Improving fine needle aspiration to predict the tumor biological aggressiveness in pancreatic neuroendocrine tumors using Ki-67 proliferation index, phosphorylated histone H3 (PHH3), and BCL-2.

INTRODUCTION: Surgery is the only known cure for sporadic pancreatic neuroendocrine tumors (PNETs). Therefore, the prediction of the PNETs biological aggressiveness evaluated on endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has a significant impact on clinical management. The proliferation rate of Ki-67 in PNETs can help to predict the biological aggressiveness of the tumor. In addition, there is a relatively new proliferation marker called phosphorylated histone H3 (PHH3) that can identify and quantify dividing cells in tissue samples, which is a marker highly specific to mitotic figures. Other markers such as BCL-2 also contribute to tumorigenesis and may be involved in the differentiation of neuroendocrine cells. MATERIALS AND METHODS: A retrospective observational study was performed on patients undergoing surveillance for PNETs from January 2010 to May 2021. Data collection included the patients' age, sex, tumor location, tumor size in the surgical specimen, and tumor grade in FNA. The 2019 World Health Organization (WHO) classification guideline was followed to diagnose PNETs, including grade and stage. Immunohistochemical stainings for Ki-67, PHH3 and BCL-2 in PNETs were performed. RESULTS: After excluding cell blocks containing fewer than 100 tumor cells, 44 patients with EUS-FNA and surgical resection specimens were included in this study. There were 19 cases of G1 PNETs, 20 cases of G2 PNETs, and 5 cases of G3 PNETs. The grade assigned based on the Ki-67 index was higher and more sensitive than that based on the mitotic count using H&E slides in some cases of G2 and G3 PNETs. However, there was no significant difference between the mitotic count using PHH3-positive tumor cells and the Ki-67 index to grade PNETs. All grade 1 tumors (19 cases) on surgical resection specimens were correctly graded on FNA (100 % concordance rate). Within the 20 G2 PNETs, 15 cases of grade 2 on surgical resection specimens were graded correctly on FNA based on the Ki-67 index only. Five cases of grade 2 PNETs on surgical resection specimens were graded as grade 1 on FNA when using only the Ki-67 index. Three of five grade 3 tumors on surgical resection specimens were graded as grade 2 on FNA based on the Ki-67 index only. Using only FNA Ki-67 to predict PNET tumor grade, the concordance (accuracy) rate was 81.8 % in total. However, all these eight cases (5 cases of G2 PNETs and 3 cases of G3 PNETs) were graded correctly by using the Ki-67 index plus mitotic rate (using PHH3 IHC stains). Four of 18 (22.2 %) patients with PNETs were positive for BCL-2 stain. In these 4 cases positive for BCL-2 stains, 3 cases were G2 PNETs and one case was G3 PNETs. CONCLUSION: Grade and the proliferative rate in EUS-FNA can be used to predict the tumor grade in surgical resection specimens. However, when using only FNA Ki-67 to predict PNET tumor grade, about 18 % of cases were downgraded by one level. To solve the problem, immunohistochemical staining for BCL-2 and especially PHH3 would be helpful. Our results demonstrated that the mitotic count using PHH3 IHC stains not only improved the accuracy and precision of PNET grading in the surgical resection specimens, but also could reliably be used in routine scoring of mitotic figures of FNA specimens.

The concordance between wide-area transepithelial sampling with computer-assisted 3-dimensional analysis (WATS-3D) and standard endoscope biopsy in the detection of Barrett's esophagus and esophageal dysplasia.

INTRODUCTION: Barrett's esophagus (BE) is a premalignant condition that leads to susceptibility to developing adenocarcinoma. The most common endoscopic surveillance technique is forceps biopsy, which involves sampling the specimen every 1 to 2 cm along the length of the lesion. This technique has a low sensitivity and often leaves the majority of the esophageal mucosa untested. Recently, the use of wide-area transepithelial sampling with computer-assisted 3-dimensional analysis (WATS-3D) has received much attention. However, there is little known about this novel technique, and this research aims to add to our knowledge of WATS-3D by comparing it to traditional forceps biopsy. MATERIALS AND METHODS: A retrospective observational study was performed. All existing GI biopsy cases diagnosed with WATS-3D were identified from the institutional pathology databases of NYU Langone Hospital - Long Island from 2019 to 2021. Data collection included patients' age, sex, and dysplasia results. Existing pathology reports and CDx diagnostics were reviewed. All the existing slides of the biopsy cases were pulled out and reviewed. Dysplasia was classified as no dysplasia, indefinite for dysplasia, lowgrade dysplasia, and high-grade dysplasia. RESULTS: A total of 109 cases were included in this study. There are 59 cases diagnosed as BE with forceps biopsy, 72 cases by WATS-3D, and 77 cases by WATS-3D combined with forceps biopsy. The sensitivity of detecting BE was significantly increased by WATS-3D and further by WATS-3D combined with forceps biopsy. In 59 cases diagnosed as BE with forceps biopsy, 50 cases were classified as no dysplasia, 3 cases were indefinite for dysplasia, 5 cases were low-grade dysplasia, and 1 case was high-grade dysplasia. In 72 cases diagnosed as BE by WATS-3D, 64 cases were classified as no dysplasia, 7 cases were indefinite for dysplasia, 1 case was high-grade dysplasia, and no cases with low-grade dysplasia. In 77 cases diagnosed as BE by WATS-3D combined with forceps biopsy, 63 cases were classified as no dysplasia, 8 cases were indefinite for dysplasia, 5 cases with low-grade dysplasia, and 1 case was highgrade dysplasia. The maximal longitudinal extent of the esophageal mucosal changes strongly correlated with the severity of BE. CONCLUSION: Compared to traditional forceps biopsy, WATS-3D was more sensitive in finding intestinal metaplasia. However, WATS-3D could not clearly discriminate low-grade dysplasia from indefinite for dysplasia and tended to classify low-grade dysplasia as indefinite for dysplasia. The addition of WATS-3D to forceps biopsy resulted in an increase in diagnostic yield and thus an increase in the quality of patient care.

