Clinical decision making when cytology indicates a Warthin tumor.

Warthin tumor (WT) is a benign tumor usually affecting the parotid gland. The main diagnostic tool remains ultrasound combined with fine-needle aspiration cytology (FNAC). This study aims to examine how reliably FNAC indicates WT for clinical decision making regarding surgical versus conservative management. We included all patients who underwent FNAC from a parotid gland lesion between 2016 and 2018 at our institution, and whose FNAC revealed WT suspicion. The FNACs were divided into three groups based on the cytology report: certain, likely, and possible WT. The patients were divided into two groups based on having had either surgery or follow-up. We sent a questionnaire to patients who had not undergone surgery in order to obtain follow-up for a minimum of four years. Altogether, 135 FNAC samples, from 133 tumors and 125 patients, showed signs of WT. Of the 125 patients, 44 (35%) underwent surgery, and 81 (65%) were managed conservatively. Preoperative misdiagnosis in FNAC occurred in three (7%) surgically treated tumors. Their FNACs were reported as possible WTs, but histopathology revealed another benign lesion. In the conservatively treated group, two patients underwent surgery later during the follow-up. Cytological statements of WT were seldom false, and none were malignant. The majority of the patients were only followed-up and rarely required further treatment. A certain or likely diagnosis of WT in the FNAC report by an experienced head and neck pathologist is highly reliable in selecting patients for conservative surveillance.

Oncocytoid Salivary Tumors: Differential Diagnosis and Utility of Newly Described Immunohistochemistry.

BACKGROUND: Oncocytoid salivary tumors include several entities such as oncocytoma, Warthin tumor, secretory carcinoma (SC), salivary duct carcinoma (SDC), acinic cell carcinoma (AciCC), oncocytic mucoepidermoid carcinoma (OMEC), intraductal carcinoma, and epithelial myoepithelial carcinoma (EMC). This review investigates the differential diagnosis of oncocytoid salivary tumors and explore the role of newly described immunostains as valuable tools for their diagnosing and potentially guiding treatment options. METHODS: We assess the utility of incorporating new immunohistochemical markers in routine practice to aid in diagnosing oncocytoid salivary tumors and potentially provide treatment options. RESULTS: In SDC, AR and Her2 immunostains are utilized as diagnostic tools and biomarkers for selecting patients who might benefit from Androgen-deprivation therapy (ADT) and HER2-targeted therapy. Furthermore, nuclear Pan-Trk immunostaining can aid in diagnosing SC. Additionally, NR4A3 immunostaining has been shown high sensitivity and specificity in identifying AciCC in both surgical and cytologic specimens. Similarly, RAS Q61R mutant-specific immunostaining, detected in EMC, may offer a cost-effective diagnostic marker for this tumor. Although further studies are required to evaluate the role of BSND, this marker has been reported to be positive in Warthin tumor and oncocytoma, aiding in differentiating them from other oncocytoid tumors, particularly OMEC. In addition, BRAFV600E mutant-specific immunostaining can serve as a diagnostic and potentially therapeutic marker for oncocytic intraductal carcinoma in mutation positive cases. CONCLUSION: Oncocytoid salivary tumors may have overlapping morphologies, posing diagnostic challenges for pathologists. Recently described immunohistochemical markers may offer valuable tools for diagnosing and potentially guiding treatment options for these tumors.

Differentiation of parotid pleomorphic adenoma from Warthin tumor using signal intensity ratios on fat-suppressed T2-weighted magnetic resonance imaging.

