Acinic Cell Carcinoma Research Articles

Rare Non-Neuroendocrine Pancreatic Tumours

The most common tumour of the pancreas is ductal adenocarcinoma (PDAC). It remains one of the most lethal non-neuroendocrine solid tumours despite the use of a multi-approach strategy. Other, less-common neoplasms, which are responsible for 15% of pancreatic lesions, differ in treatment and prognosis. Due to the low incidence rate, there is a lack of information about the rarest pancreatic tumours. In this review, we described six rare pancreatic tumours: intraductal papillary mucinous neoplasm (IPMN), mucinous cystadenoma (MCN), serous cystic neoplasm (SCN), acinar cell carcinoma (ACC), solid pseudopapillary neoplasm (SPN) and pancreatoblastoma (PB). We distinguished their epidemiology, clinical and gross features, covered the newest reports about courses of treatment and systematised differential diagnoses. Although the most common pancreatic tumour, PDAC, has the highest malignant potential, it is still essential to properly classify and differentiate less-common lesions. It is vital to continue the search for new biomarkers, genetic mutations and the development of more specific biochemical tests for determining malignancy in rare pancreatic neoplasms.

Genomic landscape and clinical features of rare subtypes of pancreatic cancer: analysis with the national database of Japan

BackgroundSpecial subtypes of pancreatic cancer, such as acinar cell carcinoma (ACC), adenosquamous carcinoma (ASC), and anaplastic carcinoma of the pancreas (ACP), are rare, and so data on them are limited. Using the C-CAT database, we analyzed clinical and genomic characteristics of patients with these and evaluated differences on comparison with pancreatic ductal adenocarcinoma (PDAC) patients.MethodsWe retrospectively reviewed data on 2691 patients with unresectable pancreatic cancer: ACC, ASC, ACP, and PDAC, entered into C-CAT from June 2019 to December 2021. The clinical features, MSI/TMB status, genomic alterations, overall response rate (ORR), disease control rate (DCR), and time to treatment failure (TTF) on receiving FOLFIRINOX (FFX) or GEM + nab-PTX (GnP) therapy as first-line treatment were evaluated.ResultsNumbers of patients with ACC, ASC, ACP, and PDAC were 44 (1.6%), 54 (2.0%), 25 (0.9%), and 2,568 (95.4%), respectively. KRAS and TP53 mutations were prevalent in ASC, ACP, and PDAC (90.7/85.2, 76.0/68.0, and 85.1/69.1%, respectively), while their rates were both significantly lower in ACC (13.6/15.9%, respectively). Conversely, the rate of homologous recombination-related (HRR) genes, including ATM and BRCA1/2, was significantly higher in ACC (11.4/15.9%) than PDAC (2.5/3.7%). In ASC and ACP, no significant differences in ORR, DCR, or TTF between FFX and GnP were noted, while ACC patients showed a trend toward higher ORR with FFX than GnP (61.5 vs. 23.5%, p = 0.06) and significantly more favorable TTF (median 42.3 vs. 21.0 weeks, respectively, p = 0.004).ConclusionsACC clearly harbors different genomics compared with PDAC, possibly accounting for differences in treatment efficacy.

Roseate and merest-acinar cell carcinoma-pancreas

Acinar cell carcinoma pancreas is an epithelial, malignant neoplasm of exocrine pancreas comprised of cells resembling pancreatic acinar cells which are immune reactive to BCL10 and trypsin. Tumefaction arises due to accumulated genetic alterations, chromosomal instability or allelic copy number variation. Cogent clinical symptoms as abdominal pain, dorso-lumbar pain, loss of weight, nausea or vomiting or subcutaneous fat necrosis may ensue. Grossly, a solid, enlarged, well circumscribed, partially encapsulated tumefaction of fleshy consistency is encountered. Neoplastic cells demonstrate granular, eosinophilic cytoplasm pervaded with zymogen granules stainable with periodic acid Schiff’s (PAS) stain with diastase resistance, uniform nuclei and a singular, prominent nucleolus. Scanty and fibrous encompassing stroma exhibits foci of perineural and vascular invasion. Acinar cell carcinoma pancreas is immune reactive to keratins as CK7, CK8, CK18, CK19, BCL10, trypsin nuclear beta catenin or CD200. Computerized tomography (CT) and magnetic resonance imaging (MRI) delineates an enlarged tumefaction with well-defined perimeter, an exophytic pattern of tumour evolution and heterogeneous image enhancement. Surgical resection, chemotherapy with gemcitabine or radiofrequency ablation are appropriate modes of therapy.

