Current controversies in the management of Warthin

Downloaded from pmj.bmj.com on April 6, 2011 - Published by group.bmj.com

Review

Current controversies in the management of Warthin tumour T Thangarajah, V M Reddy, F Castellanos-Arango, A Panarese Department of Otolaryngology, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK Correspondence to: Dr T Thangarajah, Department of Otolaryngology, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Prescot Street, Liverpool L7 8XP, UK; [email protected] Received 16 May 2008 Accepted 7 September 2008

ABSTRACT Warthin tumour is the second most common benign neoplasm of the parotid gland. It has a low rate of growth and exhibits malignant transformation in 0.3% of cases. Although its aggressiveness has not been a concern, surgical resection remains the most common treatment modality. This entails the risk of a general anaesthetic and those pertaining to the procedure itself, most notably permanent facial nerve damage. This has led some authors to use conservative management, albeit rarely. There are those who condemn such a policy despite the encouraging results reported thus far. To understand the rationale underpinning non-operative management, it is imperative that one has a comprehensive understanding of the pathogenesis, clinical presentation and diagnosis of Warthin tumour. The aim of this review therefore is to detail these elements and clarify the current controversies in managing this lesion.

Warthin tumour (WT) is the second most common benign neoplasm of the parotid gland. It accounts for 14–30% of all parotid tumours and is more common in men.1–5 Treatment has long been a contested issue, with surgical resection most commonly used. Several operative strategies have been described in the literature ranging from enucleation to superficial parotidectomy. Although the latter is more prevalent, less radical excision procedures are strongly advocated by some centres because of fewer associated complications, particularly facial nerve injury.3 6–10 To obviate all problems associated with surgery, a conservative approach to management has also been alluded to, albeit rarely. Little guidance is provided in the literature as to its specific indications, but it has largely been confined to those who are unfit for surgery or in those who decline. There are reports, however, of some centres using it for cytologically confirmed WTs, and others using it for a second salivary gland tumour in a patient with a previous WT.11–14 Patients treated in this way typically have an uneventful follow-up because of the low rate of growth and malignant transformation of the tumour (0.3%).12 15 That being said, the expansion of this treatment modality to involve other patient subgroups remains to be seen. There is clearly a lack of uniformity regarding the management of WT. Although surgery is most commonly practised, the specific technique used varies considerably because of concerns of recurrence and complications. Conservative management on the other hand is harmless to the patient and is already an established treatment modality in some centres. Its uptake is limited though because Postgrad Med J 2009;85:3–8. doi:10.1136/pgmj.2008.071282

of the paucity of literature on the outcome of patients with tumours that have not been excised and the absence of studies comparing it with the mainstay of operative intervention. To clarify the aforementioned management dilemmas, it is imperative that one has a comprehensive understanding of the pathogenesis, clinical presentation and diagnosis of WT. Only then can the rationale for conservative management be understood and an accurate comparison be made with surgical intervention. By detailing these elements and describing the available treatment options, we aim to clarify the current controversies in managing this lesion.

PATHOLOGY WTs are encapsulated lesions with both solid and cystic areas. They consist of an epithelial component arranged in two layers and a variable lymphoid stroma consisting of both B and T cells.15 16 The origin of these components is a contentious issue with several plausible theories. These identify an immunological reaction and late encapsulation of the parotid gland as the principal causes.5 17 The latter is thought to permit epithelial precursors of the salivary duct–acinar system to remain within lymphoid tissue and subsequently give rise to WTs. This is known as heterotopia.5 Perhaps the most controversial concept though is the suggestion that WT is in fact an adenoma with concomitant lymphocytic infiltration. When they are small, WTs consist mainly of epithelial components, in contrast with when they are larger, when they exhibit additional lymphoid constituents. As the epithelial elements are recognised first, they are thought to be the neoplastic component.5 This was disproved by Honda et al,18 who demonstrated that both the epithelial and lymphoid constituents were in fact polyclonal.19 If, however, neoplasia is regarded as a monoclonal process, WT cannot be regarded as a true neoplastic lesion, a view also supported by its extremely low rate of malignant transformation and recurrence.5 13 15 The former has been estimated by Batsakis15 to occur in ,0.3% of cases, and the lesions noted to arise include squamous cell carcinoma, mucoepidermoid carcinoma and malignant follicular lymphoma.20–22 Several triggers for the events described above have been proposed. These include smoking, steroid hormones, viruses such as Epstein–Barr, and hypertension.5 23–25 Smoking is the focus of much of the literature and is thought to have a significant role by way of its function in increasing reactive oxygen species, which result in damage to mitochondrial DNA.23 Although this has been shown to exist in normal parotid tissue, a higher 3


Review rate has been found in the oncocytes of WTs.26 The prevalence of smoking in patients with WT has been reported to be as high as 79–100%, whereas a similar association has not been shown in other salivary gland neoplasias.4 27–30

element in particular is common to squamous cell carcinoma and mucoepidermoid carcinoma.51 56 58 This highlights the difficulty of diagnosing WTs and the range of pathology that may display a similar cytological appearance.

