Acinic Cell Carcinoma Research Articles

Parapharyngeal Acinic Cell Carcinoma: A Case Report of a Rare Extra-Parotid Occurrence

Parapharyngeal space (PPS) tumors are among the most challenging tumors of the head and neck region to diagnose and treat. Acinic cell carcinoma (ACC) is an extremely rare extra-parotid malignant neoplasm of the PPS. Herewith, we report a case of extra-parotid, low-grade solid pattern ACC diagnosed in a 55-year-old male who presented with a left parapharyngeal bulge. Despite its rare occurrence, ACC of the PPS should be included in the differential diagnosis of PPS tumors.

Germline BRCA2 Mutations Are Prevalent in Pancreatic Acinar Cell Carcinoma.

Pancreatic acinar cell carcinoma (PACC) has a high prevalence of BRCA2 germline pathogenic variants.

A resected case of acinar cell carcinoma of the pancreas with liver metastasis following chemotherapy using modified FOLFIRINOX

BackgroundAcinar cell carcinoma of the pancreas is a rare exocrine malignancy representing less than 1% of all pancreatic neoplasms. It has been reported that it responds to treatment differently from pancreatic ductal adenocarcinoma and the treatment algorithm for acinar cell carcinoma usually depends on the stage of the respective tumor and the patient’s current status.Case presentationA 60-year-old man presented with upper abdominal pain and anorexia. Abdominal ultrasonography showed a large-sized hepatic mass and he was referred to our hospital. Contrast-enhanced computed tomography demonstrated a 110-mm low-density area occupying the right hemi-liver and an enhanced mass of 70 × 56 mm in the tail of the pancreas, which seemed to directly infiltrate into the spleen. The case was diagnosed as acinar cell carcinoma with a simultaneous liver metastasis identified by liver biopsy. Upfront resection of pancreatic cancer with distant metastasis might not be considered as an optimal choice, and in this case chemotherapy was administered prior to curative resection. Chemotherapy using the modified FOLFIRINOX regimen was undertaken, resulting in a partial remission; the liver tumor reduced in size from 110 to 47 mm and the pancreatic tumor from 70 to 40 mm. The patient then safely underwent curative hepatic resection with distal pancreato-splenectomy. Histological examinations revealed small-sized atypical cells with large nuclei that had formed acinar patterns, and immunostaining with trypsin was positive in tumor cells, which was in accordance with acinar cell carcinoma. More than 3 years later, the patient is doing well without any recurrence.ConclusionAggressive and curative surgery in combination with chemotherapy such as FOLFIRINOX could be a treatment option to achieve long-term survival in cases of acinar cell carcinoma with liver metastases.

Genomic Profiling Reveals Germline Predisposition and Homologous Recombination Deficiency in Pancreatic Acinar Cell Carcinoma.

To determine the genetic predisposition underlying pancreatic acinar cell carcinoma (PACC) and characterize its genomic features. Both somatic and germline analyses were performed using an Food and Drug Administration-authorized matched tumor/normal sequencing assay on a clinical cohort of 28,780 patients with cancer, 49 of whom were diagnosed with PACC. For a subset of PACCs, whole-genome sequencing (WGS; n = 12) and RNA sequencing (n = 6) were performed. Eighteen of 49 (36.7%) PACCs harbored germline pathogenic variants in homologous recombination (HR) and DNA damage response (DDR) genes, including BRCA1 (n = 1), BRCA2 (n = 12), PALB2 (n = 2), ATM (n = 2), and CHEK2 (n = 1). Thirty-one PACCs displayed pure, and 18 PACCs harbored mixed acinar cell histology. Fifteen of 31 (48%) pure PACCs harbored a germline pathogenic variant affecting HR-/DDR-related genes. BRCA2 germline pathogenic variants (11 of 31, 35%) were significantly more frequent in pure PACCs than in pancreatic adenocarcinoma (86 of 2,739, 3.1%; P < .001), high-grade serous ovarian carcinoma (67 of 1,318, 5.1%; P < .001), prostate cancer (116 of 3,401, 3.4%; P < .001), and breast cancer (79 of 3,196, 2.5%; P < .001). Genomic features of HR deficiency (HRD) were detected in 7 of 12 PACCs undergoing WGS, including 100% (n = 6) of PACCs with germline HR-related pathogenic mutations and 1 of 6 PACCs lacking known pathogenic alterations in HR-related genes. Exploratory analyses revealed that in PACCs, the repertoire of somatic driver genetic alterations and the load of neoantigens with high binding affinity varied according to the presence of germline pathogenic alterations affecting HR-/DDR-related genes and/or HRD. In a large pan-cancer cohort, PACC was identified as the cancer type with the highest prevalence of both BRCA2 germline pathogenic variants and genomic features of HRD, suggesting that PACC should be considered as part of the spectrum of BRCA-related malignancies.

