The differential diagnosis of lymphoepithelial lesion of the salivary gland.

The differential diagnosis of salivary gland lesions with epithelial components and lymphoid stroma is often challenging. Salivary gland carcinoma with tumor-associated lymphoid proliferation, tumors composed of both epithelial and lymphoid components, lymphoid neoplasms in the salivary gland, and inflammatory lesions are all included in this category. It encompasses inflammatory lesions and neoplastic lesions. With the exception of Warthin tumors, these lesions are rare, making them more difficult to diagnose. Carcinoma showing thymus-like elements has recently been reported in the salivary gland. Similar to thymic carcinoma, tumor cells are positive for CD5 and are accompanied by T lymphocytes.

Case report: The diagnostic pitfall of Warthin-like mucoepidermoid carcinoma.

Warthin-like mucoepidermoid carcinoma (WL-MEC) is a newly reported variant of mucoepidermoid carcinoma. Its histological feature is easy to confused with metaplastic Warthin Tumor, and its relationship with Warthin tumor in histogenesis is controversial. In this study, we presented two cases of WL-MEC, discussing their clinicopathological and molecular features. Notably, one case was initially misdiagnosed during the first onset of the tumor. Case 1 was a 60-year-old female with a mass in the right parotid gland. Case 2 featured a 29-year-old male who developed a lump at the original surgical site 6 months after a "Warthin tumor" resection from the submandibular gland. Histologically, both tumor exhibited a prominent lymphoid stroma and cystic pattern, accompanied by various amounts of epithelial nests composed of squamoid cells, intermediate cells and mucinous cells. The characteristic eosinophilic bilayer epithelium of Warthin tumor was not typically presented in either case. Both cases tested positive for MAML2 gene rearrangement. To contextualize our findings, we conducted a comprehensive review of forty-eight WL-MEC cases documented in the English literature, aiming to synthesizing a reliable differential diagnostic approach. WL-MEC is a rare yet clinically relevant variant, posing a diagnostic pitfall for pathologists. Our study underscores the importance of a meticulous evaluation of both clinical and histological features, coupled with the detection of MAML2 rearrangement, as a credible method for distinguishing WL-MEC from other benign and malignant lesions, particularly metaplastic Warthin tumor.

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.

Proceedings of the North American Society of Head and Neck Pathology, Los Angeles, CA, March 20, 2022: Emerging Entities in Salivary Gland Tumor Pathology.

Salivary gland tumor pathology is one of the most challenging areas in all head and neck surgical pathology. Compounding its inherent difficulty are numerous novel entities, variants and concepts, most of which have been based on recent molecular discoveries. This review will serve to update the practicing pathologist on a selected group of emerging entities in salivary gland tumor pathology.

Warthin-Like Mucoepidermoid Carcinoma: A Morphological Spectrum - A Report of 3 Cases with Histological and Cytological Findings and Review of the Literature.

BACKGROUND: Mucoepidermoid carcinoma (MEC) showing Warthin's tumor (WT)-like features is a low-grade malignancy which should be differentiated from WT. Morphological features may be distinctly different in each case, causing diagnostic difficulties. CASE PRESENTATION: Three cases were presented and discussed with their morphologies. All cases that presented with a mass in the parotid gland went to parotidectomy, and all had preoperative fine-needle aspirations (FNAs). Case 1 was a 16-year-old female; FNA was suggestive of WT and initially interpreted as WT histologically. Case 2 was a 27-year-old male; FNA was interpreted as noninformative due to the presence of cyst fluid only. Case 3 was a 53-year-old male and cytologically was found to be suspicious for MEC which contained squamous and goblet cells on a mucoid background. On histopathological examination, case 2 and case 3 were morphologically consistent with low-grade MEC with WT-like features. Prominent lymphoid stroma and the cystic pattern were the characters of these tumors. Case 1 had the classical WT appearance with some mucinous and squamous metaplasia which could only be interpreted as MEC after the detection of MAML2 rearrangement by FISH. The other 2 showed either focal or relatively diffuse usual low-grade MEC findings, and case 3 was also confirmed by MAML2 rearrangement. CONCLUSION: Cytological and histopathological features revealed a spectrum. Differentiating WT-like MECs from ordinary WTs may be challenging. On the one end of the spectrum, they may look very much like WT, and on the other end, even though usual MEC features are present, still, WT-like appearance may pose diagnostic difficulty. Showing MAML2 rearrangement in these cases is very helpful. The presence of mucinous and squamous cells in an otherwise WT-like looking tumor should be alarming for MEC, and if possible, each case should be analyzed for MAML2 rearrangement.

Fine-needle aspiration cytology of Warthin-like mucoepidermoid carcinoma: A case report with cytological review.