Referral and treatment patterns in pancreatic acinar cell carcinoma: A regional population-level analysis

BackgroundPancreatic acinar cell carcinoma (PACC) is a rare exocrine tumor of the pancreas. We evaluated the effect disease stage, surgical intervention, and institutional volume status plays in survival. MethodsWe queried the Oregon State Cancer Registry for patients with PACC from 1997 to 2018. Treatment and referral patterns were analyzed, and overall survival (OS) was evaluated with Kaplan-Meier and Cox-proportional hazard analysis. Results43 patients were identified. Median OS was 33.1 and 7.1 months in those with locoregional and metastatic disease respectively (p ​= ​0.008). Surgical intervention was associated with improved OS (hazard ratio 0.28, p ​< ​0.0001). High volume center (HVC) care trended towards improving OS. While the majority of cases were diagnosed at low volume centers (74%), referral to HVCs was rare (n ​= ​4) and limited to advanced (stage III/IV) disease. ConclusionStage and surgical resection influence survival outcomes in PACC, more data is needed to delineate the impact of institutional volume status.

Fluorescence in situ hybridization for ETV6 gene rearrangements on destained cytological smears: Role in diagnosis of secretory carcinoma of salivary gland.

Fine-needle aspiration cytology (FNAC) is the first-line diagnostic procedure for salivary gland masses. Secretory carcinoma (SC) is characterized by ETV6 and RET rearrangements detected by fluorescence in situ hybridization (FISH) or reverse transcriptase-polymerase chain reaction optimized for paraffin-embedded and fresh-frozen tissue, respectively. The authors performed FISH on cytological material to assess its role in the diagnosis of SC. FNACs with SC as a diagnostic consideration and cases diagnosed as SC on histology with a corresponding FNAC with any diagnosis were evaluated for ETV6 rearrangement by FISH. If acinic cell carcinoma (ACC) was a differential diagnosis and ETV6 rearrangement was absent, NR4A3 FISH was performed. FISH results were compared with those on histological specimens, where available. Fifteen cases were included. FISH initially performed on three cell blocks did not yield good results, was then performed on direct smears, and was interpretable in 14 cases (93.3%). An ETV6 rearrangement was identified in seven cases (50%), and an NR4A3 rearrangement was identified in three cases (21.4%), providing a confirmatory diagnosis in 10 of 15 cases (66.7%). The Milan System for Reporting Salivary Gland Cytopathology category was altered in two cases (6.7%). Complete correlation (100%) was seen with FISH on corresponding histological specimens. With minor modifications, the FISH procedure can be optimized for FNAC smears with results comparable to those on histological specimens. ETV6 FISH testing on cytological smears in cases suspected as SC improves the diagnostic accuracy of FNAC and can help lower the proportion of the Milan categories salivary gland neoplasm of uncertain malignant potential and suspicious for malignancy, maximizing diagnostic information from less invasive samples and aiding in patient management.

Primary salivary gland tumors from a pathology perspective : Morphomolecular peculiarities and diagnostic and therapeutic challenges

Similar to tumors of other organs, salivary gland neoplasms were historically viewed as asingle neoplastic entity and mostly treated as such. Accordingly, only the clinical tumor stage, and not the histological subtype, was considered to be of significant prognostic impact. However, over the years, several distinct sub-entities have been characterized based on morphological features, such as adenoid cystic carcinoma, mucoepidermoid carcinoma, acinic cell carcinoma, and salivary duct carcinoma. Most importantly, the nosology of salivary gland carcinomas has undergone adynamic "splitting" on the basis of morphological, immunophenotypic, and molecular characteristics, so that 21independent carcinomas are now listed in the current World Health Organization (WHO) classification. Moreover, it has become evident that splitting of these carcinoma subtypes no longer represents a"pathologist's hobby," but carries significant prognostic and therapeutic relevance for optimized cancer surgery and potentially systemic therapy. The current review summarizes the major features of salivary gland tumors, both benign and malignant, and gives an account of their classification systems and genetic profiles.

