Acinic Cell Carcinoma Research Articles

Diagnostic accuracy of pan-TRK immunohistochemistry in differentiating secretory carcinoma from acinic cell carcinoma of salivary gland-A systematic review.

Secretory carcinoma (SC) is a well-established salivary gland malignancy that has earned its popularity for its unique clinicopathological behavior. Although it is an indolent malignancy, few of them have been reported with high grade transformation making it mandatory to differentiate it from its prime histological mimicker, acinic cell carcinoma (AciCC). Recently, many studies have been directed toward validating the sensitivity and specificity of pan-TRK IHC for confirming ETV6::NTRK3 gene fusion in SCs involving salivary gland. The aim of the present systematic review was to establish the diagnostic utility of pan-TRK immunostaining in histological differentiation of SC from AciCC. An electronic search was carried out using MEDLINE by PubMed, Scopus, Google scholar, Trip, Cochrane library and EMBASE databases. Articles in which SC assessed with pan-TRK immunohistochemical expressions were included for systematic review and their staining pattern (cytoplasmic, nuclear and/or combined), sensitivity, specificity, positive as well as negative predictive were gathered. Risk of bias was analyzed for each study using QUADAS-2 tool. Thirteen eligible articles were included for the quantitative analysis, which revealed positive immunostaining of pan-TRK by nearly all the ETV6::NTRK3 fusion prevalent SCs alongside negative expression in almost all the cases of AciCC with 100% of sensitivity as well as specificity. The evidence from the included studies supports that pan-TRK immunostaining could be used as a reliable preliminary screening tool for discerning SC from AciCC. PROSPERO No: CRD42022308913.

Outcomes Following Proton Radiotherapy for Pediatric Salivary Gland Tumors

<h3>Purpose/Objective(s)</h3> In contrast to adult salivary gland tumors, our institutional guidelines in children utilize lower radiation doses, smaller target margins, and proton therapy to minimize radiation to the developing skull base anatomy. Furthermore, we do not routinely recommend prophylactic nodal irradiation or elective neck dissection. Previous series of children treated with adjuvant radiation therapy report 5-year local control ∼85%. Herein we report treatment outcomes using our pediatric approach. <h3>Materials/Methods</h3> Twenty-seven consecutive pediatric patients were treated with proton therapy between 2006 and 2020 for mucoepidermoid carcinoma (n= 13), acinic cell carcinoma (n= 5), adenoid cystic carcinoma (n= 4), pleomorphic adenoma (n= 2), myoepithelial carcinoma (n= 1), adenocarcinoma (n= 1), and sialoblastoma (n= 1) at our institution. The 8 patients with radiographic lymphadenopathy (cN1) underwent neck dissection prior to presentation (7/8 selective dissections involving <4 nodal levels). The most common indications for adjuvant radiotherapy were microscopic positive or close (<1 mm) margins (n=15), perineural invasion (PNI; n=9), high-grade histology (n=6), and gross residual disease (n=4). Radiotherapy was delivered in sequential plans using 2 clinical target volumes (CTV1, CTV2). Gross tumor volume (GTV=CTV2) included the residual tumor and tumor bed. CTV1 received 50.4 Gy and was defined as GTV + 1 cm and the at-risk neck if indicated. The dose to CTV2 depended on histology, grade, and margin status. The median total dose was 64.8 Gy (range, 61.2-70.2 Gy). Only 3 patients underwent prophylactic nodal irradiation. Toxicity data was graded based on CTCAE v3 or v4 using patient-reported and physician-reported outcomes according to our prospective outcome registry. <h3>Results</h3> The median follow-up was 5.5 years. Overall survival was 100% and local control was 96% with a single local recurrence seen in a patient with gross unresectable disease. There were no nodal recurrences. In terms of acute toxicity, 3 patients experienced mucositis requiring opioid pain medication and 2 patients developed grade 3 radiation dermatitis. The most serious late toxicity involved the ear or auditory system including 4 patients requiring hearing aids, 1 with chronic otitis media, 1 with osteonecrosis of the mastoid bone, and 1 with external ear canal stenosis. Four additional patients reported variable hearing loss not requiring hearing aids. Other serious late toxicity included 1 patient with persistent trismus, 1 with growth hormone deficiency, and 1 with excessive dental caries along the ipsilateral maxilla. No secondary malignancies nor toxicities grade ≥ 4 were seen. <h3>Conclusion</h3> An approach of conservative neck management and moderate-dose proton radiotherapy delivered to small volumes resulted in excellent disease control and limited toxicity in children with common salivary gland tumors at elevated risk of local recurrence.

