Recent Articles on Pancreatobiliary #Pathology – 2020-09-14

These are the recent articles on Pancreatobiliary Pathology:

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New Pancreas Articles


  • Zinc: Roles in pancreatic physiology and disease

Pancreatology : official journal of the International Association of Pancreatology (IAP) … [et al.] 2020 Sep;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32917512

Zinc is an essential trace element. Deficiencies are frequently seen with gastrointestinal diseases, including chronic pancreatitis, nutritional deficiency, and reduced intestinal absorption. Additionally, reduced zinc levels have been linked to cellular changes associated with acute pancreatitis such as enhanced inflammation with increased macrophage activation and production of inflammatory cytokines such as IL-1β, impaired autophagy, and modulation of calcium homeostasis. Preliminary data suggest that zinc deficiency may lead to pancreatic injury in animal models. The purpose of this review is to explore the biologic effects of zinc deficiency that could impact pancreatic disease. MESH KEYWORDS: Malnutrition, inflammation, trace element.

doi: https://doi.org/10.1016/j.pan.2020.08.016



  • Clinicopathological heterogeneity between primary and metastatic sites of gastroenteropancreatic neuroendocrine neoplasm

Diagnostic pathology 2020 Sep;15(1):108

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32917216

BACKGROUND: Chromogranin A (CgA), synaptophysin (Syn) and the Ki-67 index play significant roles in diagnosis or the evaluation of the proliferative activity of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). However, little is known about whether these biological markers change during tumor metastasis and whether such changes have effect on prognosis.
METHODS: We analyzed 35 specimens of both primary and metastatic tumor from 779 patients who had been diagnosed as GEP-NENs at Wuhan Union Hospital from August 2011 to October 2019. The heterogeneity of CgA, Syn and Ki-67 index was evaluated by immunohistochemical analysis.
RESULTS: Among these 779 patients, the three most common sites of NENs in the digestive tract were the pancreas, rectum and stomach. Metastases were found in 311 (39.9%) patients. Among the 35 patients with both primary and metastatic pathological specimens, differences in the Ki-67 level were detected in 54.3% of the patients, while 37.1% showed a difference in CgA and only 11.4% showed a difference in Syn. Importantly, due to the difference in the Ki-67 index between primary and metastatic lesions, the WHO grade was changed in 8.6% of the patients. In addition, a Kaplan-Meier survival analysis showed that patients with Ki-67 index variation had a shorter overall survival (p = 0.0346), while neither Syn variation nor CgA variation was related to patient survival (p = 0.7194, p = 0.4829).
CONCLUSIONS: Our data indicate that primary and metastatic sites of GEP-NENs may exhibit pathological heterogeneity. Ki-67 index variation is closely related to the poor prognosis of patients with tumor metastasis, but neither Syn variation nor CgA variation is related to patient prognosis. Therefore, clinicopathologic evaluation of the primary tumor and metastatic sites could be helpful for predicting the prognosis.

doi: https://doi.org/10.1186/s13000-020-01030-x



  • Simultaneous Discordant B-Lymphoblastic Lymphoma and Follicular Lymphoma

American journal of clinical pathology 2020 Sep;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32915189

OBJECTIVES: We report a rare case of B-lymphoblastic lymphoma (B-LBL) and low-grade follicular lymphoma (FL) identified concurrently in biopsies from different sites at the initial diagnosis in a 39-year-old man. The clonal relationship between the 2 histologic subtypes was investigated.
METHODS: A diagnosis of FL grade ½ (low grade) was made by bone marrow (BM) biopsy. B-LBL was identified in biopsies from the testis and pancreas. Cytogenetic and molecular analyses were performed to investigate their clonal relationship.
RESULTS: Interphase fluorescence in situ hybridization analyses and G-banding karyotype analyses identified the BCL2-IGH and MYC-IGH translocation in tumor cells from both the BM and testis. The tumor cells from the BM and testis shared the same IGH VDJ usage and a high degree of somatic mutations. These findings suggest that acquisition of MYC gene rearrangement is a critical event for lymphoblastic transformation of FL. Of note, the presence of intraclonal diversity in the B-LBL sample further suggests an earlier or concurrent event of MYC translocation than the somatic IGH mutation in the germinal center and the dedifferentiation of lymphoma cells to a precursor stage of B-cell development.
CONCLUSIONS: B-lymphoblastic transformation of FL can occur with MYC gene rearrangement.

doi: https://doi.org/10.1093/ajcp/aqaa126



  • SATB2 in Neoplasms of Lung, Pancreatobiliary, and Gastrointestinal Origins

American journal of clinical pathology 2020 Sep;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32914850

