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Concurrent Hepatoblastoma and Wilms Tumor Leading to Diagnosis of Beckwith-Wiedemann Syndrome

Wolfe, Danielle M; Webster Carrion, Andrea; Masukhani, Mahesh M; Oberg, Jennifer A; Pavisic, Jovana; El-Ali, Alexander; Gupta, Mala; Weng, Katherine; Glasser, Chana L
Beckwith-Wiedemann syndrome (BWS) is an epigenetic overgrowth disorder and cancer predisposition syndrome caused by imprinting defects of chromosome 11p15.5-11p15.4. BWS should be considered in children with atypical presentations of embryonal tumors regardless of clinical phenotype. Risk of malignancy correlates with specific molecular subgroups of BWS making molecular subclassification important for appropriate cancer screening. We report the first case of concurrent embryonal tumors in a phenotypically normal child, leading to the diagnosis of BWS with paternal uniparental disomy and describe the molecular classification of BWS as it relates to malignancy risk, along with approach to management.
PMID: 36730589
ISSN: 1536-3678
CID: 5420412

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

Zhao, Chaohui Lisa; Dabiri, Bahram; Hanna, Iman; Lee, Lili; Xiaofei, Zhang; Hossein-Zadeh, Zarrin; Cao, Wenqing; Allendorf, John; Rodriguez, Alex Pipas; Weng, Katherine; Turunbedu, Solomon; Boyd, Adrienne; Gupta, Mala
INTRODUCTION/BACKGROUND: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/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/CONCLUSIONS: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.
PMID: 37119647
ISSN: 1532-8198
CID: 5465742

A CASE OF SMALL CELL OSTEOSARCOMA WITH RARE REARRANGEMENT OF EWSR1 (22Q12.2) LOCI BY FISH [Meeting Abstract]

Glasser, Chana; Joshi, Vivek; Gupta, Mala; Manukyan, Irena; Mansukhani, Mahesh; Subramaniyam, Shivakumar
ISI:000788322300391
ISSN: 1545-5009
CID: 5243902

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

Zhao, Chaohui Lisa; Rapkiewicz, Amy; Maghsoodi-Deerwester, Mona; Gupta, Mala; Cao, Wenqing; Palaia, Thomas; Zhou, Jianhong; Ram, Bebu; Vo, Duc; Rafiee, Behnam; Hossein-Zadeh, Zarrin; Dabiri, Bahram; Hanna, Iman
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.
PMCID:7722493
PMID: 33307078
ISSN: 1532-8392
CID: 4770842

Proteomic analyses of ECM during pancreatic ductal adenocarcinoma progression reveal different contributions by tumor and stromal cells

Tian, Chenxi; Clauser, Karl R; Öhlund, Daniel; Rickelt, Steffen; Huang, Ying; Gupta, Mala; Mani, D R; Carr, Steven A; Tuveson, David A; Hynes, Richard O
Pancreatic ductal adenocarcinoma (PDAC) has prominent extracellular matrix (ECM) that compromises treatments yet cannot be nonselectively disrupted without adverse consequences. ECM of PDAC, despite the recognition of its importance, has not been comprehensively studied in patients. In this study, we used quantitative mass spectrometry (MS)-based proteomics to characterize ECM proteins in normal pancreas and pancreatic intraepithelial neoplasia (PanIN)- and PDAC-bearing pancreas from both human patients and mouse genetic models, as well as chronic pancreatitis patient samples. We describe detailed changes in both abundance and complexity of matrisome proteins in the course of PDAC progression. We reveal an early up-regulated group of matrisome proteins in PanIN, which are further up-regulated in PDAC, and we uncover notable similarities in matrix changes between pancreatitis and PDAC. We further assigned cellular origins to matrisome proteins by performing MS on multiple lines of human-to-mouse xenograft tumors. We found that, although stromal cells produce over 90% of the ECM mass, elevated levels of ECM proteins derived from the tumor cells, but not those produced exclusively by stromal cells, tend to correlate with poor patient survival. Furthermore, distinct pathways were implicated in regulating expression of matrisome proteins in cancer cells and stromal cells. We suggest that, rather than global suppression of ECM production, more precise ECM manipulations, such as targeting tumor-promoting ECM proteins and their regulators in cancer cells, could be more effective therapeutically.
PMID: 31484774
ISSN: 1091-6490
CID: 4115312