Modern Outcomes of Pediatric and Young Adult Patients with Parotid Gland Tumors Treated with Highly-Conformal Radiation Therapy

<h3>Purpose/Objective(s)</h3> Parotid tumors in the pediatric and young adult (PYA) population are a rare entity with a paucity of data available regarding treatment outcomes and toxicities. Most reports are long-term results of small series of patients treated with a wide variety of historical techniques. We aim to report our experience with modern highly-conformal radiation techniques for this unique population. <h3>Materials/Methods</h3> IRB approved retrospective review of 9 PYA patients (defined as age 0-25 at diagnosis) with parotid tumors treated with radiation therapy (RT) at one institution. Tumor characteristics, treatment modality, disease status, dosimetry, and acute and late toxicities were collected from the medical record. <h3>Results</h3> Nine PYA patients (5 female, 4 male) with received RT for parotid gland tumors from 2015-2022. The median age at diagnosis was 22 years (range 12-24). Median follow up was 34.4 months from RT completion. No patient had metastasis at diagnosis. Tumor histologies were: 4 mucoepidermoid carcinomas (n=1 sclerosing subtype); 1 acinic cell carcinoma, 1 adenocarcinoma, 1 NUT midline carcinoma, and 2 benign recurrent pleomorphic adenomas. All underwent total parotidectomy before RT. Three had disease involving only the deep lobe, 3 had only superficial involvement, and 3 had multifocal disease. Six patients underwent unilateral neck dissection at the time of parotidectomy; only 1 patient with a malignant tumor did not. Three patients had lymph node positive disease. The median time from surgery to RT was 6.7 weeks (range 4.7-10.7). Seven patients were treated using intensity modulated proton RT (IMPT), 1 started with intensity modulated RT (IMRT) for the first 20 of 30 fractions (fx) and transitioned to IMPT, and 1 was treated with IMRT alone. The most common dose and fractionation was 60 Gy in fx (n=7). One patient was treated using 66 Gy in 33 fx and n=1 with recurrent unresected gross disease received 69.96 Gy in 33 fx. The most common acute toxicities were grade 1-2 xerostomia, RT dermatitis, mucositis, alopecia, dysgeusia, and fatigue. No patient required a feeding tube or hospitalization during RT. One patient with NUT midline carcinoma histology received concurrent chemotherapy with cisplatin and etoposide. The most common late toxicities were grade 1-2 trismus, RT fibrosis, alopecia, lymphedema, and hearing loss. Two patients required thyroid supplementation after completing treatment – both received IMRT. There were no reported instances of osteoradionecrosis or extensive dental caries. All patients were alive at the time of data collection. There were no locoregional recurrences, and one patient (NUT midline carcinoma) developed distant metastatic disease. <h3>Conclusion</h3> Highly conformal proton/IMRT following surgical resection provides excellent local control with an acceptable toxicity profile for PYA patients with parotid gland tumors.

Pancreatic acinar cell carcinoma: A comprehensive review.

Acinar cell carcinoma (ACC) is a rare pancreatic malignancy with distinctive clinical, molecular, and morphological features. The long-term survival of ACC patients is substantially superior to that of pancreatic adenocarcinoma patients. As there are no significant patient series about ACCs, our understanding of this illness is mainly based on case reports and limited patient series. Surgical resection is the treatment of choice for patients with the disease restricted to one organ; however, with recent breakthroughs in precision medicine, medicines targeting the one-of-a-kind molecular profile of ACC are on the horizon. There are no standard treatment protocols available for people in which a total surgical resection to cure the condition is not possible. As a result of shared genetic alterations, ACCs are chemosensitive to agents with activity against pancreatic adenocarcinomas and colorectal carcinomas. The role of neoadjuvant or adjuvant chemoradiotherapy has not been established. This article aims to do a comprehensive literature study and present the most recent information on acinar cell cancer.

Frontiers in Breast Pathology.

Frontiers in Breast Pathology.

Warthin Tumor - Diagnostic Dilemma- Case Report

Warthin Tumor is also known as Papillary Cystadenoma lymphomatosum, is a fairly common tumor. Cytologically, it simulates many other lesions of salivary glands like chronic sialadenitis, low grade mucoepidermoid carcinoma, acinic cell carcinoma, squamous cell carcinoma, oncocytic carcinoma, lymphoepithelial cyst etc which poses a diagnostic dilemma.

Inhibin Alpha Expression in Human Tumors: A Tissue Microarray Study on 12,212 Tumors.

