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Pleomorphic adenoma is the most common benign salivary gland tumour of the head and neck region, most commonly seen in parotid glands. These may arise also from minor salivary glands of the upper aerodigestive tract comprises the upper lip, cheek, floor of the mouth and rarely from mucoserous glands in the nasal cavity and paranasal sinuses. A middle-aged man, who had undergone surgery for a nasal mass 14 years ago, presented with headache and visual complaints from a recurrent mass originating from the sphenoid sinus. Isolated sphenoid sinus space-occupying lesions have always been a diagnostic challenge. The mass was biopsied and diagnosed as pleomorphic adenoma on histopathology, and then excised endoscopically. Early and accurate diagnosis on a biopsy may result in complete excision of the tumour and prevent recurrence. The endoscopic route is preferred for surgical excision and the patient should be followed up clinically and radiologically to detect early recurrence.

PURPOSE The androgen receptor (AR) is expressed (+) in a subset of salivary gland cancers (SGCs). This phase II trial evaluated the efficacy of the antiandrogen enzalutamide in AR+ SGC. METHODS Patients with locally advanced/unresectable or metastatic AR+ SGCs were enrolled. Enzalutamide (160 mg) was given orally once daily. The primary end point was the best overall response rate per RECIST v1.1 within eight cycles. Confirmed responses in ≥ 5 of 41 patients would be considered promising. Secondary end points were progression-free survival, overall survival, and safety. RESULTS Forty-six patients were enrolled; 30 (65.2%) received prior systemic therapy, including 13 (28.3%) with AR-targeted drugs. Of seven (15.2%) partial responses (PRs), only two (4.3%) were confirmed per protocol and counted toward the primary end point. Twenty-four patients (52.2%) had stable disease; 15 (32.6%) had progression of disease as best response. Twenty-six patients (56.5%) experienced tumor regression in target lesions; 18 (39.1%) had partial response/stable disease ≥ 6 months. Tumor regressions were observed in female patients (5 of 6 [83.3%]) and those who received prior AR– (6 of 13 [46.2%]) or human epidermal growth factor receptor 2–targeted therapies (5 of 8 [62.5%]). Three patients remained on treatment at data cutoff (duration, 32.2-49.8 months). The median progression-free survival was 5.6 months (95% CI, 3.7 to 7.5); the median overall survival was 17.0 months (95% CI, 11.8 to 30.0). The most common adverse events were fatigue, hypertension, hot flashes, and weight loss. Total and free testosterone levels increased by a mean of 61.2% and 48.8%, respectively, after enzalutamide. CONCLUSION Enzalutamide demonstrated limited activity in AR+ SGC, failing to meet protocol-defined success in part because of a lack of response durability. Strategies to enhance the efficacy of antiandrogen therapy are needed.

Salivary gland neoplasia is uncommon in veterinary species and has rarely been reported in cattle. Adenocarcinoma, squamous cell carcinoma, and pleomorphic carcinoma have been described in the parotid gland of dairy cows. Here we describe a case of high-grade mucoepidermoid carcinoma in a bull. The bull had a chronic history of caudal mandibular soft tissue swelling. Postmortem examination revealed a 30 × 30-cm mass with a caseonecrotic center, hemorrhage and necrosis of the ipsilateral cervical musculature, osteolysis of the right paracondylar process of the skull and right horn base, pulmonary nodules, and enlarged tracheobronchial lymph nodes. Histology of the mass, lungs, and lymph nodes revealed an invasive neoplasm composed of epithelial cells arranged in nests and ductular structures supported by a spindle cell stroma, with frequent central necrosis. Immunohistochemistry revealed that epithelial cells were diffusely positive for pancytokeratin and p63 with multifocal vimentin positivity; stromal cells were diffusely positive for vimentin and α-SMA. A salivary gland mucoepidermoid carcinoma was diagnosed based on these findings. Although rare, salivary gland neoplasia should be considered a differential diagnosis for mandibular masses in cattle.

Intercalated duct lesions (IDLs) are usually asymptomatic. We report a case of IDL, in which a palpable mass formed. The patient was a 45-year-old Japanese male, who noticed a mass in the left parotid region. The nodular lesion was well-circumscribed, but did not have a fibrous capsule or exhibit infiltrative growth. It contained a small cystic space and consisted of basaloid cells arranged in a cribriform pattern and inner ductal cells. It had some solid areas of nest-like proliferation displaying mild cellular atypia. Immunohistochemically, the luminal cells were positive for cytokeratin (CK)7 and epithelial membrane antigen, and the abluminal cells were positive for CK5/6, p63, and DOG1. S-100 protein-positive stromal cells were also seen. The lesion's cells were all positive for SOX10, and the nuclei of some basaloid cells were positive for β-catenin. The Ki-67 labeling index was 3.8%. The ductal cells contained diastase-digestion-resistant, Periodic acid Schiff-positive zymogen granules. Genetically, the lesion harbored a missense mutation in the CTNNB1 gene. We diagnosed the lesion as an IDL. As IDLs are usually small non-neoplastic lesions, symptomatic cases are rare. Based on its common immunohistochemical and genetic features, IDL may be a precursor of basal cell adenoma/adenocarcinoma, such as intercalated duct adenoma.

To estimate the proportion of de novo lacrimal gland pleomorphic adenomas (PAs) and carcinomas expleomorphic adenomas (CEPAs), together with age at presentation and first symptom. Conjectural models of tumor growth are considered.Retrospective review of patients with orbital lobe PA or CEPA. The presenting age was examined for conformation to a Gaussian distribution and the cumulative distribution function derived for both tumor types. The risk of CEPA with age was estimated by logistic regression.About one-sixth (27/172; 16%) of these primary orbital lobe tumors were CEPAs, with 145 PAs (76/145 male; 52%) and 27 CEPAs (12/27 male; 44%). The mean presenting age for PAs was 48.3 years (median 47.7; range 11-84 years) and 57.7 years for CEPAs (median 61.2, range 27-91 years) ( p = 0.0062), and the standard deviations for each group are almost identical (16.3 for PAs, 15.9 for CEPAs; p = 0.92). Five (3.4%) PAs and 1 (3.7%) CEPA were asymptomatic: otherwise, the median symptom duration was 24 months for both PAs and CEPAs ( U test: p = 0.65). The odds of CEPA rises significantly with age, increasing 1.04-fold annually ( p = 0.0079).The almost identical measures of dispersion for the presenting ages of PA and CEPA suggests that, once malignant transformation occurs, there might be a relatively constant period before it is evident. CEPAs present about a decade after PAs, this unexpectedly later presentation for the malignancy possibly being explained by a gradual replacement of the PA by the newly arising carcinoma within the preceding benign tumor.

