Expanding the histological spectrum of salivary gland neoplasms with HMGA2::WIF1 fusion emphasising their malignant potential: a report of eight cases.

AIMS: Recently, HMGA2::WIF1 fusion has been reported in pleomorphic adenoma (PAs) originating from the parotid gland with a characteristic canalicular adenoma (CAA)-like pattern. However, it is unclear whether HMGA2::WIF1 fusion may occur in salivary gland carcinoma or tumours originating from the minor salivary glands. We herein conducted a detailed clinicopathological review of eight salivary gland tumours harbouring HMGA2::WIF1 fusions. METHODS AND RESULTS: The reviewed diagnoses of salivary gland neoplasms with HMGA2::WIF1 fusion were PA (n = four), myoepithelioma (n = one), myoepithelial carcinoma ex PA (n = two) and high-grade carcinoma with basaloid features (n = one). Two tumours originated from the minor salivary glands. Six tumours (80%) contained areas reminiscent of CAA characterised by interconnected trabeculae/canaliculi of monotonous oncocytic or cuboidal tumour cells associated with a hypocellular, hyalinised to myxoid stroma. Areas typical of PA were seen in four (50%) cases. All tumours showed diffuse S100 and CK7 immunopositivity. Adverse events were detected in two cases, including local recurrence in a patient with PA, and local and distant recurrences and disease-related death in a patient with a high-grade carcinoma of the minor salivary gland of the buccal space, showing tumour necrosis and perineural invasion. CONCLUSION: Salivary gland neoplasms with HMGA2::WIF1 fusion are predominantly characterised by CAA/striated duct adenoma-like histology and a S100+/CK7+ immunoprofile. These tumours are not always benign, as among all reported cases approximately 20% showed malignancy (six of 28) and adverse outcome (three of 15), including recurrence, distant metastasis and disease-specific mortality.

Central Pleomorphic Adenoma of Mandible Mimicking Ameloblastoma - A Rare Case Report.

Salivary gland neoplasms account for 3% of all head and neck tumours. Pleomorphic adenoma (PA) is the most common salivary gland tumour that mainly occurs in the parotid gland, followed by minor salivary glands of the oral cavity, however, the occurrence of PA inside the jaw bones is exceedingly rare and very few cases have been reported in the literature. Inside jaw bones these lesions tend to imitate large osteolytic lesions encompass a diagnostic challenge. An exhaustive review of the literature revealed only 10 cases of central pleomorphic adenoma. We present a rare case of primary PA that occurred inside the mandible and was provisionally diagnosed as ameloblastoma.

Utility of MUC4 in the diagnosis of secretory carcinoma of salivary glands.

Salivary gland tumors are diverse in morphology and both benign and malignant tumors may pose diagnostic challenges especially in small biopsies. Secretory carcinoma (SC) is histologically characterized by microcysts, follicles, solid growth pattern and occasional papillary structures, and absence of zymogen granules. SC is molecularly defined by the presence of novel gene fusion ETV6::NTRK3. Among the positive stains (S100 and mammaglobin), MUC4 is now another promising marker for the diagnosis of SC, that would enable the pathologists to exclude other morphologically close simulators. Aim of this study was to report clinicopathological features and assess utility of MUC4 in the diagnosis of SC. MUC4 was performed on 22 cases of SC. Glass slides were reviewed to record morphological patterns and staining of S100, mammaglobin, DOG1 and MUC4. Age ranged from 9 to 63 years with mean age of 34.41 ± 16.28 years. The male: female ratio was 72.7 %:27.3 %. The majority occurred in major salivary glands. A combination of patterns was seen; microfollicles were the most prevalent (90 %) followed by papillary-cystic and macrofollicles. MUC4 was positive in 19/21 (90 %) cases with almost equal number of 2+ and 3+ staining. MUC4 was negative in all cases of acinic cell carcinoma, polymorphous adenocarcinoma, adenoid cystic carcinoma, salivary duct carcinoma, myopepithelioma and myoeithelial carcinoma, cystadenoma and cribriform adenocarcinoma and all except 3 cases of mucoepidermoid carcinoma tested. Overall sensitivity of MUC4 was 95.4 %, specificity 90 %, p-value being <0.01, positive predictive value 87.5 % and negative predictive value 96.4 %. A characteristic cytoplasmic granular pattern was observed in 76.1 % tumors. S100 and mammaglobin were positive in all the performed cases. DOG1 was positive in 6/11 (28.5 %) tumors. In conclusion, MUC4 is a useful addition to a diagnostic immunohistochemical panel for SC, and to distinguish it from close potential mimickers such as acinic cell carcinoma, especially in practice settings where molecular testing is unavailable.

