Experience with follow-up strategy in selected patients with Warthin tumour diagnosed by ultrasound-guided fine-needle aspiration biopsy (FNAB).

PURPOSE: Warthin tumour (WT) management options comprise surgery or follow-up. The purpose of this study was to asses our experience with the follow-up strategy in selected patients with an ultrasound-guided fine-needle aspiration biopsy (FNAB) showing WT. METHODS: We performed a retrospective analysis of patients diagnosed with WT using FNAB between 1.1.2006 and 31.12.2019. Patients were divided into three groups according to the therapeutic approach-immediate surgery, follow-up or surgery and follow-up. RESULTS: 323 patients were diagnosed with WT and met the study's inclusion criteria (154 women, 47.7% and 169 men, 52.3%). 192 patients were operated right after the diagnosis, 109 patients were observed with their first detected tumour and 22 patients had parotid WT surgery and were in the wait-and-scan protocol with a contralateral tumour, recurrence or both. The growth rate (GR) of observed WT was highly variable (mean GR 1.0 mm/year (5%), median GR 0.8 mm (9%), range - 19.7 to +20.0 mm/year). From 131 patients in the follow-up group, 19 patients underwent surgery and definitive histology revealed 17 WTs and 2 adenocarcinomas. However, these 2 patients had changes in sonographic findings at their next control. The mean observation time was 44.7 months (range 12-138 months) in patients followed exclusively at our institution and 50.9 months (range 12-110 months) in patients observed in cooperation with an otorhinolaryngologist at the patients' place of residence. CONCLUSION: Ultrasound-guided FNAB is an accurate and simple method in WT diagnosis and based on its result a follow-up strategy can be chosen for selected patients with WT.

Cytopathology and diagnostics of Warthin's tumour.

Warthin's tumour (WT) is a benign epithelial salivary tumour, one type of salivary adenoma. Histologically, WT is structured of two components, epithelial tissue that often lines cystic formations and lymphoid tissue in the tumour stroma. FNA is a reliable diagnostic approach in the diagnosis of salivary gland lesions allowing a highly accurate categorization of benign tumour-like lesions, benign tumours and malignant tumours. In the proposed Milan reporting system of salivary gland lesions, WT is categorized in the IVA group of benign neoplasms. Accurate cytological diagnosis is straightforward when three characteristic components are present: oncocytes, either isolated or associated in clusters, lymphocytes and lymphoid cells and often an inflammatory/necrotic-like substance. Also, specific features of scintigraphy and radiological imaging contribute to the diagnosis of WT. WT is categorized according to Seifert G. et al in 4 types, depending on the proportions of the epithelial component and lymphoid stroma. Differential cytopathological and pathohistological diagnosis include other salivary gland lesions with lymphoid, oncocytic epithelial and cystic components. In some cases, such as the metaplastic WT variant, there are additional cytopathological and histological diagnostic difficulties. Moreover, bilateral, multicentric or multiple and infrequently seen extra-salivary localizations of WT are associated with further cytopathological diagnostic difficulties. Also, a rare possibility of malignant transformation of the epithelial or lymphoid component of WT as well as possible association with other primary tumours remains a challenge in accurate cytopathological and histological diagnosis of WT.

Warthin's tumour seems to be the most common benign neoplasm of the parotid gland in Germany.

PURPOSE: Recent reports indicate an increase in the prevalence of Warthin's tumours (adenolymphoma) with percentages which exceed that of pleomorphic adenomas (PA) in the same registries. The purpose of this study is to analyse a large cohort of benign parotid tumours in relation to various demographic and other patients' characteristics that might affect their incidence. METHODS: A retrospective review of prospective collected data was performed on all patients who have been operated for a parotid mass in the last 5 years. A total of 474 patients with benign lesion were included in the study. Age, gender, smoking status, histological diagnosis, site of lesion, and size of tumour were recorded. RESULTS: Warthin's tumours were the most common benign lesions, found in 201 (42.4%) parotic glands followed by pleomorphic adenomas found in 138 (29.1%) of these surgical cases. Patients with WT had a mean age of 61.6 years instead of 52 years for PA patients (t = 6.589, p < 0.001). The vast majority (93%) of patients with WT had a current or previous history of smoking compared with 47% of PA patients (p = 0.001). There was a male predominance regarding WT with a male:female (M:F) ratio of 2.3:1, whereas the corresponding ratio of PA was 1:1.4. CONCLUSIONS: This study confirms the increased regional prevalence of WT reported in studies mainly carried out in central Europe. This could affect future management of WT, which remains largely controversial due to the extremely low malignant potential reported, concurrently with its higher rates of multiplicity and recurrence, as well as the moderately accurate results of FNA biopsies.

