Expanding the cytological and architectural spectrum of mucoepidermoid carcinoma: The key to solving diagnostic problems in morphological variants.

Mucoepidermoid carcinoma (MEC) is the most common malignant salivary gland tumor. Varying sized cysts and sheets composed of three cell types (epidermoid, intermediate, and mucous cells) with varying degrees of atypia form the characteristic histological appearance of MEC. MEC frequently contains a wide variety of modified tumor cells and can be entirely cystic or completely solid. Under these circumstances, MEC requires critical differentiation from many mimickers, ranging from simple cysts and benign tumors to high-grade carcinomas. Tumor-associated lymphoid proliferation and sclerotic changes in the stroma also contribute to diagnostic difficulties. Several well-known diagnostically challenging variants (oncocytic, clear cell, spindle cell, and sclerosing) exist in MEC. With the advent of studies on specific CRTC1/3::MAML2 fusion genes in MEC, newly proposed subtypes have emerged, including Warthin-like and non-sebaceous lymphadenoma-like MECs. In addition to the recently defined mucoacinar variant with a serous cell phenotype, MEC devoid of squamous differentiation has also been reported, implying the need to reconsider this basic concept. In this article, we outline the general clinical features and MAML2 status of conventional MEC and review the cytoarchitectural subtypes, with an emphasis on a pitfall in the interpretation of this histologically diverse single entity.

An ultrasound-based ensemble machine learning model for the preoperative classification of pleomorphic adenoma and Warthin tumor in the parotid gland.

OBJECTIVES: The preoperative classification of pleomorphic adenomas (PMA) and Warthin tumors (WT) in the parotid gland plays an essential role in determining therapeutic strategies. This study aims to develop and validate an ultrasound-based ensemble machine learning (USEML) model, employing nonradiative and noninvasive features to differentiate PMA from WT. METHODS: A total of 203 patients with histologically confirmed PMA or WT who underwent parotidectomy from two centers were enrolled. Clinical factors, ultrasound (US) features, and radiomic features were extracted to develop three types of machine learning model: clinical models, US models, and USEML models. The diagnostic performance of the USEML model, as well as that of physicians based on experience, was evaluated and validated using receiver operating characteristic (ROC) curves in internal and external validation cohorts. DeLong's test was used for comparisons of AUCs. SHAP values were also utilized to explain the classification model. RESULTS: The USEML model achieved the highest AUC of 0.891 (95% CI, 0.774-0.961), surpassing the AUCs of both the US (0.847; 95% CI, 0.720-0.932) and clinical (0.814; 95% CI, 0.682-0.908) models. The USEML model also outperformed physicians in both internal and external validation datasets (both p < 0.05). The sensitivity, specificity, negative predictive value, and positive predictive value of the USEML model and physician experience were 89.3%/75.0%, 87.5%/54.2%, 87.5%/65.6%, and 89.3%/65.0%, respectively. CONCLUSIONS: The USEML model, incorporating clinical factors, ultrasound factors, and radiomic features, demonstrated efficient performance in distinguishing PMA from WT in the parotid gland. CLINICAL RELEVANCE STATEMENT: This study developed a machine learning model for preoperative diagnosis of pleomorphic adenoma and Warthin tumor in the parotid gland based on clinical, ultrasound, and radiomic features. Furthermore, it outperformed physicians in an external validation dataset, indicating its potential for clinical application. KEY POINTS: • Differentiating pleomorphic adenoma (PMA) and Warthin tumor (WT) affects management decisions and is currently done by invasive biopsy. • Integration of US-radiomic, clinical, and ultrasound findings in a machine learning model results in improved diagnostic accuracy. • The ultrasound-based ensemble machine learning (USEML) model consistently outperforms physicians, suggesting its potential applicability in clinical settings.

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.

Deep learning based ultrasound analysis facilitates precise distinction between parotid pleomorphic adenoma and Warthin tumor.