Salivary duct carcinoma (SDC) is an uncommon and aggressive salivary malignancy. The oncocytoid variant of salivary duct carcinoma (OSDC) has only been reported in the English literature once before. Here we detail two new patients. A 71-year-old female presented with a painless enlarging left parotid mass. Imaging and fine-needle aspiration were nondiagnostic. The second patient, a 79-year-old male, presented with painless swelling in the right cheek. Imaging was nondiagnostic. Both patients underwent surgical resection. Histopathology revealed bland yet infiltrative OSDC in both cases. These tumors were AR+ (androgen receptor) by immunohistochemistry. Potential difficulty exists in distinguishing the oncocytoid variant of SDC, a rare and relatively bland tumor, from oncocytoma, a more commonly encountered entity. AR expression can aid in the correct diagnosis.

Parapharyngeal space salivary gland tumors are very rare. The authors sought to examine the clinical features, treatment methods, and treatment results of parapharyngeal space salivary gland tumors in our hospital.The authors retrospectively enrolled 15 patients who were finally diagnosed as having parapharyngeal space salivary gland tumors from January 2010 to January 2021.All parapharyngeal space salivary gland tumors arose from the prestyloid compartment. This study included 3 males and 12 females. The main symptoms were incidental diagnosis during imaging tests, followed by neck discomfort, oral mass, neck mass, and headache. Surgical methods for parapharyngeal space salivary gland tumors were performed in the following order: transcervical approach (n = 10), transcervical-parotid approach (n = 3), transoral approach (n = 1), and transparotid approach (n = 1). Pleomorphic adenoma was the most common tumor among parapharyngeal space salivary gland tumors.In the surgery of parapharyngeal space salivary gland tumors, a transcervical or transcervical-parotid approach was mainly used by predicting the origin site through radiologic examinations.

The efficacy of programmed cell death 1 (PD-1) inhibitor therapy for patients with recurrent and/or metastatic salivary gland carcinoma (R/M SGC) remains unclear.We retrospectively analyzed 36 patients with R/M SGC treated with PD-1 inhibitor. The expression of programmed cell death ligand 1 (PD-L1) and mismatch repair (MMR) proteins was also analyzed.The objective response rate (ORR) was 11.1%. The histopathological subtypes of patients who achieved complete response or partial response were salivary duct carcinoma (SDC) in three patients and poorly differentiated carcinoma in one patient, all of whom showed a positive PD-L1 expression. The expression of MMR proteins was not associated with the efficacy of PD-1 inhibitors.Although the efficacy of PD-1 inhibitor therapy in R/M SGC is limited, certain patients may respond and achieve long-term disease control. There is a potential therapeutic effect in SDC patients with positive PD-L1 expression.

Contains fulltext : 249093.pdf (Publisher’s version ) (Open Access) Cabozantinib is registered in fixed 60 mg dose. However, 46% to 62% of patients in the registration studies needed a dose reduction due to toxicity. Improved clinical efficacy has been observed in renal cell carcinoma patients (RCC) with a cabozantinib exposure greater than 750 μg/L. In our study we explored the cabozantinib exposure in patients with different tumour types. We included RCC patients from routine care and salivary gland carcinoma (SGC) patients from a phase II study with ≥1 measured C(min) at steady-state. The geometric mean (GM) C(min) at the starting dose, at 40 mg and at best tolerated dose (BTD) were compared between both tumour types. Forty-seven patients were included. All SGC patients (n = 22) started with 60 mg, while 52% of RCC patients started with 40 mg. GM C(min) at the start dose was 1456 μg/L (95% CI: 1185-1789) vs 682 μg/L (95% CI: 572-812) (P

Contains fulltext : 249569.pdf (Publisher’s version ) (Open Access) AIM: Because the tyrosine kinases c-MET and vascular endothelial growth factor receptors (VEGFR) are often overexpressed in salivary gland cancer (SGC), this study evaluated the efficacy and safety of cabozantinib in patients with recurrent/metastatic (R/M) SGC. PATIENTS AND METHODS: A single-centre phase II study was conducted. Patients with immunohistochemical c-MET-positive R/M SGC were included in three cohorts: adenoid cystic carcinoma (ACC); salivary duct carcinoma (SDC) and other miscellaneous SGCs. No prior systemic treatments were required. Patients started cabozantinib 60 mg once daily. The primary outcome was the objective response rate (ORR). Secondary outcomes included survival, safety and quality of life. Per Simon-two-stage design, depending on efficacy, a maximum of 43 patients would be included. RESULTS: In total, 25 patients were included until premature closure owing to severe toxicity. Six patients (24%) had grade 3-5 wound complications, occurring at a median of 7.1 months on cabozantinib treatment (range 2.1-12.6). Remarkably, four of these six patients developed this complication in the area prior exposed to high-dose radiotherapy. Other grade ≥3 adverse events in >1 patient were hypertension (20%), diarrhoea (8%) and dehydration (8%). Twenty-one patients were evaluable for response; 1/15 ACC (ORR: 7%); 1/4 SDC and 0/2 patients with other miscellaneous SGC responded. Median progression-free survival was 9.4 months (95% confidence interval [CI] 7.4-11.4 months), 7.2 months (95%CI 0.0-15.1) and 6.9 months (95%CI 0.0-15.1), respectively. CONCLUSION: This study showed too many severe cabozantinib-associated wound complications in patients with SGC, especially in prior irradiated areas. Therefore, the study closed prematurely. The efficacy in the limited number of evaluable patients was low to moderate. TRIAL REGISTRATION: This trial was registered on ClinicalTrials.gov: NCT03729297.

Using a population-based database, this study investigates the risk factors, epidemiology, and outcomes of basal cell adenocarcinoma (BCAC) of the head and neck.The Surveillance, Epidemiology, and End Results database was analyzed for all patients with BCAC of the head and neck from 1973 to 2015.Three hundred and twenty-two cases of BCAC of the head and neck were identified. Mean age of diagnosis was 64.1 years. 52.5% were male and 77.3% were white. The most common primary site was the parotid gland (71.7%). Most patients underwent surgery alone (51.9%). Five-year disease-specific survival (5Y-DSS) was 95.6%, and 10Y-DSS was 90.3%. Highest survival was seen with surgery alone followed by combined surgery and radiation (10Y-DSS: 93.9% vs. 88.9%, p = 0.001). Age, primary site, T-classification, grade, and treatment type significantly affected survival.BCAC of the head and neck presents most frequently in the parotid glands. Surgery alone is associated with highest survival.