Warthin-like mucoepidermoid carcinoma (MEC) is a novel and rare subtype of MEC and is characterized histopathologically by the presence of abundant lymphocytic infiltration and cystic changes. A small number of cytological reports of this MEC variant is currently available. The present study reported on the sixth cytological case of Warthin-like MEC, reviewed the cytological features of the tumour and discussed the cytological differential diagnosis. A 16-year-old Japanese female presented with a painful mass in the left parotid gland. Fine-needle aspiration for cytological examination of the parotid gland tumour was performed, followed by partial parotidectomy. Cytological examination revealed sheet-like and folded epithelial cell clusters in a mucinous background accompanying abundant lymphocytic infiltration. Epithelial clusters comprised round cells with mildly enlarged round to oval nuclei, polygonal cells with relatively rich cytoplasm and slightly enlarged round to oval nuclei. Certain polygonal cells contained intracytoplasmic mucin. Histopathological examination of the resected parotid gland tumour indicated multiple cystic lesions with abundant lymphocytic infiltration accompanying lymphoid follicle formation. The cysts were lined by intermediate cells with occasional mucinous cells. Fluorescence in situ hybridization using the surgically resected specimen indicated mastermind-like transcriptional coactivator 2 (MAML2) rearrangement, a characteristic of Warthin-like MEC. Consequently, the patient was diagnosed with Warthin-like MEC. The literature review revealed that the characteristic cytological features of Warthin-like MEC are the presence of intermediate cells and lack of oncocytic cells in the mucinous material under an abundant lymphocytic background. Clinicopathological features may help with a differential diagnosis, particularly from Warthin's tumour, and detection of MAML2 rearrangement is able to improve the accuracy of diagnosis.

Pediatric Warthin-like Mucoepidermoid Carcinoma: Report of Two Cases with One Persistent/Recurrent as Conventional Mucoepidermoid Carcinoma.

Mucoepidermoid carcinoma (MEC) is the most common primary salivary gland malignancy. While salivary gland neoplasia is rare in children, MEC is much more likely to occur in the pediatric population than Warthin tumor, a common benign salivary gland neoplasm associated with smoking and older age. The recently-reported Warthin-like variant of MEC bears a striking histologic resemblance to Warthin tumor, representing a potential diagnostic pitfall. Therefore, low-power observation of Warthin-like features in pediatric salivary gland tumors should prompt careful diagnostic consideration of Warthin-like MEC. Two cases of Warthin-like MEC in the parotid glands of teenaged patients were identified in the archives of the Department of Pathology at Children's Medical Center in Dallas, Texas. Surgical material for each case was reviewed and both diagnoses were verified. Fluorescence in situ hybridization (FISH) for CRTC1-MAML2 fusion was performed in both cases. Histologically, neither tumor exhibited the classic bilayer of oncocytic epithelial cells characteristic of Warthin tumor. Instead, the neoplastic epithelial cells exhibited architectural and cytologic atypia, with mucous cells interspersed. CRTC1-MAML2 gene fusions were identified via FISH and confirmed the diagnosis of MEC in both cases. Of note is that the second patient's tumor recurred with features of conventional MEC, indicating the potential for Warthin-like MEC to undergo this morphologic change. The present cases illustrate that Warthin-like MEC, like conventional MEC, may occur in the pediatric population. Pediatric and head and neck pathologists must be aware of this variant's existence and diagnostic criteria to avoid misdiagnosis as benign Warthin tumor.

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.

The significance of mucinous metaplasia in Warthin tumor: a frequent occurrence and potential pitfall.

Mucinous metaplasia in Warthin tumor (WT) is a recognized phenomenon. Nevertheless, its presence can create a diagnostic challenge in the distinction from the newly proposed variant of mucoepidermoid carcinoma (MEC), Warthin-like MEC. In this study, we evaluated the significance and diagnostic relevance of mucinous metaplasia in WTs. A total of 30 WTs diagnosed based on resection specimens formed the basis of this retrospective study. Mucicarmine staining was performed to identify mucinous metaplasia, and fluorescence in situ hybridization (FISH) analysis was used to detect MAML2 gene rearrangement. After review, one MAML2 rearranged case was reclassified as Warthin-like MEC as the classic bilayered epithelium in WT was not identified. The diagnosis of WT was confirmed in the remaining 29 cases. Mucinous metaplasia was encountered in 24 WTs (83%), with 14% (4/29) having an abundant amount. We found that mucinous metaplasia correlated with tumor size (p < 0.05). Age and sex distribution were similar in WT cases with or without mucinous metaplasia. In addition, neither the presence of squamous metaplasia nor the time interval between fine-needle aspiration and surgery was related to mucinous metaplasia (p > 0.05). The MAML2 FISH analyses performed in 18 WTs with variable amounts of mucinous metaplasia were negative for rearrangement. In conclusion, mucinous metaplasia is fairly common in WTs and shows a significant correlation with tumor size. Therefore, caution should be taken to avoid overinterpretation of WT with mucinous metaplasia as MEC in cases showing the classic bilayered oncocytic lining epithelium.