Background: Pleomorphic adenoma (PA), often with the benign-like imaging appearances similar to Warthin tumor (WT), however, is a potentially malignant tumor with a high recurrence rate. It is worse that pathological fine-needle aspiration cytology (FNAC) is difficult to distinguish PA and WT for inexperienced pathologists. This study employed deep learning (DL) technology, which effectively utilized ultrasound images, to provide a reliable approach for discriminating PA from WT. Methods: 488 surgically confirmed patients, including 266 with PA and 222 with WT, were enrolled in this study. Two experienced ultrasound physicians independently evaluated all images to differentiate between PA and WT. The diagnostic performance of preoperative FNAC was also evaluated. During the DL study, all ultrasound images were randomly divided into training (70%), validation (20%), and test (10%) sets. Furthermore, ultrasound images that could not be diagnosed by FNAC were also randomly allocated to training (60%), validation (20%), and test (20%) sets. Five DL models were developed to classify ultrasound images as PA or WT. The robustness of these models was assessed using five-fold cross-validation. The Gradient-weighted Class Activation Mapping (Grad-CAM) technique was employed to visualize the region of interest in the DL models. Results: In Grad-CAM analysis, the DL models accurately identified the mass as the region of interest. The area under the receiver operating characteristic curve (AUROC) of the two ultrasound physicians were 0.351 and 0.598, and FNAC achieved an AUROC of only 0.721. Meanwhile, for DL models, the AUROC value for discriminating between PA and WT in the test set was from 0.828 to 0.908. ResNet50 demonstrated the optimal performance with an AUROC of 0.908, an accuracy of 0.833, a sensitivity of 0.736, and a specificity of 0.904. In the test set of cases that FNAC failed to provide a diagnosis, DenseNet121 demonstrated the optimal performance with an AUROC of 0.897, an accuracy of 0.806, a sensitivity of 0.789, and a specificity of 0.824. Conclusion: For the discrimination of PA and WT, DL models are superior to ultrasound and FNAC, thereby facilitating surgeons in making informed decisions regarding the most appropriate surgical approach.

Pathogenesis of Warthin's Tumor: Neoplastic or Non-Neoplastic?

Warthin's tumor is the second most frequent neoplasm next to pleomorphic adenoma in the salivary gland, mostly in the parotid gland. The epithelial cells constituting a tumor are characterized by the presence of mitochondria that undergo structural and functional changes, resulting in the development of oncocytes. In addition to containing epithelial cells, Warthin's tumors contain abundant lymphocytes with lymph follicles (germinal centers) that are surrounded by epithelial cells. The pathogenesis of Warthin's tumor is not fully understood, and several hypotheses have been proposed. The risk factors for the development of Warthin's tumor, which predominantly occurs in males, include aging, smoking, and radiation exposure. Recently, it has been reported that chronic inflammation and aging cells promote the growth of Warthin's tumor. Several reports regarding the origin of the tumor have suggested that (1) Warthin's tumor is an IgG4-related disease, (2) epithelial cells that compose Warthin's tumor accumulate mitochondria, and (3) Warthin's tumor is a metaplastic lesion in the lymph nodes. It is possible that the pathogenesis of Warthin's tumor includes mitochondrial metabolic abnormalities, accumulation of aged cells, chronic inflammation, and senescence-associated secretory phenotype (SASP). In this short review, we propose that DNA damage, metabolic dysfunction of mitochondria, senescent cells, SASP, human papillomavirus, and IgG4 may be involved in the development of Warthin's tumor.

Differentiation of salivary gland tumors using diffusion-weighted image-based virtual MR elastography: A pilot study.

OBJECTIVES: Differentiation among benign salivary gland tumors, Warthin tumors, and malignant salivary gland tumors is crucial to treatment planning and predicting patient prognosis. However, differentiation of those tumors using imaging findings remains difficult. This study evaluated the usefulness of elasticity determined from Diffusion-weighted image (DWI)-based virtual MR elastography (MRE) compared with conventional MRI findings in differentiating the tumors. METHODS: This study included 17 benign salivary gland tumors, six Warthin tumors, and 11 malignant salivary gland tumors scanned on neck MRI. The long and short diameters, T1 and T2 signal intensities, tumor margins, ADC values, and elasticity from DWI-based virtual MRE of the tumors were evaluated. The interobserver agreement in measuring tumor elasticity and the ROC curves were also assessed. RESULTS: The long and short diameters and the T1 and T2 signal intensities showed no significant difference among the three tumor groups. Tumor margins and the mean ADC values showed significant differences among some tumor groups. The elasticity from virtual MRE showed significant differences among all three tumor groups and the interobserver agreement was excellent. The area under the ROC curves of the elasticity were higher than those of tumor margins and mean ADC values. CONCLUSION: Elasticity values based on DWI-based virtual MRE of benign salivary gland tumors, Warthin tumors, and malignant salivary gland tumors were significantly different. The elasticity of Warthin tumors was the highest and that of benign tumors was the lowest. The elasticity from DWI-based virtual MRE may aid in the differential diagnosis of salivary gland tumors.