PURPOSE The activity of androgen-deprivation therapy (ADT) in androgen receptor–positive (AR+) salivary gland carcinomas (SGCs) has been established in the past few years. Second-line treatment in castration-resistant patients is still unknown. We investigated the activity of abiraterone acetate as second-line treatment in ADT-resistant, AR+ patients with SGC. METHODS This was a single-institution phase II trial. A two-stage Simon's design was applied. The primary end point was confirmed objective response rate. Secondary end points were disease control rate, safety, progression-free survival, and overall survival. Patients were eligible when the following criteria were met: histologic diagnosis of AR-overexpressing SGC, measurable disease according to RECIST 1.1, clinical and/or radiologic progression on ADT, suppressed serum testosterone, and no limits for the number of previous chemotherapy lines. All patients received abiraterone 1 g daily plus prednisone 10 mg and luteinizing hormone-releasing hormone agonist until progression or unacceptable toxicities. RESULTS From 2015 to 2019, 24 AR+ patients with SGC (23 men; median age 65.8 years) were treated within the study. The overall response rate was 21% (5 partial responses), with a disease control rate of 62.5%. The median duration of response was 5.82 months. Median progression-free survival was 3.65 months (95% CI, 1.94 to 5.89), and median overall survival was 22.47 months (95% CI, 6.74 to not reached). Objective response to previous ADT did not correlate with the activity of abiraterone. Adverse events (AEs) were recorded in 22 cases (92%) with grade 3 AEs in six patients (25%): fatigue (two), flushing (one), supraventricular tachycardia (one), and two non–drug-related AEs. No drug-related grade 4 or 5 AEs were recorded. CONCLUSION Abiraterone plus luteinizing hormone-releasing hormone agonist is active and safe as a second-line option in AR-expressing, castration-resistant SGC.

Myoepithelial carcinoma (MEC) of salivary gland is an uncommon tumor with no specific age or sex predilection. Most of the cases (~90%) arise in parotid and submandibular glands followed by palate. MEC of maxillary sinus is rare. We describe an extremely rare case of high grade MEC with rhabdoid differentiation and INI-1 loss involving maxillary sinus of an elderly male.

While salivary gland tumors have considerable plasticity, juxtaposition of the morphologies of two named tumor types is rare. Tumors with both mucoepidermoid and serous acinar components, dubbed "mucoacinar" carcinomas were recently characterized, and based on morphologic and molecular features, considered variants of mucoepidermoid carcinoma. Here we describe a unique case of a 59-year-old male with a 0.9 cm right parotid mass with a similar blend of mucoepidermoid-like and acinar elements that instead has a molecular phenotype of acinic cell carcinoma, essentially the reverse of mucoacinar carcinoma. The tumor was fairly well circumscribed with a prominent tumor associated lymphoid response. It consisted of a predominant bland but basaloid squamoid proliferation with scattered pockets of serous acinar differentiation as well as rare mucous cells and tubules. The tumor showed diffuse cytokeratin and DOG1 reactivity as well as p40 expression in the squamoid components. Immunostaining for NR4A3 was diffusely positive, and an NR4A3 rearrangement was noted on fluorescence in situ hybridization, while testing for MAML2 and MSANTD3 rearrangements were negative. Based on these findings, this tumor is best considered a "squamoglandular variant of acinic cell carcinoma." Morphologic and clinical evidence argues against this representing a form of high-grade transformation. While overall bland, the differential diagnosis may include various basaloid tumors in the parotid gland, both primary and metastatic.

Chronic granulomatous inflammation occurs rarely alongside pleomorphic adenomas of the major salivary glands but would not appear to have been reported with lacrimal gland adenomas. We describe the clinical features, imaging and histopathology for 4 patients (3 female) who had granulomatous inflammation alongside lacrimal gland adenomas-the patients being with age 39, 44, 48, and 53 years at time of surgery. One patient had an asymptomatic lesion found on imaging, and the other 3 had symptoms for between 3 years and several decades. Conjecturally, this rare phenomenon might arise from an inflammatory response to leakage of secretions from the ductular components of the glands.

Background Secretory carcinoma of salivary glands (SCSGs) are generally low-grade salivary gland carcinomas, and are characterized by morphological resemblance to mammary analogue secretory carcinoma and ETV6–NTRK3 gene fusion. Several reports on histopathological features of SCSG have recently been published; however, little is known about the clinical characteristics of this new tumor, including its outcomes. The research is to investigate the clinicopathological characteristics of secretory carcinoma of major salivary glands and to analyze outcomes of these carcinomas as a reference for standardizing their diagnosis and treatment. Methods The cohort of this retrospective study comprised 23 patients treated for histopathologically-confirmed SCSG between January 2010 and December 2020. Their clinical characteristics and outcomes were retrieved from patient files. Results The 23 patients comprised 13 male and 10 female patients (male:female ratio 1.3:1). They were aged 10–69 years (median 45 years) and the average duration of disease was 2.44 years (0.25–20 years). Twenty-one patients (91.3%) had SCSGs in the parotid gland and two (8.7%) in the submandibular gland. All 23 patients had single nodules with diameters of 0.8–4.8 cm (average 2.6 cm). Five patients had lymph node metastases and two had distant metastases. All tumors were pathologically diagnosed as SCSGs. Immunohistochemical staining was strongly positive for S-100, mammaglobin, CK7, and Gata3, and negative for Dog1, P63 and calponin. Ki-67 positivity ranged from 1–50%. Fluorescence in situ hybridization data were available for 15 patients, in all of whom ETV6 gene rearrangement was confirmed. All patients had undergone oncological resections. Four had radioactive particles implanted postoperatively, one received chemotherapy, and seven underwent chemoradiotherapy. Six patients had regional recurrences, two distant metastases, and one had died at the time of last follow-up. Conclusions SCSGs are typically indolent with a low rate of locoregional recurrence and excellent survival. Their prognosis is correlated with clinical stage, pathological grade, and surgical procedures performed.

