Parotid gland biopsy for investigation of xerostomia J. W. Ferguson,
J. L. Edwards,
P. I. Christmas,
M. M. Ferguson
Department of Oral Medicine and Oral Surgery, School of Dentistry, University of Otago, Dunedin, New Zealand and Dental Department, Southland Hospital, Invercargill, New Zealand _-----.
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SUMMARY. A technique is described for biopsy of the parotid salivary gland under local anaesthesia, which has been undertaken for a series of 59 patients who presented with suspected inflammatory exocrinopathy. The procedure is reliable and is associated with negligible postoperative discomfort. The advantages of the technique suggest that parotid gland biopsy is an acceptable alternative to conventional lower lip biopsy of minor salivary glands in theinvestigation of xerostomia. --------
with labial gland biopsy, including postoperative discomfort, localised infection, wound breakdown and localised paraesthesia. The present report describes an efficient method for obtaining a biopsy of the parotid gland under local anaesthcsia.
INTRODUCTION Xerostomia or persistent dryness of the mouth is a relatively common complaint which may have a variety of causes, including therapeutic irradiation, certain drugs and dehydration. A further important cause is salivary inflammatory exocrinopathy (Wiesenfeld & Ferguson, 1983) or Sjiigren’s syndrome, which may exist as part of a more generalised condition affecting exocrine glands throughout the body. The other glands commonly affected are the lacrimal glands, where the term xerophthalmia is used to denote persistent reduction of secretion. Sjdgrcn’s syndrome is further subdivided by some authors into a primary form consisting of inflammatory exocrinopathy only, and a secondary form which includes the presence of a connective tissue disease (Manthorpe et al., 1986a; Maran, 1986). Criteria for confirmation of the diagnosis of xerostomia vary between different centres but attempts have been made to become increasingly objective (Homma et al., 1986; Manthorpe etal., 1986a, 1986b; Moutsopoulos et al., 1986; Prausc et al., 1986; Skopouli et al., 1986). Xerostomia as a subjective symptom may be assessed in a semi-objective fashion by applying the questionnaire developed by Moutsopoulos et al. (1980). Objective tests of salivary gland function include flow rate measurements, scintigraphy, sialography (Manthorpe et al., 1986a), and the widely-used labial salivary gland biopsy (Chisholm & Mason. 1968; Greenspan et al., 1974; Daniels, 1984). With the exception of labial salivary gland biopsy, the most widely used objective tests of salivary gland function are applied to major salivary glands, particularly the parotid gland and this is appropriate since the major glands produce most of the saliva. It would therefore appear advantageous that histopathological changes in these major glands be correlated with the clinical abnormality clearly derived from malfunction of these glands. Furthermore, there are a number of potential problems associated
METHOD Patients Fifty-nine patients were subjected to parotid gland biopsy, all having complained of xerostomia or oral discomfort, a majority of patients also having a documented history of a connective tissue disorder, particularly rheumatoid arthritis. Some of the latter group also had objectively confirmed xerophthalmia. Patients ranged in age from 10 to 89 years (mean age 56.7 years), and the group included 45 females and 14 males. Controls Four patients provided specimens of normal parotid gland for control purposes. These specimens were obtained under general anaesthcsia at the same time that temporomandibular joint surgery for internal derangement was performed. Informed consent was obtained. Surgical anatomy The parotid gland (Fig. 1) is closely applied to the posterior part of the ramus of the mandible, with the larger superficial lobe lying. over the masseter muscle, and the deep lobe extending into the space posteromedial to the ramus. Important anatomical structures pass through the gland, in particular the retromandibular vein and external carotid artery lie deep, while the facial nerve enters the posteromedial 234
Parotid gland biopsy for investigation
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v.-
VII Fig. 1 - Surgical anatomy
relevant
to the technique
described.
aspect of the gland and divides into branches which pass anterolaterally to emerge onto the anterolateral surface of the superficial lobe. Passing diagonally across the gland, in the subcutaneous tissue, are branches of the great auricular nerve. As may be seen in the diagram (Fig. 1) an incision placed directly below the lobe of the ear will involve no anatomical structures, other than branches of the great auricular nerve, before the capsule of the parotid gland is encountered. The gland is enclosed by a dense well-defined capsule which is derived from the deep cervical fascia. The superficial or investing lamina of the cervical fascia forms a loose tenuous fusion with the lateral aspect of the gland. Surgical technique
Following appropriate skin preparation, 1 ml of a local anaesthetic solution is infiltrated about the proposed site of incision (Fig. 2). An incision, 1.5 cm in length, is placed in or parallel to a skin wrinkle immediately below or just behind and beneath the ear lobe, and deepened by blunt dissection to the parotid capsule. If the great auricular nerve or its branches are encountered, they may be gently retracted to one side. A self-retaining retractor is placed (Fig. 3) and held by an assistant while the parotid capsule is incised. The upper edge of the capsule is retracted with a skin hook (Fig. 4) while lobules of gland are removed. To remove individual lobules, the delicate connective tissue capsule of the lobule is held with fine toothed dissecting forceps (Fig. 4) while the lobule is severed from its attach-
ment with scissors. Some bleeding will then result but ceases spontaneously within 1 to 2 minutes. If any discomfort is felt at this stage, a small amount of local anaesthetic solution is infiltrated into the gland just deep to the lobules. The parotid capsule is carefully closed with a continuous 4-O plain catgut suture and the skin with interrupted 5-O silk or nylon sutures (Fig. 5). It is essential to achieve tight closure of the parotid capsule, to avoid postoperative bleeding into the adjacent tissues.