The role of fine-needle aspiration biopsy (FNAB) in Warthin tumour diagnosis and management.

PURPOSE: Warthin tumour (WT) is the second most common benign tumour of the parotid gland. The aim of this study was to assess the value of the FNAB in the diagnosis and treatment decision in patients with WT. MATERIALS AND METHODS: We performed a retrospective study of patients treated for parotid gland mass between 2006 and 2016. Patients who underwent the surgery with preoperative FNAB were considered. The first group was comprised of patients with preoperative FNAB showing WT and the second group was formed by patients with definitive histology of WT. RESULTS: 216 patients had FNAB with the result of WT and underwent surgery (98 women-45.4% and 118 men-54.6%). The definitive histology corresponded with the preoperative diagnosis in 201 cases (93.1%). The other way round, 222 patients were operated with definitive histology showing WT and we correlated this finding with preoperative FNAB. The result of FNAB corresponded with definitive histology of WT in 201 cases (90.5%). Counted sensitivity and specificity of the ultrasound-guided FNAB for the diagnosis of WT were, respectively: 96.63% (CI 93.19-98.64%) and 96.21 (CI 93.83-97.86%). The accuracy of this method was 96.36% (CI 94.54-97.70%). CONCLUSION: Ultrasound-guided FNAB is a safe, accurate and important method in WT diagnosis. The therapeutic approach can be chosen based on FNAB results correlated with other clinical findings. We propose that when WT is suspected, follow-up or enucleation of the tumour are appropriate treatments. Patient preferences should be also considered.

Increased incidence of Warthin tumours of the parotid gland: a 42-year evaluation.

AIM: To evaluate the frequency of Warthin tumours among parotid neoplasms over the past 42 years in a population in rural Germany and to identify potential risk factors. METHODS: We conducted a retrospective case note evaluation from all patients who underwent parotid surgery between 1975 and 2017. The 42-year time period was evenly split into four quartiles. RESULTS: A Warthin tumour was diagnosed in 265 out of 806 patients (32.9%). The frequency of Warthin tumour increased steadily from 20.6% in the first decade between 1975 and 1986 to 44.9% in the fourth decade between 2008 and 2017. The age of the patients decreased from 68 years in the first to 62 years in the fourth decade. The male-to-female ratio in Warthin tumour was reduced from 1:5.3 in the first to 1:2.1 in the fourth decade. CONCLUSION: A Warthin tumour was the most common histological tumour type in the period from 1997 to 2017. We also found a high incidence of multiple tumours, a growing incidence in women and a decreasing age of patients. We propose a re-evaluation of the existing view of the epidemiology of benign parotid tumours, which proposes that pleomorphic adenoma is the most common benign parotid tumour.

Fine-needle aspiration cytology for parotid lesions, can we avoid surgery?

OBJECTIVE: Salivary gland neoplasms are rare tumours, with most arising in the parotid gland. Fine-needle aspiration cytology (FNAC) is a common method for preoperative evaluation of parotid masses, although its usefulness is controversial. This study was designed to evaluate the accuracy of FNAC in a large cohort of patients, with emphasis on diagnosis of benign tumours and especially Warthin tumour which can be managed conservatively. STUDY DESIGN: Retrospective case series with chart review. SETTING: Tertiary medical centre. SUBJECTS AND METHODS: From 1991 to 2014, all patients 18 or older with both preoperative FNAC and postoperative pathology report were included. Patients with a history of head and neck malignancy or chronic sialoadenitis and patients who had undergone prior oncological treatment were excluded. RESULTS: 470 patients were available for analysis. Overall accuracy was 82.6%. Positive predictive value (PPV) varied between 88.6% and 94.3% for pleomorphic adenoma and 77.1%-100% for Warthin tumour, with values varying depending on different characteristics of patients (eg age, smoking status). For pathologically proven malignant tumours, the FNAC diagnosis was benign or non-diagnostic in 26% of the cases. CONCLUSION: Fine-needle aspiration cytology has limited utility in confirming a benign diagnosis of a parotid mass for most patients, although for some subpopulations, the PPV may be high enough to defer surgery.