CLINICAL PRESENTATION

Imaging Ultrasonography

WT is more common in men, with a peak incidence in the seventh decade.3 4 The most common focus for growth is the inferior pole of the parotid gland; however, occurrences at other sites have been reported but should be considered ectopic. These include the submandibular gland, tonsil, lip, palate, mandible, oral cavity and pharynx.31–33 An affected patient typically presents with a slowly growing spherical or ovoid parotid mass that is moderately firm to fluctuant on palpation. Other features are seldom present.33–36 The swelling is 1–4 cm in diameter and can appear dormant over a number of years, with a sudden increase in size attributable to malignant change or inflammation.13 34 35 37–39 Bilaterality and multifocality have been reported in 2–10% and 20–23% of cases, respectively, making it the most common parotid tumour to exhibit these features.1 3 5 31 34 40 Furthermore, it has been noted to coexist with other benign neoplasms of the parotid gland such as pleomorphic adenoma41 and benign oncocytoma.42

DIAGNOSIS Histological analysis after surgery was thought to be the only accurate method of diagnosing swellings of the parotid gland. Operative treatment therefore prevailed because diagnosis depended on obtaining a sample of tissue. Recently though, other methods, including fine-needle aspiration cytology (FNAC) and various imaging techniques, have been shown to be effective. If the accuracy of such diagnostic techniques is sufficient, mandatory surgical resection can potentially be prevented.

FNAC Although the use of FNAC in the diagnosis of parotid neoplasms has been extensively studied, there remains much controversy about its role in guiding treatment.11 In one centre’s experience, it reduced the number of patients undergoing surgery by 31%, but there are those that do not recognise it as being sufficiently accurate to influence such decisions.11 43–47 Furthermore, the risk of neoplastic seedling has led some authors to discourage its use completely.48 The sensitivity, specificity and diagnostic accuracy of FNAC in diagnosing WT ranges from 74% to 100%. The two main sources of error include failure to obtain a representative sample and the variable cytological appearance of WT.51 53 The former can be minimised by recruiting a cytopathologist to perform the procedure. This has the added advantage of limiting histological alterations after biopsy, another major operator-related problem.53 The cytological appearance of WT is characterised by cellular debris mixed with lymphocytes and oncocytes. This is not a consistent finding, with a further 10 common and eight uncommon elements found in 17–66% and 2–8% of all specimens, respectively.43 47 51 54–57 In their review of 16 fineneedle aspiration biopsies of histologically confirmed WTs, Ballo et al50 found that 13 (81%) possessed typical features. The remaining three cases showed a predominance of the lymphoid component, squamous cells and necrotic/mucoid debris. This creates a significant diagnostic challenge because the squamous 49–52

4

The roles of imaging in the investigation of parotid tumours are to define the anatomical boundaries of a lesion and determine its pathological nature.25 35 In current practice, few methods can achieve this, with the exception of ultrasonography. This is a cheap, accessible, simple investigation that does not subject patients to ionising radiation.59 The appearance of WT is characterised by multiple anechoic areas, clear boundaries, ovoid appearance and hypoechoic internal echoes.8 59 60 On the basis of these features, Shimizu et al8 found that ultrasonography had a sensitivity, specificity and diagnostic accuracy for WT of 93.1%, 95.9% and 94.9%, respectively. Its reliability has been questioned though, particularly as other lesions such as pleomorphic adenoma and acinic cell carcinoma display a similar appearance.60 Moreover, it does not provide accurate visualisation of the deep lobe of the parotid gland and the facial nerve.61 The role of ultrasonography has been extended to assist in the diagnosis of lesions via FNAC. Owing to the association between sampling errors and incorrect interpretation on biopsy, its use provides reassurance that the needle is sufficiently within the mass. The complementary use of ultrasonography and FNAC has three main advantages over using needle aspiration alone: it permits confident biopsy of masses seen on other investigations, it can distinguish between perisalivary lymph nodes and true intrasalivary gland masses, and it allows accurate sampling.62 Feld et al62 analysed the records of 18 patients who had undergone ultrasound-guided FNAC and found that it had established a definite or suggestive diagnosis in 16 (89%) cases. In a further study by Akbas et al,63 the results of ultrasonography-guided FNAC were compared with postoperative histological findings in 82 patients with parotid masses. The sensitivities, specificities and diagnostic accuracies were 94.1%, 98.4% and 97.6%, respectively.