RESULTS No significant complications were encountered or developed in the 59 patients operated on. One patient developed a mild regional lymphadenitis 1 week following surgery. which rapidly resolved with a short course of antibiotic. Two patients early in the series exhibited substantial ecchymosis below the incision site at the time of suture removal, clearly due to failure to achieve complete closure of the parotid capsule. For this reason, the technique for closing the capsule was changed from interrupted to continuous suturing. No significant pain was experienced postoperatively by any patient and none required analgesics. The results of microscopic examination of spccimens obtained in this study (awaiting publication) revealed a high proportion of glands to exhibit inflammatory and/or degenerative changes, and such changes were usually present in patients who had Sjdgren’s syndrome confirmed by other diagnostic
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Surgery
Fig. 2 - Skin incision marked. This may be placed slightly more anteriorly or posteriorly if desired, to make use of existing skin creases.
Fig. 3 - Inctsion deepened to parotid capsule. Note fusion of the tenuous superficial cervical fascia with the capsule.
Fig. 4 - Parotid capsule incised and retracted anteriorly to expose gland parenchyma. An individual gland lobule is being gently held with toothed forceps prior to excision.
Fig. 5 - Skin incision
criteria. changes.
over labial salivary gland biopsy, as other objective tests of salivary gland function usually involve the parotid gland then biopsy of the same gland allows correlation of altered function with altered form. A cited disadvantage of major salivary gland biopsy (Grecnspan et al., 1974; Danicls, 1984) is a high level of localised inflammatory changes present in these glands in random series obtained at postmortem. In particular, the study of Waterhouse and Doniach (1966) involving 525 subjects, revealed an overall incidence of 48% of major salivary glands to contain some areas of lymphocytic infiltration, although fewer than 10% of males and 20% of females exhibited severity greater than Grade 1 or ‘slight’, based upon the number of foci present per standard 4 cm2 sections. By contrast however, the study by Greenspan et al. (1974), in which labial salivary glands were obtained at post-mortem from 53 subjects, revealed an overall incidence of 81% of labial glands exhibiting localised areas of adenitis, with 56% of all specimens having severity rated at higher than Grade I, using however a grading system based upon foci present in standard sections of only 4 mm*. It is thus critical for interpretation of these
Control
specimens
exhibited
no abnormal
DISCUSSION The technique as described for biopsy of the parotid gland is safe and quick to perform, but should be undertaken only by persons with some experience of salivary gland surgery. Provided the skin incision is carefully placed as illustrated, damage to important anatomical structures is not likely. It is necessary to confine removal of gland lobules to the more superficial part of the gland and this must be carried out under direct vision. Blind dissection into the deeper part of the superficial lobe may result in damage to the facial nerve. If deep dissection is avoided and tight closure of the parotid capsule obtained, there is little possibility that a salivary fistula will result. The technique should be used only in those conditions where generalised changes can be expected in the glands, and is not appropriate for biopsy of discrete lesions within the gland. Biopsy of the parotid gland offers some advantages
closed
Parotid
results to appreciate that the grading systems used respectively in these two studies are different, with the result that the grading used by Greenspan et al. (1974) indicates the presence of significantly greater focal adenitis in labial glands than the results would at first suggest, compared to major glands. These differences result from different numbers of foci being designated for the individual grades and, more significantly, the use of different ‘standard’ section areas, which differ 100-fold, for counting foci. Based on these studies, there is a definite possibility that focal adcnitis, particularly if tending towards being severe, is more likely to be a chance finding in labial minor salivary glands than in the major salivary glands. Other post-mortem studies have confirmed the presence of focal adenitis in both major and minor salivary glands of normal subjects and show this to be age-dependent (Waterhouse, 1963; Scott, 1976). Chisholm et al. (1970) have also shown a correlation between the prevalence of focal adentis in major salivary glands and the degree of lymphocytic infiltration in labial minor salivary glands for individual subjects. For patients who have established xerostomia, there is frequently some degree of stomatitis present and it is likely that this will lead secondarily to inflammatory changes extending to involve the minor salivary glands. Xerostomia also results in greater mucosal trauma during mastication which may produce inflammatory changes and, in any event, the inner aspects of the lips arc often traumatiscd in normal patients, as evidenced by the common devclopment of mucoceles in these sites. The surgical technique of labial salivary gland biopsy is straightforward but the sutures on the inner aspect of the lower lip are disliked by patients and the sutures may be dislodged during mastication with the wound healing by secondary intention. Patients who arc at risk of infective endocarditis may require antibiotic cover for the procedure and could still be at risk of bacteracmia during the period of time the sutures remain in place. Peripheral fibres of the mental nerve lie in the submucosal tissue of the lip and may be damaged during labial gland removal, particularly by inexperienced operators. Taking into account the relatively uncomplicated technique of parotid gland biopsy as described, the logic of correlating altered function with altered form, and the uncertainty which continues to exist regarding the absolute reliability of labial salivary gland biopsy, it is suggested that parotid gland biopsy is an acceptable alternative method for objective confirmation by histopathology of the diagnosis of salivary inflammatory exocrinopathy.