OBJECTIVES: Special AT-rich binding protein 2 (SATB2) immunohistochemistry (IHC) has high sensitivity and specificity for colorectal adenocarcinoma (CRC), but data on its expression in specific subsets of pulmonary, gastric, small bowel, and pancreatobiliary adenocarcinomas (ADCAs) are relatively limited or discordant. We assessed SATB2 expression in a large cohort of ADCAs from these sites to determine its reliability in distinguishing CRC from them.
METHODS: SATB2 IHC was performed on 335 neoplasms, including 40 lung ADCAs, 165 pancreatobiliary neoplasms (34 intraductal papillary mucinous neoplasms [IPMNs], 19 pancreatic ADCAs, 112 cholangiocarcinomas [CCs]), and 35 gastric, 13 small bowel, 36 ampullary (AMP), and 46 CRC ADCAs. The cases were evaluated for positivity (defined as ≥5% nuclear staining), and an H-score was calculated based on the percentage of SATB2+ cells and staining intensity. Analysis was performed to determine the optimal H-score threshold to separate CRC and non-CRC.
RESULTS: SATB2 was positive in 3% of lung, 2% of CC, 17% of gastric, 38% of small bowel, and 6% of AMP ADCAs. All pancreatic ADCA/IPMNs were negative, and 87% CRCs were positive.
CONCLUSIONS: SATB2 is not entirely specific for colorectal origin and can be expressed in a subset of gastrointestinal ADCAs. It is most useful in the differential of CRC vs lung and pancreatobiliary ADCAs.

doi: https://doi.org/10.1093/ajcp/aqaa118



  • Adaptable haemodynamic endothelial cells for organogenesis and tumorigenesis

Nature 2020 Sep;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32908310

Endothelial cells adopt tissue-specific characteristics to instruct organ development and regeneration1,2. This adaptability is lost in cultured adult endothelial cells, which do not vascularize tissues in an organotypic manner. Here, we show that transient reactivation of the embryonic-restricted ETS variant transcription factor 2 (ETV2)3 in mature human endothelial cells cultured in a serum-free three-dimensional matrix composed of a mixture of laminin, entactin and type-IV collagen (LEC matrix) 'resets' these endothelial cells to adaptable, vasculogenic cells, which form perfusable and plastic vascular plexi. Through chromatin remodelling, ETV2 induces tubulogenic pathways, including the activation of RAP1, which promotes the formation of durable lumens4,5. In three-dimensional matrices-which do not have the constraints of bioprinted scaffolds-the 'reset' vascular endothelial cells (R-VECs) self-assemble into stable, multilayered and branching vascular networks within scalable microfluidic chambers, which are capable of transporting human blood. In vivo, R-VECs implanted subcutaneously in mice self-organize into durable pericyte-coated vessels that functionally anastomose to the host circulation and exhibit long-lasting patterning, with no evidence of malformations or angiomas. R-VECs directly interact with cells within three-dimensional co-cultured organoids, removing the need for the restrictive synthetic semipermeable membranes that are required for organ-on-chip systems, therefore providing a physiological platform for vascularization, which we call 'Organ-On-VascularNet'. R-VECs enable perfusion of glucose-responsive insulin-secreting human pancreatic islets, vascularize decellularized rat intestines and arborize healthy or cancerous human colon organoids. Using single-cell RNA sequencing and epigenetic profiling, we demonstrate that R-VECs establish an adaptive vascular niche that differentially adjusts and conforms to organoids and tumoroids in a tissue-specific manner. Our Organ-On-VascularNet model will permit metabolic, immunological and physiochemical studies and screens to decipher the crosstalk between organotypic endothelial cells and parenchymal cells for identification of determinants of endothelial cell heterogeneity, and could lead to advances in therapeutic organ repair and tumour targeting.

doi: https://doi.org/10.1038/s41586-020-2712-z


New GallBladder Articles


  • Secondary Involvement of the Uterine Cervix by Nongynecologic Neoplasms: A Detailed Clinicopathologic Analysis

The American journal of surgical pathology 2020 Sep;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32910021

Secondary involvement of the uterine cervix by nongynecologic neoplasms is rare accounting for 50.5) (P=0.01). Mean time to identification of cervical metastases was <1 year for gallbladder carcinoma, melanomas, and gastrointestinal signet ring cell carcinomas (P=0.03). Features that varied with different types of metastatic tumor included lymphovascular space invasion, depth of stromal invasion, growth pattern (glands lacking architectural complexity, cribriforming, solid), presence of goblet cells, and signet ring cells, degree of cytologic atypia, and overall findings mimicking a benign/noninvasive process (P≤0.027). Six tumors (12.8%) were initially misdiagnosed as cervical primary. Metastatic nongynecologic tumors can mimic primary in situ or invasive neoplasms in both ectocervix and endocervix. In patients with a known prior malignancy, the clinical history with ancillary studies and a high level of suspicion are crucial to ensure accurate diagnosis.

doi: https://doi.org/10.1097/PAS.0000000000001578


New BileDuct Articles


  • Histological evaluation of tumor differentiation score and prognosis of extrahepatic bile duct cancer: A proposal for a new histological grading system

Pathology international 2020 Sep;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32909295

