalcification front to be examined which can yield use- Mitchell's trimmer. before it can be processed. The time for the ful prognostic information.5 The centre of decalcification will vary according to the larger tumours should be avoided as this is Precancerous lesions size and consistency of the specimen as often necrotic and will not yield diagnostic For the precancerous lesions of leukoplakia well as the methods employed by a particu- material. A recent study has demonstrated and erythroplakia, the adequate and correct lar laboratory, but it should be borne in that cytokeratins were present in the sampling of lesions may prove more diffi- mind that it can be a matter of weeks peripheral blood of two out of ten patients cult. It is now well recognised that lesions before a histopathology report is available. 15 minutes after the incisional biopsy of an showing a non-homogenous or speckled oral squamous cell carcinoma, thereby appearance and lesions of erythroplakia Mucosal biopsies demonstrating that there was dissemina- are potentially more serious with a gener- Biopsy technique for the sampling of tion of cancer cells which may result in ally higher incidence of dysplasia and mucosal biopsies can be critical. If a metastasis.6 These authors suggested that malignant transformation.7 These areas, if tumour or premalignant disease is suspect- chemotherapeutic drugs should be admin- present, should be the site of choice for ed, or when widespread mucosal disease is istered prior to biopsy to minimise the risk biopsy. If the lesion is extensive or there are suspected, we would strongly advocate the of metastasis in such patients. However, the numerous erythematous regions it may be biopsy being undertaken in a hospital set- incidence of blood borne metastasis in prudent to biopsy more than one area. ting following appropriate referral; such relation to oral cancer is low, but this area lesions should not be biopsied in general merits further investigation. Handling of mucosal biopsies dental practice. Such biopsies should be Care should be exercised when handling performed by the clinician who is going to Mucocutaneous lesions mucosal biopsy specimens as they can be initiate the treatment. Some of the follow- Biopsies are commonly taken to confirm particularly prone to damage. Sometimes ing section is, therefore, for information for the clinical diagnosis of lichen planus, specimens can be rendered of little diag- general dental practitioners and of more lichenoid reactions or other similar muco- nostic value due to poor handling which relevance to junior hospital staff. cutaneous conditions. To aid in the histo- produce a crush artefact in histological Simple excisional biopsies of polyps or logical diagnosis of such lesions, an area of section. There are various methods avail- epulides are suitable for general dental non-erosive lesional tissue should be cho- able to reduce traumatic damage to the practice, and can be both diagnostic and sen. Sampling of an erosive area will often specimens. curative at the same time. Before embark- show non-specific inflammatory changes A popular method is to place a suture ing on a biopsy the question of what the associated with ulceration and will not aid within the mucosa that is to be removed, biopsy is being taken for must be answered in the diagnosis. Adjacent normal tissue is and hold the ends of the suture in an (Table 1). The provisional clinical diagno- not generally required for such lesions. artery forcep or sometimes tie a loose knot sis is especially important in guiding the Similarly for suspected vesiculobullous above the mucosa, while undertaking the technique and tissue handling to be used disorders, the site of the biopsy should be biopsy. A tight knot close to the specimen, (Table 2). adjacent to bulla where the epithelium is however, is to be avoided as it may result still intact. For these lesions it is desirable in the tissue being crushed. The use of Suspected malignancy also for the laboratory to receive a fresh such a suture can aid the biopsy procedure If the reason for the biopsy was to exclude specimen of tissue in addition to a formalin by providing traction and preventing malignancy in a long-standing ulcer, a fixed one to allow direct immunofluores- unwanted movement of tissue when tak- biopsy of the ulcer to include some adja- cence (see later regarding fresh specimens). ing a biopsy from mobile structures such cent clinically normal epithelium would be When desquamative gingivitis is present, as the tongue. It also helps the pathologist desirable. If the lesion is a carcinoma this the biopsy should be taken from the most to orientate the biopsy sample for section- ing. The ‘traditional’ technique using toothed tissue forceps to grasp the speci- Table 1 Points to consider prior to mucosal biopsy men is acceptable providing care is taken and the area grasped is away from the 1. Why is biopsy being taken? Eg to confirm a mucosal disease such as lichen main site of interest. planus or to