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.

Oncocytic papillary cystadenoma of the larynx: a case report.

BACKGROUND: Cystadenoma of the salivary glands is a rare benign clinical condition affecting both major and minor salivary glands equally. It constitutes approximately 2% of total neoplasms and 4.2-4.7% of benign formations in minor salivary glands. Typically presenting as a slow-growing, painless neoplasm, it can be distinguished from Cystadenolymphoma (Whartin's Tumor) by the absence of lymphoid elements in histological examination. While mostly located in the oral cavity and oropharynx, it can also be found in sinonasal mucosa, and rare cases have been identified in the larynx. CASE PRESENTATION: A 75-year-old Caucasian woman presented to the ear, nose, and throat department with complaints of dysphonia and headaches persisting for several months. Dysphonia had developed months after an unspecified vocal cord surgery elsewhere. Flexible laryngoscopy identified a left-sided cystic swelling affecting the supraglottic space, leading to respiratory obstruction and dysphonia. Head and neck computed tomography confirmed a 1.9 × 1.7 cm bilobed cystic mass originating from the left Morgagni ventricle. Microlaryngoscopy with CO2 laser excision and biopsy revealed a histopathological diagnosis of oncocytic papillary cystadenoma. Post-surgery, the patient fully recovered from dysphonia, with no significant complications noted. Long-term clinical surveillance was advised to detect potential recurrences promptly. CONCLUSION: Ectopic minor salivary gland tumors, both benign and malignant, should be taken into consideration as potential differential diagnosis for any swelling arising within the upper digestive tract mucosa. Ears, nose, and throat clinical examination completed by videolaryngoscopy can easily point out the location of the mass. Imaging is mandatory for differential diagnosis and for surgical planning. Surgical excision can provide both diagnosis and definitive cure.

Risk factors for oral mucositis in patients with solid tumorsunder treatment with cetuximab: a retrospective cross-sectional study

Background: This study retrospectively analyzed the risk factors for oral mucositis (OM) during cetuximab treatment. Material and Methods: We screened patients using cetuximab and retrospectively evaluated the presence of OM based on medical records. We collected information from 2 years of evaluations. Patient medical records were reviewed to obtain data on chemotherapy cycle and dose, sex, age, primary tumor, TNM stage, and head and neck radiotherapy (HNR) history. The X2 test and multinomial logistic regression were used for statistical analysis (SPSS 20.0, p < 0.05). Results: Among 1831 patients, OM was showed in 750 in any grade (41%), during cetuximab treatment. Most patients were female (n=944, 51.6%), <70years-old (n=1149, 62.8%), had larynx cancer (n=789, 43.1%) in T4 (n=579, 47.7%), N0 (n=509, 52.6%) stages. Primary tumor surgery was performed in 1476 (80.6%) patients, radiotherapy in 606 (33.1%) patients and cetuximab protocols most used involved up to four cycles (n=1072, 58.5%) of <400mg (n=996, 54.4%) cetuximab doses. Female (OR [odds ratio] = 2.17, CI95% = 1.26-3.75), >70 years-old patients (OR = 16.02, CI95% = 11.99-21.41), with HHNR (OR = 1.84, 1.41-2.40), treated with >4 cycles (OR = 1.52, CI95% = 1.16-2.01) and high doses of cetuximab (OR = 3.80, CI95% = 2.52-5.71) are the greatest risk factors for OM. Conclusions: Since the clinical benefit of cetuximab in the treatment of older patients is limited and there is a high OM, especially in women with head and neck treated with radiotherapy, high doses and a high number of cetuximab cycles must be administered with caution. (AU)

Salivary Gland Tumors: A 20 Year Review From a Single Community Practice.

