Exploring cytologic features and potential diagnostic challenges of metastatic NUT carcinoma to the parotid gland: A case report and a comprehensive literature review.

NUT carcinoma (NC) is a highly aggressive, poorly differentiated carcinoma that harbors a t(15:19) translocation, leading to the fusion of the NUTM1 gene. While the upper aerodigestive tract along the midline (head, neck, thorax, and mediastinum) is commonly reported as the primary site of NC, subsequent cases have emerged in diverse locations. Achieving a definitive diagnosis based solely on morphology is challenging; however, it can be achieved using immunohistochemistry (IHC) specific to the NUT antibody or by demonstrating the characteristic BRD4::NUTM1 fusion. Accurate and timely diagnosis can potentially inform patient management and guide treatment. While histologic documentation of NC is commonly found, there is a limited description of its cytologic features. A 39-year-old male with a history of sinonasal squamous cell carcinoma (SCC) presented with a right parotid mass aspirated via fine needle aspiration cytology (FNA). Histologic examination of the previous sinonasal pathology reviewed at our institution revealed sheets of primitive-appearing, monotonous, undifferentiated cells with distinct, prominent nucleoli. Additionally, there were foci of abrupt keratinization, accompanied by a notable neutrophilic infiltrate. The initial diagnosis of SCC was reclassified to NC and confirmed through NUT IHC and molecular testing. Although the parotid FNA initially suggested the possibility of a variety of small round blue cell tumors, it exhibited morphological similarities to the sinonasal tumor, leading to the diagnosis of metastatic NC. Cytomorphologic features of NC are limited and can overlap with various small round blue cell tumors. Correct classification is especially pivotal in the era of targeted therapy, considering the ongoing development and evaluation of BET inhibitors targeting BRD4.

Molecular Aspects of Mucoepidermoid Carcinoma and Adenoid Cystic Carcinoma of the Salivary Gland.

BACKGROUND: Salivary gland tumors (SGTs) are rare and highly heterogeneous lesions, making diagnosis a challenging activity. In addition, the small number of studies and samples evaluated difficults the determination of prognosis and diagnosis. Despite the solid advances achieved by research, there is still an intense need to investigate biomarkers for diagnosis, prognosis and that explain the evolution and progression of SGTs. METHODS: We performed a comprehensive literature review of the molecular alterations focusing on the most frequent malignant SGTs: mucoepidermoid carcinoma and adenoid cystic carcinoma. RESULTS: Due to the importance of biomarkers in the tumorigenenic process, this review aimed to address the mechanisms involved and to describe molecular and biomarker pathways to better understand some aspects of the pathophysiology of salivary gland tumorigenesis. CONCLUSIONS: Molecular analysis is essential not only to improve the diagnosis and prognosis of the tumors but also to identify novel driver pathways in the precision medicine scenario.

Prognostic factors of palatal adenoid cystic carcinoma: A single-center analysis of 85 cases.

Objective: The purpose of this retrospective study was to describe the clinicopathological characteristics of primary adenoid cystic carcinoma (ACC) of the palate and to identify the factors affecting prognosis. Methods: The medical records of 85 patients with primary ACC of the palate treated with surgery, with or without adjuvant radiotherapy/chemotherapy, from 2009 to 2019 were reviewed. The relationship of different clinical parameters with locoregional recurrence (LR), distant metastasis (DM), and overall survival (OS) were analyzed. Results: Median follow-up time was 44.6 months. LR and DM rates were 24.7% and 25.9%, respectively, and the 5-year OS and disease-free survival (DFS) rates were 85.9% and 55.1%, respectively. Multivariate analysis showed that positive margins were independently associated with the risk of LR (p < .001). Positive margins (p = .001) and high histological grade (p = .031) were significantly associated with shorter OS. Conclusion: Positive surgical margins are a strong adverse prognostic factor affecting LR and OS in patients with ACC; apart from that, high histopathological grade is an independent predictor of poor OS. Level of Evidence: Level 3 (Prognosis - Cohort study).

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.