As a result of its expression in corresponding normal cell types, inhibin alpha (INHA) is used as an immunohistochemical marker for adrenocortical neoplasms and testicular or ovarian sex cord stromal tumors. However, other tumors can also express INHA. To comprehensively determine INHA expression in cancer, a tissue microarray containing 15,012 samples from 134 different tumor types and subtypes was analyzed by immunohistochemistry. INHA positivity was found in 72 of 134 tumor categories, including 26 categories with ≥1 strongly positive case. A moderate to strong INHA positivity was found in 100% of 37 granulosa cell tumors of the ovary, 100% of 43 other sex cord stromal tumors of the ovary/testis, 100% of 31 granular cell tumors, 78.5% of 28 adenomas, 44% of 25 carcinomas of the adrenal cortex, and 46.7% of 15 pancreatic acinar cell carcinomas. At least a weak INHA positivity was seen in <33% of cases of 46 additional tumor entities. In summary, these data support the use of INHA antibodies for detecting sex cord stromal tumors, granular cell tumors, and adrenocortical neoplasms. Since INHA can also be found in other tumor entities, INHA immunohistochemistry should only be considered as a part of any panel for the distinction of tumor entities.

Painful lower limb nodules as first symptom of resectable pancreatic acinar cell cancer: a case report

BackgroundPancreatic panniculitis is characterized by subcutaneous fat necrosis and is a rare presentation of an underlying pancreatic disease, appearing in approximately 2–3% of all patients with a pancreatic disease. The nodules usually involve the lower extremities. Pancreatic panniculitis is commonly associated with acute or chronic pancreatitis, and occasionally with pancreatic cancer, especially acinar cell carcinoma.Case presentationA 77-year-old Caucasian woman with no significant medical history was referred to our center with multiple painful, itchy, and warm red/blue cutaneous nodules on the left lower leg. These skin lesions were consistent with the clinical diagnosis of panniculitis. The skin biopsy obtained showed a predominantly lobular panniculitis with fat necrosis of which the aspect was highly suspicious for pancreatic panniculitis. Further analysis revealed high lipase serum of > 3000 U/L (normal range < 60 U/L), and on computed tomography scan a mass located between the stomach and the left pancreas was seen. Endoscopic ultrasonography-guided fine-needle biopsy confirmed the diagnosis of acinar cell carcinoma. After discussing the patient in the pancreatobiliary multidisciplinary team meeting, laparoscopic distal pancreatectomy including splenectomy and en bloc wedge resection of the stomach due to tumor in-growth was performed. The cutaneous nodules on both legs disappeared 1–2 days after surgery. No long-term complications were reported during follow-up. One year after surgery, the patient presented with similar symptoms as preoperatively. Computed tomography scan showed local recurrence and distal metastases, which were subsequently confirmed by biopsy. She started with palliative folinic acid–fluorouracil–irinotecan–oxaliplatin chemotherapy but stopped after two cycles because of disease progression. The patient died 2 months later, 13 months after surgical resection.ConclusionThis case illustrates the importance of clinically recognizing cutaneous nodules and pathological recognizing the specific microscopic changes as sign of a (malignant) pancreatic disease.

S3115 Pancreatic Cancer Without Pancreatic Lesion: Pancreatic Acinar Cell Carcinoma (PACC) Presenting as Isolated Hepatic Lesion Without Primary Organ Involvement

Introduction: Pancreatic cancer are diagnosed in advanced stages and by that time the treatment options are often limited. We report a rare case, showing metastatic pancreatic acinar cell carcinoma (PACC) in the liver without any evidence of primary lesion in the pancreas based on imaging studies. Case Description/Methods: A 78-year-old male with a past medical history of prostate cancer, pancreatic insufficiency due to recurrent pancreatitis and irritable bowel syndrome was seen in gastroenterology clinic for epigastric pain. Patient’s family history was significant for prostate cancer and social history was pertinent for alcohol abuse in the past. He underwent endoscopic evaluation with EGD and colonoscopy, both of which were unremarkable. Thereafter, MRI abdomen with contrast revealed a 6 cm right hepatic lobe lesion concerning for malignancy along with multiple cysts approximately 15 mm in size, and no other lesion was identified in the abdomen. Lab work was also unremarkable (see Table 1). Subsequently he underwent IR guided liver biopsy of the mass. The final histopathological diagnosis of the biopsy was acinar cell carcinoma of pancreatic origin and likely metastatic lesion. Looking back at the MRI abdomen there were no findings to suggest of pancreatic lesion, consequently he underwent EUS which showed normal esophagus, stomach and duodenum, the pancreatic parenchyma was consistent with fatty infiltration however no cyst, pseudocyst or mass was identified through the entire pancreas. At this point, patient already followed with medical oncology and was started on systemic pancreatic regimen therapy. He tolerated chemotherapy well and repeat CT scans in subsequent months showed overall stable disease (Figure 1). Discussion: Hepatologists routinely come across liver lesions suspicious for malignancy. Liver is the second most common site of metastasis after lymphatic system. Pancreatic acinar cell carcinomas (PACC) are rare, accounting for 1-2% of adult pancreatic tumors. On MRI, PACC appear as large, oval mass with moderate and heterogenous enhancement after intravenous contrast. Our case is one of its kind due to the detection of significantly sized pancreatic acinar cell tumor in the liver prior to it being detectable in the pancreas itself (see Figure-1 for imaging details). This case highlights the importance of prompt diagnosis and management especially in challenging cases which present with discordance between histopathological and imaging studies.Figure 1.: A, Post-contrast T1-weighted MRI; images showing predominantly peripheral enhancement of segment 6/7 hepatic lesion (red arrows). B, Pre-contrast T1-weighted MRI; images showing predominantly peripheral enhancement of segment 6/7 hepatic lesion (red arrows). C, Post-contrast T1-weighted MRI; Left image marks pancreatic body and tail, Right image marks the uncinate/head, does not show any lesion or mass in pancreas. Table 1. - Diagnostic Lab work up Lab Values/Reference Range &Units Patient Result WBC 4.50-13.50 K/uL 7.06 Hemoglobin 13.0-16.0 g/dL 13.8 Platelets 150-450 K/uL 231 Albumin 3.2-4.7 g/dL 3.3 INR 0.8-1.2 1.1 Total Bilirubin 0.1-1.0 mg/dL 0.9 Alkaline Phosphatase 89-365 U/L 98 AST 10-40 U/L 22 ALT 10-44 U/L 15 Cancer Antigen 19-9 0.0-40.0 U/Ml 13.3 CEA 0.0-5.0 ng/mL 1.7 AFP 0.0-8.4 ng/mL < 2.0 PSA, Screening 0.00-4.00 ng/mL < 0.01