An algorithm for preoperative differential diagnostics of parotid tumours on the basis of their dynamic and diffusion-weighted magnetic resonance images: a retrospective analysis of 158 cases.

BACKGROUND: To verify the usefulness of a new algorithm for preoperative differential diagnostics of parotid tumours on the basis of their dynamic and diffusion- -weighted magnetic resonance imaging (MRI). MATERIALS AND METHODS: The retrospective analysis included 158 consecutive surgical patients with parotid tumours. Aside from ultrasound-guided fine needle biopsy, the protocol of preoperative evaluation included dynamic and diffusion-weighted MRI. According to the new diagnostic algorithm, the result of fine needle biopsy was considered only in the case of lesions with time to peak enhancement (Tpeak) > 60 s and washout rate (WR) ≤ 30% on dynamic MRI and apparent diffusion coefficient (ADC) ≤ 1.7 × 103 mm/s2 on diffusion-weighted MRI, or those presenting with concomitant lymphadenopathy. The accuracy of this algorithm was verified against final histopathological diagnoses. RESULTS: The new algorithm gave 10 true positive and 2 false positive results, as well as 132 and 14 true and false negative results, respectively. Its sensitivity and specificity (41.7% and 98.5%, respectively) were the same as in the case of fine needle biopsy alone. None of the 59 tumours that were qualified as benign solely on the basis of preoperative MRI turned out to be malignant on postoperative histopathological examination. CONCLUSIONS: Interpreted together, dynamic and diffusion-weighted MRIs provide the same accuracy in preoperative differential diagnostics of parotid tumours as fine needle biopsy. This substantiates the use of diagnostic algorithms in which biopsy would serve mostly as a secondary test to verify selected ambiguous radiological diagnoses. (Folia Morphol 2018; 77, 1: 29-35).

Perfusion imaging of parotid gland tumours: usefulness of arterial spin labeling for differentiating Warthin's tumours.

OBJECTIVE: To assess prospectively the efficacy of arterial spin labelling (ASL) against conventional and diffusion-weighted (DW) MR imaging for differentiating parotid gland tumours. METHODS: We included 10 pleomorphic adenomas, 12 Warthin's tumours, and nine malignant tumours of the parotid glands. Only tumours larger than 10 mm were included in this study. All parotid gland tumours underwent T1-weighted, T2-weighted, DW, and ASL imaging. Tumour-to-parotid gland signal intensity ratios (SIRs) and apparent diffusion coefficients (ADCs) of solid components were correlated with these pathologies. RESULTS: SIRs on T2-weighted images and ADCs were higher in pleomorphic adenomas than in Warthin's tumours (p < .01) and malignant tumours (p < .01). SIRs on ASL were higher in Warthin's tumours than in pleomorphic adenomas (p < .01) and malignant tumours (p < .05). Az value of SIRs on ASL for differentiating Warthin's tumours from the other pathologies was 0.982. The sensitivity, specificity, and accuracy of SIRs on ASL for the diagnosis of Warthin's tumours at an optimal SIR threshold of over 8.70 were 91.7%, 94.7%, and 93.5%, respectively. CONCLUSIONS: ASL with SIR measurements could non-invasively evaluate tumour blood flow of parotid gland tumours and differentiate Warthin's tumours from pleomorphic adenomas and malignant tumours. KEY POINTS: • ASL non-invasively evaluates tumour blood flow of parotid gland tumours • ASL differentiates Warthin's tumours from pleomorphic adenomas and malignant tumours • ASL cannot differentiate between pleomorphic adenomas and malignant tumours.

PRDM1 expression on the epithelial component but not on ectopic lymphoid tissues of Warthin tumour.