Dynamic Role of miRNAs in Salivary Gland Carcinomas: From Biomarkers to Therapeutic Targets.

BACKGROUND: Salivary gland carcinomas (SGCs) are a rare group of malignant neoplasms of the head and neck region. MicroRNAs (miRNAs) are a class of small non-coding RNAs that have been associated with the control biological process and oncogenic mechanism by the regulation of gene expression at the post-transcriptional level. Recent evidence has suggested that miRNA expression may play a role in the tumorigenesis and carcinogenesis process in SGCs. METHODS: This review provides a comprehensive literature review of the role of miRNAs expression in SGCs focusing on the diagnostic, prognostic, and therapeutic applications. RESULTS: In this review, numerous dysregulated miRNAs have demonstrated an oncogenic and suppressor role in SGCs. CONCLUSION: In the future, these miRNAs may eventually constitute useful diagnostic and prognostic biomarkers that may lead to a better understanding of SGCs oncogenesis. Additionally, the development of therapeutic agents based on miRNAs may be a promising target in SGC treatment.

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.

Polymorphous Adenocarcinoma: A Systematic Review of the Literature and Presentation of Two Cases in a Less-Considered Anatomical Site.

BACKGROUND: Polymorphous adenocarcinoma (PAC) is the second-most common malignant tumour of the minor salivary glands. Although PAC predominantly affects the palate, it can also involve the buccal mucosa. This systematic review aims to investigate the literature data about PAC. Furthermore, we report two cases of patients affected by PAC in an infrequently considered anatomical site. METHODS: According to PRISMA guidelines, a systematic review search was conducted on PubMed, Scopus, and Web of Science. Observational studies conducted on patients with a histological diagnosis of PAC were selected and analysed. Furthermore, two cases of patients with PAC affecting the buccal mucosa were reported. RESULTS: Twenty-nine studies were included, and 143 patients affected by PAC were analysed (62 males, 75 females, and 6 undefined, with a mean age of 57.4 ± 14.5 years). The palate was the most affected site (99/143, 69.2%), followed by the buccal mucosa (12/143, 8.4%). Moreover, we report two cases of patients with PAC affecting the buccal mucosa (one male and one female, with a mean age of 70.5 ± 2.5 years). CONCLUSIONS: The present study underscores the importance of considering the buccal mucosa as a possible location of minor salivary gland tumours; although it is a less-considered affliction, it is not uncommon.

Pleomorphic adenoma of the nasal septum: A case report.

INTRODUCTION: Pleomorphic adenomas are benign salivary gland tumors with epithelial, myxoid, and mucoid components. They rarely occur in the upper respiratory tract where the predominant site is the nasal septum, leading to symptoms of nasal obstruction. Identifying these tumors requires histopathological examination, and they are usually managed surgically. PRESENTATION OF CASE: A middle-aged lady presented to the outpatient otorhinolaryngology clinic with symptoms of unilateral nasal obstruction. Nasal endoscopy in the clinic revealed a right-sided anterior nasal septal vascular mass, which was confirmed with a contrast-enhanced CT scan with suspicion of septal hemangioma. Surgical examination and endoscopic removal of the septal mass were carried out under anesthesia, and histopathology of the specimen showed predominant myoepithelial cellularity with scanty stroma, consistent with a diagnosis of pleomorphic adenoma. The patient had an uneventful post-operative stay and follow-up with no recurrence. DISCUSSION: Nasal cavity pleomorphic adenomas are important to identify and treat, as they can recur and potentially turn malignant. Endoscopic endonasal surgery is emerging as the treatment of choice for these adenomas, as it is associated with minimal morbidity and cosmetic impact. CONCLUSION: We report a rare case of nasal septal pleomorphic adenoma in a middle-aged female, which was successfully treated with endoscopic endonasal surgery.

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.

Molecular Factors in Carcinoma Ex Pleomorphic Adenoma: Systematic Review and Meta-Analysis.