Ga-68 DOTATATE PET/CT in the Evaluation of Paragangliomas and Other Indeterminate Lesions in the Head and Neck.

Paragangliomas (PGLs) are rare neuroendocrine tumors with imaging features that can overlap with other entities. This study hypothesizes that given overexpression of somatostatin receptor (SSTR) 2, PGLs can be differentiated on Ga-68 DOTATATE positron emission tomography/computed tomography (PET/CT) from other benign or malignant lesions. Ninety-six patients with known tumors of the head and neck who underwent Ga-68 DOTATATE PET/CT from May 2017 to December 2021 were retrospectively reviewed from a single institution. Of these, 43 patients had histopathological confirmation and 66 positive lesions were discovered on PET/CT. For each lesion, the SUV max, the SUV lesion to liver ratio, and the SUV lesion to spleen ratio were analyzed. PGLs (n = 37) showed the most intense uptake, and the mean of SUVmax was 69.3 (range 3.7-225.9). Metastatic PGL and metastasis from other neuroendocrine tumors (n = 13) demonstrated intermediate uptake, the mean of SUVmax was 15.16 (range 2.3-40.3). Meningiomas (n = 3) had intermediate uptake, and the mean of SUVmax was 12.37 (range 2.5-19.4). One patient with esthesioneuroblastoma had 5 lesions in the head and neck, and the mean of SUVmax was 18.9 (range 6.9-49.4). Schwannomas (n = 4) had very low uptake, and the mean of SUVmax was 1.75 (range 1.1-2.2). Other rare cases with low uptake included 1 each of osteosarcoma, acinic cell carcinoma, ectopic thyroid tissue, and plasmacytoma, and the mean of SUVmax was 4.75 (range 2.3-6.1). Ga-68 DOTATATE PET/CT can be a useful adjunct in differentiating tumors in the head and neck. PGLs demonstrate the highest uptake. Meningioma, esthesioneuroblastoma, and neuroendocrine tumor metastasis have intermediate uptake. Schwannomas and other rare tumors exhibit low uptake.

Diagnostic and prognostic role of pancreatic secretory granule membrane major glycoprotein 2 (GP2) immunohistochemistry: A TMA study on 27,681 tumors.

Pancreatic secretory granule membrane major glycoprotein 2 (GP2) is a membrane component of zymogen granules which is abundantly secreted by pancreatic acinar cells. Because RNA based analyses suggest a strict limitation of GP2 expression to the pancreas in normal tissues, and a strong preference to pancreatic cancer among tumors, GP2 expression analysis might have diagnostic utility. To better understand the role of GP2 protein expression, GP2 was successfully analyzed in 27,965 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). GP2 immunostaining was seen in 14 of 16 (87.5%) acinar cell carcinomas, 6 of 507 (1.2%) ductal adenocarcinomas, and 3 of 99 neuroendocrine neoplasms of the pancreas (3.0%). GP2 was also found in 23 extra-pancreatic tumor entities including several types of neuroendocrine neoplasms (14.3-58.8%), prostatic adenocarcinomas (8.2-18.8%), various other adenocarcinomas (0.1-7.7%), and several categories of benign and malignant salivary gland tumors (2.3-3.1%). A strong GP2 positivity was only seen in 6 tumor categories including 50% of 16 pancreatic acinus cell carcinomas, 11.8% of 17 neuroendocrine tumors of the lung, 1.3% of 80 primary Gleason 4+4% and 0.6% of 181 recurrent prostate cancers, as well as 0.8% of 133 adenocarcinomas of the lung. In a cohort of 14,747 prostate cancers with follow up data, GP2 immunostaining was strongly linked to advanced pT stage, high Gleason grade, lymph node metastasis, and recurrence free survival (p<0.0001 each). The prognostic impact of GP2 positivity was independent of established parameters in TMPRSS2:ERG fusion-negative cancers (p<0.0001). In summary, our data show that GP2 is preferentially expressed in acinar cell carcinomas of the pancreas but the glycoprotein can - rarely - also be expressed in a variety of other tumor entities.