Multifocal intraoral ductal ectasia with metaplasia and focal epithelial proliferation: A case report.

Ductal ectasia with metaplasia and focal epithelial proliferation in the oral cavity does not correspond to any existing salivary gland lesion. A 72-year-old man presented with a mass in the buccal mucosa, which was excised and initially diagnosed as a cystadenoma. An upper lip mass on the right side, which developed later, was also excised. The lesions were histologically similar, and since they were multifocal and in non-contiguous and independent sites with multiple dilated cystic structures that did not destroy the lobar architecture, the final diagnosis was confirmed as ductal ectasia with metaplasia and focal epithelial proliferation. This condition may mimic various neoplastic lesions.

Mucoepidermoid carcinoma of the palate mimicking a pyogenic granuloma in a 30-year-old woman.

Mucoepidermoid carcinoma (MEC) is the most common salivary gland adenocarcinoma, more frequently affecting female patients in the fifth decade of life. When MEC arises in the minor salivary glands, the palate is the primary site. This case report describes an MEC on the palate of a 30-year-old woman. The lesion was initially treated as a pyogenic granuloma, but the final diagnosis based on histopathology was low-grade MEC. The patient was referred for cancer treatment, and no recurrence was observed during 3 years of follow-up. Some malignant tumors can mimic nonneoplastic reactive lesions clinically, which highlights the importance of biopsy and proper microscopic analysis of the resulting specimens.

Adenoid cystic carcinoma presenting as a midpalatal nodular mass with slow growth and long evolution: a case report with review of differential diagnosis.

Adenoid cystic carcinoma is an aggressive but slow-growing salivary gland tumor most commonly appearing in the palate. Though it is well recognized that this tumor has a slow-growing course, a clinical presentation of 10 years is uncommon. This article presents a case of a midpalatal nodular mass with a reported history of 10 years. The patient did not seek evaluation due to its small and asymptomatic clinical presentation, but an incisional biopsy later revealed the palatal nodular mass to be adenoid cystic carcinoma. The patient underwent surgical resection of the mass followed by adjuvant radiation therapy. This case report highlights the importance of prompt biopsy of a pathologic lesion despite an indolent history and benign clinical presentation. The various clinical differential diagnoses for a palatal nodular mass are also discussed.

CD138 Is Expressed in Different Entities of Salivary Gland Cancer and Their Lymph Node Metastases and Therefore Represents a Potential Therapeutic Target.

Advanced salivary gland carcinomas (SGC) often lack therapeutic options. Agents targeting CD138 have recently shown promising results in clinical trials for multiple myeloma and a preclinical trial for triple-negative breast cancer. Immunohistochemistry for CD138 was performed for all patients who had undergone primary surgery for SGC with curative intent. Findings were validated using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) imaging. Overall, 111 primary SGC and 13 lymph node metastases from salivary duct carcinomas (SaDu) were evaluated. CD138 expression was found in 60% of all SGC with differing expression across entities (p < 0.01). A mean of 25.2% of the tumor cells in mucoepidermoid carcinoma (MuEp) were positive, followed by epithelial-myoepithelial carcinoma (20.9%), acinic cell carcinoma (16.0%), and SaDu (15.2%). High-/intermediate-grade MuEp showed CD138 expression in a mean of 34.8% of tumor cells. For SaDu, lymph node metastases showed CD138 expression in a mean of 31.2% of tumor cells which correlated with CD138 expression in their primaries (p = 0.01; Spearman's ρ = 0.71). MALDI-MS imaging confirmed the presence of the CD138 protein in SGC. No significant association was found between clinicopathological data, including progression-free survival (p = 0.50) and CD138 expression. CD138 is expressed in the cell membrane of different entities of SGC and SaDu lymph node metastases and therefore represents a potential target for CD138 targeting drugs.

HER-2 Neu gene: A valuable therapeutic target in metastatic mucoepidermoid carcinoma.