OBJECTIVE: Carcinoma ex pleomorphic adenoma (CXPA) is a rare malignant salivary gland tumor. Although multiple reviews have been published on salivary gland malignancies, it has been a decade since the last dedicated systematic review pertaining to CXPA alone was published. This study examines molecular factors in CXPA diagnosis. DATA SOURCES: MEDLINE, CINAHL, Embase, Scopus, Web of Science (BIOSIS), Cochrane CENTRAL, Health Collection (Informit), OpenDOAR, and GreyNet International. REVIEW METHODS: Systematic review and meta-analysis from inception to October 31, 2022 for all English language studies pertaining to "carcinoma ex pleomorphic adenoma." Predicted incidence of each biomarker was calculated with meta-analysis. Comparison against pleomorphic adenoma (PA) and salivary duct carcinoma (SDC) when reported within the same study are performed. Risk of bias performed with JBI tool for prevalence studies. RESULTS: Of 19151 unique studies undergoing abstract screening, 55 studies (n = 1322 patients) underwent data analysis. Biomarkers with >3 studies were p53, HER2, AR, EGFR, PLAG1, ERBB, ER, PR, HMGA2, p16, p63, a-SMA, RAS, PTEN, PDL1, BRAF, PIK3CA, and c-kit. Highest incidence was seen in AR, EGFR, p16, and p53. Significant differences were demonstrated compared with PA and SDC. There was high heterogeneity and overall high risk of bias within studies. CONCLUSION: Molecular factors are an area of interest in the diagnosis of CXPA. Our study results support examining CXPA as a discrete cohort in future targeted therapy trials. Laryngoscope, 134:1042-1053, 2024.

Clinicopathological features and prognostic factors of salivary gland myoepithelial carcinoma: institutional experience of 42 cases.

Myoepithelial carcinoma (MECA) is a rare type of carcinoma for which the clinicopathological features and prognostic factors have not yet been fully clarified. A retrospective study of 42 patients diagnosed with salivary gland MECA was performed, focusing on the clinicopathological features and prognostic factors. Of the 42 patients, 20 died of cancer, 20 lived without tumour, one lived with distant metastasis, and one was lost to follow-up. Overall, 69.0% had tumour recurrence, 16.7% had cervical nodal metastasis, and 21.4% had distant metastasis. The 5-year overall survival rate was 70.2%. Kaplan-Meier analysis revealed that patients with pathological positive lymph nodes (pN+), multiple recurrences of tumour, and higher histological grade had worse overall survival. Multivariate Cox analysis indicated pN+ and higher histological grade to be independent predictors of decreased survival. The 5-year overall survival rate in the pN0 group was 87.5%, while that in the pN+ group was 28.6%. In conclusion, myoepithelial carcinoma can be defined as a tumour with a high incidence of recurrence and poor prognosis, especially in pN+ patients. Pathological positive lymph nodes and histological grade may serve as predictors of survival.

Don't SUMP it! Utility of PLAG1 immunocytochemistry in basaloid SUMP subcategory.

BACKGROUND: Basaloid salivary gland neoplasm of uncertain malignant potential (B-SUMP) is an indeterminate diagnostic subcategory, with pleomorphic adenoma (PA) representing the most common benign neoplasm. Pleomorphic adenoma gene 1 (PLAG1) staining is frequently seen in PAs and could aid in distinguishing them from other basaloid neoplasms. The authors evaluated the utility of PLAG1 immunocytochemistry (ICC) in differentiating PAs from other basaloid neoplasms in smears and liquid-based cytology (LBC) specimens. METHODS: In total, 45 B-SUMP cytology aspirates and corresponding surgical excision specimens were identified. PLAG1 immunostaining was performed in all aspirates and surgical excision specimens and was scored as positive (strong/diffuse), equivocal (focal/weak), or negative. RESULTS: PLAG1 ICC was performed directly on 38 smears and seven LBC specimens. PLAG1 was positive in 29 of 45 cases (64%), whereas six of 45 (13%) were equivocal, and 10 of 45 (22%) were negative. PLAG1-positive aspirates included 26 (90%) PAs, two (7%) basal cell adenomas (BCAs), and one (3%) carcinoma ex-PA. PLAG1-equivocal aspirates included four (67%) PAs and two (33%) BCAs, whereas negative aspirates included five (50%) BCAs, four (40%) adenoid cystic carcinomas, and one (10%) metastatic adenosquamous carcinoma. The sensitivity, specificity, positive, and negative predictive values were 87%, 86%, 93%, and 75%, respectively. Diagnostic accuracy was 87%. CONCLUSIONS: PLAG1 ICC is useful when positive (strong/diffuse) and can be reliably performed on smears and LBC specimens. PLAG1 was positive in most PAs and in a small subset of BCAs. Therefore, in the absence of atypical cytologic features, PLAG1-positive tumors could be diagnosed as benign, with a note favoring PA versus BCA. In contrast, PLAG1-negative/equivocal tumors should remain in the B-SUMP category.