OBJECTIVE: To investigate the value of magnetic resonance imaging (MRI) signal intensity ratios (SIRs) based on fat-suppressed T2-weighted imaging (FS-T2WI), together with demographic features, MRI anatomical characteristics, and SIRs of histopathological patterns of the tumors, in the differentiation of parotid pleomorphic adenoma (PA) from Warthin tumor (WT). STUDY DESIGN: In total, 90 patients with PA and 56 patients with WT were enrolled in the study. SIRs of tumor to normal parotid gland (SIR-T/P), spinal cord (SIR-T/S), and muscle (SIR-T/M) were calculated. Demographic and radiological features of the 2-patient groups were compared with univariate analysis and multivariate logistic regression analysis. The area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were analyzed to evaluate the utility of SIRs in distinguishing between PA and WT. RESULTS: SIR-T/P exhibited outstanding discriminating ability (AUC = 0.934), SIR-T/S had excellent discrimination (AUC = 0.839), and SIR-T/M showed acceptable discrimination (AUC = 0.728). When SIR-T/P of 1.96 was selected as the cutoff value, sensitivity and specificity were 0.756 and 0.982, respectively. SIR-T/P, age, sex, and number of lesions were identified as independent predictors by multivariate logistic regression analysis. Differences in SIRs between histopathological patterns were significant. CONCLUSION: SIR-T/P based on FS-T2WI is an effective discriminator in the differential diagnosis between PA and WT. Age, sex, and number of lesions provided additional value in differentiation.

Primary intranodal Warthin-like variant of mucoepidermoid carcinoma.

This report describes a rare case of primary intranodal Warthin-like mucoepidermoid carcinoma (WL-MEC) presenting as a left level II lymph node mass in a 48-year-old man. Warthin-like mucoepidermoid carcinoma is a recently defined variant of MEC that bears a close histologic resemblance to Warthin tumor. Whereas MEC has readily identifiable key histologic features that render diagnosis relatively straightforward, WL-MEC is a challenging diagnosis due to overlapping histologic features and only limited case reports in the literature. This case was initially diagnosed as primary intranodal MEC after the exclusion of metastasis by imaging. It was not until years later, upon review of historic cases, that the diagnosis of WL-MEC was established. This diagnosis was further supported by molecular testing that was not available at the time of the original diagnosis.

Bilateral intra-lymph node Warthin's tumor as a potential diagnostic pitfall mimicking metastatic carcinoma.

Warthin's tumor (WT) is a benign and frequent salivary gland tumor primarily affecting the parotid gland. In some cases, this tumor can involve the extra parotid region and affect cervical lymph nodes. Fine-needle aspiration can be the first step in the diagnostic approach to lymphadenopathy; however, specimens from intra-nodal WT can present a potential pitfall, leading to a misdiagnosis of metastasis. Here, we report an unusual case of a patient with bilateral WT in parotid lymph nodes misdiagnosed as metastases. In addition, we highlight the cytopathological aspects of WT to alert cytopathologists about this challenging diagnosis.

A Safety and Feasibility Trial of Ultrasound-Guided Radiofrequency Ablation of Parotid Warthin's Tumor.

OBJECTIVE: To determine if ultrasound-guided (USG) radiofrequency ablation (RFA) of Parotid Warthin's tumor under local anesthesia is a safe and effective procedure. STUDY DESIGN: Safety and feasibility study. SETTING: Tertiary academic medical center. METHODS: This is an IDEAL phase 2a trial in a tertiary referral center. Twenty patients with Parotid Warthin's tumor were recruited. RFA was done between September and December 2021 for all 20 patients using a CoATherm AK-F200 machine with a disposable, 18G × 7 mm radiofrequency electrode. Results and follow-up statistics were compared with a historic sample of patients with parotid Warthin's tumor who underwent parotidectomy between 2019 and 2021 in the same center. RESULTS: Nineteen patients were included in the analysis as 1 patient dropped out after 4 weeks of follow-up. The mean age for the RFA group was 67 years old with most of them being male smokers. At a median of 45 weeks (44-47 weeks) postprocedure there was a 7.48 mL (68.4%) volume reduction compared to baseline. Three patients had transient facial nerve (FN) paresis, 1 recovered within hours, and the other 2 by 12 weeks follow-up. Three patients had great auricular nerve numbness; 1 patient had infected hematoma treated in an out-patient manner. Compared to a historic cohort of parotidectomy patients for Warthin's tumor, there was no significant difference in FN paresis and other minor complications between the 2 treatment modalities. CONCLUSION: The current analysis suggests that USG RFA of Warthin's Tumor is a safe alternative to parotidectomy with shorter operative time and length of stay.

Keratocystoma: A Distinctive Salivary Gland Neoplasm Characterized by RUNX2 Rearrangements.