INTRODUCTION: Salivary gland neoplasms (SGNs) respond poorly to the traditional chemotherapy agents limiting the availability of systemic treatment options in the metastatic setting. The recent identification of actionable molecular targets in SGNs has led to the evaluation of targeted therapies in non-approved advanced SGNs. CASE REPORT: We present the case of an elderly male with HER-2 Neu overexpressing metastatic mucoepidermoid carcinoma (MEC) who demonstrated a prompt and sustained disease response to targeted therapies directed against HER-2 Neu with long survival interrupted by hepatoxicity to Trastuzumab emtansine (TDM-1) treatment.Management and Outcome: The patient was started on Trastuzumab and Pertuzumab on a clinical trial and resulted in an objective improvement sustained over 3 years. Following the disease progression, TDM-1 was started with a response until the patient developed severe hepatotoxicity as an adverse effect of TDM-1 therapy resulting in its discontinuation. Close follow-up post-treatment-discontinuation demonstrated continued clinical improvement until 6 months, when the patient developed brain metastasis. He passed away a few months later in hospice care. DISCUSSION: The metastatic MEC in our patient overexpressed HER-2 Neu. Owing to Trastuzumab and Pertuzumab response, Trastuzumab emtansine (TDM-1) was initiated on a compassionate basis which further extended the survival but had to be terminated owing to adverse effects. Given the paucity of data on targeted therapies in the treatment of metastatic SGNs and the safety, tolerability, and efficacy of TDM-1 therapy among the elderly, further studies are warranted to answer these important questions and to identify eligible patients for this novel treatment option.

Epithelial myoepithelial carcinoma of the parotid gland: A rare tumor with oncocytic changes.

Epithelial myoepithelial carcinoma (EMC), a very rarely seen, low-grade, malignant, salivary gland tumor is most commonly located in the parotid gland followed by the submandibular gland. It is more often observed in females and in the 6th decade of life. Although primary treatment of the tumor is surgical resection, adjuvant radiotherapy may be applied to the adjacent area or close follow-up can be done if the surgical margin is closed. Patients must be followed up closely for recurrence and metastasis. Physical and radiological examinations (USG and MRI) should be performed to see for any recurrence in the operated area during the first year for every 2-3 months. This study presents the clinical, radiological, and pathological characteristics of a 59-year-old female patient with low-grade, oncocytic variant of EMC located in the left parotid gland.

Descriptive epidemiology of salivary gland neoplasms in Nigeria: An AOPRC multicenter tertiary hospital study.

OBJECTIVES: Accurate diagnosis of salivary gland neoplasms (SGN) in many centers in Africa is limited by poor diagnostic resources and ancillary services. Hence, we have carried out a multicenter epidemiological study to understand the true burden of SGN in Nigeria. METHOD: In this descriptive cross-sectional study, we have deployed resources available to members of the African Oral Pathology Consortium (AOPRC) to examine the burden of salivary gland lesions in Nigeria, using a multicenter approach. Data from seven major tertiary health institutions in northern, western, and southern Nigeria were generated using a standardized data extraction format and analyzed using the Epi-info software (Version 7.0, Atlanta, USA). RESULT: Of the 497 cases examined across the seven centers, we observed that SGN occurred more in females than males. Overall, pleomorphic salivary adenoma (PA) was found to be the most common. PA was found to be the commonest benign SGN while adenocystic carcinoma (ADCC) was the commonest malignant SGN. Regional variations were observed for age group, diagnosis, and gender distribution. Significant statistical differences were found between males and females for malignant SGNs (p-value=0.037). CONCLUSION: We found regional variation in the pattern of distribution of SGN in Nigeria. This is the largest multicenter study of SGN in Nigeria, and our findings are robust and representative of the epidemiology of this neoplasm in Nigeria.

t(6;9)(MYB-NFIB) in head and neck adenoid cystic carcinoma: A systematic review with meta-analysis.

The presence of a translocation involving MYB and NFIB genes have been described in adenoid cystic carcinoma (AdCC) from different anatomical regions. However, the exact frequency of this genetic event and its prognostic impact for patient survival remain obscure. The aim of this study was to carry out a systematic review to address the prevalence and the prognostic potential of t(6;9)(MYB-NFIB) in head and neck AdCC. Quantitative analysis was done to determine the prevalence of the translocation. A total of 1,107 articles were initially retrieved with 36 remaining for data extraction. The prevalence of t(6;9)(MYB-NFIB) varied significantly (16%-100%), especially due to methodological heterogeneity among studies. A total of 11 studies attempted to determine the prognostic importance of the translocation, but no study found any significant association with survival rates; only three studies observed a significant association with age, sex, tumour location and the presence of recurrences and metastases. The prevalence of t(6;9)(MYB-NFIB) in head and neck AdCC varies according to the laboratorial methods used, and the best evidence available demonstrates that t(6;9)(MYB-NFIB) does not seem to be a prognostic determinant.