exclude malignancy. The punch biopsy technique is an alternative to the traditional incisional biopsy.8 2. What information is required from the pathologist? Eg is the lesion completely excised. Essentially the punch comprises a circular blade attached to a plastic handle. Diame- 3. Is the biopsy to exclude malignancy? Therefore take the biopsy from the edge ters of two to ten millimetres are available. of the lesion This removes a core of tissue the base of 4. Is the biopsy incisional or excisional? Eg For excisional biopsies a margin of which can be simply and atraumatically surrounding normal tissue will be required. released using curved scissors. Alternative- ly, the specimen can be lifted from the 5. Will the specimen be required to be orientated? This is important for excisional biopsies so that if residual tumour is left or the excision is close to the mucosal surface and the base undermined margin, the surgeon knows where to perform a re-excision if necessary. with a scalpel. Care should be taken if aspiration is being used to prevent the speci- 6. Is a fresh specimen required? For vesiculobullous lesions these are often men being sucked away. The resultant required for direct immunofluorescence. They are also used if a rapid diagnosis wound may not require suturing if using is required. the smaller diameter punches. This technique is described and reviewed in detail by

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Table 2 Guidelines for an appropriate biopsy SOFT TISSUE BIOPSIES Biopsies of the soft tissues are a less common Clinical diagnosis Type of biopsy Suitable for general dental practice procedure. Indications include the diagnosis of granulomatous conditions such as Crohn's Chronic ulcer or Incisional biopsy of No, urgent referral squamous cell carcinoma margin of ulcer to hospital disease and the diagnosis of salivary lesions. In the case of the former, an incisional biopsy Leukoplakia/erythroplakia Incisional or punch No, referral to hospital of adequate depth is required. Punch biopsies biopsy of worst area consider multiple can sometimes be used but their depth of biopsies if extensive penetration is often limited. lesion When performing labial gland biopsies Mucosal lichen planus Incisional biopsy of a Only very experienced in the diagnosis of Sjögren's syndrome, a representative area practitioners minimum of five minor salivary gland lob- ules should be obtained. The lower lip is the Bullous lesions Incisional or punch No, referral to hospital (pemphigus pemphigoid, biopsy of unaffected site of choice and care should be taken to etc) mucosa close to bulla or minimise trauma to adjacent glandular tis- erosion plus fresh tissue sue which is not being removed. Addition- specimen ally, minimal sharp dissection of the area Granulomatous diseases Deep incisional biopsy No, referral to hospital should be performed to lessen the chance (Crohn's, orofacial plus fresh sample to of sensory nerve damage. granulomatosis, microbiology if infective Mucocoeles arise from the blockage and ulcerative colitis, TB) agent suspected subsequent rupture of minor salivary gland Mucocoele Careful excision biopsy Yes, with care ducts. It is important when excising such Fibroepithelial polyp, Excision biopsy Yes lesions to remove the associated minor pyogenic granuloma, salivary glands to help prevent recurrence. epulis As with labial gland biopsies, care should Minor salivary gland Palate: deep incisional No, urgent referral be exercised to minimise trauma to adja- tumour biopsy to hospital cent tissues. Mucocoeles are extremely Upper lip: excisional uncommon in the upper lip, so swellings in biopsy this site should be treated as minor salivary Major salivary gland FNAC/FNCB (Seek No, urgent referral gland tumours, until proved otherwise, and tumour advice) to hospital carefully and completely excised. For palatal swellings which are suspected salivary tumours, incisional biopsies Lynch and Morris.9 Punch biopsies have using the punch biopsy technique, and should be as deep as possible and down to been shown to have fewer artefacts than access to some sites such as the lingual bone if appropriate after due attention to conventional incisional biopsies,10 although gingivae may be impossible using this the position of the palatal vessels and Kerwala11 argued that careful handling technique. nerves. This is due to the anatomy of the using a suture during an incisional biopsy region as lesions can be a considerable would also produce minimal artefacts. Orientation of biopsies depth beneath the mucosa and so a superfi- A case has been reported of surgical The majority of mucosal biopsies are inci- cial biopsy may give a false negative result. emphysema following an intra-oral punch sional, however, occasionally small Vascular lesions, haemangiomas for biopsy caused by the patient sneezing lesions may be excised encompassing example, should be approached with cau- shortly after the procedure.12 The use of diagnosis and treatment in one operation. tion. Incisional