CT and MRI CT has been widely used for the evaluation of salivary gland tumours.64 65 Two of its diagnostic pitfalls include the inability for conventional scanning to distinguish between parotid tumours and difficulty in evaluating the muscle–tumour interface. The use of two-phase helical CT has somewhat overcome the former.65–67 When Choi et al67 investigated nine WTs by these means, four (44%) were found to exhibit strong enhancement at early-phase scanning, whereas eight (89%) were found to have a decrease at delayed-phase scanning. Diagnosis was therefore based on these criteria. MRI too can be limited in terms of tumour differentiation, but, according to Ikeda et al,34 the extra information provided by dynamic contrast-enhanced and diffusion-weighted images is sufficient to make a diagnosis of WT. Its characteristics on this technique include early enhancement, high washout ratio, and low apparent diffusion coefficient.

Tc-99m-pertechnetate scanning Tc-99m-pertechnetate salivary gland scanning is a simple and non-invasive investigation.68 WT shows increased uptake of Tc99m-pertechnetate, giving it a ‘‘hot appearance’’. Miyake et al68 analysed 114 patients with a suspected diagnosis of WT and Postgrad Med J 2009;85:3–8. doi:10.1136/pgmj.2008.071282


Review found an association between the diagnosis on scanning and after histological evaluation. The sensitivity, specificity and diagnostic accuracies in the study were all 94%.68 This positive result is not absolute though and also occurs in an oncocytoma, partial obstruction of the parotid gland, and in a normally functioning gland.12 To better evaluate the method, Motoori et al35 compared it with MRI for diagnosing WTs. Sensitivities and specificities for Tc-99m-pertechnetate salivary gland scanning were 56–63% and 94–100%, respectively, compared with 75– 94% and 88–94%, respectively, for MRI. Consequently, MRI was considered to be more useful.

Key learning points c

c

c

c

MANAGEMENT Surgery The surgical approach to WT has evolved over several years. Facial nerve injury initially compelled surgeons to adopt conservative resections such as enucleation and local excision procedures, but tumour recurrence was a major problem. This led to superficial parotidectomy being considered the most suitable option.9 Early concerns have now been dispelled, and excellent outcomes have been noted in patients treated by limited resections.10 52 Nevertheless, there is still no unified opinion among authors as to the most appropriate operative strategy, and therefore treatment varies considerably. Lewis et al52 performed controlled enucleation for 12 out of 33 patients with cytologically confirmed WTs. There were no recurrences and no cases of facial nerve injury. This was in contrast with the 11 patients who received superficial parotidectomy, in whom facial nerve damage was temporary in two and permanent in one. Yu et al10 compared the results of a local excision procedure performed on 61 patients with WT with those of a superficial parotidectomy carried out on 88 patients. No recurrent tumours were found in the local excision group, but two patients developed recurrent tumours in the superficial parotidectomy group. Despite comparably better results with less invasive surgical resections, it is still superficial parotidectomy that remains the most common operative strategy. Dunn et al48 retrospectively reviewed 250 parotid neoplasms that were almost exclusively subjected to surgery. Benign lesions were diagnosed in 173 patients on intraoperative frozen section. The recurrence rate at the 5-year follow-up was noted to be 6%, and it was concluded that limited surgical approaches were unacceptable and that superficial parotidectomy was the preferred treatment. O’Brien9 held a different view having evaluated 363 parotidectomies. The study showed that superficial parotidectomy was unnecessary and should be replaced by a limited resection, which was associated with low rates of recurrence and morbidity. Facial nerve injury in the above studies was temporary in 8–24% of cases and permanent in 2–3%.9 48

Conservative Parotid gland surgery is associated with several risks, most notably injury to the facial nerve.9 48 Conservative management does not carry this complication and has produced encouraging results thus far. Furthermore, owing to the low rate of growth and malignant transformation exhibited by WT, it is a favourable treatment option.12 15 Owing to the paucity of literature on the outcome of tumours that have not been excised, in addition to the few patient subgroups that have been managed non-operatively, it is difficult to compare conservative management with the mainstay of surgery.33 69 70 Postgrad Med J 2009;85:3–8. doi:10.1136/pgmj.2008.071282

c

c

Warthin tumour (WT) is the second most common benign neoplasm of the parotid gland. The histiogenesis of WT is somewhat undetermined, but two theories predominate: the lesion either occurs as a result of late embryonic encapsulation of the parotid gland or it is in fact an adenoma with concomitant lymphocytic infiltration. Doubts have been raised as to whether WT is in fact a true neoplasm, as its cellular components are polyclonal and not monoclonal. WT exhibits both a slow rate of growth and malignant transformation. The latter has been estimated to occur in 0.3% of cases. Fine-needle aspirate cytology can accurately diagnose WT and has also been known to influence management decisions. Although most centres manage WT surgically, there is evidence that a conservative approach may be applicable.