Rare Solid Pancreatic Lesions on Cross-Sectional Imaging.

Several solid lesions can be found within the pancreas mainly arising from the exocrine and endocrine pancreatic tissue. Among all pancreatic malignancies, the most common subtype is pancreatic ductal adenocarcinoma (PDAC), to a point that pancreatic cancer and PDAC are used interchangeably. But, in addition to PDAC, and to the other most common and well-known solid lesions, either related to benign conditions, such as pancreatitis, or not so benign, such as pancreatic neuroendocrine neoplasms (pNENs), there are solid pancreatic lesions considered rare due to their low incidence. These lesions may originate from a cell line with a differentiation other than exocrine/endocrine, such as from the nerve sheath as for pancreatic schwannoma or from mesenchymal cells as for solitary fibrous tumour. These rare solid pancreatic lesions may show a behaviour that ranges in a benign to highly aggressive malignant spectrum. This review includes cases of an intrapancreatic accessory spleen, pancreatic tuberculosis, solid serous cystadenoma, solid pseudopapillary tumour, pancreatic schwannoma, purely intraductal neuroendocrine tumour, pancreatic fibrous solitary tumour, acinar cell carcinoma, undifferentiated carcinoma with osteoclastic-like giant cells, adenosquamous carcinoma, colloid carcinoma of the pancreas, primary leiomyosarcoma of the pancreas, primary and secondary pancreatic lymphoma and metastases within the pancreas. Therefore, it is important to determine the correct diagnosis to ensure optimal patient management. Because of their rarity, their existence is less well known and, when depicted, in most cases incidentally, the correct diagnosis remains challenging. However, there are some typical imaging features present on cross-sectional imaging modalities that, taken into account with the clinical and biological context, contribute substantially to achieve the correct diagnosis.

Diagnostic Utility of Expression Pattern of S100/Mammaglobin/SOX10/DOG 1 Immunohistochemistry in Differentiation of Secretory and Acinic Cell Carcinoma: A Systematic Review and Meta-Analysis.

Secretory carcinoma (SC) is a relatively new disease entity, separate from acinic cell carcinoma (AciCC), which frequently displays ETV6-NTRK3 gene fusion. However, the differences between SC and AciCC remain ambiguous. Genetic diversity makes its diagnosis complicated. In this regard combined expression of immunohistochemistry markers S100/Mammaglobin/SOX10 and DOG1 is need of the hour as alternative methodology. The current systematic review was to investigate the diagnostic utility of combined immunohistochemical expression of S100/Mammaglobin/SOX10/DOG1 in distinction of SC from AciCC histologically. An electronic search of databases was carried out using MEDLINE by PubMed, Google scholar, Scopus and Web of science. Articles inclusive of SC and AciCC were assessed with S100/Mammaglobin/SOX10/DOG1 immunohistochemistry and their predominant expression pattern, predictive values, sensitivity and specificity were gathered. Fourteen eligible articles were analysed, which revealed predominant immunostaining pattern of S100 + /Mammaglobin + /SOX10 + /DOG1- by nearly all ETV6::NTRK3 fusion prevalent SCs alongside with other gene fusions like RET, MET and MAML3 with 98.4% sensitivity as well as 86.1% specificity. The evidence supports that S100/Mammaglobin/SOX10/DOG1 combined immunostaining can serve as a reliable diagnostic method to differentiate secretory from acinic cell carcinoma.

TRPS1 immunohistochemical expression in salivary gland tumors: A pilot study.