DOG-1 positive primary acinic cell carcinoma of the lung and investigation of molecular status

Primary acinic cell carcinoma (ACC) of the lung is an extremely rare neoplasm that more often arises near to a right bronchus. It is characterized by two populations of clear and dark eosinophilic cells, arranged in a glandular acinar pattern. Mitosis are rare and tumor cells show small and eccentric nuclei. Positive stain for PAS, PAS-D, cytokeratin, A1AT and A1ACT is reported, while TTF1, p40, synaptophysin, SMA, and S100 are substantially negative. DOG-1 positive stain was observed in ACC of the salivary glands and its negativity was proposed to distinguish between primary and metastatic ACC of the lung. Here, we report the 30th case of primary ACC of the lung, describing the immunohistochemical positivity for DOG-1 and the molecular status of the neoplasm for the first time.

Artificial intelligence using deep learning analysis of endoscopic ultrasonography images for the differential diagnosis of pancreatic masses.

BACKGROUND : There are several types of pancreatic mass, so it is important to distinguish between them before treatment. Artificial intelligence (AI) is a mathematical technique that automates learning and recognition of data patterns. This study aimed to investigate the efficacy of our AI model using endoscopic ultrasonography (EUS) images of multiple types of pancreatic mass (pancreatic ductal adenocarcinoma [PDAC], pancreatic adenosquamous carcinoma [PASC], acinar cell carcinoma [ACC], metastatic pancreatic tumor [MPT], neuroendocrine carcinoma [NEC], neuroendocrine tumor [NET], solid pseudopapillary neoplasm [SPN], chronic pancreatitis, and autoimmune pancreatitis [AIP]). METHODS : Patients who underwent EUS were included in this retrospective study. The included patients were divided into training, validation, and test cohorts. Using these cohorts, an AI model that can distinguish pancreatic carcinomas from noncarcinomatous pancreatic lesions was developed using a deep-learning architecture and the diagnostic performance of the AI model was evaluated. RESULTS : 22 000 images were generated from 933 patients. The area under the curve, sensitivity, specificity, and accuracy (95 %CI) of the AI model for the diagnosis of pancreatic carcinomas in the test cohort were 0.90 (0.84-0.97), 0.94 (0.88-0.98), 0.82 (0.68-0.92), and 0.91 (0.85-0.95), respectively. The per-category sensitivities (95 %CI) of each disease were PDAC 0.96 (0.90-0.99), PASC 1.00 (0.05-1.00), ACC 1.00 (0.22-1.00), MPT 0.33 (0.01-0.91), NEC 1.00 (0.22-1.00), NET 0.93 (0.66-1.00), SPN 1.00 (0.22-1.00), chronic pancreatitis 0.78 (0.52-0.94), and AIP 0.73 (0.39-0.94). CONCLUSIONS : Our developed AI model can distinguish pancreatic carcinomas from noncarcinomatous pancreatic lesions, but external validation is needed.

Morphologic and Ancillary Studies of Pediatric Acinic Cell Carcinoma: A Single Institute Experience.

Acinic cell carcinoma (AciCC) is the second most common pediatric malignant salivary gland tumor. However, there are limited pathology publications about this tumor in the pediatric population. We describe four pediatric AciCC cases diagnosed between 2000 and 2021 in our institute. Reticulin histochemistry plus immunohistochemistry for NR4A3 and DOG1 were performed on all cases. Histologically, all four cases featured a tumor-associated lymphoid proliferation and collagenous stroma, in which two formed central scars. The tumors were predominantly solid, with a lobular pattern and variably sized dilated spaces, including one case with focal microcysts. High-grade transformation was not observed in any of our cases. Reticulin stain and immunohistochemistry for NR4A3 showed distinct features between AciCC and non-neoplastic salivary gland parenchyma. DOG1 immunohistochemistry confirmed the acinar origin of AciCC. Our study reveals that pediatric AciCCs often present with tumor-associated lymphoid proliferation (TALP) and sclerosis. Special stains such as reticulin histochemistry and NR4A3 immunohistochemistry are helpful to separate tumor from adjacent benign parenchyma. The ancillary study is helpful for the diagnosis of small specimens. Our study is limited by its low case number, but we hope that our results will promote more studies on this rare salivary gland tumor in the pediatric population.