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correlation in post-mortem subjects. Journal of Clinical Purhology, 23, 690. Dan&, T. E. (1984). Labial salivary gland biopsy in SjBgren’s syndrome. Arthritis and Rheumutism, 27, 147. Greenspan, J. S., Daniels, T. E., Talal, N. & Sylvester, R. A. (1974). The histopatholoav of Siiieren’s svndrome in labial salivary gland bi&ies. &I S&&y, Oral Medicine, Oral Purhology, 31,217. Homma, M., Tojo, T., Akizuki, M. & Yamagata, H. (1986). Criteria for Sjiigren’s syndrome in Japan. Scandinavian Journal of Rheumatology. Supplement 61, 26. Maran, A. G. D. (1986). Sjiigren’s syndrome. Journal of Laryngology and Otology, 100, 1299. Manthorpe. R., Andcrsen, V., Jensen, 0. A., Oxholm, P., Prause, J. U. & Schiodt, M. (1986a). Editorial comments to the four sets of criteria for Sjligrcn’s svndromc. Scandinavian Journal of Rheur&kogy. iupplcment 61, 31. Manthome, R.. Oxholm. P.. Prausc. J. U. & Schiodt. M. (198tib). The Copenhagen criteria for SjBgren’s sindrome. Scandinavian Journal of Rheumatology. Supplement 61, 19. ltioutsopoulos, Il. M., Klippel, J. fj., Pavlidis, N., Wolf, R. O., Sweet, J. B., Steinberg, A. D., Chu, F. C. & Tarpley, T. M. (1980). Correlative histologic and serologic findings of sicca syndrome in patients with systemic Iup& _ ervthematosus. Arthritis and Rheumukrm. 23. 27. Prause; J. U., Manthorpe, R., Oxholm, P. LYL Schiodt, IM. (1986). Definition and criteria for Sjiigren’s syndrome used by the contributors to the First International Seminar on Scandinuviun Journal of Sjegren’s syndrome-1986. Rheumatology. Supplement 61, 17. Scott, J. (1976). The incidence of focal chronic inflammatory changes in human submandibular salivary glands. Journal of Oral Pathology, 5, 334. Skopouli, F. N.. Drosos, A. A., Papaioannou, T. & Moutsopoulos, 1-f. M. (1986). Preliminary diagnostic criteria for Sjiigren’s syndrome. Scandinavian Journal of Rheumurology. Supplement 61, 22. Waterhouse, J. P. (1963). Focal adenitis in salivary and lacrimal glands. Proceedings of the Royal Society of Medicine, 56, 911. Waterhouse, J. P. & Doniach, 1. (1966). Post-mortem prevalence of focal lymphocytic adenitis of the submandibular salivary gland. Journul of Parhology and Bacteriology, 91, 53. Wiescnfeld, D. & Ferguson, M. M. (1983). Salivary inflammatory cxocrinopathy: diagnosis and treatment. Ausrruliun Dental Journal, 2U, 87.
The Authors J. W. Ferguson MDS, PhD, FDSRCS, FFDRCS Senior Lecturer J. L. Edwards BDS, FDSRCS, FRACDS Associate Professor M. M. Ferpson BSc, BDS, MB, ChB, FDSRCPS Professor Department of Oral Medicine and Oral Surgery School of Dentistry University of Otago Dunedin New Zealand P. 1. Christmas BDS, FDSRCS Consultant Oral Surgeon Dental Department Southland flospital Invercargill New Zealand
References Chisholm, D. & Mason, D. (1968). Labial salivary gland biopsy in Sjiigren’s disease. Journal of Clinical Parhology, 21, 656. Chisholm, D. M.. Waterhouse, J. I’. & Mason, D. K. (1970). Lymphocytic sialadenitis in the major and minor glands: a
Correspondence
and requests
Paper received 13 March Accepted 5 July 1Y89
I989
for offprints
to Dr J. W. Fcrguson