Objectives: Adenoid cystic carcinoma (ACC) is a commonly encountered salivary gland malignancy. However, it rarely occurs in the gingiva, an area generally thought to be devoid of minor salivary glands. We present a case occurring in this unusual site and review other reported cases. Methods: A 56 year-old male presented with a right-sided mandibular toothache for 1 year and underwent dental extraction. Due to persistent pain, follow up examination revealed a large gingival lesion. A biopsy was positive for adenoid cystic carcinoma. Results: The patient underwent a complete right segmental mandibulectomy and was reconstructed with a fibular osteocutaneous free flap. Three months postoperatively, during the planning for adjuvant radiation therapy, the patient developed pain in the left mandible. Imaging revealed extensive involvement of the left native mandible. Deep bone biopsies in several areas of the left mandible revealed ACC. He then underwent a complete left hemi-mandibulectomy and reconstruction with a fibular osteocutaneous free flap. Tensor fascia lata suspension slings were placed due to concern for an open mouth deformity attributable to disruption of bilateral masticator slings. He will undergo adjuvant radiation therapy. Our review of the literature revealed 50 cases of gingival ACC published since 1972. Disease recurrence and distant metastases were noted in several patients, occurring at the latest after 30 years follow-up. Conclusions: Given its indolent behavior, high proclivity for late recurrence and metastasis, and overall infrequency, ACC represents a pathology that requires early diagnosis and comprehensive long-term surveillance. While ACC is well described in oral cavity sites with high densities of minor salivary glands, it is not commonly seen in the gingiva. As such, gingival ACC may display a unique biological and/or clinical character. We offer the first literature review of this rare entity.

Background The aim of the present study was to establish a competing risk nomogram to predict parotid gland cancer-specific mortality (PGC-SM). Methods Seven thousand nine hundred and sixty-two patients extracted from SEER database were randomly categorized into training and validation sets. The competing risk model was used to identify factors associated with PGC-SM. The nomogram was evaluated via concordance indexes (C-indexes), calibration plots, and decision curve analysis (DCA). Results Male, elderly, white, widowed, larger tumor, no surgery, advanced tumor grade, lymph node (LN) metastasis, adenocarcinoma (ADC), and higher TNM stage were associated with higher incidence of PGC-SM. Calibration plots showed that the nomogram was well calibrated. C-indexes for nomogram were 0.84 (95% CI: 0.81-0.86) and 0.84 (95% CI: 0.82-0.86) in training and validation sets, respectively. DCA demonstrated the clinical usefulness of nomogram. Conclusions The competing risk nomogram shows high performance in predicting PGC-SM, which might enable clinicians formulate suitable treatment protocols for patients with parotid gland carcinoma (PGC).

Introduction Mammary analogue secretory carcinoma (MASC) is a recent discovered entity of salivary glands tumors, reported for first time in 2010. The presence of a translocation encodes the ETS variant transcription factor 6-neurotrophic tyrosine receptor kinase (ETV6-NTRK3) gene fusion differences MASC from other tumors. Case presentation A 68-year-old male showed a non-painful right parotid enlargement, came from dermatology service, and followed by some facial squamous cell carcinomas. A computed tomography (CT) scan showed a 1.7×1.6 cm right parotid enlargement in superficial lobe. The patient underwent a right superficial parotidectomy. The final pathology confirmed the presence of ETV6-NTRK3-positive MASC. Complete right deep parotidectomy and functional cervical emptying were performed. Discussions and conclusions It is necessary to establish an appropriated differential diagnosis between salivary gland tumors. MASC is a low-grade malignancy cancer that sometimes can evolve to a high-grade tumor that might produce local and distance dissemination. Most times, these tumors are only treated by surgical resection and evaluating by a multidisciplinary team the need of more treatments. In our case, the patient showed a primary parotid tumor, removed surgically with free edges, and being identified as MASC. We decided to underwent neck dissection and discovered a second MASC focus on cervical salivary gland; however, there was no nodal dissemination. The patient remains disease-free after 14 months from last surgery. It is important to keep studying genetic therapy targets to ETV6-NTRK3 to obtain a new therapy line to treat those cases that require.

This retrospective study aimed to investigate the radiological features of head and neck mammary analogue secretory carcinoma (MASC) and systematically review previous publications and 11 new cases. We included patients with pathologically proven MASCs with preoperative CT or MRI images, including 11 patients from our hospital and 29 patients from 28 publications extracted after screening 645 abstracts. Two board-certified radiologists reviewed and evaluated all radiological images. The frequency of metastasis during the follow-up period in tumors with well- and ill-defined margins was compared using a Fisher’s exact test. The median age at diagnosis was 52.5 years (range, 7–78 years; 20 males). Of the 40 patients, those in their 50 s were the most common (10/40, 25.0%), and the main tumor site was the parotid gland (27/40, 42.5%). Characteristic radiological features included high intensity on T1WI in the cystic components and tumors frequently showed “papillary and cystic,” which showed a projection into the cystic components, or “non-papillary and cystic” morphology, which did not show projection of the solid components. Tumor metastasis was found in 10/35 patients (28.6%) during the follow-up period, with a significant difference in frequency between the tumors with well- and ill-defined margin (well-defined (4/26) vs. ill-defined (6/9); P = 0.0074). MASCs are newly recognized malignant tumors. Characteristic T1WI high intensity on MRI and predominant cystic morphology may reflect its unique histological profile. Ill-defined tumor margin status was related to frequent metastasis. Awareness of these characteristic radiological features can assist radiologists in better detection of this novel entity.

Background: Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein that is overexpressed in the prostate gland and prostate cancer. PSMA has been recently used in positron emission tomography/computed tomography (PET/CT) imaging and targeted alpha-radiation therapy (TAT) for prostate cancer. Recently, the tubarial gland, a type of minor salivary gland that is described as a new organ situated in the pharynx, is reported to express PMSA. Here, we studied the expression of PSMA in common benign and malignant salivary gland tumors., Methods: We performed immunohistochemistry for PSMA in 55 salivary gland tumors comprising 10 pleomorphic adenomas, 10 Warthin tumors, 9 basal cell adenomas, 9 adenoid cystic carcinomas, 9 mucoepidermoid carcinomas, and 8 salivary duct carcinomas., Results: PSMA was expressed in 97% of benign tumors and 77% of malignant tumors. Moreover, PSMA was expressed in 59% of normal salivary glands adjacent to the tumor., Conclusions: PSMA is relatively expressed in salivary gland tumors and salivary glands. Therefore, salivary gland neoplasm, and normal salivary gland, possibly demonstrate the accumulation of PSMA in PET/CT. Thus, we need to monitor the side effects in the salivary glands during TAT for prostate cancer.