Simultaneous Expression of PD-1 and PD-L1 in Peripheral and Central Immune Cells and Tumor Cells in the Benign and Malignant Salivary Gland Tumors Microenvironment.

To investigate the differential expression of PD-1 and PD-L1 in salivary gland tumors (SGTs, malignant and benign subtypes) and determine their association with the clinicopathological characterization of the patients. The immunohistochemistry was used to examine PD-1 and PD-L1 expression in specimens from 83 patients with primary SGTs including salivary ductal carcinoma (SDC), adenoid cystic carcinoma (AdCC), acinic cell carcinoma (ACC), mucoepidermoid carcinoma (MEC), warthin's tumors (WT), poleomorphic adenoma (PA) and other subtypes. The expression of PD-1 in peripheral and central immune cells (ICs) of MEC, and peripheral ICs of ACC was significantly higher than those with AdCC (P = 0.02, P = 0.02, P = 0.03, respectively). Interestingly, the expression of PD-1 was also observed in peripheral and central malignant tumor cells (TCs), particularly in SDC and ACC. Despite no significant difference in PD-L1 expression of TCs among malignant subtypes, the peripheral and central ICs of ACC and MEC were revealed to express PDL-1 significantly more than those with AdCC (P < 0.05). WTs were rich in PD-1/PD-L1 expressing ICs. However, the tumor microenvironment of PA generally had low levels of PD-1/PD-L1 expression. In general, the expression of PD-1 in peripheral and central TCs was found to be significantly higher in malignant tumors than in benign ones (P = 0.002 and P = 0.003, respectively). The simultaneous presentation of PD-1 and PD-L1 in TCs and ICs of SGTs, their significant association with disease severity as well as the positive correlation between these immune checkpoints may suggest the therapeutic potential of anti-PD-1 and anti-PDL-1 combinational immunotherapy for SGTs.

Gastrointestinal: Pitfalls of an abruptly elevated alpha-fetoprotein in a chronic hepatitis B carrier.

A 31-year-old male with a history of diabetes mellitus and viral hepatitis B was admitted to our hospital in March 2021 for epigastric pain, steatorrhea, and increased alpha-fetoprotein (AFP). He had a history of excessive drinking for more than a decade. Two years ago, he was admitted to another institution due to abdominal distention, and computed tomography (CT) showed enlargement of the pancreas. He then received endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) and was diagnosed with chronic pancreatitis. Since then, he lost 25 kg, despite relief of associated symptoms after medical treatment, including pancreatic enzyme preparations and prokinetics. Physical examination showed tenderness in the upper abdomen. Laboratory examination revealed the following abnormalities: white blood cell count (11.01 × 109/L), erythrocyte sedimentation rate (120 mm/h), alkaline phosphatase (163 U/L; reference range, 45–125 U/L), γ-glutamyl transpeptidase (223 U/L; reference range, 10–60 U/L), CEA (9.32 ng/mL; reference range, 0–5.00 ng/mL), AFP (3473 ng/mL; reference range, 0–20 ng/mL). Measurements of CA19–9 (21.70 U/mL; reference range, 0–34.00 U/mL) and IgG4 (0.263 g/L, reference range, 0.030–2.100 g/L) were normal. A plain/contrast CT of the abdomen revealed diffuse enlargement of the pancreas with hypodensity, focal coarse calcifications, and a capsule rim sign (Fig. 1a). Positron emission tomography demonstrated an increased uptake of 18F-FDP in the pancreatic head and uncinate process (Fig. 1b). Endoscopic ultrasound examination showed a hypoechoic mass located at the pancreatic head, and fine needle aspiration was performed (Fig. 2a–d). Based on the patient's symptoms and history (male, alcohol consumption, viral hepatitis and significantly increased AFP), the initial consultant doctor focused on screening for hepatocellular carcinoma (HCC). However, CT and positron emission tomography revealed no obvious abnormality of the liver but showed a suspicious pancreatic tumor and chronic pancreatitis (Fig. 1a,b). Though the IgG4 level was normal, considering the “sausage-like” appearance and capsule rim sign of the pancreas revealed by CT, we considered the differential diagnosis of autoimmune pancreatitis. Therefore, EUS-FNA was scheduled for further assessment. Ultrasonographic imaging showed a 4.5 × 4.2 cm hypoechoic mass in the pancreatic head, with an ill-defined border, heterogenous internal echogenicity, and diffusely scattered calcifications (Fig. 2a). Cytological examination revealed the morphology and size of the tumor cells were relatively consistent but moderately enlarged with salt-and-pepper nuclei, which are characteristics of pancreatic neuroendocrine tumors (Fig. 2b). Histopathologic findings showed a heterogenous gland pattern with irregular enlarged nuclei (Fig. 2c). The abnormal cells were found to be positive for CK7 and negative for Hep-par 1 (Fig. 2d), chromogranin A, synaptophysin, or CD56 by immunohistochemical staining (IHS). After a multidisciplinary discussion, final diagnosis was determined as pancreatic ductal adenocarcinoma (PDAC) based on histology and IHS. The patient eventually received chemotherapy consisted of gemcitabine plus capecitabine. After one cycle of treatment, the serum level of AFP rapidly decreased to 1347 ng/mL and related symptoms were relieved significantly. The patient has not returned for follow-up since then. AFP is generally used as a biomarker for HCC, yolk sac tumor, gonadal tumors, and certain types of gastric carcinomas. There are also some reports of AFP-producing pancreatic tumors, usually hepatoid carcinoma and acinar cell carcinoma. The reports of AFP-producing PDAC are rare. One possible explanation for AFP production in pancreatic cancer is the activation of the hepatic gene within the pancreas during carcinogenesis. To identify the diagnosis, histopathology and immunohistochemistry can be crucial. The level of AFP after treatment of the AFP-producing pancreatic tumor may serve as an indicator to monitor therapeutic response and recurrence.