Treatment outcomes in metastatic and localized high-grade salivary gland cancer: high chance of cure with surgery and post-operative radiation in T1-2 N0 high-grade salivary gland cancer.

BACKGROUND: High-grade salivary gland cancer is a distinct clinical entity that has aggressive disease progression and early systemic spread. However, because of the rarity of the disease, the clinical outcomes, prognostic factors and clinical decision on the optimal treatments have not been fully understood. METHODS: In this study, we retrospectively analyzed the clinical data of 124 patients with high-grade salivary gland cancers and performed multivariate survival analyses to evaluate the clinico-pathological factors affecting the treatment outcomes. RESULTS: The 5-year disease-specific survival was 63.4% in patients with high-grade salivary gland cancers. Among the clinico-pathological factors, presence of lymph node metastasis (hazard ratio 5.63, 95% confidence interval 2.64-12.03, P < 0.001) and distant metastasis (hazard ratio 4.59, 95% confidence interval 2.10-10.04, P < 0.001) at diagnosis were the most potent unfavorable prognostic factors. Importantly, patients with early-stage disease (T1-2N0M0) showed apparently a relatively excellent prognosis (93.2% 5-year disease-specific survival); meanwhile N (+) and M1 status at diagnosis resulted in dismal outcomes (44.6 and 21.1% 5-year disease-specific survival, respectively). On comparing surgery alone as a treatment modality, surgery plus postoperative radiation significantly benefited the patients, but the difference between adjuvant radiation and chemoradiation was not found to be significant. Pathological subtypes of high-grade salivary gland cancers were not significantly associated with prognosis. CONCLUSIONS: Despite of an overall unfavorable prognosis in high-grade salivary gland cancer, patients with early-stage disease are expected to have excellent prognosis (over 90% survival rates) with surgery plus adjuvant radiation, which may implicate the patients' consultation, therapeutic decision making, and the need for early detection of the disease.

Diagnostic utility of C-kit protein (CD117) expression in differentiating adenoid cystic carcinoma and polymorphous low grade Adenocarcinoma.

BACKGROUND & OBJECTIVE: To evaluate usefulness of immunohistochemical marker C-kit (CD117) in differentiating Adenoid cystic carcinoma (AdCC) from Polymorphous low-grade adenocarcinoma (PLGA) in patients of salivary gland carcinomas. AdCC is a malignant salivary gland neoplasm with poor prognosis. PLGA is a salivary gland malignancy with indolent growth pattern. Differentiating between the two entities is a diagnostic challenge. We evaluated the role of C-kit in differentiating the two. METHODS: This is a Cross sectional study. Samples of 19 tumors including 12 AdCC and 4 PLGA was evaluated at Department of Histopathology, Armed Forces Institute of Pathology, Rawalpindi from December 2015 to August 2016. Immunohistochemical techniques were used to analyze the level of c-kit expression in AdCC (n = 12), polymorphous low-grade adenocarcinoma (PLGA) (n = 6). Samples were stained using monoclonal antibody against C-kit. Statistical analysis of the data was done using SPSS version 21. RESULTS: Strong diffuse cytoplasmic reactivity was observed in more than 50% of the tumor cells of AdCC whereas less than 20% of cells showed negative to weak positivity in PLGA. Hence, the difference in the expression of c-kit between AdCC and PLGA was statistically significant (p value <0.002). CONCLUSIONS: CD117 expression itself can be used as a marker in differential diagnosis of salivary gland neoplasms. However, the percentage of the CD117 immunoreactive cells and the staining intensities appeared to be important factors in distinguishing AdCC from PLGA.

Intraosseous mucoepidermoid carcinoma of maxilla: a rare entity.

Mucoepidermoid carcinoma (MEC) is the malignant salivary gland neoplasm chiefly occurred in minor salivary gland. One of the rare variant of MEC is intra-osseous variant found in the jaws known as central mucoepidermoid carcinoma. Presently in this case report, we described a 28-year-old male diagnosed with central low grade mucoepidermoid carcinoma subsequently with the presence of asymptomatic swelling with a history of trauma. Clinically mimicking a cystic lesion and radiographically gives an idea of mixed radio-opaque radiolucent lesion which creates a confusion to render a final diagnosis. The site, duration and history of the case are uncommon for the occurrence of intra-osseous malignant lesion of salivary glands. Present case adds new dimensions to the present knowledge about the clinical and radiographical picture that a central mucoepidermoid carcinoma can mimic.