Objective: Salivary gland tumors are a heterogenous group of lesions with variable pathology and clinical outcomes. Most published data are derived from studies conducted at tertiary care centers. Our study analyzed the experience from a community setting to determine significant differences, if any, in pathological distribution and clinical outcomes compared to the existing literature. Methods: We performed a retrospective analysis of all major salivary gland tumors that presented to a large community practice over a 20 year period. Retrospective chart analysis was performed for demographics, clinical presentation, imaging, cytology, histopathology, and clinical outcome data. Results: Of 806 patients, the parotid gland was the most common site in 683 patients (84.7%), followed by submandibular in 78 (9.7%) and sublingual in 45 (5.6%). A total of 203 patients were managed conservatively with observation without definitive diagnosis or lost to follow-up. A total of 495 patients underwent surgical intervention within the community practice. Twenty-six patients underwent surgical excision at an outside hospital. Eighty-two patients were determined to have a benign diagnosis based on ultrasound-guided fine needle aspiration or excisional biopsy alone. Final histopathology was benign in 505 cases (83.7%), while 98 tumors (16.3%) received a diagnosis of primary or secondary malignancy. For the parotid gland, pleomorphic adenoma (155) and Warthin's tumor (155) were the most common benign diagnoses, while mucoepidermoid carcinoma (13), adenocarcinoma (8), and acinic cell carcinoma (8) were the most common primary malignancies. Conclusions: We found a higher rate of benign tumor pathology compared to the existing literature. While the outcome data on surgical treatment of benign tumors are comparable to the existing literature, the same conclusion cannot be drawn for malignant tumors, given relatively small numbers in our series and likely disparity in the complexity of the surgical cases in tertiary care centers.

Validation of the VisionArray® Chip Assay for HPV DNA Testing in Histology Specimens of Oropharyngeal Squamous Cell Carcinoma.

BACKGROUND: The detection of human papillomavirus (HPV) has several implications in the diagnostic work-up and management of oropharyngeal squamous cell carcinoma (OPSCC). The choice of HPV detection assay and testing algorithms differ across institutions and vary in cost, detection targets, technical feasibility, and turnaround time. In this study, we aimed to validate the VisionArray® HPV Chip for formalin-fixed and paraffin-embedded (FFPE) samples of OPSCC using the previously applied standard pan-HPV DNA PCR assay as a reference. METHODS: The validation cohort consisted of FFPE tissue samples from patients previously diagnosed with HPV DNA-positive OPSCC (n = 80), HPV DNA-negative OPSCC (n = 21), and a benign group of tumor samples consisting of Warthin's tumors (n = 20) and branchial cleft cysts of the lateral neck (n = 14). All samples were tested with p16 immunohistochemistry, pan-HPV DNA PCR, and the VisionArray® HPV Chip. RESULTS: The overall sensitivity and specificity of the VisionArray® HPV Chip assay were 100% [95% CI 95.5%; 100.0%] and 96.3% [95% CI 87.3%; 99.6%] and the positive predictive value and negative predictive value were 97.6% [95% CI 91.5%; 99.7%] and 100% [95% CI 93.2%; 100%], respectively. CONCLUSIONS: The VisionArray® HPV Chip assay can be recommended for high-risk HPV testing in FFPE tissue samples from OPSCC, providing both a fast and simultaneous genotyping for 41 clinically relevant HPV types.

Pitfalls in Salivary Gland Cytology.

BACKGROUND: Salivary gland lesions possess diagnostic challenges on fine needle aspiration (FNA) material. They are relatively uncommon, yet present with a wide spectrum of cytomorphology. Herein, we review common salivary gland neoplasms, their cytomorphologic features, their diagnostic pitfalls, and ancillary studies helpful in achieving an accurate diagnosis. SUMMARY: There are many cytomorphologic overlaps between benign and malignant salivary gland entities. Moreover, metaplasia, cystic changes, and degenerative changes are common findings adding to diagnostic dilemmas. These complicating factors contribute to a minute risk of malignancy in salivary gland lesions that are interpreted as benign on FNA. In rare cases, even malignant salivary gland neoplasms are misinterpreted as benign on aspirated material due to the many cytomorphologic overlaps. For example, benign and malignant neoplasms containing stroma such as myoepithelioma and adenoid cystic carcinoma may be misinterpreted as pleomorphic adenoma. Moreover, diagnosis of salivary gland neoplasms with basal cell features can be confusing on FNA materials; for example, basal cell adenoma can be misinterpreted as adenoid cystic carcinoma. Mucoepidermoid carcinomas have many different appearances on aspirated material due to variable amounts of mucin, degree of nuclear atypia, cellular content, and squamous metaplasia. Acinic cell carcinoma exhibits large cells with abundant cytoplasm on FNA, which can be mistaken for oncocytic cells in oncocytoma or Warthin tumor. Salivary duct carcinoma shows distinct features of malignancy and thus can be mistaken for secondary tumors involving the salivary glands or other malignant salivary gland tumors. The presence of tumor-associated lymphocytes is another underlying cause of misdiagnosis, especially when considering the differential diagnosis of an an intraparotid lymph node. Ancillary studies such as immunohistochemistry and molecular studies are gaining more attention to be utilized on FNA cases. PLAG1 immunostaining, CD117 , DOG1, mammaglobin, and androgen receptor (AR) are examples of commonly used immunostains in diagnosis of salivary gland lesions. MYB gene fusion , rearrangements of the MAML2 gene, ,and ERBB2/HER2 are examples of molecular alterations useful in diagnosis of salivary gland neoplasms. In conclusion, the aim of salivary gland cytology is to differentiate benign entities from the malignant ones and to prevent unnecessary aggressive treatments.