BubR1 and cyclin B1 immunoexpression in pleomorphic adenoma and polymorphous adenocarcinoma of minor salivary glands.

The immunoexpression of BubR1 and cyclin B1 in pleomorphic adenoma (PA) and polymorphic adenocarcinoma (PAC) in minor salivary glands is poorly studied. Thus, a retrospective and observational study was performed to provide a better understanding of the role and immunopositivity patterns of these proteins in these lesions. Sixteen cases of PA and 16 cases of PAC were selected. Parenchyma cells were submitted to quantitative immunohistochemical analysis through the labeling index. Cytoplasmic immunoexpression of BubR1 was observed in neoplastic cells from all analyzed PA and PAC cases. All PA cases and 93.7% of PAC exhibited nuclear immunoexpression of BubR1. Higher cytoplasmic and nuclear immunoexpression of BubR1 was observed in PAC (p = 0.001 and p = 0.122, respectively). Cytoplasmic immunoexpression of cyclin B1 was observed in all cases of PA and PAC, with a higher labeling index in the latter (p < 0.001). There was a significant positive correlation between nuclear and cytoplasmic BubR1 immunoexpressions (p < 0.001) in PA and a significant negative correlation between BubR1 and cyclin B1 cytoplasmic immunoexpressions (p = 0.014) in PAC. The higher cytoplasmic and nuclear immunoexpression of BubR1 in PACs suggests the continuous maintenance of neoplastic cells in the cell cycle and migration. Higher immunoexpression of cyclin B1 supports this lesion's enhanced proliferative and migration ability.

Lacrimal gland pleomorphic adenoma: a narrative review / Adenoma pleomórfico de glândula lacrimal: uma revisão narrativa

ABSTRACT We present a literature review of 57 publications describing this pathology, published from the year 2012. In all these studies patients were reported to depict a slow-growing, motionless mass, which is painless at most times. All cases were managed by total excision, except for one report where adjuvant radiotherapy was applied. Among the several therapeutic strategies, the total tumor resection, preserving the tumor pseudocapsule intact, appears to be a consensus in treating the disease efficiently. Furthermore, fine-needle aspiration biopsy, including the assessment of genetic alterations, has proved to be a valuable tool in the diagnosis of challenging cases. Our literature survey also suggests that an incisional biopsy before the surgery may lead to the pseudocapsule disruption, thus considerably increasing the chances of adenoma recurrence, enabling its malignization. At present, genetics studies indicate that the molecular aberrations involved in the adenoma are similar to those represented in the salivary gland tumor pathogenesis. Further, in the recurrent cases, the pathology becomes difficult to treat and multiple surgeries may be required, occasionally, leading to radical surgery treatment.