TRPS1 is a new, sensitive marker for breast carcinoma (BC). Salivary glands and breasts are both exocrine glands; thus, their tumors may share similar morphology and immunophenotype. Among salivary gland-type BC, TRPS1 is reported to be positive in secretory carcinomas (SCs) but negative in acinic cell carcinomas (AciCCs) and most adenoid cystic carcinomas (AdCCs). A subset of salivary duct carcinomas (SDCs) is positive for TRPS1. Herein, we investigate TRPS1 immunohistochemical expression in salivary gland tumors (SGTs). A retrospective search yielded 110 SGTs (97 primary and 13 metastatic). TRPS1 immunohistochemistry was scored as negative, low positive, intermediate positive, or strongly positive. TRPS1 was expressed in 78% (14/18) of pleomorphic adenoma (PA) cases but negative/low positive in all Warthin tumors (6/6 [100%]). In basal cell adenoma (BCA), TRPS1 expression was intermediate to strong (13/14 [92%]) in the stromal cells, whereas ductal or basal cells showed low expression. TRPS1 expression varied in malignant SGTs, with intermediate to strong staining in 100% (15/15) of AdCCs, 100% (5/5) of basal cell adenocarcinoma, 100% (3/3) of intraductal carcinoma, 89% (8/9) of polymorphous adenocarcinoma, and 89% (7/8) of SDCs; negative/low positive expression was observed in 100% (3/3) of SCs, 89% (8/9) of AciCCs, and 50% (3/3) of mucoepidermoid carcinomas. In addition, strong and intermediate TRPS1 expression was observed in metastatic SGT to the lungs, lymph nodes, and soft tissue. Overall, TRPS1 is strongly expressed in PA as well as malignant and metastatic SGT. In addition, TRPS1 is positive in stromal cells of BCA but negative or low positive in ductal and basal cells.

APPLICATION OF ENDOSCOPIC ULTRASOUND GUIDED FNAC(EUS-FNAC) IN DIAGNOSING PANCREATIC MASS LESIONS

Introduction: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNAC) has become an important modality for identification of pancreatic masses. It is a minimally invasive procedure that provides excellent cell yield even in deep seated lesions. The preoperative diagnosis of pancreatic mass by EUS-FNAC can help the surgeons in early detection and confirmation of neoplasm as pancreatic mass lesions are highly concerning for pancreatic carcinoma. This study was aimed at application of EUS-FNAC in diagnosing pancreatic mass lesions. Methods: A study was conducted for 20 cases who underwent EUS guided FNAC for pancreatic mass lesions. EUS-FNAC was performed by using a curvilinear array echo endoscope. The technique was carried out by a skilled endoscopist, and the glass slides were used to make smears from fluid that was aspirated containing corpuscular fractions. The slides were air dried before being examined cytopathologically. Results: Out of 20 cases,10 were of pancreatic Ductal adenocarcinoma, 3 of Neuroendocrine tumor of pancreas, 2 of Acinar cell carcinoma, 1 of Solid pseudopapillary tumor, 2 of Serous cystadenoma and 2 of Mucinous cystadenoma. This was confirmed later, on further Immunocytochemical stains. Conclusions:Out of 20 cases, 16 were malignant and 4 were benign. EUS-FNAC can help in early diagnosis and can improve the patient outcome. It is safe, cost-effective and reliable. It not only gives precise cytological diagnosis, but it also allows for the exact site of tiny lesions.

Treatment characteristics and outcomes of pure Acinar cell carcinoma of the pancreas – A multicentric European study on radically resected patients