OBJECTIVE: To determine the role of PRDM1, a key molecule for modulating the immune cells, in Warthin tumour (WT) pathogenesis. SUBJECTS AND METHODS: Forty paraffin-embedded parotid tissues of patients (mean age: 62.08 ± 11.90) with WT were retrieved from the pathology archives of Qindu Hospital from January 2012 to December 2012. The PRDM1 expression was investigated in a cohort of WT by immunohistochemistry. RESULTS: PRDM1 was expressed only on the epithelial component but not on ectopic lymphoid tissue of the tumour. Statistically, PRDM1 expression rates between WT glandular epithelial cells (40/40 cases) and the tumour-adjacent tissues (0/9 cases), and WT germinal centres (0/34 cases) and tonsil tissues (10/10 cases) were significantly different (P < 0.001), respectively. CONCLUSIONS: The PRDM1 expression appeared to play an essential role in WT pathogenesis. A better understanding of it might give options for revealing possible novel management strategies.

The extracapsular dissection technique in the management of benign tumours of the parotid gland: our experience in 194 patients.

OBJECTIVE: The indications for and approaches to extracapsular dissection for parotid gland benign tumours are debated in the literature. This study retrospectively evaluates a single site's short- and long-term results with a standardised extracapsular dissection approach to benign parotid tumours. METHODS: A retrospective review of a single institution's records identified cases with extracapsular dissection as the primary surgery for non-recurrent benign parotid tumours. A total of 194 eligible patients were identified (124 women and 70 men, age 47.75 ± 15.62 years). Pre-, intra- and post-surgical data were reviewed for complications and recurrences. RESULTS: Histology reported pleomorphic adenoma in 165 patients, Warthin's tumour in 28 patients and both in one patient. Mean follow up was 36 ± 16 months (range, 12-84 months). The incidences of complications following extracapsular dissection were temporary (n = 13) and permanent (n = 0) facial nerve dysfunction, Frey's syndrome (n = 1)) and recurrences (n = 5). These rates align with prior literature. CONCLUSION: This case series shows how a standardised approach to extracapsular dissection for benign parotid tumours yields favourable results, supporting a progressive change of strategy towards reduced invasiveness.

Parotid gland oncocytoma mimicking local malignancy of Warthin's tumour on contrast-enhanced ultrasound.

Not required for Clinical Vignette.

Oncocytic Salivary Gland Tumours: Cytological Features and Diagnostic Pitfalls.

Oncocytes are epithelial cells having abundant eosinophilic cytoplasm. The presence of oncocytes in salivary glands pose a diagnostic challenge since they can be present in lesions ranging from non-neoplastic, benign to malignant. FNAC is a simple procedure which can aid in the pre-operative diagnosis of these lesions. This study is an eight year retrospective study in which salivary gland aspiration cytology cases having oncocytic cells and with available corresponding histopathology were included. These slides were reviewed for features like cellularity, presence of oncocytic cells, glandular elements, squamoid cells, nuclear atypia, mitosis, lymphoid tissue, necrosis. Twenty cases were included in the study. The mean age of presentation was 60 years showing male preponderance with parotid gland being the most common site of involvement. Concordant diagnosis on cytology and histopathology was seen in 16 cases and discordance was seen in 4 cases. All the discordant cases were reported as benign on cytology but on histopathology they were labelled as acinic cell carcinoma, squamous cell carcinoma, mucoepidermoid carcinoma and an intraparotid lymph node respectively. Review of discordant cases showed subtle findings like ill-formed acini, cytoplasmic vacuolation, goblet cells and dysplastic foci raising suspicion of a different diagnosis. The potential areas of pitfall and cause of discrepancy have been discussed in this study. It is crucial to be aware of the spectrum of lesions in which oncocytes are seen, to enable an accurate diagnosis on cytology. Careful evaluation of smears for subtle clues can minimize errors.

Warthin-like mucoepidermoid carcinoma of the parotid gland: a clinicopathological analysis of two cases.

Mucoepidermoid carcinoma (MEC) is the most common malignant tumour of the salivary gland, primarily involving the parotid gland. Here, the cases of two patients, aged 47 and 67 years, respectively, who underwent surgery for pathologically confirmed Warthin-like MEC of the parotid gland between January 2019 and December 2019 in Anyang Tumour Hospital, are described. In each case, the tumour consisted of epithelial and lymphoid cell components, covered with two or more layers of epithelium, with visible scattered mucous cells, and lymphoid stroma with a large number of lymphocytes and germinal centres formed. Most importantly, the tumours lacked the well-organized, bilayered oncocytic epithelial structure that is characteristic of Warthin's tumour. Mastermind like transcriptional coactivator 2 (MAML2) gene rearrangements were identified in the tumour cells using break-apart fluorescence in situ hybridization (FISH) probes, confirming the diagnosis of Warthin-like MEC. Post-operatively, patients have remained disease free for 31 and 27 months, respectively. Warthin-like MEC of the parotid gland is rare and is often misdiagnosed as metaplastic Warthin's tumour. Diagnosis depends mainly on the unique clinicopathologic features together with FISH analyses.