Keratocystoma is a rare salivary gland lesion that has been reported primarily in children and young adults. Because of a scarcity of reported cases, very little is known about it, including its molecular underpinnings, biological potential, and histologic spectrum. Purported to be a benign neoplasm, keratocystoma bears a striking histologic resemblance to benign lesions like metaplastic Warthin tumor on one end of the spectrum and squamous cell carcinoma on the other end. This overlap can cause diagnostic confusion, and it raises questions about the boundaries and definition of keratocystoma as an entity. This study seeks to utilize molecular tools to evaluate the pathogenesis of keratocystoma as well as its relationship with its histologic mimics. On the basis of targeted RNA sequencing (RNA-seq) results on a sentinel case, RUNX2 break-apart fluorescence in situ hybridization (FISH) was successfully performed on 4 cases diagnosed as keratocystoma, as well as 13 cases originally diagnosed as tumors that morphologically resemble keratocystoma: 6 primary squamous cell carcinomas, 3 metaplastic/dysplastic Warthin tumors, 2 atypical squamous cysts, 1 proliferating trichilemmal tumor, and 1 cystadenoma. RNA-seq and/or reverse transcriptase-PCR were attempted on all FISH-positive cases. Seven cases were positive for RUNX2 rearrangement, including 3 of 4 tumors originally called keratocystoma, 2 of 2 called atypical squamous cyst, 1 of 1 called proliferating trichilemmal tumor, and 1 of 6 called squamous cell carcinoma. RNA-seq and/or reverse transcriptase-PCR identified IRF2BP2::RUNX2 in 6 of 7 cases; for the remaining case, the partner remains unknown. The cases positive for RUNX2 rearrangement arose in the parotid glands of 4 females and 3 males, ranging from 8 to 63 years old (mean, 25.4 years; median, 15 years). The RUNX2 -rearranged cases had a consistent histologic appearance: variably sized cysts lined by keratinizing squamous epithelium, plus scattered irregular squamous nests, with essentially no cellular atypia or mitotic activity. The background was fibrotic, often with patchy chronic inflammation and/or giant cell reaction. One case originally called squamous cell carcinoma was virtually identical to the other cases, except for a single focus of small nerve invasion. The FISH-negative case that was originally called keratocystoma had focal cuboidal and mucinous epithelium, which was not found in any FISH-positive cases. The tumors with RUNX2 rearrangement were all treated with surgery only, and for the 5 patients with follow-up, there were no recurrences or metastases (1 to 120 months), even for the case with perineural invasion. Our findings solidify that keratocystoma is a cystic neoplastic entity, one which appears to consistently harbor RUNX2 rearrangements, particularly IRF2BP2::RUNX2 . Having a diagnostic genetic marker now allows for a complete understanding of this rare tumor. They arise in the parotid gland and affect a wide age range. Keratocystoma has a consistent morphologic appearance, which includes large squamous-lined cysts that mimic benign processes like metaplastic Warthin tumor and also small, irregular nests that mimic squamous cell carcinoma. Indeed, RUNX2 analysis has considerable promise for resolving these differential diagnoses. Given that one RUNX2 -rearranged tumor had focal perineural invasion, it is unclear whether that finding is within the spectrum of keratocystoma or whether it could represent malignant transformation. Most important, all RUNX2 -rearranged cases behaved in a benign manner.

Fine needle aspiration as a diagnostic modality for Warthin tumors identified as fluorodeoxyglucose positron emission tomography/computed tomography-positive.