Hancock13 discussed the Christie Hospital series in which 133 patients with WT received 136 surgical resections, three of which were for bilateral tumours. During the follow-up period (median 5.4 years), the rate of recurrence and second tumours were 2% and 5–10%, respectively. The latter was not influenced by the extent of surgery, suggesting that an untreated WT would probably remain unchanged or, at worst, fluctuate in size as the result of infection. Consequently, a non-surgical approach was deemed applicable to a second salivary gland tumour in a patient with a previous WT. Six out of 13 second tumours in the Christie series were managed in this way. This conservative approach to management was also practised by Chapnik,12 who managed four out of 12 patients with WT non-operatively not only because of the presence of comorbidities, but also because of patient preference. Lim et al71 described their series of 118 patients undergoing parotid gland surgery. The prevalence of WT in their population was 37% among all parotid tumours (the only series in which it exceeds the prevalence of pleomorphic adenoma), although they suggest that the true value may be much higher, as some older patients may not have been operated on. Both in this subset of patients and in those with serious comorbidities and anaesthetic risks, FNAC provided sufficient information to justify a nonoperative approach. Other authors also concur with the view of Lim et al71 that FNAC can influence the choice of treatment. Deans et al72 reported a series of 50 patients undergoing parotid surgery for all pathologies and disclosed that, in conjunction with ultrasonography, FNAC affected their decision-making with regard to the numbers operated on. Only one out of 21 patients investigated by these means underwent surgery. Finally, Heller et al14 studied the effect of FNAC on patient management, reporting that, of 23 patients with a clinical diagnosis of WT, 14 were diagnosed by FNAC and eight were managed conservatively.

CONCLUSIONS The treatment of WT remains a controversial issue. Most patients are managed surgically, but there is no general consensus about the specific operative strategy that should be used. Although superficial parotidectomy has been traditionally favoured, less radical excision procedures have emerged as a superior option because they are associated with decreased risk of damage to the facial nerve, shorter operating time and, in one 5


Review Outstanding research questions c

c c

c

Further study is required to determine the precise histiogenesis of Warthin tumour (WT). Should WT continue to be classified as a neoplastic lesion? What is the long-term outcome of WTs that have not been excised? Should conservative management supersede operative intervention as the mainstay of treatment for WT?

Key References c

c

c

c

c

Teymoortash A, Werner JA. Tissue that has lost its track: Warthin’s tumour. Virchows Arch 2005;446:585–8. Batsakis JG. Carcinoma ex papillary cystadenoma lymphomatosum malignant Warthin’s tumour. Ann Otol Rhinol Laryngol 1987;96:234–5. Chapnik JS. The controversy of Warthin’s tumour. Laryngoscope 1983;93:695–716. Lewis DR, Webb AJ, Lott MF, et al. Improving cytological diagnosis and surgical management of parotid adenolymphoma. Br J Surg 1999,86:1275–9. Flezar M, Pognacnik A. Warthin’s tumour: unusual vs common morphological findings in fine needle aspiration biopsies. Cytopathology 2002;13:232–41.

study, a lower risk of tumour recurrence.9 10 73 Continuing this trend of less invasive treatment, some have also advocated conservative management. This is harmless to the patient and has produced encouraging results in the few studies that have used it.12 13 Its uptake has been relatively poor though, despite the extremely low rate of malignant transformation exhibited by WT and doubts regarding its classification as a true neoplasm.5 13 15 It is conceivable that, as there is little concern about the aggressiveness of WT, the predominance of surgical management may in fact result from diagnostic uncertainty. Currently there are several diagnostic modalities that can reliably identify the tumour, and, of these, FNAC has been studied most extensively. Stewart et al44 have reported it to have a sensitivity, specificity and diagnostic accuracy as high as 97%, 100% and 100%, respectively. Although such results have been used to influence management decisions, not all centres are able to carry out the procedure with such precision, creating considerable doubt as to the true nature of the lesion at hand. The controversies discussed here parallel those encountered by breast surgeons faced with a fibroadenoma. This benign lesion also consists of polyclonal cellular components and has a low rate of malignant transformation (0.02–0.3%), similar to that of WT.74 Recommendations for conservative treatment have been made for all affected women provided that there is an unequivocal diagnosis of a benign lesion on triple assessment.75 Moreover, there are also reports that 6-monthly follow-up in those under 35 years may be sufficient.76 The evidence outlined in this review suggests that, provided that there is a reliable diagnosis of WT, conservative management can be used.14 72 If such an approach is used, the importance of observing clinical changes should be stressed to the patient, particularly in the case of a rapid growth rate, as 6

this has been shown to herald malignant transformation.38 39 Conversely, centres with poor diagnostic capabilities should continue with surgical resection, as the risks associated with missing an underlying malignancy must surely outweigh those of an operation.