biopsies should never be punch biopsies does require the receiving If malignancy is suspected, the biopsy performed. Smaller lesions obviously with- laboratory to be familiar with the handling should be of sufficient depth and have a in the soft tissues can safely be excised. of such specimens. If in doubt, contact the surrounding margin to ensure adequate Larger lesions, particularly those affecting laboratory prior to performing the biopsy. clearance. In case the lesion was not com- the lip are best ablated with either laser or Also, it is generally safer to use the larger pletely excised it should be orientated. cryosurgery. The disadvantage of these diameter punches to avoid handling prob- This can be achieved by placing a suture techniques is the lack of material for histo- lems both clinically and in the laboratory. at one known margin, for example the logical examination. This is especially true when material for anterior or superior margin. This would For the diagnosis of extra-oral soft tis- both formalin-fixed and frozen processing enable the pathologist to confidently sue swellings the techniques of fine needle is required, such as in the diagnosis of indicate the precise location of any resid- aspiration cytology (FNAC) and fine needle vesiculobullous disorders. ual tumour. The same applies for surgical cutting biopsy (FNCB) are advocated in Generally when performing a mucosal resection specimens. certain situations. These techniques are biopsy an adequate depth of tissue should A technique new to the oral cavity but specialised and the reader is directed be obtained to include the epithelium and a established for other bodily sites is that of towards other publications for details of few millimetres of underlying lamina pro- the brush biopsy. Essentially a hybrid of FNAC15 and FNCB16 techniques. The for- pria. Traditional incisional biopsies are in fine needle aspiration biopsy and exfolia- mer is often best performed by or under the the shape of an ellipse, the length of which tive cytology, this technique uses a small guidance of an experienced cytologist. should be approximately three times the brush to sample cells from all the layers of width.13 the epithelium. Only one large study from FIXATION AND TRANSPORT The site of the biopsy may determine the United States has yet been published Ensure the specimen is placed in an ade- which of the above techniques are possible. but they claimed a high sensitivity and quate volume of fixative, this should be at For example, palatal and gingival sites do specificity using the technique to detect least ten times the volume of the specimen. not generally allow adequate biopsies dysplasia.14 Avoid the use of gauze to place the speci-

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Table 3 Information to accompany mucosal biopsies detailed elsewhere.20 Fulguration artefact 1. Patient demographic data is an important problem induced during 2. Description of the clinical appearance of the lesion and suspected diagnosis electrosurgical or laser cutting of tissue. 3. The site of the biopsy The resulting effect of a layer of carbonised 4. The relationship of the lesion to restorations, particularly amalgam tissue, a zone of thermal necrosis and a zone of tissue exhibiting thermal damage 5. A detailed drug history makes histopathological interpretation 6. Medical history including blood dyscrasias more difficult.21 As such these methods of 7. Smoking and alcohol consumption cutting should not be used for diagnostic incisional biopsies. men onto as it merely absorbs the fixative placed in a sealed plastic bag which should Consideration should also be given to and can make separation of the specimen then be placed in a rigid outer container healing of the biopsy site. It has been sug- from the gauze difficult. The fixative which is capable of being secured by adhe- gested that punch biopsies can be left should be 10% neutral buffered formalin sive tape. Specific cardboard boxes with unsutured.9 Conventional incisional biop- which has a pungent and distinct odour. full-depth lids or grooved polystyrene con- sies are usually closed. The traditional use Occasionally, formalin is further diluted tainers are available for this purpose. A of silk is now being replaced by resorbable with water by ancillary staff or specimens further outer padded bag is recommended sutures such as polyglactin, formulations are placed in alternative solutions such as which should be labelled ‘PATHOLOGICAL of which exist which resorb more rapidly saline or water which results in poor fixa- SPECIMEN — FRAGILE WITH CARE’ and (Vicryl® Rapide, Ethicon Ltd, Edinburgh). tion and artefactual change. Formalin fixes the name and address of the sender should The supply of catgut (manufactured from specimens by forming intermolecular be clearly displayed. Recent correspon- bovine intestine) sutures for human use in bridges between proteins and cross-links dence in this journal has highlighted the the UK has recently ceased because