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Intraductal Papillary Mucinous Neoplasm (IPMN) of the Pancreas: it’s Histopathologic Difference Between 2 Major Types Shinichi Ban, MD,* Yoshihisa Naitoh, MD,* Mari Mino-Kenudson, MD, Takaki Sakurai, MD, Makoto Kuroda, MD,J Isamu Koyama, MD, Gregory Y. Lauwers, MD, and Michio Shimizu, MD* Am J Surg Pathol 2006, November ;Vol. 30: 1561–1569 指導老師:方嘉郎;報告人:李俊志
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Introduction IPMN is characterized by a predominantly noninvasive growth pattern with mucin production and cystic duct dilatation. The distinction between IPMN and pancreatic intraepithelial neoplasia (PanIN) ,which is the common precursor of invasive carcinomas
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Introduction 1999, Yonezawa
Villous dark cell type--- resembles colorectal villous; MUC2 (+); intestinal type Papillary clear cell type--- resembles gastric foveolar epi. MUC (-); gastric type gastric type have not been fully described.
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Introduction Mucin profiles MUC1--- membrane-bound mucin
MUC2--- secretory mucins, intestinal MUC5AC--- secretory mucins, gastric foveolar MUC6--- secretory mucins, pyloric gland.
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Introduction GOALS: Evaluate the distribution of the IPMNs and their derived invasive carcinomas Refine their differences of gastric-type and intestinal-type--- regard to their histopathologic characteristics and mucin profiles Better characterize the gastric type
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Materials and Methods Patients’ data--- 80 cases: M/F(49/31)
Mean age(65.3y/o, 37-83y/o); From1983 to 2003; from 4 hospitals (Saitama Medical School, Japan; Kyoto University Hospital, Japan; Fujita Health University, Japan, and Massachusetts General Hospital, USA) Exclusion: IPMNs of other type (ex:pancreatobiliary,oncocytic) and IPMN-like lesions
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Materials and Methods based on
WHO classification on tumors of the digestive system international consensus guidelines for IPMN and mucinous cystic neoplasms (MCNs) Gastric type--- clear/lightly eosinophilic; columnar; round to ovoid nuclei; no/minimal pseudostratified Intestinal type--- dark eosinophilic; columnar; oval to spindle nuclei; pseudostratified
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Materials and Methods Evaluation of 8 histologic features:
distribution--- main duct or branch duct histologic grade---benign/borderline/noninvasive intraluminal nodular growth pyloric glandlike structures low-grade PanIN-like complex within the tumor, atrophy of the surrounding pancreas tissue mucous lake formation occurrence of invasive carcinoma.
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B. main duct-type IPMN A. branch duct-type IPMN
intraluminal nodular growth atrophy of the surrounding pancreas tissue with fibrosis mucous lakes devoid of neoplastic cells
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A, benign(hyperplasia)
B, borderline; C, noninvasive carcinoma (high-grade dysplasia) Benign-borderline Borderline-noninvasive
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A. Pyloric glandlike: 2-3 glands lined by clear columnar epi
A. Pyloric glandlike: 2-3 glands lined by clear columnar epi., located at the base of papilla B. PanIN-like complex: collection of small ducts lined by tall columnar mucinous cell
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Materials and Methods Mucin profiles (Semiquantitative)
Extent of staining(extent score)--- 0(no staining), 1(<1/3 positive), 2(1/3-2/3 positive), and 3(>2/3 positive) intensity of staining (intensity score)---0(no staining), 1(weak), and 2(strong). labeling score--- extent score+ intensity score
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Results no significant difference between gender and age. Number
GENDER: M/F MEAN AGE GASTRIC TYPE 50 31/19 65.5 (47-83) INTESTINAL TYPE 30 18/12 65.1(37-81) no significant difference between gender and age.
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Results
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Results
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A. mucinous adenocarcinoma derived from intestinal-type IPMN; intestinal-type IPMN (upper left) and mucinous adenocarcinoma (lower right); B. invasive ductal adenocarcinoma of the conventional type (desmoplasia and infiltration)derived from gastric-type IPMN ; gastric-type IPMN (upper right); conventional-type invasive ductal adenocarcinoma (lower left)
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Results
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A, gastric type, MUC5AC(Foveolar);
B, intestinal type, MUC5AC; C, gastric type, MUC2; (+) in scattered goblet cells D, intestinal type, MUC2;
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E, gastric type, MUC6(pyloric gland);
F, intestinal type, MUC6; G, gastric type, MUC1;H, intestinal type, MUC1.
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Discussion Larger main duct-type (73%) + Rare (3%) (33%) high (50%)
Intra-luminal nodular growth Low grade PanIN complex Pyloric gland-like structure grade atrophy and fibrosis Mucous lake invasive Intestinal type Larger main duct-type (73%) + Rare (3%) (33%) high (50%) 7/30 (23%) Gastric type Branch duct-type (98%) rare (82%) (96%) low 1/50 (2%)
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Discussion Intestinal-type IPMNs MUC2(+), whereas most gastric-type IPMNs are not. MUC5AC--- Both(+) in papilla, like organoid differentiation in stomach and pancreas. MUC6, both (+) ; more frequent in pyloric glandlike structures of gastric type MUC1--- a marker for aggressiveness. both (-)--- IPMNs progress slowly
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Discussion Malignant change: intestinal >gastric
Mucin pools --- associated with mucinous adenocarcinoma in intestinal-type IPMNs; lead to muconodular infiltration, like occurred in invasive colorectal villous tumors; sign of invasive Gastric-type IPMNs--- conventional type
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Discussion Gastric-type IPMNs V.S Low-grade PanIN
Both have “pyloric gland-like structures” and “low-grade PanIN-like complex” Both are MUC5AC+/MUC2- Both have genetic alterantions associated with ductal carcinoma, ex: K-ras, p53, DPC4/Smad4, p16 (more common in Low-grade PanIN) Low-grade PanIN gastric-type IPMNs Further molecular studies still needed
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Discussion Two hypothesis
Gastric type, which being called “null-type” by Adsay et al, may progress to intestinal type or others Different phathogenesis between the two types different mode of spreading through the pancreatic ductal system Gastric type --- low-grade PanIN-like complex Intestinal type --- involving small ducts with complete atrophy of surrounding parenchyma
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