MULTIPLE CHOICE QUESTIONS (TRUE (T)/FALSE (F); ANSWERS AFTER THE REFERENCES) 1. The aetiology of Warthin tumour (WT) A.

Smoking decreases reactive oxygen species that result in damaged mitochondrial DNA. B. Epstein–Barr virus is thought to have a role in the development of WT. C. The lymphoid stroma of WT only contains T cells. D. 79–100% of patients are found to have a history of smoking. E. Hypertension does not have a role in the aetiology of WT.

2. The pathological basis of WT A.

WTs are encapsulated lesions with both epithelial and lymphoid components. B. The parotid gland is encapsulated early in its embryological development. C. Neoplasia is regarded as a monoclonal process. D. It has been estimated that 0.3% of WTs undergo malignant transformation. E. Both squamous cell carcinoma and mucoepidermoid carcinoma may develop from a pre-existing WT.

3. Clinical presentation of WT A.

Men in their seventh decade most commonly develop the tumour. B. The superior pole of the parotid gland is the usual focus for growth. C. A rapid growth rate may indicate malignant transformation. D. Over 30% of patients exhibit both bilaterality and multifocality. E. WT is the second most common benign neoplasm of the parotid gland.

4. Diagnosis of WT A.

Fine-needle aspiration cytology can affect decision-making about the choice of treatment. B. On biopsy, WTs are characterised by cellular debris, lymphocytes and oncocytes. C. The appearance of WT on MRI is of early enhancement, low washout ratio and high apparent diffusion coefficient. D. The typical appearance of WT on ultrasonography includes multiple anechoic areas, clear boundaries, ovoid appearance and hypoechoic internal echoes. E. Tc-99m-pertechnetate scanning is usually the investigation of choice.

5. Management of WT A. B. C.

The hypoglossal nerve is at risk during surgery of the parotid gland. Enucleation and local excision procedures are initially favoured by surgeons treating WT. A conservative approach may be used for all patients. Postgrad Med J 2009;85:3–8. doi:10.1136/pgmj.2008.071282


Review D. The facial nerve is at risk during surgery of the parotid gland. E. The majority of patients are offered conservative treatment.

33. 34.

35.

Funding: None. Competing interests: None.

REFERENCES 1.

2.

3.

4.

5. 6.

7. 8.

9. 10. 11. 12. 13.

14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31.

32.