Implementation of Synoptic Reporting for Early Carcinomas of the Gastrointestinal Tract, removed by Endoscopic Submucosal Dissection, Significantly Improves the Completeness of Pathology Report in Six Parameters [Meeting Abstract]

Rafiee, Behnam; Gupta, Mala
ISI:000478081103446
ISSN: 0023-6837
CID: 4047782

Implementation of Synoptic Reporting for Early Carcinomas of the Gastrointestinal Tract, removed by Endoscopic Submucosal Dissection, Significantly Improves the Completeness of Pathology Report in Six Parameters [Meeting Abstract]

Rafiee, Behnam; Gupta, Mala
ISI:000478915503468
ISSN: 0893-3952
CID: 4048292

Endoscopic ultrasound guided fine-needle aspiration: What variables influence diagnostic yield?

Mohanty, Sambit K; Pradhan, Dinesh; Sharma, Shivani; Sharma, Anurag; Patnaik, Niharika; Feuerman, Martin; Bonasara, Robert; Boyd, Adrienne; Friedel, David; Stavropoulos, Stavros; Gupta, Mala
BACKGROUND:Endoscopic ultrasound (EUS) guided fine-needle aspiration (FNA) plays an important role in the diagnosis of various lesions. We sought to determine factors that influence the diagnostic yield of EUS-FNA, specifically, the presence of a cytopathologist, FNA site, and the endoscopist's skill. METHODS:The data on cytopathologist's availability, duration of procedure, number of passes made, and diagnostic material for cell block (CB) preparation was collected over an 18 months period. RESULTS:230 specimens (218 patients) were obtained from pancreas (114), lymph node (64), submucosal lesions of the gastrointestinal tract (27), liver (8), and miscellaneous (17) sites. The results were classified as informative (77.8%) and non-informative (NI) (22.2%). The NI rate was significantly high, when a cytopathologist was absent (P = .0008). As the likelihood of cytopathologist's presence increased from 35.8% to 82.9%, the CB quality increased (P < .0001). In the absence of a cytopathologist, the likelihood of NI result increased more than 2-fold (P = .03) and of an inadequate CB increased 3-fold (P < .0001). The more experienced endoscopist "C" (compared to the less experienced "A + B") was less likely to get inadequate material (40.5% vs. 66.3%) (P = .0001). CONCLUSION/CONCLUSIONS:The diagnostic yield of EUS-FNA is significantly related to the presence of an on-site cytopathologist and endoscopist's skill in procuring diagnostic material.
PMID: 29280329
ISSN: 1097-0339
CID: 3484272

Prospective, Randomized Comparison of 3 Endoscopic Submucosal Dissection (ESD) Knives in an Acute Porcine Model [Meeting Abstract]

Stavropoulos, Stavros; Ghevariya, Vishal; Cho, Jaehoon; DeJesus, Dolorita; Katsogridakis, Ioannis; Gupta, Mala; Rodriguez, Katherine; Barkan, Alexander; Angelos, George; Iqbal, Shahzad; Grendell, James; Grendell, James H. H.
ISI:000439259002064
ISSN: 0002-9270
CID: 3522552

Magnetic resonance imaging as an adjunct to ultrasound in evaluating cesarean scar ectopic pregnancy

Wu, Rebecca; Klein, Michelle A; Mahboob, Sabrina; Gupta, Mala; Katz, Douglas S
Cesarean scar pregnancies (CSPs) are a relatively rare form of ectopic pregnancy in which the embryo is implanted within the fibrous scar of a previous cesarean section. A greater number of cases of CSPs are currently being reported as the rates of cesarean section are increasing globally and as detection of scar pregnancy has improved with use of transvaginal ultrasound (TVUS) with color Doppler imaging. Delayed diagnosis and management of this potentially life-threatening condition may result in complications, predominantly uterine rupture and hemorrhage with significant potential maternal morbidity. Diagnosis of a cesarean scar pregnancy (CSP) requires a high index of clinical suspicion, as up to 40% of patients may be asymptomatic. TVUS has a reported sensitivity of 84.6% and has become the imaging examination of choice for diagnosis of a CSP. Magnetic resonance imaging (MRI) has been used in a small number of patients as an adjunct to TVUS. In the present report, MRI is highlighted as a problem-solving tool capable of more precisely identifying the relationship of a CSP to adjacent structures, thereby providing additional information critical to directing appropriate patient management and therapy.
PMCID:3692029
PMID: 23814688
ISSN: 2156-7514
CID: 2061972