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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

Primary small bowel adenocarcinoma with loss of nuclear expression of PMS2 after resection of mucinous cholangiocarcinoma [Case Report]

Mujeeb Ullah, Ateeqa; Jaysing, Anna; Hashmi, Hassan Raza; Sohail, Amir Humza; Li, Wendi; Allendorf, John D; Sarkar, Suparna A
Mucinous cholangiocarcinoma is an extremely rare form of intrahepatic cholangiocarcinoma that has been characterized by rapid growth, widespread metastasis and poor prognosis. These tumors have been shown to be a part of the Lynch syndrome tumor spectrum, however, the role of DNA mismatch repair (MMR) deficiency in their development is poorly understood. We present the case of a 74-year-old male with cholangiocarcinoma, who underwent Roux-en-Y hepaticojejunostomy and extended left hepatectomy and was diagnosed with a primary small bowel adenocarcinoma 2 years later. Immunohistochemistry testing for mismatch repair proteins was significant for the loss of nuclear expression of PMS2. Taken together, the cause of both the mucinous cholangiocarcinoma and primary small bowel adenocarcinoma with PMS2 loss in the patient presented here is likely genetic, suggestive of a cancer syndrome.
PMID: 35111293
ISSN: 2042-8812
CID: 5153712

The Role of Endoscopic Ultrasound-Guided Ki67 in The Management of Non-Functioning Pancreatic Neuroendocrine Tumors

Cui, YongYan; Khanna, Lauren G; Saqi, Anjali; Crapanzano, John P; Mitchell, James M; Sethi, Amrita; Gonda, Tamas A; Kluger, Michael D; Schrope, Beth A; Allendorf, John; Chabot, John A; Poneros, John M
Background/Aims/UNASSIGNED:The management of small, incidentally discovered nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs) has been a matter of debate. Endoscopic ultrasound with fine-needle aspiration (EUS-FNA) is a tool used to identify and risk-stratify PNETs. This study investigates the concordance rate of Ki67 grading between EUS-FNA and surgical pathology specimens in NFPNETs and whether certain NF-PNET characteristics are associated with disease recurrence and disease-related death. Methods/UNASSIGNED:: We retrospectively reviewed the clinical history, imaging, endoscopic findings, and pathology records of 37 cases of NFPNETs that underwent pre-operative EUS-FNA and surgical resection at a single academic medical center. Results/UNASSIGNED:: There was 73% concordance between Ki67 obtained from EUS-FNA cytology and surgical pathology specimens; concordance was the highest for low- and high-grade NF-PNETs. High-grade Ki67 NF-PNETs based on cytology (p=0.028) and histology (p=0.028) were associated with disease recurrence and disease-related death. Additionally, tumors with high-grade mitotic rate (p=0.005), tumor size >22.5 mm (p=0.104), and lymphovascular invasion (p=0.103) were more likely to have poor prognosis. Conclusions/UNASSIGNED:: NF-PNETs with high-grade Ki67 on EUS-FNA have poor prognosis despite surgical resection. NF-PNETs with intermediate-grade Ki67 on EUS-FNA should be strongly considered for surgical resection. NF-PNETs with low-grade Ki67 on EUSFNA can be monitored without surgical intervention, up to tumor size 20 mm.
PMID: 31302988
ISSN: 2234-2400
CID: 4014882


Stavropoulos, Stavros N.; Modayil, Rani J.; Zhang, Xiaocen; Peller, Hallie; Brathwaite, Collin E.; Allendorf, John; Widmer, Jessica L.; Friedel, David; Grendell, James H.
ISSN: 0016-5107
CID: 4790372


Zhang, Xiaocen; Modayil, Rani J.; Badshah, Maaz B.; Brathwaite, Collin E.; Allendorf, John; Friedel, David; Stavropoulos, Stavros N.
ISSN: 0016-5107
CID: 4790332

Painless Jaundice: A Rare Presentation of Uterine Leiomyosarcoma With Pancreatic Metastasis [Meeting Abstract]

Ali, Mohammad; Sticco, Kristen; Shah, Rakesh; Schneider, Jeffrey; Allendorf, John; Widmer, Jessica
ISSN: 0002-9270
CID: 3897702


Widmer, Jessica L.; Modayil, Rani J.; Friedel, David; Allendorf, John; Grendell, James H.; Stavropoulos, Stavros N.
ISSN: 0016-5107
CID: 3522472

A Prospective Randomized Multicenter Trial of Distal Pancreatectomy With and Without Routine Intraperitoneal Drainage