Guntinas-Lichius O, Klussmann JP, Wittekindt C, et al. Parotidectomy for benign parotid disease at a university teaching hospital: outcome of 963 operations. Laryngoscope 2006;116:534–40. Renehan A, Gleave EN, Hancock BD, et al. Long-term follow-up of over 1000 patients with salivary gland tumours treated in a single centre. Br J Surg 1996;83:1750–4. Maiorano E, Lo Muzio L, Favia G, et al. Warthin’s tumour: a study of 78 cases with emphasis on bilaterality, multifocality and association with other malignancies. Oral Oncol 2002;38:35–40. Teymoortash A, Krasnewicz Y, Werner JA. Clinical features of cystadenolymphoma (Warthin’s tumour) of the parotid gland: a retrospective comparative study of 96 cases. Oral Oncol 2006;42:569–73. Teymoortash A, Werner JA. Tissue that has lost its track: Warthin’s tumour. Virchows Arch 2005;446:585–8. Al Salamah SM, Khalid K, Khan IAR, et al. Outcome of surgery for parotid tumours: 5-year experience of a general surgical unit in a teaching hospital. ANZ J Surg 2005;75:948–52. Licitra L, Grandi C, Prott FJ, et al. Major and minor salivary glands tumours. Crit Rev Oncol Hematol 2003;45:215–25. Shimizu M, Ussmuller J, Hartwein J, et al. Statistical study for sonographic differential diagnosis of tumourous lesions in the parotid gland. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;88:226–33. O’Brien CJ. Current management of benign parotid tumours-the role of limited superficial parotidectomy. Head Neck 2003;25:946–52. Yu GY, Ma DQ, Liu XB, et al. Local excision of the parotid gland in the treatment of Warthin’s tumour. Br J Oral Maxillofac Surg 1998;36:186–9. Raymond MR, Yoo JH, Heathcote JG, et al. Accuracy of fine-needle aspiration biopsy for Warthin’s tumours. J Otolaryngol 2002;31:263–70. Chapnik JS. The controversy of Warthin’s tumour. Laryngoscope 1983;93:695–716. Hancock BD. The influence of multicentricity in the treatment of Warthin’s tumour: the Manchester experience. In: McGurk M, Renehan A, eds. Controversies in the management of salivary gland disease. Oxford: Oxford University Press, 2001:117–22. Heller KS, Dubner S, Chess Q, et al. Value of fine needle aspiration biopsy of salivary gland masses in clinical decision-making. Am J Surg 1992;164:667–70. Batsakis JG. Carcinoma ex papillary cystadenoma lymphomatosum malignant Warthin’s tumour. Ann Otol Rhinol Laryngol 1987;96:234–5. Finkelstein DM, Noyek AM, Chapnik JS. Multiple bilateral synchronous Warthin’s tumours: a case report and review of the literature. J Otolaryngol 1989;18:357–61. Allegra SR. Warthin’s tumour: a hypersensitivity disease? Ultrastructural, light, and immunofluorescent study. Hum Pathol 1971;2:403–20. Honda K, Kashima K, Daa T, et al. Clonal analysis of the epithelial component of Warthin’s tumour. Hum Pathol 2000;31:1377–80. Takezawa K, Jackson C, Gnepp DR, et al. Molecular characterization of Warthin tumour. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998;85:569–75. Melato M, Falconieri G, Fanin R, et al. Hodgkin’s disease occurring in a Warthin’s tumour: first case report. Pathol Res Pract 1986;181:615–20. Therkildsen MH, Christensen N, Andersen LJ, et al. Malignant Warthin’s tumour: a case study. Histopathology 1992;21:167–71. Moosavi H, Ryan C, Schwartz S, et al. Malignant adenolymphoma. Hum Pathol 1980;11:80–3. Allen JA, Coombs MM. Covalent binding of polycyclic aromatic compounds to mitochondrial and nuclear DNA. Nature 1980;287:244–5. Lewis PD, Baxter P, Paul Griffiths A, et al. Detection of damage to the mitochondrial genome in the oncocytic cells of Warthin’s tumour. J Pathol 2000;191:274–81. Santucci M, Gallo O, Calzolari A, et al. Detection of Epstein-Barr viral genome in tumour cells of Warthin’s tumour of parotid gland. Am J Clin Pathol 1993;100:662–5. Lin C-C, Tsai M-H, Huang C-C, et al. Parotid tumours: a 10 year experience. Am J Otolaryngol 2008;29:94–100. Yoo GH, Eisele DW, Askin FB, et al. Warthin’s tumour: a 40-year experience at The Johns Hopkins Hospital. Laryngoscope 1994;104:799–803. de Ru JA, Plantinga RF, Majoor MH, et al. Warthin’s tumour and smoking. B-Ent 2005;1:63–6. Gallo O, Bocciolini C. Warthin’s tumour associated with autoimmune diseases and tobacco use. Acta Otolaryngol 1997;117:623–7. Yu GY, Liu XB, Li ZL et al. Smoking and the development of Warthin’s tumour of the parotid gland. Br J Oral Maxillofac Surg 1998;36:183–5. Leverstein H, Van der Wal JE, Tiwari RM, et al. Results of the surgical management and histopathological evaluation of 88 parotid gland Warthin’s tumours. Clin Otolaryngol Allied Sci 1997;22:500–3. Baum RK, Perzik SL. An evaluation of Warthin’s tumour: a clinical review of 59 cases. Am Surg 1964;30:420–2.

Postgrad Med J 2009;85:3–8. doi:10.1136/pgmj.2008.071282

36. 37. 38. 39. 40.

41. 42.

43. 44. 45. 46.

47. 48. 49. 50.

51. 52. 53. 54.

55.

56. 57.

58.

59. 60. 61.

62.

63. 64. 65.

66.