Expression of FOXI1 and POU2F3 varies among different salivary gland neoplasms and is higher in Warthin tumor.

PURPOSE: Salivary gland tumors are histologically diverse. Ionocytes and tuft cells, rare epithelial cells found in normal salivary glands, might be associated with salivary tumors. Here, we explored the expression of FOXI1 and POU2F3, master regulators of ionocytes and tuft cells, respectively, for common salivary neoplasms using immunohistochemistry. METHODS: We analyzed normal salivary tissues and nine salivary gland tumors; Warthin tumors (WT), pleomorphic adenomas (PA), basal cell adenomas, and oncocytomas were benign, whereas mucoepidermoid, adenoid cystic, acinic cell, salivary duct carcinomas, and polymorphous adenocarcinomas were malignant. RESULTS: Normal salivary glands contained a few FOXI1- and POU2F3-positive cells in the ducts instead of the acini, consistent with ionocytes and tuft cells, respectively. Among the benign tumors, only WTs and PAs consistently expressed FOXI1 (10/10 and 9/10, respectively). The median H-score of WTs was significantly higher than that of PAs (17.5 vs. 4, P = 0.01). While WTs and PAs harbored POU2F3-positive cells (10/10 and 9/10, respectively), the median H-score was higher in WTs than in PAs (10.5 vs 4, respectively). Furthermore, WTs exhibited a unique staining pattern of FOXI1- and POU2F3-positive cells, which were present in luminal and abluminal locations, respectively. Whereas none of the malignant tumors expressed FOXI1, only adenoid cystic carcinoma consistently expressed POU2F3 (5/5), with a median H-score of 4. CONCLUSION: The expression patterns of the characteristic transcription factors found in ionocytes and tuft cells vary among salivary gland tumor types and are higher in WT, which might be relevant for understanding and diagnosing salivary gland neoplasms.

MAML2 gene rearrangement occurs in all Warthin-like mucoepidermoid carcinoma: A reappraisal in a series of 29 cases.

Background: Warthin-like Mucoepidermoid carcinoma (MEC) is a new and rare morphological variant of MEC, with only a few case reports in the literature. The clinicopathological, molecular features and bio-behaviors of Warthin-like MEC has not been studied extensively. We reappraisal all Warthin-like MEC patients diagnosed and treated at our hospital. Methods: Patient characteristics including clinicopathological features, genetic aberrations, treatment, and prognostic information were assessed and evaluated. Results: Twenty-nine Warthin-like MEC patients were identified, 19 patients were female (65.5 %), and 10 were male (34.5 %). The patients' age varied widely from 8 to 68 years (mean 42.3 years). Genetic aberrations of MAML2 rearrangement were detected in all Warthin-like MEC patients, which suggesting this genetic event is the unique feature of Warthin-like MEC. Twenty-five patients (86.2 %) were assessed as having a low-stage disease (I/II), and four (13.8 %) as having high-clinical stage disease (III/IV). More than half of the patients (16/29) underwent only partial sialoadenectomy; 2 patients underwent extended sialoadenectomy, and 11 patients underwent extended sialoadenectomy with cervical lymph node dissection. After a median follow-up time of 73 months (5-128 months), Twenty-eight patients were alive without recurrence at the end of the follow-up period, one patient died 1 year after surgery due to lung metastasis. Conclusion: Our data suggested that most Warthin-like MEC exhibited mild clinicopathological course and less aggressive bio-behavior, and an aggressive bio-behavior seemed to be very rare. In addition, in the salivary gland, MAML2 rearrangement seems to be a unique molecular feature of salivary Warthin-like MEC.

