O R I G I N A L A R T I C L E
A retrospective analysis of post-operative outcomes in a series of 108 labial gland biopsies
S. Ali1,2, N. Patel3& S. Challacombe1
1Department of Oral Medicine, King’s College London and Guy’s & St. Thomas’ NHS Foundation Trust, London, UK
2Department of Special Care Dentistry, Bristol Dental Hospital, Bristol, UK
3Department of Oral Surgery, Manchester Dental Hospital, Manchester, UK
Key words:
labial gland biopsy, lip numbness, paraesthesia, Sjogren’s syndrome
Correspondence to:
Dr S Ali
Department of Oral Medicine
King’s College London and Guy’s & St. Thomas’
NHS Foundation Trust London
UK
Tel.: +020 7188 4399 Fax: +020 7188 4401
email: shabnum_ali@hotmail.com Accepted: 19 January 2014 doi:10.1111/ors.12085
Abstract
Aim: Histopathological assessment of labial salivary glands has long been a core part of the diagnostic criteria for Sjogren’s Syndrome. Biopsy of labial salivary glands is technique sensitive and has post-operative complications which can affect the patient’s quality of life. Varying techniques for labial gland biopsy and associated complications are described in the literature.
This article gives a step-by-step account of an effective technique for labial gland biopsy as described by Daniels in 1984 and provides a retrospective analysis of the post-operative complications in a series of 108 labial gland biopsies.
Materials and methods: A retrospective, post-operative telephone survey was carried out to study the post-operative complications of labial gland biopsies performed by a single operator. All consecutive patients (180) who had labial gland biopsies between October 2010 and August 2012 at the Department of Oral Medicine at Guy’s Hospital were called, and 108 surveys were successfully completed. The telephone questionnaires aimed to find out medium and long-term complications of labial gland biopsies to include subjective measures of post-operative pain, swelling and paraesthesia.
Results: One patient out of 108 patients (0.9%) reported pain that lasted
≥ 6 months, and six patients (5.5%) reported swelling that lasted > 2 weeks. Three patients (2.8%) reported paraesthesia lasting ≥ 6 months with a median bother score of 0. All biopsies provided sufficient glands to allow for histopathological diagnosis.
Conclusions: This article describes a safe and effective technique for labial gland biopsy. Despite a low complication rate, informed consent is essential.
Clinical relevance
Scientific rationale for study
Labial gland biopsy (LGB) is an important com- ponent in the diagnosis of Sjogren’s Syndrome. It is technique-sensitive and has post-operative complica- tions which can affect the patient’s quality of life.
Principal findings
This article provides a retrospective analysis of the post-operative complications in a series of 108 LGB carried out using a technique which has proved to be effective in delivering histopathological diagnosis and has a low level of post-operative complications.
Oral Surgery ISSN 1752-2471
Practical implications
This article gives a step-by-step account of an effective technique for LGB which can be used by clinicians, as well as rates of post-operative complications which are useful when obtaining informed consent from the patient.
Introduction
Sjogren’s syndrome (SS) is a systemic autoimmune disease that initially targets primarily the lacrimal and salivary glands, resulting in keratoconjunctivitis sicca (dry eye disease) and/or stomatitis sicca (dry mouth disease)1. These symptoms are caused by destruction of the exocrine glands by infiltrating lymphocytes, and patients can also develop systemic symptoms such as fatigue and arthralgia2.
The most commonly accepted international criteria are currently the American–European consensus cri- teria3, which requires either one of two in vitro tests to be positive, either extractable nuclear antigens or sali- vary gland investigations as well as 3/4 signs or symp- toms of dry eyes or mouth. The international collaboration into SS (Sjogren’s International Collabo- rative Clinical Alliance)3–6, which has recruited over 1700 patients from oral medicine, rheumatology and ophthalmology departments and SS clinics from around the world, has led to a detailed analysis and recently proposed new data-driven diagnostic criteria7. Case definition requires at least two of three of the fol- lowing: (1) positive serum anti-SSA and/or anti-SSB or positive rheumatoid factor and antinuclear antibody titre>1:320; (2) Keratoconjunctivitis sicca with ocular staining score>3; or (3) presence of focal lymphocytic sialadenitis with a focus score>1 focus/4 mm2in labial salivary gland biopsy samples. Labial gland biopsy remains an integral component of the diagnosis of SS.