Malignant salivary gland tumours: treatment outcomes from a tertiary referral centre in the UK

Salivary gland malignant tumours are a complex and highly variable pathological group. Their diagnosis can be challenging, and management is guided by multidisciplinary teams. This project aimed to establish clinicopathological and sociodemographic features that significantly impacted overall disease-free or progression-free survival in patients diagnosed with malignant salivary gland disease between 2010 and 2019 in a tertiary referral centre. In total, 86 patients were included for analysis, with a female:male gender ratio of 1.3:1. Mean age at diagnosis was 57.7 years. Mucoepidermoid carcinomas constituted almost 25% (n = 20) of all cases, with adenoid cystic carcinomas (20%, n = 17) and acinic cell carcinomas (17.5%, n = 15) being the next most frequently diagnosed. The parotid gland was the most frequently affected site (80.2%, n = 69). Perineural and lymphovascular invasion, and a maximum tumour dimension of ≥4 cm were highly associated with the decision to provide a neck dissection as part of treatment. Involved margins, extracapsular spread, and lymphovascular and perineural invasion were associated with the need for adjuvant treatment. However, no factors remained statistically significant on multivariate analysis. This retrospective service evaluation demonstrates the difficulty of predicting treatment outcomes for patients diagnosed with malignant salivary gland disease.

Nasal Acinic Cell Carcinoma Misdiagnosed as Hemangioma of the Nasal Septum.

Acinic cell carcinoma (AciCC) is a low-grade, slow-growing malignant tumor that commonly originates from the parotid gland and occasionally from the minor gland of the oral cavity, but rarely from the nasal cavity. Here, we present a 57-year-old woman who presented with an 8-month history of obstruction and epistaxis of the right nasal cavity. Rhinoscopy revealed a reddish-gray fleshy mass with tiny blood vessels on the surface blocking the right postnaris. Computed tomography showed a 3 × 2 cm2 well-demarcated tumor filling the right nasal common meatus with a clear boundary. There were no signs of local bone erosion in the bony window. Magnetic resonance imaging revealed abnormal signals in the nasal meatus with iso-intensity in the T1W1 sequence with homogeneous enhancement. We diagnosed it as a right nasal hemangioma, and the patient underwent endoscopic resection. However, histopathological evaluation of the surgical specimen confirmed a primary AciCC. The patient refused further radical surgery and instead underwent adjuvant radiotherapy. There was no clinical evidence of recurrence for 2years, and the patient has returned for follow-up yearly. We discuss the clinical nature of sinonasal AciCC and the treatment of this rare condition.

Acinar cell carcinoma of gastric ectopic pancreas origin: a case report and literature review

BackgroundPrimary pancreatic-type acinar cell carcinoma of the stomach is extremely rare, often misdiagnosed, and of unclear origin.Case presentationWe report the case of a primary pure pancreatic-type acinar cell carcinoma of the stomach in a 58-year-old woman. This is the first reported case to exhibit residual ectopic pancreatic tissue adjacent to the tumor serving as evidence for the origin of the carcinoma. Furthermore, we summarized the clinicopathological features of pancreatic-type acinar cell carcinoma of the stomach in order to further understand this solid tumor.ConclusionsPrimary pancreatic-type acinar cell carcinoma of the stomach is rare. Data on tumors of this histological type are still relatively scarce, and more in-depth research is needed to elucidate their molecular biological characteristics and prognosis.