Hilton JM, Phillips JS, Hellquist HB. Multifocal multi-site Warthin tumour. Eur Arch Otorhinolaryngol. 2008 Feb 27 [Epub ahead of print]. Ikeda M, Motoori K, Hanazawa T, et al. Warthin tumour of the parotid gland: diagnostic value of MR imaging with histopathologic correlation. Am J Neuroradiol 2004;25:1256–62. Motoori K, Ueda T, Uchida Y, et al. Identification of Warthin tumour magnetic resonance imaging versus salivary scintigraphy with technetium-99m-pertechnetate. J Comput Assist Tomogr 2005;29:506–12. Jung SM, Hao SP. Warthin’s tumour with multiple granulomas: a clinicopathologic study of six cases. Diagn Cytopathol 2006;34:564–7. Starek I, Tichy T, Skypalova, et al. Ulcerating Warthin’s tumour. Acta Otolaryngol 2004;124:744–6. Ferrero S, Cattaneo L, Peri A, et al. Poorly differentiated carcinoma arising from adenolymphoma of the parotid gland. BMC Surg 2003;3:1–5. Gunduz M, Yamanaka N, Hotomi M, et al. Squamous call carcinoma arising in a Warthin’s tumour. Auris Nasus Larynx 1999;26:355–60. Ethunandan E, Pratt CA, Morrison A. Multiple synchronous and metachronous neoplasms of the parotid gland: the Chichester experience. Br J Oral Maxillofac Surg 2006;44:397–401. Gaynor EB, Hershberg R. Unilateral multiple tumours of the parotid gland. J Laryngol Otol 1976;90:295–8. Shikhani AH, Shikhani LT, Kuhajda FP, et al. Warthin’s tumour-associated neoplasms: report of two cases and review of the literature. Ear Nose Throat J 1993;72:264–9, 272–3. Qizilbash A, Sianos J, Young JEM, et al. Fine needle aspiration biopsy cytology of major salivary glands. Acta Cytol 1985;29:503–12. Stewart CJR, MacKenzie K, McGarry GW, et al. Fine-needle aspiration cytology of salivary gland: a review of 341 cases. Diagn Cytopathol 2000;22:139–46. Behzatoglu K, Bahadir B, Kaplan H, et al. Fine needle aspiration biopsy of the parotid gland. Acta Cytol 2004;48:149–54. Bajaj Y, Singh S, Cozens N, et al. Critical clinical apprasial of the role of ultrasound guided fine needle aspiration cytology in the management of parotid tumours. J Laryngol Otol 2005;119:289–92. Edwards P, Wasserman P. Evaluation of cystic salivary gland lesions by fine needle aspiration. Acta Cytol 2005;49:489–94. Dunn EJ, Kent T, Hines J, et al. Parotid neoplasms: a report of 250 cases and review of the literature. Ann Surg 1976;184:500–6. Fulciniti F, Califano L, Zupi A, et al. Accuracy of fine needle aspiration biopsy in head and neck tumours. J Oral Maxillofac Surg 1997;55:1094–7. Ballo MS, Shin HJC, Sneige N. Sources of diagnostic error in the fine needle aspiration diagnosis of Warthin’s tumour and clues to a correct diagnosis. Diagn Cytopathol 1997;17:230–4. Parwani AV, Ali SZ. Diagnostic accuracy and pitfalls in fine-needle aspiration interpretation of Warthin’s tumour. Cancer 2003;99:166–71. Lewis DR, Webb AJ, Lott MF, et al. Improving cytological diagnosis and surgical management of parotid adenolymphoma. Br J Surg 1999;86:1275–9. Filopoulos E, Angeli S, Daskalopoulou D, et al. Pre-operative evaluation of parotid tumours by fine needle biopsy. Eur J Surg Oncol 1998;24:180–3. Klijanienko J, Vielh P. Fine needle sampling of salivary gland lesions. II. Cytology and histology correlation of 71 cases of Warthin’s tumour (adenolymphoma). Diagn Cytopathol 1997;16:221–5. Das DK, Petkar MA, Al-Mane NM, et al. Role of fine needle aspiration cytology in the diagnosis of swellings in the salivary gland regions: a study of 712 cases. Med Princ Pract 2004;13:95–106. Flezar M, Pognacnik A. Warthin’s tumour: unusual vs common morphological findings in fine needle aspiration biopsies. Cytopathology 2002;13:232–41. Verma K, Kapila K. Salivary gland tumours with a prominent oncocytic component. Cytological findings and differential diagnosis of oncocytomas and Warthin’s tumour on fine needle aspirates. Acta Cytol 2003;47:221–6. Van den Brekel MWM, Risse EKJ, Tiwari RM, et al. False-positive fine needle aspiration cytologic diagnosis of a Warthin’s tumour with squamous metaplasia as a squamous-cell carcinoma. Acta Cytol 1991;35:477–8. Zajkowski P, Jakubowski W, Bialek EJ, et al. Pleomorphic adenoma and adenolymphoma in ultrasonography. Eur J Ultrasound 2000;12:23–9. Kim J, Kim EK, Park CS, et al. Characteristic sonographic findings of Warthin’s tumour in the parotid gland. J Clin Ultrasound 2004;32:78–81. De Ru JA, Van Leeuwen MS, Van Benthem PPG, et al. Do magnetic resonance imaging and ultrasound add anything to the preoperative workup of parotid gland tumours? J Oral Maxillofac Surg 2007;65:945–52. Feld R, Nazarian LN, Needleman L, et al. Clinical impact of sonographically guided biopsy of salivary gland masses and surrounding lymph nodes. Ear Nose Throat J 1999;78:905, 908–12. Akbas¸ Y, Tuna EU, Demireller A, et al. Ultrasonography guided fine needle aspiration biopsy of parotid gland masses. Kulak Burun Bogaz Ihtis Derg 2004;13:15–18. Urquhart A, Hutchins LG, Berg RL. Preoperative computer tomography scans for parotid tumour evaluation. Laryngoscope 2001;111:1984–8. Koyuncu M, Sesen T, Akan H, et al. Comparison of computer tomography and magnetic resonance imaging in the diagnosis of parotid tumours. Otolaryngol Head Neck Surg 2003;129:726–3. Arbab AS, Koizumi K, Toyama K, et al. Various imaging modalities for the detection of salivary gland lesions: the advantages of 201T1 SPET. Nucl Med Commun 2000;21:277–84.