Biopsy of the labial minor salivary glands in order to diagnose Sjogren’s disease was first introduced in 1968 by Chisholm and Mason8. The advantages of biopsy within the lower lip include the large number of minor salivary glands available, accessibility, ease of anaes- thesia, lack of major structures susceptible to damage, avoidance of skin incisions and the relative absence of post-operative pain9.
Post-operative complications which have been reported following labial gland biopsies include post- operative pain, paraesthesia, haematoma and swell- ing10. Lower lip numbness has consistently been reported as the only long-term complication of lip biopsy, occurring in 0–11.4% of patients6,10–14. Opera- tors also often fail to sample sufficient glandular tissue
in order to make a pathological diagnosis15. This article gives a step-by-step account of an effective technique for labial gland biopsy as described by Daniels in 198416 and to analyse the post-operative complications.
Clinical steps
Following are the clinical steps involved in a labial gland biopsy based on the technique described by Daniels in 198416.
1 Ensure that the patient is sitting in a calm environ- ment and has been adequately consented and warned of serious or frequently occurring post-operative com- plications. The patient should be asked to partially open their mouth, and the assistant should evert the lower lip (left or right side). Identify an area of mucosa of the lower lip that appears normal clinically and is not inflamed because mucosal inflammation will cause inflammatory cell infiltration of the salivary glands (Fig. 1).
2 Local anaesthetic is infiltrated into the sub-epithelial area that will be incised. Topical anaesthetic maybe applied prior to infiltration. The needle is inserted only once to a depth of 2 mm into the labial mucosa, just proximal to the midline as shown in the image. While slowly injecting local anaesthetic into the sub- epithelial tissues, the needle is extended laterally into the lip towards the angle of the mouth, parallel to the epithelium. Usually 1 ml of local anaesthetic is suffi- cient to adequately anaesthetise the tissues. Using local anaesthetic with vasoconstrictor is beneficial because it reduces bleeding (Fig. 2).
3 A no.15 blade is used to make a 1.5–2.0 cm hori- zontal linear incision through the epithelium and not the underlying connective tissue. The incision will be
Figure 1 Identification of biopsy site.
made to the right or left of the midline, approximately halfway between the vestibule and the vermilion border and halfway between the midline and the labial commissure. This area is chosen as the biopsy site in order to avoid damage to the branches of the mental nerve and also because this is the region where numerous labial glands can be found. The depth of the incision is only through the epithelium because the glands are located within the lamina propria under- neath the epithelium and will be difficult to find if the incision goes any deeper (Fig. 3).
4 Incision through the epithelium is confirmed when the incision margins separate, creating an elliptical shape (Fig. 4).
5 Use small curved dissection scissors for blunt dissec- tion of the lamina propria adjacent to the epithelial margins to release the minor salivary glands from
lamina propria and identify any nerve fibres passing through the surgical field. Careful blunt dissection is required in order to reduce post-operative swelling and bruising (Fig. 5).
6 Approximately 6–8 minor salivary glands should be removed, one at a time. This is done by lifting them slightly with toothed forceps, gently dissecting with the dissecting scissors, while avoiding any sensory nerves.
Any additional minor salivary glands present in the field should be removed to reduce the possibility of the patient developing a mucocoele post-operatively (Fig. 6A,B).
7 Closure is achieved with two to four simple interruped resorbable sutures (Fig. 7).
8 Pressure is applied to the biopsy site to achieve hae- mostasis, and post-operative instructions are given.
Figure 2 Administration of local anaesthetic.
Figure 3 Incision through epithelium.
Figure 4 Separation of incision margins creating an elliptical shape.