Cytological evaluation of spectrum of Hepatobiliary and Pancreatic mass lesions

Hepatobiliary and Pancreatic mass lesions are commonly occurring intra-abdominal space occupying lesions. Image guided FNAC enables exact localization of the lesion, assessment of nature and invasion and is a useful tool in the diagnosis of such lesions. The present study aims to evaluate the spectrum of hepatobiliary mass lesions diagnosed by Image guided FNAC. We have conducted a retrospective study in Department of Pathology, Gauhati Medical College &amp; Hospital, Guwahati, for a period of 5 years, including patients of all ages and both sexes presenting with clinical and radiological suspicion of hepatic, biliary or pancreatic mass lesion. Under aseptic conditions USG guidance FNAC was done from the appropriate site and smears were examined. Out of the total 135 patients, there were 70 cases of Hepatic lesions (51.8%), followed by 54 cases taken from Gall bladder (GB) (40%), 5 cases from Common Bile Duct (CBD) (3.7%) and 6 cases (4.44%) from Pancreatic lesions. There were 51 cases of hepatic malignancies, 36 GB malignancies, 4 cases each of CBD and pancreatic malignancies. The most common Hepatic malignancies were Metastases followed by Hepatocellular carcinoma. The most common GB malignancy was Adenocarcinoma, followed by Cholangiocarcinoma. There was 1 case each of Solid Pseudopapillary Neoplasm of Pancreas, Acinar Cell carcinoma, Mucinous Adenocarcinoma and HCC. These findings were in concordance with our reference studies. Image guided FNAC has proved to be a versatile tool in provide an early and accurate diagnosis of hepatobiliary and pancreatic mass lesions.

Primary acinic cell carcinoma in an adolescent female

Acinic cell carcinoma (ACC) is a rare, low-grade tumour, accounting for about 17% of all primary salivary gland malignancies in adults. ACC most commonly affects the parotid gland, predominating fifth and sixth decades of life and a female predilection. In the paediatric population, mucoepidermoid carcinoma is the most common parotid malignancy, followed by ACC.We report a case of a 16-year-old female, presenting with a slow-growing right parotid lump. Clinical examination revealed a small right parotid nodule, grade I House-Brackmann score and cervical lymphadenopathy. Radiological investigations revealed a well-circumscribed lobulated lesion in the anterior right parotid gland and reactive lymph nodes. Surgical management included a right partial parotidectomy. Immunohistochemistry was negative for S100, positive with DOG-1 and widespread PAS-D-resistant granules throughout the tumour cells, confirming a diagnosis of ACC.ACC is an important differential diagnosis to consider in salivary gland pathology in the female adolescent patient.

Diagnosis of acinic cell carcinoma of the salivary gland on cytology specimens: Role of NOR-1 (NR4A3) immunohistochemistry.

Acinic cell carcinoma (AcCC) is often a challenging diagnosis on cytology. Recently, NOR-1 (NR4A3) has been demonstrated as a sensitive and specific marker for AcCC. Therefore, we conducted this study to evaluate NOR-1 expression in AcCC cytology specimens and to compare its reactivity in other salivary gland tumours (non-AcCC). We retrospectively reviewed our database and selected cytology cases with available cell blocks, including 10 AcCC and 24 non-AcCC tumours (12 benign tumours and 12 malignant tumours). NOR-1 (1:50 dilution; SC393902 [H-7]; Santa Cruz Biotech) immunohistochemistry (IHC) was performed on all cases. All AcCC cases except two (2/10, 80%) showed positive nuclear staining of variable intensity for NOR-1, with the majority of cases (75%) demonstrating at least moderately intense nuclear expression. All non-AcCC cases were negative for NOR-1, demonstrating a specificity of 100%. We conclude that NOR-1 IHC is sensitive and very specific on cytology specimens and is able to distinguish AcCC from its mimickers reliably and classify them appropriately for further management.