there between protein end-groups.17 If this fact that oral pathology services do not get are acceptable synthetic alternatives avail- process does not occur, soon after removal any part of the fee paid to the GDP for the able although there is no evidence that from the body the specimen will undergo biopsy.19 there is any risk to human health.22 A non- autolysis rendering the tissues progressively Occasionally, specimens are required for eugenol-containing periodontal dressing undecipherable histologically. electron microscopy, these should ideally (Coe-PakTM, GC America Inc.) can be used A disadvantage of the protein cross-link- be fixed in glutaraldehyde, but formalin is for covering gingival biopsy sites. Where ing produced by formalin is that the speci- an acceptable alternative; again this will large palatal biopsies are planned, the men is rendered unsuitable for immunofluo- require some pre-arrangement. Specimens securing of a periodontal dressing under- rescent antibody staining. The diagnosis of for cytogenetics may be required to con- neath a denture or pre-constructed acrylic vesiculobullous autoimmune disorders is firm genetic changes in rare tumours (for base plate can be helpful. aided by direct immunofluorescence of peri- example, synovial sarcoma), these should Label the specimen container with the lesional tissue which requires fresh material be submitted in universal transport medi- patient’s name, date of birth, date of biop- that can be immediately frozen. Most other um which has been stored at 4°C. sy and the site of the biopsy together with immunohistochemical methods used in the hospital number if appropriate. The diagnosis can now be performed on fixed GENERAL POINTS site of the biopsy is especially important tissue with the use of antigen retrieval.18 The Local anaesthesia should be administered if there are specimens from more than other main situation where fresh tissue is deep to or in a field around the proposed one site in an individual patient. If more processed is when frozen sections are used to biopsy site. A regional block can also be than one specimen has to be placed in the examine surgical margins perioperatively. used although the haemostatic effect of the same container, they must be clearly Again the specimen should be delivered to adrenaline within the anaesthetic solution marked, which is most readily done by the laboratory fresh in a sterile universal will be lost. Sampling of tissues at the site means of sutures; do not rely on describ- container or petri-dish. Prior to taking the of the local anaesthetic will produce arte- ing the shapes of the pieces of tissue sub- specimen at operation, it is both advisable factual tissue oedema or distortion. For mitted because when they are fixed this and courteous to telephone the laboratory to example bulla formation in gingival tissue will probably have altered. For mucosal ensure technical support and a pathologist or oedema which may lead to confusion in disease it is desirable for the pathologist are available. the diagnosis of Crohn's disease or orofa- to know details of the factors outlined in Sometimes it is necessary to send patho- cial granulomatosis where interstitial oede- Table 3. Accompanying information such logical specimens through the post to the ma is one of the diagnostic features. as this will enable a more comprehensive laboratory. Both the tissue and the formalin The biopsy should be planned before local interpretation of the specimen, in turn, in which it is placed are potentially harmful anaesthetic is administered. Major vessels producing a more meaningful and useful to those handling the specimen. Precise and nerves should be avoided and to min- report to the clinician. details of the regulations governing the imise the risk of damage to smaller struc- Adequate clinical history supplied on the posting of pathological specimens will be tures, incisions should be made parallel to request form relevant to the suspected diag- available from the laboratory or the Post their expected position. For example, in the nosis is essential to enable the pathologist to Office. Most of the regulations are common palate, incisions should run parallel to the provide a useful and meaningful diagnosis. sense and apply to the packaging of the palatal nerves (ie antero-posteriorly) rather Additionally, on the request form, it is desir- specimen. The primary container in which than across the nerves (medio-laterally). able to have previous biopsy numbers to the specimen is placed with the formalin Attention to the surgical technique will enable comparison to be made if necessary. should be tightly sealed and wrapped in minimise the introduction of artefacts into For example, to comment on the progres- sufficient absorbent material to absorb the the tissues which can hinder pathological sion or regression of a dysplastic lesion. fixative if leakage occurs. Paper towels or diagnosis or even render the specimen It is advised that all patients give cotton wool are suitable for this purpose. non-diagnostic. Some such artefacts have informed written consent to having a The wrapped container should then be been mentioned above and others are biopsy as it is an unusual procedure for