Combined salivary duct carcinoma and squamous cell carcinoma suspected of carcinoma ex pleomorphic adenoma.

A 76-year-old Japanese woman had noticed an asymptomatic and palpable mass in her left parotid gland region for 20 years. The tumor had showed rapid growth during the last two months. Therefore, the tumor was clinically suspected of being a malignant tumor and was surgically resected. A histopathological examination revealed that the tumor consisted of two different histopathological neoplastic components accompanied by hyalinized fibrosis at the center of the tumor. The two-neoplastic components were squamous cell carcinoma and salivary duct carcinoma. The tumor was suspected to be a carcinoma ex pleomorphic adenoma after considering the clinical course and the histopathological findings, such as hyalinized fibrosis at the center of the tumor. There was no evidence of recurrence at 30 months after the surgical resection.

Initial Experience With Ultrasound Elastography for Diagnosis of Major Salivary Gland Lesions.

OBJECTIVES: The aim of this study was to evaluate the usefulness of ultrasound elastography, including conventional strain elastography, acoustic radiation force impulse (ARFI)-induced strain elastography, and point shear wave elastography (SWE) for diagnosis of major salivary gland lesions. METHODS: Forty major salivary gland lesions underwent conventional sonography, conventional strain elastography, ARFI strain elastography, and point SWE before surgery or biopsy. The diagnostic performances of the sonographic and elastographic techniques were assessed with reference to histopathologic results. RESULTS: There were 32 benign (7 Warthin tumors, 17 pleomorphic adenomas, and 8 other benign lesions) and 8 malignant (1 squamous carcinoma, 2 metastases, 2 mucoepidermoid carcinomas, 1 anaplastic carcinoma, and 2 malignant lymphomas) major salivary gland lesions on pathologic analysis. No conventional sonographic features or conventional strain elastographic scores were found to be associated with malignancy (all P > .05). The ARFI strain elastographic scores between benign and malignant lesions were statistically different (P = .032) and an ARFI strain elastographic score of 4 or greater was highly predictive of malignancy (P= .025). An ARFI strain elastographic score of greater than 3 achieved specificity of 81.3% (26 of 32) and sensitivity of 62.5% (5 of 8) in differentiating benign from malignant lesions. The shear wave velocity on point SWE did not show a significant difference in distinguishing between malignant and benign lesions (6.07 versus 4.43 m/s; P > .05). However, Warthin tumors had a trend to show lower shear wave velocities compared with pleomorphic adenomas (2.84 versus 5.27 m/s; P = .024). CONCLUSIONS: Acoustic radiation force impulse strain elastography may be potentially useful for diagnosing major salivary gland lesions, whereas conventional strain elastography and point SWE are not helpful.

Role of p63 in Determining the Histogenesis of Low-Grade Neoplasms versus Cystic Lesion.

The biological nature of salivary gland neoplasms and the overlapping characteristics that result from the heterogeneity of the cells of origin make diagnosis difficult. Hence, we intend to present a case of low grade mucoepidermoid carcinoma (MEC) on the palate and to understand the importance of biomarker such as p63 in the early diagnosis of tumor as it also has a role in its histogenesis. A 53-year-old female reported with a unilateral swelling for 3 months on posterolateral palatal region of the right side. Clinical differentials for such palatal swellings include a varied spectrum of lesions such as reactive, benign, and malignant lesions. Based on the incisional and excisional biopsy, histopathological findings and immunohistochemical examination with p63 the case were diagnosed with low grade MEC. The tumor cell differentiation in MEC could be the result of multiplicity of differentiation pathways leading to the formation of various histological patterns. This case report highlights the complexity of salivary gland pathology diagnosis and role of specific tumor marker such as p63 as an early marker for differentiation of salivary gland tumor such as low grade MEC from other cystic lesions occurring on the palate.

Molecular analysis using SalvGlandDx improves risk of malignancy estimation and diagnosis of salivary gland cytopathology: An exploratory multicenter study.