Survival outcomes, prognostic factors, and effect of adjuvant radiotherapy and prophylactic neck dissection in salivary acinic cell carcinoma: A prospective multicenter REFCOR study of 187 patients

BackgroundAcinic cell carcinomas (AciCCs) are malignant tumours of the salivary glands. The aim of this work was to analyse data from the national REFCOR multicenter cohort (i) to investigate the prognostic factors influencing survival outcomes in AciCC, (ii) to assess the impact on survival of postoperative radiotherapy (RT) in patients treated for AciCC without high-grade transformation and (iii) to explore the prognostic impact of prophylactic neck dissection (ND) in patients treated for AciCC of the major salivary glands. Patients and methodsData from all the patients treated for salivary AciCC between 2009 and 2020 were extracted from the REFCOR database. Survival outcomes and prognostic factors influencing Disease-Free Survival (DFS) and Overall Survival (OS) were investigated using univariate and multivariate analyses. Propensity score matching was used to assess the impact of postoperative RT and prophylactic ND on DFS. ResultsA total of 187 patients were included. After a median follow-up of 53 months, their 5-year OS and DFS rates were 92.8% and 76.2%, respectively. In multivariate analysis, male sex, older age, higher T and N status, and high grade were independently associated with a worse DFS. In the subpopulation analysed after propensity score matching, patients with cN0 AciCC without high-grade transformation who were treated by surgery and RT did not have an improved DFS compared to patients who were treated by surgery alone (hazard ratio (HR) = 0.87, p = 0.8). Factors associated with nodal invasion were T3–T4 status and intermediate/high histological grade. After propensity score matching, prophylactic ND was associated with a trend toward a better DFS (HR = 0.46, p = 0.16). ConclusionsThese results suggest that (i) long-term follow-up (>5 years) should be considered in patients with AciCC, (ii) treatment by surgery alone could be an option in selected cN0 patients with AciCC without high-grade transformation and (iii) prophylactic ND may be considered preferentially in patients with T3–T4 status and/or intermediate/high histological grade.

A rare case of pancreatic acinar cell carcinoma presenting a submucosal tumor.

A 66-year-old man, who underwent distal gastrectomy with Billroth I reconstruction for gastric cancer, regularly underwent upper endoscopy as a routine examination. Unlike 1 year earlier [Figure 1a], a submucosal tumor-like lesion was identified near the minor papilla [Figure 1b], but the opening of the minor papilla could not be confirmed. Computed tomography revealed a mass (26 mm × 10 mm) protruding from the duodenal wall into the duodenal lumen [Figure 2] without pancreatic duct dilation. EUS using a linear array echoendoscope showed that the hypoechoic and smooth-marginal mass adjacent to the pancreatic head [Figure 3a] and the accessory pancreatic duct could not be recognized. EUS using a miniature probe showed that the mass was mainly located in the muscularis propria of the duodenal wall [Figure 3b]. The initial diagnosis was a duodenal gastrointestinal stromal tumor; however, EUS-guided fine-needle biopsy of the mass revealed suspicious pancreatic acinar cell carcinoma (PACC). A pancreaticoduodenectomy was performed. Macroscopically, a gray-white mass with a 25-mm maximum diameter was found in the duodenal submucosa on the cut surface [Figure 4a]. The boundary between the mass and the pancreatic parenchyma was unclear. Predominant growth of the tumor was observed within the accessory pancreatic duct by loupe image [Figure 4b]. No invasive growth or cystic formation was found. The tumor cells having irregular, hyperchromatic nuclei and eosinophilic cytoplasm proliferated mainly in an acinar or tubular pattern [Figure 4c]. The neoplastic cells were diffusely positive for anti-trypsin [Figure 4d] and bcl-10, whereas they were negative for a neuroendocrine marker, chromogranin or synaptophysin. Finally, the pathological diagnosis was a PACC at stage TisN0M0.Figure 1: (a) Endoscopic image showing no abnormality of the duodenal wall and minor papilla 1 year ago. (b) Endoscopic image showing a submucosal tumor-like lesion near the original minor papillaFigure 2: Contrast-enhanced computed tomography showing a mass (arrow) protruding from the duodenal wall into the duodenal lumen located in contact with the pancreatic headFigure 3: (a) EUS using a linear array echoendoscope showing a hypoechoic and smooth-marginated mass outside the pancreatic head. (b) EUS using a miniature probe showing the mass mainly located in the muscularis propria of the duodenal wallFigure 4: (a) Gross examination of resected specimen revealed a gray-white, solid lesion mainly occupying the duodenal submucosa on the cut surface. (b) A tumor with intraductal growth was observed by loupe image of histologic specimen (H and E). Normal pancreatic parenchyma (arrow). (c) Tumor cells having irregular, hyperchromatic nuclei and eosinophilic cytoplasm proliferated resembling acini of the pancreas (H and E, × 200). (d) Immunohistochemically, the neoplastic cells were positive for anti-trypsin (×40)PACC is a rare pancreatic tumor,[1] which is typically a solid tumor with expansive growth.[2] A PACC that predominantly grows within the main pancreatic ducts is extremely rare.[3] There has not been any reported case of PACC growing in the accessory pancreatic duct and presenting a submucosal tumor. In this case, there are some hypotheses regarding the specific tumor appearance: PACC originating from (1) pancreatic parenchyma near the accessory pancreatic duct and (2) ectopic pancreas[4] or submucosal pancreatic parenchyma.[5] However, it is a limitation that it was difficult to prove the hypotheses. Authors’ contributions R.S. treated the patient and wrote the manuscript; H.K., H.N., S.H., T.M., K.S., T.Y., H.A., M.K., M.F., T.M., M.F., K.O., E.T., T.U., A.T., and A.I. treated the patient and contributed writing the manuscript; T.T. performed pathological diagnosis and contributed writing the manuscript; all authors approved the final manuscript. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest Masaki Kuwatani is an Editorial Board Member of the journal. This article was subject to the journal’s standard procedures, with peer review handled independently of the editor and his research group.