BackgroundAcinar cell carcinomas (ACC) belong to the exocrine pancreatic malignancies. Due to their rarity, there is no consensus regarding treatment strategies for resectable ACC. MethodsThis is a retrospective multicentric study of radically resected pure pancreatic ACC. Primary endpoints were overall survival (OS) and disease-free survival (DFS). Further endpoints were oncologic outcomes related to tumor stage and therapeutic protocols. Results59 patients (44 men) with a median age of 64 years were included. The median tumor size was 45.0 mm. 61.0% were pT3 (n = 36), nodal positivity rate was 37.3% (n = 22), and synchronous distant metastases were present in 10.1% of the patients (n = 6). 5-Years OS was 60.9% and median DFS 30 months. 24 out of 31 recurred systemically (n = 18 only systemic, n = 6 local and systemic). Regarding TNM-staging, only the N2-stage negatively influenced OS and DFS (p = 0.004, p = 0.001). Adjuvant treatment protocols (performed in 62.7%) did neither improve OS (p = 0.542) nor DFS (p = 0.159). In 9 cases, radical resection was achieved following neoadjuvant therapy. DiscussionRadical surgery is currently the mainstay for resectable ACC, even for limited metastatic disease. Novel (neo)adjuvant treatment strategies are needed, since current systemic therapies do not result in a clear survival benefit in the perioperative setting.

Cytomorphologic, immunophenotypical and molecular features of pancreatic acinar cell carcinoma.

As a rare tumor in pancreas, pancreatic acinar cell carcinoma (PACC) possesses a distinct molecular feature from pancreatic ductal carcinoma (PDAC). Though the diagnosis of PACC is often established based on cytology specimens, its cytologic diagnosis can be challenging. Furthermore, the correlation between PACC cytomorphology and its unique different molecular alterations have not been fully explored. Cytology features were analyzed in 8 histologically proven PACC and cytohistological correlation was performed. Immunocytochemistry for trypsin, chymotrypsin, BCL10, synaptophysin, chromogranin A, INSM1, β-catenin, and Ki-67 was assessed. Comprehensive molecular profiling and additional targetable treatment biomarker assessment were also performed. The cohort included 4 mixed acinar-neuroendocrine carcinomas, 3 pure PACCs, and 1 mixed acinar-ductal carcinoma. Immunophenotypical features are consistent with diagnoses of PACC or PACC with neuroendocrine features. Identified genetic alterations included somatic mutations of CTNNB1, TP53, MAP2K1, PTEN, RAC1, germline mutations of NBN and BRAC2, and gene fusion of CCDC6-RET. The current study is the first attempt to explore the correlation between the cytomorphology characteristics and molecular features of PACC and a few intriguing findings were observed. Further validation in larger cohorts is warranted.

PhD Project: Predictive and Functional Evaluation of Patients Derived Tumor Spheroids and Organoids-Investigating the Relationship between Size and Testing Performance

PhD Project: Predictive and Functional Evaluation of Patients Derived Tumor Spheroids and Organoids-Investigating the Relationship between Size and Testing Performance

The protective role of postoperative radiation therapy in low and intermediate grade major salivary gland malignancies: A study of the Canadian Head and Neck Collaborative Research Initiative.

The objective of this study was to examine the utility of postoperative radiation for low and intermediate grade cancers of the parotid and submandibular glands. The authors conducted a retrospective, Canadian-led, international, multi-institutional analysis of a patient cohort with low or intermediate grade salivary gland cancer of the parotid or submandibular gland who were treated from 2010 until 2020 with or without postoperative radiation therapy. A multivariable, marginal Cox proportional hazards regression analysis was performed to quantify the association between locoregional recurrence (LRR) and receipt of postoperative radiation therapy while accounting for patient-level factors and the clustering of patients by institution. In total, 621 patients across 14 tertiary care centers were included in the study; of these, 309 patients (49.8%) received postoperative radiation therapy. Tumor histologies included 182 (29.3%) acinic cell carcinomas, 312 (50.2%) mucoepidermoid carcinomas, and 137 (20.5%) other low or intermediate grade primary salivary gland carcinomas. Kaplan-Meier LRR-free survival at 10years was 89.0% (95% confidence interval [CI], 84.9%-93.3%). In multivariable Cox regression analysis, postoperative radiation therapy was independently associated with a lower hazard of LRR (adjusted hazard ratio, 0.53; 95% CI, 0.29-0.97). The multivariable model estimated that the marginal probability of LRR within 10years was 15.4% without radiation and 8.8% with radiation. The number needed to treat was 16 patients (95% CI, 14-18 patients). Radiation therapy had no benefit in patients who had early stage, low-grade salivary gland cancer without evidence of nodal disease and negative margins. Postoperative radiation therapy may reduce LLR in some low and intermediate grade salivary gland cancers with adverse features, but it had no benefit in patients who had early stage, low-grade salivary gland cancer with negative margins.