Introduction The cytopathology and diagnostic accuracy of salivary gland (SG) polymorphous adenocarcinoma (PAC) is the subject of a limited number of reports. We undertook a review of our experience with fine needle aspiration (FNA) biopsy and PAC. Materials and methods A search was made of our cytopathology files for PAC cases that also had histopathological confirmation. FNA biopsy smears and cell-blocks were performed and examined using standard techniques. Results Eight FNA biopsy cases of histologically proven PAC from 7 patients [F:M = 1.3:1, age 39-75 years, mean = 58] met study inclusion. Metastatic aspirates were most common (4), followed by 3 primary cases and 1 locally recurrent neoplasm. Primary FNA sites included hard palate (1 case), lip (1), and lateral tongue (1); all metastatic sites were in the neck. A precise cytologic diagnosis was made in 38% of cases; however, when applying the Milan classification system, 100% could be categorised as either malignant or of uncertain malignant potential. Ancillary immunohistochemical testing performed in 44% of the cases was non-specific. Cytologic smears showed cellular uniformity and structural variety of cell groups with tubular, branching, cribriform, and convex patterns as well as variable, but occasionally abundant globular myxoid stroma leading to confusion with adenoid cystic carcinoma. Conclusion The imitative cytopathology of PAC with other SG neoplasms as well as its infrequency in routine FNA biopsy practice makes specific interpretation difficult, but using a classification system allows for appropriate patient management. Molecular testing in future specimens holds promise for enhancing diagnostic accuracy.

Background Although largely readily recognizable in tissue sections, acinic cell carcinoma (ACC) remains diagnostically problematic in fine-needle aspiration (FNA) cytopathology. The authors undertook an analysis of a large series of ACC aspirates, including acinic cell carcinoma with high-grade transformation (ACC-HGT). Methods The authors searched their cytopathology files for ACC cases with histopathologic confirmation. FNA biopsy was performed according to standard techniques. Results Fifty FNA biopsy cases of ACC (including 36 of parotid origin [72%]) from 41 patients (female to male ratio, 1.4:1; age range, 23-84 years; average, 54 years) met the study inclusion requirements. Primary neoplasm aspirates were most common (72%), and they were followed by recurrent tumors (16%) and metastases (12%). A precise cytologic diagnosis was made for 64%. Three of 9 ACC-HGT cases (33%) were correctly interpreted as such; 98% of conventional ACC cases were correctly graded as low-grade. With the Milan classification system, 74% fit into the malignant category. Ancillary testing was performed for only 36%. Conventional ACC had moderately to highly cellular smears; monotonous cells in aggregates and single forms; rounded nuclei; and microvacuolated, finely granular, oncocyte-like, or nonspecific cytoplasm. ACC-HGT smears contained larger nuclei, high nuclear to cytoplasmic ratios, coarse nuclear chromatin, and a loss of cytoplasmic granules/vacuoles. Conclusions A correct diagnosis of ACC via FNA biopsy was made in almost two-thirds of the cases. With the Milan classification, 84% of the cases would have been classified as malignant or suspicious for malignancy. An absence of conventional serous acinar cell morphology in some cases as well as an absence of ancillary immunohistochemistry testing in almost two-thirds of the cases prevented even better diagnostic performance.

OBJECTIVE Rapid on-site evaluation (ROSE) is a fine needle aspiration (FNA) technique for ensuring sampling adequacy and triaging samples. The Milan system for reporting salivary gland cytopathology (MSRSGC) is a standardised reporting system which aims to improve risk stratification. There is scant literature on the diagnostic value and agreement of MSRSGC on ROSE with final cytological diagnosis in salivary gland FNAs. We aimed to assess the concordance of MSRSCG categorisation and diagnosis on ROSE with final cytological and histological diagnosis. METHODS This prospective study included consecutive salivary gland FNAs for which ROSE was performed over a six-month period. MSRSGC category and diagnosis on ROSE were compared with the final cytological diagnosis and MSRSGC category, and histopathological diagnosis, where available. RESULTS Sixty salivary gland aspirates were included. The adequacy rate with ROSE was 100%. Using the MSRSGC classification during ROSE, 26 (43.2%) samples were categorised as benign neoplasm, 21 (35%) as malignant neoplasm, 9 (15%) as non-neoplastic, and one each (1.7%) belonged to the remaining four categories. MSRSGC categorisation on ROSE concurred with final the cytological diagnosis in 58/60 cases (96.7%). Discrepancies in MSRSGC categories on ROSE included one atypia of undetermined significance with final report as non-neoplastic, and one non-diagnostic as suspicious for malignancy. Good correlation of MSRSGC categories on ROSE with final histopathological diagnosis (88.9% concordance) was also noted. CONCLUSIONS MSRSGC on ROSE shows good concordance with final cytology and histopathology diagnosis, indicating that categorisation according to MSRSGC has utility in ensuring that adequate material is obtained and triaged appropriately for the diagnosis of salivary gland aspirates.

Salivary gland neoplasms are uncommon, and most exhibit epithelial differentiation. Mesenchymal neoplasms of the salivary gland are rare, and the incidence ranges from 1.9% to 5%. The aim of this study is to identify the types and clinical-pathological features of mesenchymal salivary neoplasm and review their differential diagnosis. A retrospective search for mesenchymal neoplasms of salivary glands from our institution's pathology archives from the 2004–2021 period and consultation files of one of the authors (AER) was performed. The clinical data were obtained from available medical records, and the histological slides and ancillary studies were retrieved and reviewed. We identified a total of 68 cases that form the study cohort. Thirty-five patients were male, and thirty-three patients were female, with a mean age of 48 years (range, 7 months–79 years), and the male to female ratio was 1:.94. Sixty-three (92.6%) of sixty-eight tumors were benign and included: 38 (56%) lipomas, 9 (13%) hemangiomas, 7 (10.3%) schwannomas, 3 (4.4%) neurofibromas, 3 (4.4%) lymphangioma, 2 (3%) solitary fibrous tumors, 1 (1.5%) myofibroma. Five of sixty-eight (7.4%) were malignant and included: 3 (4.4%) Adamantinoma-like Ewing sarcomas, 1 (1.5%) malignant peripheral nerve sheath tumor (MPNST), and 1 (1.5%) malignant solitary fibrous tumor. The involved sites included: parotid (55), submandibular gland (5), parapharyngeal space (5), buccal mucosa minor salivary gland (2), and sublingual gland (1). Sixty-seven patients underwent surgical resection. One patient with lymphangioma manifested a recurrence/persistence a week post-surgery. One patient with a parotid hemangioma developed post-operative numbness, and another patient developed chronic postauricular pain after surgery. Two patients with MPNST and one patient with adamantinoma-like Ewing sarcoma underwent neoadjuvant chemoradiation and were disease-free after treatment. The remaining 37 patients with available follow-up ranging from 7 days to 96 months (mean, 18 months) had a favorable outcome and were disease-free after treatment. Mesenchymal neoplasms of salivary gland are rare; most are benign and demonstrate adipocytic, endothelial, and schwannian differentiation; awareness of their development is important for adequate diagnosis. The mainstay of treatment is surgical excision, with the extent determined by tumor type. Adjuvant therapy is reserved for high-grade sarcomas and may be given in a neoadjuvant or adjuvant setting.