BACKGROUND: Diagnosis of salivary gland neoplasms is challenging, especially on cytological specimens acquired by fine-needle aspiration. The recently implemented standardized Milan system for reporting salivary gland cytopathology provides an estimated risk of malignancy (ROM); yet, for two of the categories, the diagnosis of the lesion remains unclear. However, a precise diagnosis is desirable for optimal patient management, including planning of surgery and imaging procedures. METHODS: Cytological specimens (n = 106) were subjected to molecular analysis using the SalvGlandDx panel. The risk of malignancy was calculated for each detected alteration based on the diagnosis of the resection specimen. By taking into account the molecular alterations, their associated ROM, the clinical and cytological features, and the current literature, the Milan category was evaluated. RESULTS: Of n = 63 technically valid cases, 76% revealed a molecular alteration. A total of 94% of these molecularly altered cases could be assigned to a different Milan category when additionally taking molecular results into account. In only 2% of the salivary gland neoplasms of uncertain malignant potential, in which a molecular alteration was detected, the classification remained salivary gland neoplasms of uncertain malignant potential. CONCLUSION: Molecular analysis of cytological specimens provides a benefit in classifying salivary gland neoplasms on fine-needle aspiration. It can improve the ROM estimation and thus help to assign cases of formerly unknown malignant potential to clearly benign or malignant categories.

Basal cell adenoma of the deep lobe of the parotid gland misdiagnosed as mucoepidermoid carcinoma - A case report.

INTRODUCTION: Basal cell adenoma is a rare, benign epithelial tumour of the salivary gland, comprising only 1-2 % of all salivary gland tumours. Predominantly found in the parotid gland, basal cell adenoma can also occur in minor salivary glands and are often confused with other benign and malignant salivary gland tumours. A thorough histopathological examination can provide a definitive diagnosis. PRESENTATION OF CASE: A 65-year-old woman presented with a painless mass in the right infra-auricular region. Imaging revealed a well-defined hypodense lesion in the deep lobe of the right parotid gland, initially suspected as mucoepidermoid carcinoma. Fine needle aspiration was inconclusive, leading to the decision to perform a total conservative parotidectomy. Histopathology confirmed basal cell adenoma, characterized by cystic areas filled with mucoid material and basaloid cells arranged in trabecular and tubular patterns. DISCUSSION: Basal cell adenoma was classified as a distinct entity by the WHO in 1991. Cytologically, they imitate both benign and malignant salivary as well as non-salivary gland tumours. The histological hallmark of basal cell adenoma involves basaloid cells with small round nuclei showing no atypia, scant pale cytoplasm, and distinct peripheral palisading. Treatment involves surgical removal, with a more radical approach for certain variants such as the membranous type. CONCLUSION: This case highlights the clinical, radiological, and histopathological features of basal cell adenoma, emphasizing the importance of accurate diagnosis and appropriate surgical management. Early detection and appropriate treatment are crucial for optimizing patient outcomes in basal cell adenoma management.

PLAG1 overexpression in salivary gland duct-acinar units results in epithelial tumors with acinar-like features: Tumorization of luminal stem/progenitor cells may result in the development of salivary gland tumors consisting of only luminal cells.

OBJECTIVES: Details about salivary gland tumor histogenesis remain unknown. Here, we established a newly generated murine salivary gland tumor model that could overexpress pleomorphic adenoma gene 1 (PLAG1) and attempted to clarify the events that occur during the early phase of salivary gland tumor histogenesis. METHODS: Salivary gland tumors were generated using murine models (Sox9IRES-CreERT2; ROSA26-PLAG1). Lineage tracing of Sox9-expressing cells was performed using Sox9IRES-CreERT2; ROSA26-tdTomato mice, which were generated by crossing Sox9CreERT2/- and ROSA26-tdTomato mice (expressing the tdTomato fluorescent protein). Organ-cultured embryonic salivary glands from the murine model were morphologically analyzed, and mRNA sequencing was conducted two days after tumor induction for gene enrichment and functional annotation analysis. RESULTS: Salivary gland tumors exhibited epithelial features with acinar-like structures because of gene rearrangements in the luminal cells. Structural disturbances in the duct-acinar unit of the salivary gland were observed and cancer-related pathways were enriched among the differentially upregulated genes in the early phase of tumor induction in an organ-cultured embryonic salivary gland tumor model. CONCLUSIONS: The newly generated murine salivary gland tumor model may show that the tumorization of luminal stem/progenitor cells can result in the development of salivary gland tumors comprising only luminal cells.