New treatment insights into pancreatic acinar cell carcinoma: case report and literature review.

Pancreatic acinar cell carcinoma (PACC) is a rare pancreatic malignancy with unique clinical, molecular, and morphologic features. The long-term survival of patients with PACC is substantially better than that of patients with ductal adenocarcinoma of the pancreas. Surgical resection is considered the first choice for treatment; however, there is no standard treatment option for patients with inoperable disease. The patient with metastatic PACC reported herein survived for more than 5 years with various treatments including chemotherapy, radiotherapy, antiangiogenic therapy and combined immunotherapy.

CELA3B immunostaining is a highly specific marker for acinar cell carcinoma of the pancreas.

Chymotrypsin-like elastase family member 3B (CELA3B, elastase-3B) is a pancreatic enzyme with digestive function in the intestine. Since RNA analyses of normal tissues suggest that CELA3B expression is limited to the pancreas, the potential diagnostic utility of CELA3B immunohistochemistry for the distinction of pancreatic from extrapancreatic cancers and in the distinction of acinar cell carcinoma from ductal adenocarcinoma was assessed. CELA3B expression was successfully analyzed in 13,223 tumor samples from 132 different tumor types and subtypes as well as 8 samples each of 76 different normal tissue types by immunohistochemistry in a tissue microarray format (TMA). In normal tissues, CELA3B immunostaining was only seen in acinar cells and in a fraction of ductal cells of the pancreas as well as on some apical membranes of surface epithelial cells of the intestine. Among tumors, CELA3B immunostaining was seen in 12 of 16 (75%) acinar cell carcinoma of the pancreas including 6 cases with strong staining (37.5%) as well as in 5 of 13,207 other tumors (0.04%). These included 1.2% of 91 adenoid cystic carcinomas, 1.2% of 246 mucoepidermoid carcinomas and 0.8% of 127 acinic cell carcinomas of salivary glands. Our data show a good sensitivity (75%) and a high specificity (99.9%) of CELA3B immunohistochemistry for diagnosing acinar cell carcinoma of the pancreas.

Acinic Cell Carcinoma in the 21st Century: A Population-Based Study from the SEER Database and Review of Recent Molecular Genetic Advances

Background: Acinic cell carcinoma (AciCC) comprises 6–7% of all salivary gland neoplasms and is the second most common salivary gland malignancy in children. Like many salivary gland carcinomas, it is considered low grade but occasionally it behaves aggressively. Understanding the risk factors associated with recurrence, metastasis, and death is important to determine the counseling and management of individual patients. Older population-based studies are presumed to have been confounded by the misclassification of other neoplasms as AciCC, in particular secretory carcinoma and cystadenocarcinoma. Since diagnostic tools to reliably separate these entities have been available for over a decade, reevaluation of epidemiologic data limited to the 21st century should allow a better characterization of the clinicopathological characteristics of AciCC. Methods: Our study extracted data from the Surveillance, Epidemiology, and End Results (SEER) database for the period 2000 to 2018. Cox regression model analysis was performed to identify risk factors independently affecting survival. Results: Data for 2226 patients with AciCC were extracted from the database. Most patients were females: 59%, and white: 80.5%, with a mean age at diagnosis of 51.2 (SD ± 18.7) years. Most cases (81%) were localized at presentation. Tumor size was less than 2 cm in 42%, 2–4 cm in 47%, and &gt;4 cm in 11%. Low-grade tumors had 5-year survival &gt; 90%, whereas high-grade tumors had survival &lt; 50%. Of the patients with known lymph node status only 7.3% had nodal metastases. Distant metastases were documented in 1.1%, involving lungs 44%, bone 40%, liver 12%, and brain 4%. The most common treatment modality was surgery alone: 63.6% followed by surgery and adjuvant radiation: 33%. A few received chemotherapy (1.8%) or multimodality therapy (1.2%). The 5-year overall survival rate was 90.6% (95%CI 89.1–91.9), and disease-specific survival was 94.6% (95%CI 93.3–95.6). Multivariable cox regression analysis showed that undifferentiated (HR = 8.3) and poorly differentiated tumor grade (HR = 6.4), and metastasis (HR = 5.3) were the worst independent prognostic factors. Other poor risk factors included age &gt; 50 (HR = 3.5) and tumor size &gt; 4 cm (HR = 2.5). Conclusions: In the US, AciCC is more common in middle age white females, and most tumors are less than 4 cm and localized at diagnosis. The most relevant negative prognostic factor was high tumor grade which was associated with higher hazard ratios for death than all other variables, including regional or distant metastases at presentation.