Results of Primary Treatment and Salvage Treatment in the Management of Patients with Non-Squamous Cell Malignant Tumors of the Sinonasal Region: Single Institution Experience

Non-squamous cell carcinoma-related malignant sinonasal tract tumors (non-SCC MSTT) are rare and diverse malignancies. In this study, we report our experience in the management of this group of patients. The treatment outcome has been presented, involving both primary treatment and salvage approaches. Data from 61 patients treated radically due to non-SCC MSTT between 2000 and 2016 at the National Cancer Research Institute, Gliwice branch, were analyzed. The group consisted of the following pathological subtypes of MSTT: adenoid cystic carcinoma (ACC), undifferentiated sinonasal carcinoma (USC), sarcoma, olfactory neuroblastoma (ONB), adenocarcinoma, small cell neuroendocrine carcinoma (SNC), mucoepidermic carcinoma (MEC), and acinic cell carcinoma, which were found in nineteen (31%), seventeen (28%), seven (11.5%), seven (11.5%), five (8%), three (5%), two (3%) and one (2%) of patients, respectively. There were 28 (46%) males and 33 (54%) females at the median age of 51 years. Maxilla was the primary tumor localization followed by the nasal cavity and ethmoid sinus in thirty-one (51%), twenty (32.5%), and seven (11.5%) patients, respectively. In 46 (74%) patients, an advanced tumor stage (T3 or T4) was diagnosed. Primary nodal involvement (N) was found in three (5%) cases, and all patients underwent radical treatment. The combined treatment consisted of surgery and radiotherapy (RT) and was given to 52 (85%) patients. The probabilities of overall survival (OS), locoregional control (LRC), metastases-free survival (MFS), and disease-free survival (DFS) were assessed in pathological subtypes and grouped together, along with the ratio and effectiveness of salvage. Locoregional treatment failure was seen in 21 (34%) patients. Salvage treatment was performed in fifteen (71%) patients and was effective in nine (60%) cases. There was a significant difference in OS between patients who underwent salvage and those who did not (median: 40 months vs. 7 months, p = 0.01). In the group of patients who underwent salvage, OS was significantly longer when the procedure was effective (median: 80.5 months) than if it failed (median: 20.5 months), p < 0.0001. OS in patients after effective salvage was the same as in patients who were primary cured (median: 80.5 months vs. 88 months, p = 0.8). Distant metastases developed in ten (16%) patients. Five and ten year LRC, MFS, DFS, and OS were 69%, 83%, 60%, 70%, and 58%, 83%, 47%, 49%, respectively. The best treatment results were observed for patients with adenocarcinoma and sarcoma, while USC gave the poorest results in our set of patients. In this study, we indicate that salvage is possible in most patients with non-SCC MSTT with locoregional failure and that it may significantly prolong their overall survival.