RESUMO Uma revisão narrativa da literatura de 57 publicações que descrevem esta patologia, publicada a partir de 2012. Os pacientes têm uma massa de crescimento lento e imóvel, que na maioria das vezes é indolor. Todos os casos foram tratados por excisão total, com exceção de um relatório de radioterapia adjuvante. Entre as estratégias terapêuticas encontradas, a ressecção total do tumor, preservando a pseudocápsula tumoral intacta, parece ser um consenso. Alternativamente, a biópsia por aspiração de agulha fina incluindo a avaliação de alterações genéticas pode representar uma ferramenta valiosa nos casos diagnósticos desafiadores. Uma biópsia incisional antes da cirurgia não é recomendada, pois a ruptura da pseudocápsula aumenta consideravelmente a recorrência do adenoma, permitindo até mesmo sua malignização. Com relação à genética, estudos atuais indicam que as aberrações moleculares envolvidas no adenoma são semelhantes às da patogênese do tumor da glândula salivar. Para casos de recorrência, a patologia torna-se difícil de tratar e múltiplas cirurgias podem ser necessárias, às vezes levando a um tratamento cirúrgico radical.

EZH2 immunoexpression in pleomorphic adenoma and adenoid cystic carcinoma and clinicopathological features

Abstract The aim of this study was to evaluate the expression of the EZH2 protein and describe the clinical and microscopic characteristics of adenoid cystic carcinoma (ACC) and pleomorphic adenoma (PA). The study included 16 ACC cases and 12 PA. All ACC and PA cases were positive for EZH2 and the ACC samples showed significantly higher EZH2 expression. The clinical and microscopic covariates were described in relation to EZH2 staining in ACC samples. The highest mean values of EZH2 were observed in cases with local metastasis, recurrence, perineural invasion, and predominantly cribriform growth pattern without solid areas. EZH2 is a potential marker of malignancy.

Current diagnosis and treatment of salivary gland-type tumors of the lung.

Salivary gland-type tumors of the lung are thought to originate from the submucosal exocrine glands of the large airways. Due to their rare occurrence, reports of their study are limited to small-scale or case reports. Therefore, daily clinical practices often require a search for previous reports. In the last 20 years, several genetic rearrangements have been identified, such as MYB::NF1B rearrangements in adenoid cystic carcinoma, CRTC1::MAML2 rearrangements in mucoepidermoid carcinoma, EWSR1::ATF1 rearrangements in hyalinizing clear cell carcinoma and rearrangements of the EWSR1 locus or FUS (TLS) locus in myoepithelioma and myoepithelial carcinoma. These molecular alterations have been useful in diagnosing these tumors, although they have not yet been linked to molecularly targeted therapies. The morphologic, immunophenotypic, and molecular characteristics of these tumors are similar to those of their counterparts of extrapulmonary origin, so clinical and radiologic differential diagnosis is required to distinguish between primary and metastatic disease of other primary sites. However, these molecular alterations can be useful in differentiating them from other primary lung cancer histologic types. The management of these tumors requires broad knowledge of the latest diagnostics, surgery, radiotherapy, bronchoscopic interventions, chemotherapy, immunotherapy as well as therapeutic agents in development, including molecularly targeted agents. This review provides a comprehensive overview of the current diagnosis and treatment of pulmonary salivary gland tumors, with a focus on adenoid cystic carcinoma and mucoepidermoid carcinoma, which are the two most common subtypes.

Influence of p16 Protein Immunostaining on Histopathological Features of Pleomorphic Adenoma and Carcinoma ex- Pleomorphic Adenoma.

The objective of this study was to evaluate the role of p16 in histologic characteristics and transition of Pleomorphic Adenoma (PA) to Carcinoma ex-PA (CxPA). So, 60 PA and 4 CxPA were histologic reviewed based on microscopic characteristics proposed by Hellquist, Triantafyllou and Dulguerov (PA) and Morais, Antony and Toluie (CxPA). Immunostaining for p16 was associated in different parenchyma and stroma of both tumors and Fisher's/chi-square tests and Mann-Whitney test were performed (SPSS v20.0, p<0.05). In PA the periductal cells were predominantly p16- and that ductal and myoepithelial cells showed a significant increase in p16+ cells (p<0.001). In CxPA, none of the cases showed p16+ in periductal cells, most parotid cases showed p16+ in ductal cells, and one case of parotid and the submandibular case showed mild immunostaining for myoepithelial cells. There was a small reduction in p16+ in CxPA compared to PA (p=0.537), but in both tumors there was less p16+ cells in solid stroma than other (p<0.001). The p16+ cases of PA had a higher capsular thickness (p=0.047). So, the loss of p16 immunostaining does not seem to be associated with the transition from PA to CxPA, but in both tumors the loss of p16+ cells are related to microscopic aggressiveness.