Figure 5 Blunt dissection of lamina propria to release minor salivary glands and identify any nerve fibres.
Post-operative morbidity and paraesthesia survey
We carried out a post-operative telephone survey to study the medium and long-term complications of labial gland biopsies, performed as described previ- ously. All consecutive patients (180) who had labial gland biopsies between October 2010 and August 2012 at the Department of Oral Medicine at Guy’s Hospital for the diagnosis of SS were called, and 108 surveys were successfully completed. The minimum length of time between the biopsy and the survey was 6 months, and the maximum time was 25 months (mean length of time between biopsy and telephone call was 20 months). These biopsies had been carried out under local anaesthetic by a single operator. The telephone questionnaire aimed to find out the medium and long- term complications of labial gland biopsies to include subjective measures of post-operative pain, swelling and paraesthesia. Patients were verbally consented to participate in the telephone questionnaire and were
asked to rate pain scores on a VAS scale for any pain they continued to experience beyond 2 weeks post- biopsy and the duration for which it lasted. Pain that lasted>2 weeks, but <6 months was defined as a medium term or temporary post-operative complica- tion, and any pain that lasted≥6 months was defined as long term or a permanent complication. Similarly, patients were also asked to give a bother score (a score for how much these symptoms bothered them on a scale of 0–10) for any symptoms of swelling and par- aesthesia that they may have continued to experience beyond 2 weeks post-biopsy.
Results
Out of the 108 patients that completed the survey, six patients (5.5%) reported post-operative pain that lasted> 2 weeks with an average VAS pain score of 5.
For five out of the six patients, the pain resolved within 1 month post-biopsy, but one patient reported that her pain had lasted for 6 months. This particular patient also reported symptoms of swelling and paraesthesia that lasted for 6 months with a bother score of 9. Six out of the total 108 patients (5.5%) complained of post-operative swelling that lasted> 2 weeks. Four of these patients reported the swelling to be mild, and two reported it to be moderate in severity. The average bother score for the swelling was 5.
Eight out of the 108 patients (7.4%) reported some paraesthesia following biopsy. Five of these patients (4.6%) reported temporary localised paraesthesia (lasting< 6 months), average time of paraesthesia being 3 months post-biopsy with an average bother score of 5.8. Three patients (2.8%) reported permanent local- ised paraesthesia that lasted≥ 6 months, and the bother scores for these patients were 0, 0 and 9 respectively.
Discussion
This article gives a step-by-step account of a safe and effective technique for labial gland biopsy as described
Figure 6 Careful dissection of minor salivary glands.
(A) (B)
Figure 7 Closure of biopsy site.
originally by Daniels in 198416and demonstrates a low incidence of medium and long-term complications in our survey of 108 patients. Only one patient out of 108 patients (0.9%) reported pain that lasted ≥6 months, and only six patients (5.5%) reported swell- ing that lasted>2 weeks. Permanent localised paraes- thesia occurred in three out of the 108 patients (2.8%), but the bother score for two of these patients was 0 (i.e. the localised paraesthesia did not bother the patient at all and it would not have been reported if not for the telephone survey). Only one patient who had paraesthesia in the form of tingling that lasted
≥ 6 months was adversely affected by it, with a bother score of 9. This particular patient was a 53-year-old female patient who also reported during the survey that she had pain and mild swelling that lasted 6 months after the biopsy with a VAS pain score of 8 (the only patient in the survey that had pain that lasted > 1 month) and a bother score of 9 for the swelling. However, this patient had not complained of symptoms of pain and swelling when seen for a post- operative review on clinic prior to the survey, and on examination, there was no evidence of any swelling present.
A major advantage of a telephone survey to assess patients post-operatively is that it allows a large number of patients to be assessed in a short space of time17. Furthermore, it saves patients having to attend a hospi- tal appointment which may require time off work and having to travel. The use of telephone questionnaires in exploring the post-operative symptoms of a patient is a simple and convenient method, and studies which directly compare telephone and face-to-face interview- ing tend to conclude that telephone interviewing produces data which are at least comparable in quality with those attained by the face-to-face method15. All our patients were reviewed on the clinic after their biopsies in order to be given their results and diagnoses and form a management plan. All patients who participated in the telephone interview were also offered an additional face-to-face review if they wished.