Limited evidence exists regarding the 2-deoxy-2-[fluorine-18]-fluoro-D-glucose (FDG) avidity of Warthin tumors, the second most common benign parotid gland tumor. This study aims to clarify this aspect by analyzing patients who underwent FDG positron emission tomography/computed tomography (PET/CT) and quantifying tumor standardized uptake values (SUV). Medical records of 29 patients with fine needle aspiration (FNA)-confirmed Warthin tumors who underwent FDG-PET/CT near the diagnosis of Warthin tumor were reviewed. Key parameters included cancer history, cytologic diagnosis of Warthin tumor, maximum SUV on FDG PET/CT, and tumor localization. Among the cohort, 18 males and 11 females (average age: 67.9 years) were included. Most patients had malignant neoplasms (lung, head and neck, breast, others). One patient had synchronous liver cancer. Three individuals had bilateral Warthin tumors, and three had bifocal tumors, resulting in 35 tumors for analysis. Tumors were located in the parotid gland (28) and vicinity (7). SUVmax for the Warthin tumors ranged from 3.6 to 26.8, with an average SUVmax of 10.1. Warthin tumors exhibit significant and variable FDG accumulation, exceeding expectations and mimicking high-grade malignancies. Awareness of this phenomenon is crucial for accurate staging and timely management. In cases of positive FDG PET/CT uptake in periparotid, perimandibular, and upper jugular areas, FNA is recommended to avoid misinterpretation or delays in management.

The characteristics of Polish patients with salivary gland tumors: a ten-year single-center experience.

OBJECTIVES: The study aims to provide insights into the characteristics of Polish patients with different salivary gland pathologies. MATERIALS AND METHODS: This is a retrospective study conducted at a single center, including patients who underwent surgery for salivary gland pathologies between 2012 and 2022. RESULTS: This study included 239 patients who underwent surgery for salivary gland tumors or inflammatory diseases. Malignant tumors were diagnosed in 9.8% of participants, while 64% had benign tumors and 21% suffered from inflammation. The occurrence of complications after surgery was relatively low, with 9.9% of participants experiencing slight facial weakness or mild dysfunction, and 3% experiencing complete paralysis of the facial nerves. Significant differences were observed between patients with cancers and those with benign tumors and inflammation in terms of age. Cancers were more common in females (67% vs. 33%) and predominantly localized in the parotid glands (95%). CONCLUSION: Benign tumors, such as Warthin's tumors and polymorphous adenoma, were predominantly found in the parotid glands of patients aged 39-72 years. On the other hand, inflammatory diseases were primarily localized within the submandibular glands of males aged 40-68 years. Additionally, the presence of a malignant tumor was associated with longer hospitalization periods related to surgery and a higher risk of severe complications. CLINICAL RELEVANCE: This study on Polish patients with salivary gland tumors provides valuable clinical insights that can aid in diagnosis, treatment planning, patient counseling, and further research in the field of oncology. It contributes to the overall understanding of salivary gland tumors, potentially benefiting both patients and healthcare providers.

Uncommon Coexistence of Pleomorphic Adenoma and Warthin's Tumor in a Painfully Swollen Left Parotid Gland: A Surgical Case Report.

BACKGROUND Benign pleomorphic adenoma is the most common primary tumor of the salivary glands and mainly arises in the parotid gland. Warthin's tumor, or papillary cystadenoma lymphomatosum, represents <30% of benign parotid tumors. The simultaneous occurrence of multiple parotid tumors is rarely described - depending on the corresponding histology (different/identical), the time of their occurrence (synchronous/metachronous), as well as their location (unilateral/bilateral), multiple parotid tumors can be further sub-classified. CASE REPORT We describe the case of a 54-year-old female patient with progressive and painful swelling of the left parotid gland for the last 6 months. During extra-oral examination, a bulging, displaceable mass of approximately 3 cm was determined. A subsequent MRI (magnetic resonance imaging) examination revealed a multifocal lesion but failed to provide a decisive clue as to the tumor entity of the lesion, and a lateral (superficial) parotidectomy was performed. Postoperative histomorphological interpretation allowed the final pathological diagnosis of synchronous, unilateral occurrence of a pleomorphic adenoma as well as a Warthin's tumor. CONCLUSIONS This report presents a rare case of synchronous unilateral parotid tumors and supports that benign pleomorphic adenoma and Warthin's tumor are the most common associations. Since clinical examination, MRI imaging, and even cytological assessment could be misleading in the detection of synchronous ipsilateral multiple parotid gland tumors, our report also highlights the importance of timely and accurate diagnosis with histopathology to plan surgery and to exclude malignant transformation, which is a rare but important association with both types of primary salivary gland tumor.