Introduction Solitary fibrous tumor (SFT), a fibroblastic neoplasm characterized by a specific genetic alteration (NAB2-STAT6 fusion) and relatively specific immunohistochemical profile (STAT6/CD34 positivity), is seldom the subject of cytopathology data. We report our experience with scrape smears and fine-needle aspiration (FNA) biopsies of SFT in a large patient cohort. Materials and methods A search was made of our cytopathology and surgical pathology databases for cases diagnosed as solitary fibrous tumor (SFT). FNA biopsy smears, imprint smears, and cell blocks were performed and examined using standard technique. Results Thirty-four cases from 30 patients (M:F = 1.1:1; age range: 24-86 years, x = 58 years) met inclusion criteria for this study. All patients had prior or subsequent tissue confirmation of SFT. Twenty-seven (79%) specimens were FNAs, and 7 (21%) were scrape smears. Most cases (29, 85%) represented primary tumors, 4 (12%) were metastatic deposits, and 1 (3.5%) was a locally recurrent neoplasm. Sites included: pleura/lung 9 (26%), head/neck 8 (24%), lower extremity 7 (21%), trunk 4 (12%), intra-abdominal 3 (9%), upper extremity 2 (7%), and mediastinum 1 (4%). Mean tumor size was 7.2 cm (range: 1.5-19 cm). Three (9%) cases were diagnosed specifically as SFT. Remaining diagnoses were spindle cell neoplasm/proliferation 14 (41%), nondiagnostic 5 (15%), specific type of sarcoma 3 (9%), malignant round cell tumor 2 (6%), sarcoma 2 (6%), malignant tumor 2 (6%) and single cases of melanoma, pleomorphic adenoma, and mesenchymal tumor. Immunohistochemical (IHC) testing was performed in 7 of 27 (26%) cell blocks. Conclusion SFT FNA cytopathology is morphologically ambiguous, overlapping with a broad array of other spindle cell proliferations. A specific diagnosis is only possible with added staining of STAT6 coupled with a set of other IHC markers.

Salivary and mammary glands are both exocrine organs sharing multiple tumorigenic processes. To the best of our knowledge, salivary gland tumors mimicking invasive lobular carcinoma of the breast have not yet been described. Herein, we report a case of a 62-year-old male who presented with progressive facial paralysis. Pathologic examination revealed an ill-defined epithelial neoplasm exhibiting discohesive growth set within an extensively fibrotic stroma. Both perineural and intraneural invasion were present. E-cadherin and p120 immunostaining showed aberrant cytoplasmic expression. Targeted next-generation sequencing detected a frameshift mutation of the CTNNA1 gene as the only known pathogenic variant. The patient was treated with surgical resection, immunotherapy, and chemotherapy. Currently, he is alive with disease twenty months after disease onset.

Salivary gland cancers (SGCs) are rare malignancies with highly heterogeneous histological features. Patients affected with SGCs are at increased risk of secondary malignancies, including breast cancer (BC). Previous studies enlightened a possible link between SGCs and hereditary predisposition to BC. Here, we searched for SGC-affected patients in 1796 high-risk BC families recruited at the Genetic Unit of the Istituto Nazionale dei Tumori of Milan, 516 of which carried pathogenic variants in BRCA1 and/or BRCA2, the main genetic risk factors for BC. We detected five families with an individual affected with SGC, including two male patients, one carrying a constitutional mutation in BRCA1 and the other in BRCA2. Loss of heterozygosity of BRCA wild-type alleles was assessed in the patients' tumour DNA. We conclude that our observations support the hypothesis that genetic factors associated with BC susceptibility might play a role also in at least a subset of SGCs.

Mucoepidermoid carcinoma (MEC) is generally characterized by an admixture of mucous, epidermoid and intermediate type cells. Numerous variants morphologies are described and defined by stromal and/or cytoplasmic tinctorial characteristics. We now report 11 cases of MEC with serous acinar differentiation, reflecting a distal intercalated duct/acinar phenotype, which we designate as mucoacinar carcinomas. Seven patients were female while 4 were male with a mean age of 55 years (range: 21 to 72 y). Ten cases were from the parotid while 1 was from the submandibular gland. Mean size of the tumors was 1.8 cm (range: 0.7 to 4.5 cm). Three cases were low grade, 7 were intermediate grade, and 1 was high grade. Low to intermediate grade cases demonstrated prominent clear to vacuolated cells with focal serous acinar differentiation. The high-grade case showed a distinctive scattering of acinar cells interspersed between epidermoid cells. Periodic acid Schiff after diastase (9/9), SOX-10 (9/9), and DOG-1 (9/10) highlighted the acinar component. Six of 7 cases showed a focal acinar predominant NR4A3 expression. MAML2 fluorescence in situ hybridization was positive in all cases, in both acinar and mucoepidermoid components. Two cases tested by next generation sequencing showed standard CRTC1-MAML2 fusions. MSANTD3 and NR4A3 fluorescence in situ hybridization on the other hand were negative. Evidence thus suggests that mucoacinar carcinoma represents an acinar variant morphology in MEC, rather than a true MEC-acinic cell carcinoma hybrid, or collision tumor. The acinar differentiation, SOX-10, DOG-1, and even focal NR4A3 reactivity may thus be diagnostic pitfalls.

The activation of CXCL12/CXCR4 axis participated in the progression of multiple cancers, but potential effect in terms of perineural invasion (PNI) in SACC remained ambiguous. In this study, we identified that CXCL12 substantially expressed in nerve cells. CXCR4 strikingly expressed in tumour cells, and CXCR4 expression was closely associated with the level of EMT‐associated proteins and Schwann cell hallmarks at nerve invasion frontier in SACC. Activation of CXCL12/CXCR4 axis could promote PNI and up‐regulate relative genes of EMT and Schwann cell hallmarks both in vitro and in vivo, which could be inhibited by Twist silence. After overexpressing S100A4, the impaired PNI ability of SACC cells induced by Twist knockdown was significantly reversed, and pseudo foot was visualized frequently. Collectively, the results indicated that CXCL12/CXCR4 might promote PNI by provoking the tumour cell to differentiate towards Schwann‐like cell through Twist/S100A4 axis in SACC.