Loss of CDKN2A/B is a Molecular Marker of High-grade Histology and is Associated with Aggressive Behavior in Acinic Cell Carcinoma

Acinic cell carcinoma (AciCC) is a rare salivary gland cancer with excellent prognosis in most cases. However, a subset of patients will develop distant metastasis and die of disease. Recently, a 2-tiered grading scheme in AciCC was proposed to recognize patients at risk of poor outcome. We performed a genetic analysis of AciCC to explore the underlying molecular correlates of the tumor grade and examined programmed death ligand 1 (PD-L1) expression to identify potential candidates for immunotherapy. A retrospective cohort of 55 patients included 34 high-grade (HG) and 21 low-grade AciCCs. Forty-three cases were subjected to targeted exome sequencing by Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets. PD-L1 immunohistochemistry was performed in 33 cases. Tumor mutation burden was low with a median of 1 and 2 mutations in low-grade and HG AciCCs, respectively. CDKN2A/B was the most frequently altered gene, and loss-of-function mutations were found only in HG but not in low-grade AciCCs (18/31 [58.1%] vs 0/12 [0%], P < .001). CDKN2A/B alterations were significantly associated with distant metastasis, which occurred in 16/18 (88.9%) CDKN2A/B mutants versus 11/25 (44%) wild-type cases (P = .004, Fisher exact test). Sequential profiling of multiple temporally distant samples from the same patient demonstrated intratumor heterogeneity, including the detection of CDKN2A/B deletion in the second, in HG metastasis only. ATM and PTEN mutations were detected in 6/31 (19.4%) and 5/31 (16.1%); ARID2, BIRC3, and FBXW7 mutations each in 4/31 (12.9%); and TP53, MTAP, and FAT1 each in 3/31 (9.7%) HG AciCC. PD-L1–positive labeling was more common in HG AciCC (9/17, 52.9% vs 3/16, 18.9%, P = .071). CDKN2A/B mutations in AciCC represent a molecular marker of HG histology and disease progression, providing a rationale for further studies to determine their prognostic and therapeutic significance in this salivary gland cancer. AciCC with ATM mutations may be amenable to targeted therapy. Immunotherapy can be considered to be a treatment option for a subset of patients with AciCC.

Novel Insights Into Immunohistochemical Analysis For Acinar Cell Neoplasm of The Pancreas: Carboxypeptidase A2, Carboxypeptidase A1, and Glycoprotein 2.

Acinar cell carcinoma (ACC) is a rare and highly malignant pancreatic tumor. Owing to histologic similarity, ACC is often difficult to distinguish from other solid medullary pancreatic tumors, particularly neuroendocrine neoplasm (NEN) and intraductal tubulopapillary neoplasm (ITPN). We aimed to identify new immunohistochemical markers commonly expressed in tumor cells with acinar cell differentiation and useful for both surgical and small biopsy specimens. Candidate molecules exclusively expressed in neoplastic or non-neoplastic acinar cells in pancreatic tissues with specific and available antibodies suitable for immunohistochemistry were selected. We selected carboxypeptidase A1 (CPA1), carboxypeptidase A2 (CPA2), and glycoprotein 2 (GP2), which were expressed in 100%, 100%, and 96% of cases, respectively, in ACC (n=27) or neoplasia with acinar cell differentiation, including mixed acinar-neuroendocrine carcinoma (n=9), mixed acinar-ductal carcinoma (n=3), pancreatoblastoma (n=4), and acinar cystic transformation (n=2), in the cytoplasm of tumor cells with a granular pattern. Both CPA2 and CPA1 were not expressed in any other tumors without acinar cell differentiation, including NEN (n=44), pancreatic ductal adenocarcinoma (n=44), and ITPN (n=4). GP2 was not expressed in these tumors except in rare cases, including 14% of NEN, 15% of intraductal papillary-mucinous neoplasm, 25% of intraductal oncocytic papillary neoplasm, 25% of ITPN, and 7% of pancreatic ductal adenocarcinoma, wherein a small proportion of tumor cells expressed GP2 in their apical cell membrane. NEN cases also showed cytoplasmic GP2 expression. Therefore, CPA2, CPA1, and potentially GP2 may act as ACC markers.