Fatal Excipients: An Autopsy Case Series of Excipient Lung Disease.

ABSTRACT: Crushed oral tablets, when injected intravenously, may induce a foreign body granulomatous reaction in and around pulmonary arterioles, because of the presence of filler materials (excipients). This typically presents as shortness of breath in the context of pulmonary hypertension with arteriolar dilation and centrilobular nodules on imaging modalities. The constellation of findings may be overlooked or misdiagnosed by clinicians and pathologists, ultimately affecting patient care and postmortem assessment. We describe 5 patients with excipient lung disease that had antemortem chronic medical conditions that required a peripherally inserted catheter or port. All 5 patients had intravascular and perivascular deposition of polarizable foreign material within the pulmonary arteries. Foreign body granulomatosis as a result of intravenous drug use was not clinically suspected in any patient, and 2 of the 5 patients were misdiagnosed with mycobacterium infections. Pulmonary congestion, dyspnea, and symptoms of heart failure were noted in 3 patients and 2 had a history of upper arm deep vein thrombosis. We conclude that excipient lung disease may be underdiagnosed cause of dyspnea, pulmonary hypertension, and death in patients with a known history of intravenous drug use.

Pediatric hematolymphoid pathology in the gastrointestinal tract.

Hematolymphoid processes involving the gastrointestinal tract in the pediatric and adolescent young adult (AYA) populations include processes occurring primarily within the gastrointestinal tract as well as systemic diseases with predilection for gastrointestinal involvement. Here, we present a focused review of reactive and neoplastic entities occurring in the pediatric and AYA age groups.

Pathological findings in the postmortem liver of patients with coronavirus disease 2019 (COVID-19).

Although coronavirus disease 2019 (COVID-19) is transmitted via respiratory droplets, there are multiple gastrointestinal and hepatic manifestations of the disease, including abnormal liver-associated enzymes. However, there are not many published articles on the pathological findings in the liver of patients with COVID-19. We collected the clinical data from 17 autopsy cases of patients with COVID-19 including age, sex, Body mass index (BMI), liver function test (alanine aminotransaminase (ALT), aspartate aminotransaminase (AST), alkaline phosphatase (ALP), direct bilirubin, and total bilirubin), D-dimer, and anticoagulation treatment. We examined histopathologic findings in postmortem hepatic tissue, immunohistochemical (IHC) staining with antibody against COVID-19 spike protein, CD68 and CD61, and electron microscopy. We counted the number of megakaryocytes in liver sections from these COVID-19-positive cases. Abnormal liver-associated enzymes were observed in 12 of 17 cases of COVID-19 infection. With the exception of three cases that had not been tested for D-dimer, all 14 patients' D-dimer levels were increased, including the cases that received varied doses of anticoagulation treatment. Microscopically, the major findings were widespread platelet-fibrin microthrombi, steatosis, histiocytic hyperplasia in the portal tract, mild lobular inflammation, ischemic-type hepatic necrosis, and zone 3 hemorrhage. Rare megakaryocytes were found in sinusoids. COVID-19 IHC demonstrates positive staining of the histiocytes in the portal tract. Under electron microscopy, histiocyte proliferation is present in the portal tract containing lipid droplets, lysosomes, dilated ribosomal endoplasmic reticulum, microvesicular bodies, and coronavirus. The characteristic findings in the liver of patients with COVID-19 include numerous amounts of platelet-fibrin microthrombi, as well as various degrees of steatosis and histiocytic hyperplasia in the portal tract. Possible mechanisms are also discussed.

A Mucinous Cystic Neoplasm Originating from the Gallbladder: A Case Report and Literature Review.

INTRODUCTION: Mucinous cystic neoplasms of the gallbladder are extremely rare, benign, unilocular or multilocular cystic tumors that contain septations. Mucinous cystadenoma, a subtype of mucinous cystic neoplasm, is defined as epithelial cystic proliferations composed of cells that contain intracytoplasmic mucin. CASE PRESENTATION: A 70-year-old African American woman was admitted to the hospital because of progressive lower back pain and inability to walk. She was scheduled for a kyphoplasty. However, the day before surgery, she reported severe abdominal pain radiating to her right shoulder. On further workup, results of abdominal ultrasonography revealed a cystic mass in the lumen of the gallbladder. The kyphoplasty was postponed and a laparoscopic cholecystectomy was performed. Pathologic evaluation of the gallbladder revealed a multiloculated mucinous cystic neoplasm. DISCUSSION: Mucinous cystadenoma of the gallbladder account for 0.02% of the total number of cases in the hepatobiliary system. They are more frequently seen in middle-age women with a mean age at presentation of 45 years. Symptoms vary depending on the location of the tumor, but it typically presents as acute or chronic right upper quadrant pain, epigastric pain, and nausea and vomiting. The multilocular form is more common than unilocular. The cystic lesions can be filled with serous, hemorrhagic, mucinous, or mixed fluids. Clinicians should be suspicious of mucinous cystadenoma of the gallbladder when common gallbladder disease is excluded because malignant features can be present in the lesion.