7


Review 67. 68. 69. 70. 71. 72. 73.

Choi DS, Na DG, Byun HS, et al. Salivary gland tumours: evaluation with two-phase helical CT. Radiology 2000;214:231–6. Miyake H, Matsumoto A, Hori Y, et al. Warthin’s tumour of parotid gland on Tc-99m pertechnetate scintigraphy with lemon juice stimulation: Tc-99m uptake, size and pathologic correlation. Eur Radiol 2001;11:2472–8. Hisatomi M, Asaumi J, Konouchi H, et al. Assessment of dynamic MRI of Warthin’s tumours arising as multiple lesions in the parotid glands. Oral Oncol 2002;38:369–72. Sato T, Morita Y, Hamamoto S, et al. Interpretation of scintigraphy of papillary cystadenoma lymphomatosum (Warthin’s tumour) on the basis of histopatholgic findings. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1996;82:101–17. Lim LHY, Chao SS, Goh CHK, et al. Parotid gland surgery: 4-year review of 118 cases in an Asian population. Head Neck 2003;25:543–8. Deans GT, Briggs K, Spence RA. An audit of surgery of the parotid gland. Ann R Coll Surg Engl 1995;77:188–92. Iwai H, Yamashita T. Local excision procedure for Warthin’s tumour of the parotid gland. Otolaryngol Head Neck Surg 2005;132:577–80.

74.

Ozisik YY, Aurelia MM, Stephenson CF, et al. Chromosome abnormalities in breast fibroadenomas. Cancer Genet Cytogenet 1994;77:125–8. Courtillot C, Plu-Bureau G, Binart N, et al. Benign breast disease. J Mammary Gland Biol Neoplasia 2005;10:325–35. Greenberg R, Skornick Y, Kaplan O. Management of breast fibroadenomas. J Gen Intern Med 1998;13:640–5.

75. 76.

ANSWERS (A) (A) (A) (A) (A)

F; T; T; T; F;

(B) (B) (B) (B) (B)

T; F; F; T; T;

(C) F; (C) T; (C) T; (C) F; (C) F;

(D) (D) (D) (D) (D)

T; T; F; T; T;

(E) F (E) T (E) T (E) F (E) F

Save your favourite articles and useful searches Use the ‘‘My folders’’ feature to save and organise articles you want to return to quickly—saving space on your hard drive. You can also save searches, which will save you time. You will only need to register once for this service, which can be used for this journal or all BMJ Journals, including the BMJ.

8

Postgrad Med J 2009;85:3–8. doi:10.1136/pgmj.2008.071282


Current controversies in the management of Warthin tumour T Thangarajah, V M Reddy, F Castellanos-Arango, et al. Postgrad Med J 2009 85: 3-8

doi: 10.1136/pgmj.2008.071282

Updated information and services can be found at: http://pmj.bmj.com/content/85/999/3.full.html

These include:

References

This article cites 74 articles, 3 of which can be accessed free at: http://pmj.bmj.com/content/85/999/3.full.html#ref-list-1

Email alerting service

Receive free email alerts when new articles cite this article. Sign up in the box at the top right corner of the online article.

Notes

To request permissions go to: http://group.bmj.com/group/rights-licensing/permissions

To order reprints go to: http://journals.bmj.com/cgi/reprintform

To subscribe to BMJ go to: http://group.bmj.com/subscribe/