Salivary Duct Carcinoma Arising in a Warthin Tumor of the Parotid Gland: A Rare Case Report with Review of Literature and PD-L1 Expression.

Warthin's tumor is the second most common neoplasm of the parotid gland and consists of 2 components, including lymphoid stroma and glandular epithelium. Malignant transformation in this tumor is mostly seen in the lymphoid component; however, the carcinomatous transformation of the epithelial component is extremely rare. Cases of latter reported in the literature include squamous cell carcinoma, adenocarcinoma, mucoepidermoid carcinoma, oncocytic carcinoma, Merkel cell carcinoma, and undifferentiated carcinoma. We describe an extremely rare case of salivary duct carcinoma arising in a Warthin tumor in a 64-year-old male. Patient presented with an enlarging left parotid mass, biopsy of which showed salivary duct carcinoma. He subsequently underwent left parotidectomy along with left level II-IV lymph node dissection. Histology revealed both in situ as well as invasive salivary duct carcinoma arising from Warthin tumor. Immunohistochemistry showed tumor cells positive for CK7, AR, and GATA3, while p63 highlighted the myoepithelial cell layer in the in situ component. Her2 was 2+ by immunohistochemistry. In addition, PD-L1 IHC revealed positive expression with a combined positive score of 20%.

Enhanced CT combined with texture analysis for differential diagnosis of pleomorphic adenoma and adenolymphoma.

OBJECTIVE: This study sought to evaluate the worth of the general characteristics of enhanced CT images and the histogram parameters of each stage in distinguishing pleomorphic adenoma (PA) and adenolymphoma (AL). METHODS: The imaging features and histogram parameters of preoperative enhanced CT images in 20 patients with PA and 29 patients with AL were analyzed. Tumor morphology and histogram parameters of PA and AL were compared. Area under the curve (AUC), sensitivity, and subject operational feature specificity (ROC) analysis were used to determine the differential diagnostic effect of single-stage or multi-stage parameter combinations. RESULTS: The difference in CT value and net enhancement value of arterial phase (AP) were significant (p < 0.05); Flat sweep phase (FSP), AP mean, percentiles, 10th, 50th, 90th, 99th and arterial period variance and venous phase (VP) kurtosis in the nine histogram parameters of each period (p < 0.05). An analysis of the ROC curve revealed a maximum area beneath the curve (AUC) in the 90th percentile of FSP for a single-parameter differential diagnosis to be 0.870. The diagnostic efficacy of the mean value of FSP + The 90th percentile of AP + Kurtosis of VP was the best in multi-parameter combination diagnosis, with an AUC of 0.925, and the sensitivity and specificity of 0.900 and 0.850, respectively. CONCLUSION: The histogram analysis of enhanced CT images is valuable for the differentiation of PA and AL. Moreover, the combination of single-stage parameters or multi-stage parameters can improve the differential diagnosis efficiency.

A nomogram incorporating clinical, conventional ultrasound and shear wave elastography findings for distinguishing pleomorphic adenoma from Warthin's tumor of the major salivary glands.

OBJECTIVE: Pre-operative differentiation between pleomorphic adenoma (PA) and Warthin's tumor (WT) of the major salivary glands is crucial for treatment decisions. The purpose of this study was to develop and validate a nomogram incorporating clinical, conventional ultrasound (CUS) and shear wave elastography (SWE) features to differentiate PA from WT. METHODS: A total of 113 patients with histological diagnosis of PA or WT of the major salivary glands treated at Fujian Medical University Union Hospital were enrolled in training cohort (n = 75; PA = 41, WT = 34) and validation cohort (n = 38; PA = 22, WT = 16). The least absolute shrinkage and selection operator (LASSO) regression algorithm was used for screening the most optimal clinical, CUS, and SWE features. Different models, including the nomogram model, clinic-CUS (Clin+CUS) and SWE model, were built using logistic regression. The performance levels of the models were evaluated and validated on the training and validation cohorts, and then compared among the three models. RESULTS: The nomogram incorporating the clinical, CUS and SWE features showed favorable predictive value for differentiating PA from WT, with the area under the curves (AUCs) of 0.947 and 0.903 for the training cohort and validation cohort, respectively. Decision curve analysis showed that the nomogram model outperformed the Clin+CUS model and SWE model in terms of clinical usefulness. CONCLUSIONS: The nomogram had good performance in distinguishing major salivary PA from WT and held potential for optimizing the clinical decision-making process.