Microsecretory adenocarcinoma (MSA) is a recently described salivary gland tumor with a characteristic histologic and immunophenotypic profile and recurrent MEF2C-SS18 fusions. Because only six cases of MSA have been published, its complete clinicopathologic spectrum is unclear, and its biologic behavior has not been documented. Here, we present an updated and expanded experience of 24 MSA cases. All cases of MSA were obtained from the authors’ files. Immunohistochemistry for S100, SOX10, p63, p40, SMA, calponin, and mammaglobin was performed. Molecular analysis was performed by targeted RNA sequencing, SS18 break apart fluorescence in situ hybridization, and/or reverse transcriptase polymerase chain reaction for MEF2C-SS18 fusion. Clinical follow-up was obtained from medical records. A total of 24 MSA cases were collected, from 13 women and 11 men, ranging from 17 to 83 years (mean 49.5 years). The vast majority (23 of 24) arose in the oral cavity, with the palate (n = 14) and buccal mucosa (n = 6) as the most frequent subsites. Tumors showed consistent histologic features including: (1) microcystic tubules, (2) flattened intercalated duct-like cells, (3) monotonous oval hyperchromatic nuclei, (4) abundant basophilic luminal secretions, (5) fibromyxoid stroma, and (6) circumscribed borders with subtle infiltration. The tumors were very consistently positive for S100 (24 of 24), p63 (24 of 24), and SOX10 (14 of 14) and negative for p40 (0 of 21), calponin (0 of 12) and mammaglobin (0 of 16), while SMA (4 of 20) was variable. MEF2C-SS18 fusion was demonstrated in 21 of 24 cases; in the remaining 3 cases with insufficient RNA, SS18 break apart FISH was positive. Treatment information was available in 17 cases, all of which were managed with surgery only. In 14 cases with follow-up (1–216 months, mean 30), no cases recurred or metastasized. MSA is a distinct salivary gland neoplasm with remarkably consistent clinical, histologic, immunophenotypic, and genetic features that generally behaves in an indolent manner following surgery alone. These observations solidify MSA as a unique, low-grade salivary gland carcinoma that warrants inclusion in the next version of the WHO classification of head and neck tumors.

AIMS Secretory carcinoma (SC) is characterized by ETV6 rearrangements, most often ETV6-NTRK3 fusion. Given its histologic overlap with other salivary gland tumors (SGTs), SCs can be difficult to diagnose without genetic confirmation. A recently developed pan-TRK (tropomyosin receptor kinase) antibody shows promise for identifying tumors with NTRK (neurotrophic tyrosine kinase receptor 3) fusions. The aim of this study was to evaluate the utility of pan-TRK immunohistochemistry in distinguishing SCs from mimics and selecting patients eligible for TRK inhibitor clinical trials. We examined whole-tissue sections from 111 SGTs with molecular characterization, including 26 SCs (23 with ETV6-NTRK3 fusion and 3 with ETV6-RET fusion detected by ligation-dependent reverse transcription-polymerase chain reaction, next-generation sequencing and 85 non-SC SGTs (no ETV6-NTRK3 fusion). Immunohistochemistry was performed with a pan-TRK rabbit monoclonal antibody. When any pan-TRK staining (nuclear or cytoplasmic with any staining intensity) was considered to indicate positivity, 22 of 23 SCs with ETV6-NTRK3 fusion (95.7%) and 33 of 85 non-SC (38.8%) salivary neoplasms were positive, mainly basal cell adenoma, pleomorphic adenomas, adenoid cystic carcinomas, and epithelial-myoepithelial carcinomas. All SCs with ETV6-RET fusion were entirely negative. When only nuclear pan-TRK staining with any staining intensity was considered positive, 18 of 23 SCs with ETV6-NTRK3 fusion (78.3%) were positive, 11 among them with diffuse staining (>30% of cells). All non-SCs and SCs with ETV6-RET fusion were entirely negative. In comparison to molecular analysis (ligation-dependent reverse transcription-polymerase chain reaction, next-generation sequencing), nuclear pan-TRK IHC has a sensitivity of 78.3% and a specificity of 100% for diagnosing SCs with ETV6-NTRK3 fusion, 69% and 100% for SCs (all fusions). Pan-TRK is a reasonable screening test for diagnosing SCs among SGTs when taking only nuclear staining into account. Although pan-TRK expression is not entirely sensitive for SCs, nuclear staining is highly specific for SCs with ETV6-NTRK3 fusion. The lack of pan-TRK immunoreactivity in a subset of SCs is suggestive of atypical exons 4 to 14 or exons 5 to 14 ETV6-NTRK3 fusion or non-NTRK alternative fusion partners such as ETV6-RET. Pan-TRK staining can serve as a strong diagnostic marker to distinguish SC from it mimics and to select patients eligible for TRK inhibitor clinical trials.

Quantitative single-photon emission computed tomography/computed tomography (SPECT/CT) using Tc-99m pertechnetate aids in evaluating salivary gland function. However, gland segmentation and quantitation of gland uptake is challenging. We develop a salivary gland SPECT/CT with automated segmentation using a deep convolutional neural network (CNN). The protocol comprises SPECT/CT at 20 min, sialagogue stimulation, and SPECT at 40 min post-injection of Tc-99m pertechnetate (555 MBq). The 40-min SPECT was reconstructed using the 20-min CT after misregistration correction. Manual salivary gland segmentation for %injected dose (%ID) by human experts proved highly reproducible, but took 15 min per scan. An automatic salivary segmentation method was developed using a modified 3D U-Net for end-to-end learning from the human experts (n = 333). The automatic segmentation performed comparably with human experts in voxel-wise comparison (mean Dice similarity coefficient of 0.81 for parotid and 0.79 for submandibular, respectively) and gland %ID correlation (R2 = 0.93 parotid, R2 = 0.95 submandibular) with an operating time less than 1 min. The algorithm generated results that were comparable to the reference data. In conclusion, with the aid of a CNN, we developed a quantitative salivary gland SPECT/CT protocol feasible for clinical applications. The method saves analysis time and manual effort while reducing patients’ radiation exposure.