Oral Squamous Cell Carcinoma and Warthin Tumour Occurring As Synchronous Tumours: A Report of Two Cases.

Oral cancer is a common site of cancer worldwide with oral squamous cell carcinoma (OSCC) comprising the major segment. The risk factors include tobacco and alcohol abuse, betel quid, and areca nut consumption. Warthin tumour (WT), also known as papillary cystadenoma lymphomatosum is a benign tumour of the salivary gland. It is one of the most common benign parotid neoplasms with cigarette smoking and radiation exposure as possible cited etiologic factors. Rarely, two or more histologically distinct neoplasms may occur synchronously. The synchronous occurrence of OSCC and WT is infrequent. The aim of this case series is to report the incidence rate of synchronous OSCC and WT in our centre between 2010 and 2019 and their socio-demographic, clinical, histopathological features, management, and prognosis and discuss the relevant literature. Out of 143 OSCC cases reported in our centre from the year 2010 to 2019, two had synchronous OSCC and WT with an incidence rate of 1.4%. These two cases occurred in a 63-year-old female and a 68-year-old male both with smoking habits. One OSCC was present in the left buccal mucosa and the other in the right ventral surface of the tongue, whereas the WT in both cases occurred in the tail of the parotid. One patient had a recurrence and died while the other is under follow-up without any recurrence. These unusual findings of synchronous occurrence of WT at a distant site from the primary tumour may mimic a malignant disease, more likely a metastasis from the primary OSCC, which could further complicate the management of these patients. Therefore, radiologists, head and neck surgeons, and pathologists should be aware of the occurrence of these unusual presentations to avoid overtreatment in such cases.

The potential role of follicular helper T cells and helper T cells type 1 in Warthin tumour.

Warthin tumour (WT) is a benign tumour of the salivary gland that proliferates in both glandular epithelial and lymphoid tissue components, and rarely exhibits cystic changes. T follicular helper cells (Tfh) are involved in the formation and maintenance of germinal centres, the differentiation of B cells into plasma cells, and the maintenance of helper T cell type 2 (Th2)-dominant humoral immune responses. T-bet induces differentiation into helper T cell type 1 (Th1) by suppressing differentiation into Tfh and enhances cellular immune responses. The objective of this study was to enhance our understanding of the immune responses and relationship between Tfh and Th1 cells in patients with WTs. In this study, we classified WTs (n = 64) into solid-type (n = 25) and cyst-type (n = 39). We also performed immunostaining of the Tfh markers CXCR5 and CD40 L, and the Th1 marker T-bet for statistical analysis. The cyst-type exhibited significant atrophy of the germinal centre area (P = 0.0019), significantly fewer Tfh-positive lymphocytes in germinal centres (P < 0.0001), and significantly more T-bet-positive lymphocytes in the epithelium (P = 0.0017). We observed that Tfh were involved in the formation and maintenance of lymphoid follicles in WTs. In the cyst-type, Th2-dominant humoral immune responses were suppressed, and Th1-dominant cellular immune responses may have caused damage to tumour tissue.

MAML2 rearrangement as a useful diagnostic marker discriminating between Warthin tumour and Warthin-like mucoepidermoid carcinoma.