Pancreatic Acinar Cell Carcinoma Projected From the Ampulla of Vater With Extensive Intraductal Tumor Growth.

Pancreatic Acinar Cell Carcinoma Projected From the Ampulla of Vater With Extensive Intraductal Tumor Growth.

Epidemiological and clinical characteristics of 407 salivary glands neoplasms in surgically treated patients in 2010-2020

INTRODUCTION Tumors of the salivary glands account for approximately 3 to 4% of all head and neck neoplasms. It is estimated that 10-15% of them are malignant. The most common benign tumor is pleomorphic adenoma, while the most common malignant tumors are adenoid cystic carcinoma and mucoepidermoid carcinoma. Neoplasms of the salivary glands are extremely histologically diverse, which results from the complex embryogenesis of the salivary glands. The identified risk factors for tumors of the salivary glands are: ultraviolet radiation, ionizing radiation, viral infections, nicotine and alcohol. MATERIAL AND METHOD The aim of the study was an epidemiological analysis of patients with salivary gland neoplasms, the distribution and histopathological characteristics of individual neoplasms treated at the Department of Otorhinolaryngology of the Medical University of Warsaw in 2010-2020. The diagnoses were analyzed according to the latest WHO 2017 histological classification of salivary gland tumors. In addition, the material was supplemented with data on the 5-year survival rates of patients with malignant neoplasms obtained from the Registry of Marital Status. RESULTS AND DISCUSSION The material contained 407 neoplasms of the salivary glands over a 11-year period, of which malignant neoplasms accounted for 17.4%. The malignant tumors were dominated by: adenoid cystic carcinoma (28,2%), mucoepidermoid carcinoma (12,7%), and acinic cell carcinoma (9,9%). Lymphomas (15,5%) were also a large group. The benign neoplasms were dominated by pleomorphic adenoma (54.1%) and Warthin&apos;s tumor (36%). Tumors of the salivary gland the most often affected the parotid gland (92%). CONCLUSIONS The obtained data are consistent with the general epidemiological data described in the current literature.