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.

Warthin-like variant of papillary thyroid carcinoma with lymph node metastases: a case report and review of the literature.

BACKGROUND: We present a rare case of thyroid lesion marked as the Warthin-like variant of papillary thyroid carcinoma (WLV-PTC) with lymph node metastases. A proper preoperative identification is difficult because of unspecific cytology features and common ultrasound characteristics of this malignant tumor. The long-term prognosis cannot be thoroughly described due to the scarcity of data. The purpose of the presentation is to show common characteristics and long-term survival rates of an uncommon variant of differentiated thyroid cancer (DTC). Therefore, the data represented in this article can make a significant contribution to future investigations. CASE PRESENTATION: A 40-year-old Ukrainian woman had a lesion in the thyroid gland, which was accidentally diagnosed during medical checkup. Ultrasound (US) features were similar to the common suspicious nodule. It had typical signs of suspicion for malignancy (TI-RADS-4) on the background of thyroiditis. A thorough investigation of the neck showed lymph nodes with nonspecific US features on both lateral compartments. Lymph nodes were hypoechoic, oval-shaped and 10 mm wide, with regular contours, low central vascularity, with preserving hilar fat, without cystic formation. The patient did not have any complaints or changes in the hormone status. No hereditary findings linked with cancer were discovered. The woman had been living for a long time in the country with a high level of insolation, which was atypical for the ordinary environment of the patient. Fine-needle aspiration (FNA) of the lesion was done and the Bethesda system 6 result was obtained. Total thyroidectomy with central lymph node dissection was accomplished. The histological conclusion was WLV-PTC on the background of lymphocytic infiltration of the gland with metastasis to the lymph nodes. The inpatient radioactive iodine (RAI) ablation (100 mCi) was subsequently performed. Hormone withdrawal was used followed by RAI. In one year after the surgery the level of thyroglobulin (Tg) was 0.2 ng/ml. Up to the present time the five-year follow-up has not demonstrated any signs of recurrence relying on a level of Tg (< 0.04 ng/ml), Tg antibodies (< 14 IU/ml), neck US without any structural disease. CONCLUSION: WLV-PTC resembles salivary gland tumors with similar histological features. This variant is not well known, but often associated with a stroma lymphocytic infiltration and a low risk of lymph node metastases. It is regarded that this rare subtype has similar long-term survival rates as classic papillary thyroid cancer (PTC).

Surgical management of Warthin tumor: long-term follow-up of 224 patients from 2002 to 2018.

PURPOSE: Warthin tumors (WT) are the second most common benign parotid gland neoplasms. They can occur as synchronous or metachronous lesions in 6-10% of cases. This study aims to compare the complication rate in 224 patients who underwent extracapsular dissection (ECD) or superficial parotidectomy (SP) for the treatment of a WT. METHODS: This retrospective study was conducted at the Department of Maxillo-Facial Surgery at the University of Naples "Federico II" from February 2002 to December 2018 on a group of patients who underwent surgical treatment for WT. The type of surgical technique was chosen based on Quer's classification. The complications evaluated were facial nerve palsy, hematoma, Frey's syndrome, and bleeding. RESULTS: A total of 224 patients treated from 2002 to 2018 for Warthin tumor were included in the study. Two hundred elven had solitary tumors (94.1%) and 13 had multicentric lesions (5.8%), of which 9 cases presented synchronous lesions and 4 cases presented metachronous lesions. Extracapsular dissection (ECD) was performed in 130 patients (58.3% of cases) and superficial parotidectomy (SP) in the other 94 (41.7% of cases). CONCLUSIONS: We consider both surgical techniques as valid. In our opinion, it is essential to study each case based on Quer's Classification to obtain the best surgical outcome. Based on a lower observed rate of complications such as facial nerve palsy, Frey's syndrome, and bleeding, ECD seems to be the best option for the surgical treatment of Quer Class I lesions.

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.