Warthin tumour is the second most common benign neoplasm of salivary glands. Despite its relatively characteristic histology, it may sometimes mimic other lesions. Here, we report two female non-smoker patients diagnosed with low-grade mucoepidermoid carcinoma with oncocytic epithelium and prominent lymphoid (Warthin-like) stroma and with molecularly confirmed MAML2 rearrangement. In addition, we screened a consecutive series of 114 Warthin tumour cases by means of MAML2 break apart fluorescence in situ hybridization to assess its value in differential diagnosis. MAML2 rearrangement was detected in both mucoepidermoid carcinoma cases, while all Warthin tumours were negative. Taking into account the literature data, Warthin-like mucoepidermoid carcinomas are more frequently observed in women, while a slight male predominance and smoking history are typical for Warthin tumour. In addition, the patients with Warthin-like mucoepidermoid carcinoma were significantly younger than those with Warthin tumour. To conclude, Warthin-like mucoepidermoid carcinoma may usually be suspected based on histology, while the diagnosis can be confirmed by means of molecular assays such as FISH. The investigation of MAML2 status is particularly advised when Warthin tumour is considered in a young, non-smoking, female patient.

Acute Parotitis: A Rare Complication of Fine Needle Aspiration in Warthin Tumour.

Salivary gland tumours are a group of neoplasms with considerable heterogeneity regarding their histology and biological behaviour. Warthin tumour (WT) is the second most common benign parotid tumour. Options for tissue diagnosis include fine needle aspiration (FNA) and ultrasound-guided core needle biopsy. Complications related to FNA are rare. We present the case of a 49-year-old man admitted with parotitis after FNA and discuss management and an alternative investigative approach when WT is strongly suspected. LEARNING POINTS: Warthin tumour (WT) can be clinically suspected based on location (parotid gland tail), cystic texture, patient sex (male) and age (fifth and sixth decades of life), after exclusion of features related to malignancy.Complications of fine-needle aspiration (FNA) for WT diagnosis are rare and most commonly include haemorrhage, facial nerve injury, cellulitis at the needle puncture site and, less frequently, parotitis.When diagnosing tumours strongly suspected of being WT, the clinician should avoid routine FNA and instead use combined imaging studies.

Ectopic Warthin's Tumour Masquerading As Infected Branchial Cyst.

Salivary gland tumours are relatively uncommon but they present globally regardless of age. Most of these tumours are benign and involve the parotid gland. Though strictly confined to the parotid gland, Warthin's tumours can exceptionally present at an ectopic site of head and neck. Of particular significance is its striking similarity with a lymph node, an inclusion cyst, branchial cyst or a malignant mass, especially when it presents in the upper cervical region.

Watchful waiting in carefully selected metachronous cystadenolymphomas of the parotid gland: a reliable option?

The aim of this study was to evaluate the potential of watchful waiting in the treatment of metachronous cystadenolymphomas, taking the experience of our department into consideration. All patients suspected of having a metachronous cystadenolymphoma, and who had a minimum follow-up time of 12 months, were studied (n = 26). Data about the growth rate, number of lesions, and symptoms of inflammation were recorded. Mean (range) follow-up was 36 (13-94) months. Metachronous tumours developed in three cases on the ipsilateral side, in 22 cases on the contralateral side, and on both sides in one case. The mean rate of growth /lesion was 15% /year (range: 22%-158%). There were no signs of local inflammation. The extreme variability in the behaviour of metachronous cystadenolymphomas points to the need for an individualised approach, accurate investigation of the sonographic characteristics, and continuous watchful waiting in affected patients.

Warthin's tumour in oral and maxillofacial regions: an 18-year retrospective study of 1084 cases in an eastern-Chinese population.

There is little information in the English-language literature regarding Warthin's tumour (WT) in the eastern-Chinese population. A large retrospective study (1084 primary tumours over a period of 18years) was carried out to investigate the clinicopathological features (patients' gender, age and tumour location) of these tumours in this population. A total of 994 (91.7%) patients were male and 90 (8.3%) were female, with a male/female ratio of 11:1. The mean age was 56.48years (range 20-89years), with a peak incidence in the fifth to seventh decade (82.1%). The favorite primary site of the tumour was the parotid gland (n=1055), followed by intra-/peri-parotid lymph nodes (n=13), upper neck (n=10), submandibular gland (n=4) and upper lip (n=1). Multifocal WTs arose in 9.5% (103 patients) of cases whereas bilateral multifocal WTs were found in 0.65% (seven patients). In 24 (2.2%) patients, WT were found to coexist with other different types of neoplasm synchronously. The most common subtype of metaplasia was the squamous metaplasia (166/250, 66.4%). The usual treatment measure is (bilateral) superficial parotidectomy and the patients should be followed long term, in view of possible metachronous WT, even after prolonged time intervals.