Pediatric pancreatic lesions: a clinicopathological analysis of 42 cases

Objective: To investigate the clinicopathological characteristics of pancreatic lesions in children. Methods: The clinicopathological data of pancreatic lesions in children were analyzed including 42 cases of pancreatic tumors diagnosed from January 2000 to May 2021 in Guangzhou Women's and Children's Medical Center, Guangzhou, China. Histological and immunohistochemical assessments were performed. Related literature was reviewed. Results: The 42 pediatric patients with pancreatic lesions aged 1 day to 12 years (mean, 4.25 years). There were 23 males and 19 females. Clinical presentations included abdominal masses, abdominal pain, vomiting and persistent hypoglycemia after birth. Ultrasound and computerized tomography examination showed space-occupying pancreatic lesions in 31 cases, but no detectable pancreatic lesions in 11 cases. Histologically, among the 42 cases, 22 cases (52.4%) were neoplastic, including 18 cases of epithelial origin. Nine cases of pancreatoblastoma showed that the epithelial tumor cells were arranged in a trabecular pattern, with squamous nests. Six cases of solid-pseudopapillary tumors revealed hemorrhagic and necrotic cysts and monomorphic epithelioid cells arranged in solid sheets, nests or pseudopapillae. Two cases of neuroendocrine tumors showed tumor cells arranged in cords or nests; one case had a mitotic count of about 3/10 high power field, and a Ki-67 index of about 5%, which was consistent with G2 neuroendocrine tumor; the other case showed tumor cells with cytological atypia, brisk mitoses, about 25/10 HPF and a Ki-67 index of about 80%, consistent with small-cell type neuroendocrine carcinoma. The case of acinar cell carcinoma showed high cellularity, tumor cells in solid, cord-like or acinar-like arrangement with little stroma, and monotonous tumor cells with single distinct nucleolus. There were 4 cases of mesenchymal tumors, including 3 cases of Kaposi's hemangioendothelioma and 1 case of inflammatory myofibroblastic tumor. Among the 20 cases (47.6%) of non-neoplastic lesions, there were 11 cases of hyperinsulinism with ATP-sensitive potassium channel abnormality (HAPCA). Severn cases of diffuse type HAPCA in which the islets scattered between the pancreatic acinar tissue, enlarged, and prominent nuclei. Three cases of focal type HAPCA showed pancreatic islet hyperplasia in the form of nested nodules (0.6-1.5 cm). One case of atypical type HAPCA had extensive islet hyperplasia in pancreatic tissue, and scattered proliferation of nest-like nodules was noted. There were also 7 cases of pseudocyst and 2 cases of congenital cyst. Immunohistochemically, pancreatoblastomas were diffusely positive for CKpan, CK8/18, and β-catenin (nuclear staining of squamous nests only). Solid-pseudopapillary tumors expressed CD10, cyclin D1, CD99, vimentin, CD56, and β-catenin (nuclear staining). Neuroendocrine tumors were positive for CK, Syn, NSE, CgA, CD56, and β-catenin (membranous staining). The acinar cell carcinoma was positive for CK8/18, trypsin, and β-catenin (membranous staining). Conclusions: Pancreatic lesions in children have a wide range of histopathological types. HAPCA is the most common lesion of newborns. Pediatric pancreatic tumors are rare and mostly malignant. It is important to recognize them and make correct pathological diagnoses.

The value of immunohistochemical expression of Ki-67 and CD34 in differentiating ductal carcinoma in situ from ductal carcinoma in situ-like invasive breast cancer

Objective: To investigate the expression of Ki-67 and CD34 in the differential diagnosis of ductal carcinoma in situ (DCIS) and DCIS-like invasive breast cancer (DLIBC). Methods: A total of 100 cases of DCIS and 150 cases of DLIBC diagnosed pathologically in Yantai Yuhuangding Hospital from January 2019 to March 2022 were collected. The expression of p63, CK5/6, Ki-67 and CD34 in both groups were detected by immunohistochemical (IHC) staining and evaluated. Results: The 100 cases of DCIS included 11 cases of low-grade DCIS, 28 cases of intermediate-grade DCIS and 61 cases of high-grade DCIS. IHC staining of p63 and CK5/6 showed the myoepithelial cells around cancerous duct were complete or partial absence. Ki-67 expression showed two patterns: high expression in the basal layers and scattered expression within the tumor. Most cases showed mainly high basal expression (77/100, 77%), and the proportion of this pattern was significantly different between low grade and high grade DCIS (P<0.05). All cases showed complete CD34 expression surrounding the cancerous duct with different proportion (vascular necklace) suggested small vessels proliferation. The 150 cases of DLIBC included 142 cases of invasive ductal carcinoma (IDC) (three cases of basal-like breast cancer was included), two cases of secretory carcinoma, three cases of solid papillary carcinoma, two cases of adenoid cystic carcinoma and one case of acinar cell carcinoma. Among 142 cases of IDC, 13 cases were grade Ⅰ, 77 were grade Ⅱ and 52 were grade Ⅲ. IHC staining of p63 showed complete absence of myoepithelium. CK5/6 was negative in most cases and only positively expressed within the tumor in 3 cases of basal-like breast cancer. Ki-67 indicated a scattered expression pattern within the tumor. In most cases, CD34 immunostaining showed scattered positive blood vessels within the tumor while only two cases showed incomplete expression of CD34 around the tumor (2/150, 1.3%). The different expression patterns of Ki-67 and CD34 in DCIS and DLIBC was statistically significant (P<0.05). Conclusions: The different expression patterns of Ki-67 and CD34 are helpful to distinguish DLIBC from DCIS. The appearance of "vascular necklace" with CD34 and the high expression of Ki-67 around the cancerous duct highly support the diagnosis of DCIS, and the scattered expression pattern of CD34 supports DLIBC.