Extrahepatic bile duct (EHBD) cancer is a devastating cancer, and more common in Asian countries than in Western countries. Histological grading continues to be a highly relevant factor in prognosis and management of many kinds of cancer, however no uniform histological grading system exists for EHBD cancer. Histological heterogeneity within tumors is a problem in the evaluation of EHBD cancer. We developed an EHBD histological grading scheme to evaluate tumor differentiation pattern, and statistically analyzed its relationship with prognosis. In the present study, 257 surgically resected EHBD cancers were reviewed and their histological glandular differentiation (HGD) pattern was scored, and then we summed up the most and second most predominant scores. These scores were statistically analyzed for their relationship with patient prognosis. Patients showed a trend of shortening recurrence-free survival (RFS) and overall survival (OS) in association with higher HGD scores. In multivariate analyses, HGD score was determined to be an influential factor in RFS (P = 0.00041) and OS (P < 0.0001). In addition, combining HGD score and lymph node status correctly stratified patient prognosis in RFS. In conclusion, this new HGD scoring system is highly practical and has powerful prognostic value for EHBD cancer.

doi: https://doi.org/10.1111/pin.13014



  • Right Hepatectomy with Vascular and Biliary Reconstruction for a Portal Vein Leiomyosarcoma

Annals of surgical oncology 2020 Sep;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32909126

BACKGROUND: Vascular leiomyosarcomas (LMS) are rare malignant mesenchymal tumors arising from vessel smooth muscle cells. They represent only 2% of soft tissue sarcomas and most commonly (50%) originate from the inferior vena cava.1-3 Portal vein LMS are very rare, and their resection combines en bloc negative margin sarcoma surgery principles and complex liver surgery procedures with vascular reconstructions.3-5 METHODS: This is the case of a 42-year-old female presenting with a moderate cholestasis. Imaging revealed a 3-cm tumor originating from the main portal vein and its right branch while being in contact with both the right hepatic artery and biliary confluence. No metastases were identified. Core needle biopsy confirmed the diagnosis and tumor board decision was surgical resection.
RESULTS: The procedure included anatomic right hepatectomy with en bloc resection of the portal vein bifurcation, common bile duct, and biliary confluence. Portal venous reconstruction was performed using an autogenous external iliac vein interposition graft, while biliary reconstruction was performed via a Roux-en-Y end-to-side hepatico-jejunostomy. Duration of surgery was 300 min, and blood loss was 300 ml. Postoperative outcomes were uneventful and patient was discharged on postoperative day 8 with a transient right limb edema. Pathology confirmed R0 resection of a T1N0M0 leiomyosarcoma, Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grade 2 tumor. Patient was free of disease at 20 months post-surgery.
CONCLUSIONS: Portal vein leiomyosarcomas are extremely rare. En bloc extensive surgical resection should be proposed to obtain R0 resection, and achieve prolonged survival.4,6,7.

doi: https://doi.org/10.1245/s10434-020-09021-4



  • Prognostic effects of histology-based tumour microenvironment scores in resected distal bile duct cancer

Histopathology 2020 Sep;77(3):402-412

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32473032

AIMS: Histology-based tumour microenvironment (TME) scores are useful in predicting the prognosis of gastrointestinal cancer. However, their prognostic roles in distal bile duct cancer (DBDC) have not been previously studied. This study aimed to evaluate the prognostic significance of the TME scores using the Klintrup-Mäkinen (KM) grade, tumour stroma percentage (TSP) and the Glasgow microenvironment score (GMS) in resected DBDC.
METHODS AND RESULTS: Eighty-one patients with DBDC who underwent curative resection were enrolled. DBDC was graded according to KM grade, TSP and GMS. A high KM grade was found in 19 patients (24%) and a high TSP was found in 47 patients (58%). A high TSP was significantly correlated with a low KM grade (P < 0.001). The distribution of the GMS, which was developed by combining the KM grade and TSP, was as follows: 0 (n = 19, 24%), 1 (n = 19, 24%) and 2 (n = 43, 52%). A low KM grade, high TSP and high GMS were significantly associated with short overall survival (OS) (P < 0.001) and relapse-free survival (RFS) (P < 0.001). Furthermore, multivariate analysis showed that a low KM grade [hazard ratio (HR) = 3.826; confidence interval (CI) = 1.650-8.869; P = 0.014], high TSP (HR = 2.193; CI = 1.173-4.100, P = 0.002) and high GMS (HR = 7.148; CI = 2.811-18.173) were independent prognostic factors for short RFS; a low KM grade (HR = 4.324; CI = 1.594-11.733) and high GMS (HR = 6.332; CI = 2.743-14.594) were independent prognostic factors for short OS.
CONCLUSION: Histology-based TME scores, including the KM grade, TSP and GMS, are useful for predicting the survival of patients with resected DBDC.

doi: https://doi.org/10.1111/his.14163


New Ampulla Articles

Today there is no new Ampulla Article.

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