One disadvantage of a telephone survey is that results are purely a subjective measure of the patient’s reported symptoms, and physical examination cannot be conducted. In particular, paraesthesia is most reli- ably tested using an objective method of using a pin prick test or two-point discrimination, which would not be possible without a clinical exam18. Furthermore, telephone surveys can introduce some responder bias in that patients may overstate a problem if they are dissatisfied with treatment or underplay a post- operative complication in an attempt to please the telephone investigator.
The bother index19is a valuable prognostic aid and is based on what the patient believes would be his or her ability to tolerate his current level of symptoms for the rest of his life. It has widely been used as a subjective measure of the effect of a symptom on the patient20. However, the use of analgesia and non-steroidal inflammatory drugs as well as other medication that may affect post-operative pain and swelling was not taken into account. Furthermore, the interval between date of biopsy and date of telephone questionnaire varied from 6 months to 25 months and could have been standardised to ensure more accurate results.
A number of varying techniques for labial gland biopsy and complications are described in the literature (Table 1). Several studies involve the use of a horizon- tal incision with the rate of post-operative paraesthesia ranging from 1 to 11%16,21–28. Greenspan et al.21used a technique very similar to that used in this study, with a 1.5–2 cm linear incision of mucosa parallel to the vermillion border and lateral to midline, and the inci- dence of long-term paraesthesia in 75 patients was reported to be 1%. Pijpe et al.23 used a technique involving a horizontal incision of 3 cm and reported the incidence temporary paraesthesia to be 11% and long- term paraesthesia to be 6% (n= 35). Santiago et al.22 used a 2–3 mm horizontal incision, reporting a 7%
incidence of post-operative pain and 3% incidence of temporary paraesthesia but no permanent paraesthe- sia. (n= 186). However, only 90.9% of the biopsy material obtained using this technique was useful for histopathological diagnosis.
Some studies have made use of a vertical incision.
Gorson and Ropper used a 1 cm vertical incision behind the wet line through mucosa and submucosa and reported one case of persistent numbness (2%)29. Berquin et al. used an oblique incision, 1.5 cm from the midline proceeding lateroinferiorly, avoiding the glan- dular free zone in the centre of the lower lip, with a 4%
incidence of paraesthesia11. Other techniques included sampling glands through punch biopsy30 or through removing an ellipse of mucosa8with no reported long- term complications. A novel method described in a technical note by Peloro et al. outlined an X-mark pro- cedure. This involved marking the yellow papules of the salivary glands with a surgical pen, then a superfi- cial stab incision of 1.5–2 mm was made through the area identified, and a second stab incision was then made perpendicular to the first incision marking an ‘X’
overlying the gland. However, no details were given regarding the rate of complications31.
Minor gland biopsies have also been performed in the hard palate, using the technique of a punch biopsy32. However, haemostasis can be difficult to
Table 1 Literature review of labial gland biopsy techniques and complications
Paper Sample Technique Number of patients with
short-term complications n (%)
Number of patients with long-term complications n (%)
Santiago et al. 201222 186 2–3 mm incision on inner surface of lower lip
Haematoma: 5 (3) Pain: 12 (7) Inflammation: 6 (3) Granuloma: 2 (1) Temporary Numbness: 5(3)
0
Pijpe et al. 200723 35 Lower lip mucosal incision 3 cm parallel to vermillion border, lateral to midline.
Temporary paraesthesia: 2 (6) Permanent paraesthesia
>1 year: 2 (6) Richards et al. 199224 58 Horizontal mucosal incision Temporary paraesthesia: 1 (2) Permanent paraesthesia
>1 year: 1 (2) Caporali et al. 200825 502 2–3 mm incision on inner surface of
lower lip.