Comparative impact of grade on mortality across salivary cancers: A novel, unifying staging system.

The comparative impact of histologic variants and grade has not been well described. Salivary cancer histologies were profiled using hospital and population-based cancer registries. Multivariable models were employed to assess relationships between histology, grade, and survival. On univariate analysis, histologic variants exhibited a wide spectrum of mortality risk (5-year overall survival (OS): 86% (acinic cell carcinoma), 78% (mucoepidermoid carcinoma), 72% (adenoid cystic carcinoma), 64% (carcinoma ex-pleomorphic adenoma), 52% (adenocarcinoma NOS), and 47% (salivary duct carcinoma) (p < 0.001). However, on multivariable analysis these differences largely vanished. Worsening grade corresponded with deteriorating survival (5-year OS: 89% [low-grade], 81% [intermediate-grade], 45% [high-grade]; p < 0.001), which was upheld on multivariable analysis and propensity score matching. Recursive partitioning analysis generated TNM + G schema (c-index 0.75) superior to the existing system (c-index 0.73). Grade represents a primary determinant of salivary cancer prognosis. Integrating grade into stage strengthens current staging systems.

Role of Adjuvant Radiotherapy in Acinic Cell Carcinoma of the Salivary Glands: A Systematic Review

A systematic review was carried out to evaluate if adjuvant radiotherapy for acinic cell carcinomas (ACCs) of salivary glands improves survival. Twelve retrospective studies published between 2000 and 2020 that analysed the effect of radiotherapy on salivary gland neoplasms and ACCs of salivary glands and met the inclusion criteria were included in the review. The overall quality of the studies was moderate to low. There was no high-quality evidence for improved survival with radiotherapy for ACCs of the salivary gland. Some evidence suggests that there may be an advantage for patients with high-grade tumours, but these data should be interpreted with caution due to the small number of patients and low-quality evidence. Good quality of evidence is lacking. Recommendation for adjuvant radiotherapy for tumours with poor prognostic factors will require discussion and shared decision-making with the patients.

SERIES OF 62 CASES OF ACINIC CELL CARCINOMA IN THE ORAL AND MAXILLOFACIAL REGION

Objective This study aimed to integrate the clinicopathological and prognostic features of acinic cell carcinoma (AciCC) of the oral and maxillofacial regions. Study Design AciCC cases were retrospectively retrieved from 7 pathology centers of three different countries. Results Of a total of 62 cases, females (69.35%) were more affected, with a mean age of 45.96 years. The parotid gland (79.03%) was more involved with an asymptomatic (61.90%) nodule (52.63%). AciCC has four main histopathological patterns - solid, papillary-cystic, microcystic, and follicular - but the association of two patterns was the most common feature (51.28%), with a conventional histological grade (86.66%). Surgical resection (60.00%) was the main treatment choice. Only three cases recurred, while six reported some metastatic lesion. The mean follow-up time was 63.05 months and 2 patients died from the disease. Conclusion Although AciCC lesions have an indolent course in the majority of cases, high histopathological transformation, the presence of nodal metastasis, and recurrence were prognostic factors for AciCC of the oral and maxillofacial region. This study aimed to integrate the clinicopathological and prognostic features of acinic cell carcinoma (AciCC) of the oral and maxillofacial regions. AciCC cases were retrospectively retrieved from 7 pathology centers of three different countries. Of a total of 62 cases, females (69.35%) were more affected, with a mean age of 45.96 years. The parotid gland (79.03%) was more involved with an asymptomatic (61.90%) nodule (52.63%). AciCC has four main histopathological patterns - solid, papillary-cystic, microcystic, and follicular - but the association of two patterns was the most common feature (51.28%), with a conventional histological grade (86.66%). Surgical resection (60.00%) was the main treatment choice. Only three cases recurred, while six reported some metastatic lesion. The mean follow-up time was 63.05 months and 2 patients died from the disease. Although AciCC lesions have an indolent course in the majority of cases, high histopathological transformation, the presence of nodal metastasis, and recurrence were prognostic factors for AciCC of the oral and maxillofacial region.