NR4A3 Expression Is Consistently Absent in Acinic Cell Carcinomas of the Breast: A Potential Nosologic Shift

Acinic cell carcinoma (AciCC) is a tumor that is recognized in both the breast and salivary glands. Recently, the recurrent genomic rearrangement, t(4;9)(q13;q31) was identified in salivary AciCC that results in constitutive upregulation of the nuclear transcription factor NR4A3, which can be detected by immunohistochemistry. In this study, we sought to evaluate NR4A3 expression in breast AciCC using immunohistochemistry. Strong and diffuse nuclear staining was considered a positive result. Sixteen AciCCs were studied, including 8 pure AciCCs and 8 AciCCs admixed with other types (invasive carcinoma of no special type in 5 cases and metaplastic carcinoma in 3 cases). All 16 AciCCs showed negative results for NR4A3 expression. Four cases with available material were evaluated for rearrangements of the NR4A3 gene by fluorescence in situ hybridization and no rearrangements were observed. Whole-genome sequencing of 1 AciCC revealed a TP53 splice-site mutation, high levels of genomic instability, and genomic features of homologous recombination DNA repair defects; a structural variant analysis of this case did not reveal the presence of a t(4;9) rearrangement. We conclude that breast AciCCs consistently lack NR4A3 rearrangement or overexpression, unlike most of the salivary AciCCs, and that consistent with previous results, breast AciCCs are associated with genomic alterations more similar to those seen in triple-negative breast carcinomas than salivary gland AciCCs. These results suggest that unlike other salivary gland–like tumors that occur in the breast, the molecular underpinnings of the salivary gland and breast AciCCs are different and that the salivary gland and breast AciCCs likely represent distinct entities.

Speicheldrüsenkarzinome – ein aktueller Überblick

In recent years, the characterization of salivary gland tumors has undergone a major transformation. Morphologically defined entities could to a large extent also be characterized molecularly with an often distinct genotype. The first part of this article reviews the advances in the molecular characteristics of mucoepidermoid carcinoma, adenoid cystic carcinoma, acinic cell carcinoma, secretory carcinoma, intraductal carcinoma, and hyalinizing clear cell carcinoma. The molecular genotype can be particularly useful in classifying unusual morphologic variants. Recurrent NTRK or RET gene fusions can be used not only as a diagnostic tool but also for potential targeted therapy.

Misunderstood Gastric Perforation of a Pancreatic Acinar Cell Carcinoma: A Wolf in Sheep’s Clothing

A 70-year-old man was admitted to the Emergency Department (ED) for marked asthenia and severe anemia. In addition, a high level of lipase was found. During hospitalization, a locally advanced gastric cancer was diagnosed, with endoscopic evidence of a large polyploid formation originating under the cardias that occupied most of the gastric lumen. A total body CT scan was performed before surgery; the tumor affected the posterior gastric wall, with tenacious infiltration of the pancreatic body. Therefore, we performed a total gastrectomy with esophageal jejunum anastomosis and reconstruction of intestinal continuity according to Roux, distal spleno-pancreatectomy, and cholecystectomy. At histology, a pancreatic acinar cell carcinoma (PACC) with full thickness infiltration of the gastric wall was diagnosed. Acinar cell carcinomas are highly aggressive neoplasms, and surgical resection, when feasible, is the treatment of choice regardless of size, also because the role of neoadjuvant or adjuvant chemo- or radiotherapy remains uncodified.