Temporary paraesthesia: 57 (11)
Haematoma: 8 (2) Swelling: 27 (5) Bleed/scar: 5 (1)
0
Chisholm and Mason 19688 40 Ellipse of mucous membrane down to muscle
0 0
Greenspan et al. 197421 75 1.5–2 cm linear incision incision of mucosa, parallel to vermillion border and lateral to midline
Paraesthesia for several months: 1 (1)
Daniels 198416 362 Single 1.5–2 cm horizontal incision through mucosa
Temporary paraesthesia: 3 (1)
Marx et al. 198826 77 3× 0.75 cm horizontal mucosal incision
Temporary paraesthesia: 2 (3) Permanent paraesthesia
>2 years: 1 (1) Delgado and Mosqueda 198937 19 Longitudinal incision 1 cm in labial
mucosa in front of lower first premolar.
0 0
Pennec et al. 199027 50 Single 1.5–2 cm horizontal incision through mucosa
0 0
Guevara-Gutierrez et al. 200130 50 4 mm punch biopsy just penetrating epithelium between midline and commissure
Temporary paraesthesia: 2 (4)
Friedman et al. 200238 118 5–7 mm incision on inner surface of lower lip.
Pain: 3 (3) Swelling: 5 (4) Infection: 2 (2) Suture failure: 4 (3) Cheloid formation: 1 (1) Paraesthesia>3 weeks: 2 (2)
Paraesthesia>3 weeks: 2 (2)
Gorson and Ropper 200329 54 1 cm vertical incision behind wet line through mucosa and submucosa
0 Permanent paraesthesia: 1 (2)
Smith et al. 200439 11 Vertical incision made on mucosal surface lateral to midline
0 0
Berquin et al. 200611 24 Oblique incision, 1.5 cm from midline proceeding lateroinferiorly, avoiding the glandular free zone in the centre of the lower lip.
Permanent paraesthesia: 1 (4)
Teppo and Revonta 200728 191 2–3 mm horizontal incision Pyogenic granuloma in wound: 1 (1)
0
Table 1 shows a review of the literature published between December 1960 and December 2012 regarding techniques and complications of labial salivary gland biopsy for diagnosis of Sjorgren’s syndrome. Databases searched included MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials.
Sixteen studies were found which gave details of technique and any complications encountered.
achieve, and also primary closure is not possible, leading to possible increased post-operative pain and discomfort. Apart from post-operative complications, the other factor that determines the effectiveness of a labial gland biopsy technique is also whether the technique yields enough glands for diagnosis. Tech- niques that involve the use of a punch biopsy33,34 usually provide little glandular tissue for examination and do not allow for visual identification of sensory fibres, which may lead to increased incidence of post- operative paraesthesia16. Removing an ellipse of mucosa as described in several studies35,36can also lead to damage of unidentified sensory nerves, and also, the epithelium is unnecessarily lost16. Moreover, as the glands are attached to the epithelium, they are at different levels, which could make diagnosis and focus scoring inaccurate and difficult16. All biopsies carried out in this study provided sufficient glands to allow for histopathological diagnosis and focus score calculation.
Conclusion
Labial gland biopsy has played an important role in SS because of its disease specificity, wide availability, minimal invasiveness and opportunity to assess auto- immune disease-active cells within a Sjogren’s target organ4. It also remains part of the new American College of Rheumatology criteria for diagnosis of SS.
Labial gland biopsy remains a safe procedure with low complication rates. Despite a low complication rate, patients must be fully informed of possible risks associ- ated with the procedure, especially that of long-term paraesthesia. Furthermore, because of the technique- sensitive nature of labial gland biopsy, it is essential that the surgeon has experience with the procedure and that sufficient glands are sampled to avoid a repeat operation. This article outlines a technique for labial gland biopsy which has proved to be effective in deliv- ering histopathological diagnosis and has a low level of post-operative complications.
Acknowledgements
Source of funding: None.
Conflict of interest: None.
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