Pediatric primary salivary gland tumors

ObjectivesTo characterize the presentation and treatment of children presenting with primary salivary gland neoplasms. MethodsA retrospective review of primary salivary tumor patients presenting to Children's Hospital Colorado between January 2000 and August 2020. ResultsFifty children were identified with primary salivary gland tumors, comprising of 39 (78 %) benign and 11 (22 %) malignant lesions. Pleomorphic adenoma was the most common benign tumor (36/39, 92 %), while acinic cell carcinoma was the most common malignancy (7/11, 64 %). The parotid gland was the most common site, followed by the submandibular gland (66 % vs. 34 %). No tumors were found in the sublingual glands. Benign neoplasms accounted for 70 % of parotid lesions and 94 % of submandibular tumors. No significant differences in age (13.6 years, SD 4 vs. 13.0 years, SD 4.3) were noted between patients with benign and malignant disease, but tumors in females were more frequently malignant (M:F 1:1.3 vs. 1:2.7 for benign and malignant tumors, respectively). Neck dissection and/or facial nerve sacrifice were required in 27 % (3/11) and 9.1 % (1/11) of malignancies, respectively. Local recurrence was observed in 7.7 % (3/39) of benign cases and 9.1 % (1/11) of malignant cases. No salivary malignancies required chemotherapy, though one patient with neurofibromatosis received imatinib prior to resection. Two patients with locoregional malignancy received adjunctive radiation. The average duration of follow up for benign and malignant disease were 12.6 ± 25 and 45.1 ± 32 months, respectively. ConclusionsThis study presents one of the larger single institutional experiences of pediatric primary salivary neoplasms in the past 20 years, identifying pleomorphic adenoma and acinic cell carcinoma as the most common benign and malignant etiologies, respectively. While this review found most neoplasms presented as a localized mass effectively managed with conservative surgical resection, aggressive tumors required multidisciplinary care.

Comparative Genomic Analysis of Pancreatic Acinar Cell Carcinoma (PACC) and Pancreatic Ductal Adenocarcinoma (PDAC) Unveils New Actionable Genomic Aberrations in PACC.

Pure pancreatic acinar cell carcinomas (PACC) are rare malignancies with no established treatment. PACC demonstrates significant genetic intertumoral heterogeneity with multiple pathways involved, suggesting using targeted cancer therapeutics to treat this disease. We aggregated one of the largest datasets of pure PACC to examine the genomic variability and explore patient-specific therapeutic targets. PACC specimens (n = 51) underwent next-generation sequencing of DNA (n = 29) or whole exome (n = 22) and RNA (whole transcriptome, n = 29) at a commercial laboratory. We performed comparative analyses of a genomic cohort of pancreatic ductal adenocarcinomas (PDAC; n = 4,205). In parallel, we conducted a retrospective review of patients with PACC treated at Huntsman Cancer Institute (HCI). The real-world dataset included samples from 51 patients with PACC. We found key molecular differences between pure PACC and PDAC, highlighting the unique characteristics of pure PACC. Major differences in PACC include lower MAPK signaling and less stromal cell abundance compared with PDAC. Pure PACC showed genomic loss-of-heterozygosity to largely coincide with mutations in BRCA1, BRCA2, and PALB2. Of the 7 patients treated at HCI, one had a tumor that harbored a BRAF-V600E mutation. Leveraging precision oncology, this patient is being treated with encorafenib plus binimetinib, achieving an exceptionally durable and ongoing complete response of more than 3 years. There are major differences between PACC and PDAC, including downregulation of the MAPK signaling pathway, and less stromal cell abundance. In addition, genomic characterization of pure PACC revealed frequent targetable alterations, which can guide patient treatment.