Van Buren, George; Bloomston, Mark; Schmidt, Carl R; Behrman, Stephen W; Zyromski, Nicholas J; Ball, Chad G; Morgan, Katherine A; Hughes, Steven J; Karanicolas, Paul J; Allendorf, John D; Vollmer, Charles M; Ly, Quan; Brown, Kimberly M; Velanovich, Vic; Winter, Jordan M; McElhany, Amy L; Muscarella, Peter; Schmidt, Christian Max; House, Michael G; Dixon, Elijah; Dillhoff, Mary E; Trevino, Jose G; Hallet, Julie; Coburn, Natalie S G; Nakeeb, Attila; Behrns, Kevin E; Sasson, Aaron R; Ceppa, Eugene P; Abdel-Misih, Sherif R Z; Riall, Taylor S; Silberfein, Eric J; Ellison, Edwin C; Adams, David B; Hsu, Cary; Tran Cao, Hop S; Mohammed, Somala; Villafañe-Ferriol, Nicole; Barakat, Omar; Massarweh, Nader N; Chai, Christy; Mendez-Reyes, Jose E; Fang, Andrew; Jo, Eunji; Mo, Qianxing; Fisher, William E
OBJECTIVE:The objective of this study was to test the hypothesis that distal pancreatectomy (DP) without intraperitoneal drainage does not affect the frequency of grade 2 or higher grade complications. BACKGROUND:The use of routine intraperitoneal drains during DP is controversial. Prior to this study, no prospective trial focusing on DP without intraperitoneal drainage has been reported. METHODS:Patients undergoing DP for all causes at 14 high-volume pancreas centers were preoperatively randomized to placement of a drain or no drain. Complications and their severity were tracked for 60 days and mortality for 90 days. The study was powered to detect a 15% positive or negative difference in the rate of grade 2 or higher grade complications. All data were collected prospectively and source documents were reviewed at the coordinating center to confirm completeness and accuracy. RESULTS:A total of 344 patients underwent DP with (N = 174) and without (N = 170) the use of intraperitoneal drainage. There were no differences between cohorts in demographics, comorbidities, pathology, pancreatic duct size, pancreas texture, or operative technique. There was no difference in the rate of grade 2 or higher grade complications (44% vs. 42%, P = 0.80). There was no difference in clinically relevant postoperative pancreatic fistula (18% vs 12%, P = 0.11) or mortality (0% vs 1%, P = 0.24). DP without routine intraperitoneal drainage was associated with a higher incidence of intra-abdominal fluid collection (9% vs 22%, P = 0.0004). There was no difference in the frequency of postoperative imaging, percutaneous drain placement, reoperation, readmission, or quality of life scores. CONCLUSIONS:This prospective randomized multicenter trial provides evidence that clinical outcomes are comparable in DP with or without intraperitoneal drainage.
PMID: 28692468
ISSN: 1528-1140
CID: 3487002

Comment on: Clinicopathological study on metachronous double cholangiocarcinomas of perihilar and subsequent distal bile duct origin [Comment]

Allendorf, John
PMID: 28318553
ISSN: 1532-7361
CID: 3487322

Differences in single gland and multigland disease are seen in low biochemical profile primary hyperparathyroidism

Lim, James Y; Herman, Max C; Bubis, Lev; Epelboym, Irene; Allendorf, John D; Chabot, John A; Lee, James A; Kuo, Jennifer H
BACKGROUND:Primary hyperparathyroidism is characterized by increased levels of serum calcium and parathyroid hormone. Recently, 2 additional mild biochemical profiles have emerged, normocalcemic and normohormonal primary hyperparathyroidism. We reviewed our surgical experience of mild biochemical profile patients and compared them with classic primary hyperparathyroidism patients. METHODS:test. A logistic regression was performed to identify significantly independent predictor variables for multigland disease. RESULTS:A total of 573 patients underwent parathyroidectomy for primary hyperparathyroidism (classic, n = 405; normohormonal, n = 96; normocalcemic, n = 72). Normocalcemic primary hyperparathyroidism was associated with multigland disease in 43 (45%, P < .001) patients as compared with the normohormonal (7, 10%) and classic (36, 9%) groups. On logistic regression, significant predictors for multigland disease were the normocalcemic subtype and positive family history. Twelve month biochemical normalization rates after operative treatment were >98% in all 3 groups. CONCLUSION:Our series shows that normocalcemic primary hyperparathyroidism is associated with a high incidence of multigland disease. Normohormonal disease is similar to classic disease patients with >90% presenting with single adenomas. Excellent rates of biochemical normalization can be obtained by operative treatment in all 3 groups.
PMID: 27847113
ISSN: 1532-7361
CID: 3486982