Warthin-like mucoepidermoid carcinoma of the parotid gland: Clinicopathological observation and literature review.

Warthin tumor (WT)-like mucoepidermoid carcinoma resembles the histologic pattern of WT and pathologists unaware of this possibility may misdiagnose it as WT with squamous and mucous epithelium metaplasia or WT malignant transfer into mucoepidermoid carcinoma. The present study reported a case of a 41-year-old Chinese female with a solitary mass in the left parotid gland. In this case, microscopic observation revealed prominent lymph node stroma and multiple cystic structures similar to those seen in WT. However, it lacked the two layers of oncocytic epithelial tissue characteristic of WT. Furthermore, fluorescence in situ hybridization detected MAML2 rearrangement in the case. Considering the histological findings, this case was diagnosed as WT-like mucoepidermoid carcinoma. The present case report provides pathological and clinical features to differentiate it from WT malignant transition into mucoepidermoid carcinoma, WT with squamous and mucous epithelium metaplasia and non-sebaceous lymphadenoma-like mucoepidermoid carcinoma. In conclusion, WT-like mucoepidermoid carcinoma as a special subtype of mucoepidermoid carcinoma has special histological characteristics, which required further observations and more case reports to clearly define this variant.

Warthin Tumor of the Parotid Gland: The History of an Eponym.

The eponymous history of Warthin tumor (WT) is a fascinating issue in the field of salivary gland pathology. The late decades of the nineteenth century and the turn of the century saw notable German and French contributions on WT. Especially, the seminal 1910 paper of Albrecht and Arzt of Vienna is the foundation for the current knowledge of WT. It is generally believed that prior to this pioneering study, Hildebrand of Göttingen accurately described the lesion of WT in 1895. However, the historical origins of WT appear to be unsettled, and only a few German pathologists and surgeons are aware that dating back to 1885, the first recognizable reference to WT was that by the renowned German-Swiss pathologist Zahn, whose name is eponymously associated with "Zahn infarct" and "lines of Zahn". Two noted French surgeons with a major interest in pathology, Albarrán in 1885 and Lecéne in 1908, did not contribute to the topic. Since the 1950s, a mostly American group of pathologists and surgeons gradually adopted the term WT to replace the very accurate histologic descriptor "papillary cystadenoma lymphomatosum" coined by Warthin himself in 1929. It is our opinion that from a historical viewpoint, there is no particular reason why this tumor should have been named WT.

Differential diagnosis of parotid gland tumors using apparent diffusion coefficient, texture features, and their combination.

OBJECTIVES: Warthin's tumors (WT) and pleomorphic adenomas (PA) are the commonest parotid gland tumors; however, their differentiation remains difficult. This study aimed to investigate the utility of the apparent diffusion coefficient (ADC) value, texture features, and their combination for the differential diagnosis of parotid gland tumors. METHODS: Patients who underwent magnetic resonance imaging (MRI) between April 2008 and March 2021 for parotid gland tumors were included and divided into two groups according to the tumor type: WT and PA. The tumor types were used as predictor variables, while the ADC value, texture features, and their combination were the outcome variables. Texture features were measured on short tau inversion recovery (STIR) images and selected using the Fisher's coefficient method and probability of error, and average correlation coefficients. The Mann-Whitney U-test was used to analyze bivariate statistics. Receiver operating characteristic curve analysis was used to assess the ability of the ADC value, texture features, and their combination to distinguishing between the two tumor types. RESULTS: A total of 22 patients were included, 11 in each group. The ADC value, 10 texture features, and their combination were significantly different between the two groups (p < .001). Moreover, all three variables had high area under the curve values of 0.93-0.96. CONCLUSION: The ADC value, texture features, and their combination demonstrated good diagnostic ability to distinguish between WTs and PAs. This method may be used to aid the differential diagnosis of parotid gland tumors, thereby promoting timely and adequate treatment.