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patients particularly in general dental dent histological diagnosis to be reached. 11. Kerawala C J. Incisional biopsy: reducing artefact. Br J practice (Dental Protection, personal com- Inadequate care at any stage could result Oral Maxillofac Surg 1995; 33: 396. 12. Staines K, Felix D H. Surgical emphysema: an unusual munication). It would be appropriate to in a non-diagnostic biopsy and may complication of punch biopsy. Oral Diseases 1998; 4: include on the consent form the indication necessitate the patient having a repeat 41-42. for the biopsy and details of possible risks procedure with its ensuing physical and 13. Golden D P, Hooley J R. Oral mucosal biopsy procedures. Excisional and incisional. Dent Clin North involved with biopsy procedures. These psychological morbidity. Am 1994; 38: 279-300. risks are mostly site related; paraesthesia 14. Sciubba J J. Improving detection of precancerous and can be induced in the lips or the tongue, 1. Diamanti N, Duxbury A J, Ariyaratnam S, Macfarlane T cancerous oral lesions. Computer-assisted analysis of V. Attitudes to biopsy procedures in general dental the oral brush biopsy. J Am Dent Assoc 1999; 130: swelling and bruising can result from pro- practice. Br Dent J 2002; 192: 588-592. 1445-1457. cedures in the tongue, lips and buccal 2. Lavery K, Blomquist J E, Awty M D, Stevens P J. 15. Orell S R, Sterrett G F, Waters M N, Whitaker D. mucosa, and procedures in the floor of the Squamous cell carcinoma arising in a dental cyst. Br Manual and Atlas of Fine Needle Aspiration Cytology. mouth can lead to submandibular or sub- Dent J 1987; 162: 259-260. Edinburgh and London: Churchill Livingstone, 1986. 3. Walton R E. Routine histopathologic examination of 16. Southam J C, Bradley P F, Musgrove B T. Fine needle lingual duct damage. Removal of muco- endodontic periradicular surgical specimens-is it cutting biopsy of lesions of the head and neck. Br J coeles from the lip carries the risk of fur- warranted. Oral Surg Oral Med Oral Pathol Oral Radiol Oral Maxillofac Surg 1991; 29: 219-222. ther gland damage and ‘recurrence’. Kearns Endod 1998; 86: 505 17. Pearse A G E. The chemistry and practice of fixation. In 23 4. Baughman R A. To biopsy or not. (Letter). Oral Surg Pearse A G E (Ed) Histochemistry. Theoretical and et al. reported a recent study into pain Oral Med Oral Pathol Oral Radiol Endod 1999; 87: applied. Edinburgh: Churchill Livingstone, 1980: experience following oral mucosal biop- 644-645. 97-158. sies. They concluded that most patients did 5. Bànkfalvi A, Piffko J. Prognostic and predictive factors 18. Shi S R, Cote R J, Taylor C R. Antigen retrieval not experience significant pain post-oper- in oral cancer: the role of the invasive tumour front. immunohistochemistry: past, present, and future. J Oral Pathol Med 2000; 29: 291-298. J Histochem Cytochem 1997; 45: 327-343. atively and those that did were controlled 6. Kinsukawa J, Suefuji Y, Ryu F, Noguchi R, Iwamoto O, 19. Odell E W, Morgan P R. Practitioner biopsy services. adequately with analgesics; most patients' Kameyama T. Dissemination of cancer cells into (Letter). Br Dent J 2002; 193: 182. pain reduced after 3 days. It is important to circulation occurs by incisional biopsy of oral 20. Margarone J E, Natiella J R, Vaughan C D. Artefacts in squamous cell carcinoma. J Oral Pathol Med 2000; oral biopsy specimens. J Oral Maxillofac Surg 1985; give the standard post-operative oral sur- 29: 303-307. 43: 163-172. gery instructions to the patient. 7. Speight P M, Morgan P R. The natural history and 21. Krause L S, Cobb C M, Rapley J W, Kilroy W J, Spencer pathology of oral cancer and precancer. Comm Dent P. Laser irradiation of bone. I. An in vitro study Health 1993; 10 (Suppl 1): 31-41. concerning the effects of the CO2 laser on oral CONCLUSIONS 8. Eisen D. The oral mucosal punch biopsy. Report of 140 mucosa and subadjacent bone. J Periodontol 1997; When considering biopsy a little forward cases. Arch Dermatol 1992; 128: 815-817. 68: 872-880. planning and thought can greatly 9. Lynch D P, Morris L F. The mucosal punch biopsy: 22. Medical Devices Agency. Catgut sutures-cessation of improve the diagnostic value obtained. indications and technique. J Am Dent Assoc 1990; supply. 2001. http://www.medical-devices.gov.UK/ 121: 145-149. catgutsutures.htm Careful handling of the tissue and prompt 10. Moule I, Parsons P A, Irvine G H. Avoiding artefacts in 23. Kearns H P O, McCartan B E, Lamey P-J. Patients' pain appropriate fixation will enable a confi- oral biopsies: the punch biopsy versus the incisional experience following oral mucosal biopsy under local biopsy. Br J Oral Maxillofac Surg 1995; 33: 244-247. anaesthesia. Br Dent J 2001; 190: 33-35.

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