Epithelial-Myoepithelial Carcinoma of the Maxilla Arising From Minor Salivary Glands of Hard Palate: A Rare Case Report.

Epithelial-myoepithelial carcinoma is a rare malignant neoplasm of salivary glands. It is specifically found in the major salivary glands. The cases that emerge from minor salivary glands are rarely described. Histologically, it commonly exhibits a characteristic biphasic pattern consisting of epithelial and myoepithelial components. The histopathological resemblance to other benign and malignant neoplasms that also display myoepithelial characteristics makes the differential diagnosis challenging. Each differential diagnosis requires a very different management approach. Considering the difficulties of anatomopathological diagnosis and the rarity of epithelial-myoepithelial carcinomas emerging from minor salivary glands, we report a rare epithelial-myoepithelial carcinoma case of minor salivary glands in a 58-year-old woman. She was referred for a palatal swelling, evolving for more than 35 years, and reported recent pain and nasal obstruction. The mucosal swelling was located in the left maxilla within the hard palate, of a 45-mm-long axis crossing the medial line and extending to the premaxilla, without cervical lymph node involvement. A computed tomography scan revealed a palatal lesion involving the left and the right maxilla. Furthermore, the superior alveolar process, both left and right maxillary sinuses, the nasal cavities, and the nasal septum were included in the lesion. The final diagnosis was difficult to confirm despite multiple biopsies and was determined only from the excised specimen. The diagnosis of this tumor was challenging due to the clinical and histological similarities with other salivary tumors. The aim of this case report is to shed light on the distinctive features of these tumors and explore optimal screening and related management strategies.

Salivary Duct Carcinoma with Rhabdoid Features of the Parotid Gland with No E-Cadherin Expression: A Report with Anti-HER2 Therapy and Review of the Literature.

Salivary duct carcinoma with rhabdoid features (SDC-RF) is a rare form of salivary gland neoplasm that was recently described. We report a case of SDC-RF of the parotid gland with loss of E-cadherin and decreased ß-catenin expression in a 73-year-old male who presented with right facial/neck swelling and intermittent pain. Morphologically, the tumor presented with a discohesive infiltrate of isolated and cords of pleomorphic round cells containing moderate amount of eosinophilic to fine-vacuolated cytoplasm and hyperchromatic nuclei infiltrating through fibroadipose tissue and salivary parenchyma. Immunophenotypically, the tumor was positive for Cytokeratins Oscar and 7, GATA3, GCDFP, HER2, and an androgen receptor but negative for CK20, S100, p40, Melan A, CDX2, TTF1, ER, SATB2, DOG1, synaptophysin, and chromogranin. Due to its diffuse infiltrating pattern, involvement of the parapharyngeal space, supraclavicular fat pad, dermis, and skin without a defined surgical target, the tumor was deemed unresectable. Anti-HER2 therapy (Herceptin and Pertuzumab) was utilized. At the last follow-up, the patient is alive, with complete locoregional control and brain metastases. An electronic search was performed in the following registries for papers published up to June 2023: PubMed, Embase, and Web of Science. For the database searches, the keywords searched were "salivary gland", "salivary duct carcinoma", and "salivary duct carcinoma with rhabdoid features". Our review of the literature identified 30 cases of SDC-RF that reveal there is a predilection for males (83%), parotid gland (72%), and patients older than the 6th decade of life (83%). Immunophenotypically, all SDC-RF cases except one were positive for AR and GCDFP (97%), 81% were positive for HER2, and loss or decreased expression of E-cadherin in 93% of cases. In conclusion, we described a rare case of SDF-RF of the parotid gland with no E-cadherin expression, decreased ß-catenin expression, and its immunophenotypic profile.