Basaloid squamous cell carcinoma (BSCC) is an aggressive type of squamous cell carcinoma (SCC) predominant in the upper aerodigestive tract. To our knowledge, only one case of that tumor has been previously described in the parotid gland. Shadow (ghost) cell differentiation (SCD) is a specialized form of keratinization characteristic of pilomatricoma, and other skin tumors with follicular differentiation. SCD has also been described infrequently in some visceral carcinomas and rarely in the minor salivary glands. Recently, an SCC with prominent SCD has been reported in the parotid. We report for the first time the case of parotid BSCC with prominent SCD in an 87-year-old man. He was admitted due to the appearance in the last few months of a mass, painful on palpation, in the left parotid region. Imaging studies and tru-cut biopsies indicated the need for surgical removal. A left superficial parotidectomy, including the branch of the cervicofacial nerve, was performed. The BSCC showed predominance (62%) of SCD. Immunohistochemically, the basaloid cells were positive for β-catenin, pan-cytokeratin (pan-CK) AE1∕AE3, CK19, high-molecular-weight CK (HMWCK), p63, p40, and cluster of differentiation 10 (CD10) in a diffuse pattern. No signs of recurrence or metastasis were observed four months after surgery. The main differential diagnoses include nuclear protein in testis (NUT) carcinoma, adamantinoma-like Ewing sarcoma, embryonal carcinoma, and basal cell adenocarcinoma of the solid type. SCD in BSCC of the parotid should be recognized to avoid misdiagnosis, especially in small samples. Although rare, BSCC with SCD should be added to the list of tumors that may originate in the parotid gland.

Purpose: The review of indications for surgical treatment of major salivary glands in adults hospitalized in the Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Warsaw. Materials and methods: The retrospective analysis was based on the 1173 postoperative histopathological examinations of the salivary glands collected over a period of 10 years (2010-2020). Analysis included histopathological diagnosis, localization of lesions, multifocality, complete resection, lymph node involvement, as well as demographical data of sex and age. Results: Over half (61.38%) of all indications for surgical treatment of the salivary glands were benign tumors (n = 720) with the most common pleomorphic adenoma, which accounted for 33.5% of all cases (n = 393). The next most frequent group of diagnoses were non-neoplastic diseases of the salivary glands, 24.98% of all cases (n = 293). Malignant neoplasms of the salivary glands accounted for 13.64% of all diagnoses (n = 160). Salivary gland diseases slightly predominated among the female sex, with a particularly pronounced predominance in pleomorphic adenoma. Men, on the other hand, were treated more often for malignant neoplasms. The mean age of the patients was the lowest in the group of non-neoplastic diseases of the salivary glands. The mean age of patients with malignant neoplasms was significantly higher than in other pathologies. The largest tumors size was identified for malignant neoplasms. Diseases of the salivary glands treated surgically were most often located in the parotid gland, with the exception of non-neoplastic diseases, which most often involved the submandibular gland. Conclusions: Surgical management in pathologies of the salivary glands applies to all types of lesions, both neoplastic and non-neoplastic diseases. Patients with particular diseases are characterized by a different structure of age, sex and location of changes.

PURPOSE The current American Joint Cancer Committee (AJCC) staging system for salivary gland tumors does not include histology and grade in its classification despite their proven prognostic importance. We planned to analyze if a modified staging system integrating these two factors into the staging improves prognostic performance and then validate it externally. MATERIALS AND METHODS From SEER database (2000-2018), patients with major salivary gland carcinoma who underwent surgical resection between 2004 and 2015 were analyzed. Histologies were recoded into two groups based on grade and type of histology into “Low Aggression” and “High aggression” groups. Cox proportional hazards model was used to identify predictor variables for overall survival and disease-specific survival and models were generated based on least absolute shrinkage and selection operator regression. Model performance was evaluated by Akaike Information Criterion, concordance index and calibration plot. The best model chosen was externally validated from our hospital database of patients who underwent surgery for salivary gland tumor between January 1, 2012 to December 31, 2019. RESULTS Six thousand two hundred forty-six patients were analyzed with a median follow up of 58 months. Age > 65 years, male sex, metastatic disease, Histological Stratification, Grade of tumor, AJCC stage and Primary Site were the significant factors influencing overall survival and disease-specific survival. By least absolute shrinkage and selection operator regression method, Correlation analysis and Interaction testing by multiple regression, AJCC stage and Histological Risk stratification were used for generating four models, out of which the best model was selected by Akaike Information Criterion, C index and calibration plot. This model was then externally validated in our hospital database of 269 patients. CONCLUSION We propose an externally validated modified salivary gland staging system that incorporates histology and grade of tumor for improved hazard discrimination among patient subgroups.

AIMS: Salivary gland intraductal carcinoma (IDC) is a complex ductal neoplasm surrounded by a layer of myoepithelial cells. Recent insights have shown that there are three different types: intercalated duct-like, with frequent NCOA4–RET fusions; apocrine, with salivary duct carcinoma-like mutations; and mixed intercalated duct-like/apocrine, with RET fusions, including TRIM27–RET. In addition, an oncocytic IDC has been described, but it remains unclear whether it represents a fourth variant or simply oncocytic metaplasia of another IDC type. Our aim was to more completely characterize oncocytic IDC. METHODS AND RESULTS: Six IDCs with oncocytic changes were retrieved from the authors’ archives, from three men and three women ranging in age from 45 to 75 years (mean, 63 years). Five arose in the parotid gland, with one in an accessory parotid gland. Four patients with follow-up were free of disease after 1–23 months. Several immunostains (S100, mammaglobin, androgen receptor, and p63/p40) and molecular tools (RNA sequencing, RET fluorescence in-situ hybridisation, BRAF V600E VE1 immunohistochemistry, and Sanger sequencing) were applied. Histologically, the tumours were variably cystic with solid intracystic nodules often difficult to recognise as intraductal. In all, tumour ducts were positive for S100 and mammaglobin, negative for androgen receptor, and completely surrounded by myoepithelial cells positive for p63/p40. Molecular analysis revealed TRIM33–RET in two of six cases, NCOA4–RET in one of six cases, and BRAF V600E in two of six cases. One case had no identifiable alterations. CONCLUSIONS: Oncocytic IDC shares similarities with intercalated duct-like IDC. Although additional verification is needed, the oncocytic variant appears to be sufficiently unique to be now regarded as the fourth distinct subtype of IDC. Because of its indolent nature, oncocytic IDC should be distinguished from histological mimics.