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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,

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Presentation on theme: "Intraductal Papillary Mucinous Neoplasm (IPMN) of the Pancreas: it’s Histopathologic Difference Between 2 Major Types Shinichi Ban, MD,* Yoshihisa Naitoh,"— Presentation transcript:

1 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

2 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

3 Introduction  1999, Yonezawa 1. Villous dark cell type--- resembles colorectal villous; MUC2 (+); intestinal type 2. Papillary clear cell type--- resembles gastric foveolar epi. MUC (-); gastric type  gastric type have not been fully described.

4 Introduction  Mucin profiles 1. MUC1--- membrane-bound mucin 2. MUC2--- secretory mucins, intestinal 3. MUC5AC--- secretory mucins, gastric foveolar 4. MUC6--- secretory mucins, pyloric gland.

5 Introduction  GOALS: 1. Evaluate the distribution of the IPMNs and their derived invasive carcinomas 2. Refine their differences of gastric-type and intestinal-type--- regard to their histopathologic characteristics and mucin profiles 3. Better characterize the gastric type

6 Materials and Methods  Patients’ data--- 80 cases: 1. M/F(49/31) 2. Mean age(65.3y/o, 37-83y/o); 3. From1983 to 2003; 4. from 4 hospitals (Saitama Medical School, Japan; Kyoto University Hospital, Japan; Fujita Health University, Japan, and Massachusetts General Hospital, USA ) 5. Exclusion: IPMNs of other type (ex:pancreatobiliary,oncocytic) and IPMN-like lesions

7 Materials and Methods  based on 1. WHO classification on tumors of the digestive system 2. 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

8 Materials and Methods  Evaluation of 8 histologic features: 1. distribution--- main duct or branch duct 2. histologic grade---benign/borderline/noninvasive 3. intraluminal nodular growth 4. pyloric glandlike structures 5. low-grade PanIN-like complex within the tumor, 6. atrophy of the surrounding pancreas tissue 7. mucous lake formation 8. occurrence of invasive carcinoma.

9 A. branch duct-type IPMN B. main duct-type IPMN 1.intraluminal nodular growth 2.atrophy of the surrounding pancreas tissue with fibrosis 3.mucous lakes devoid of neoplastic cells

10 A, benign(hyperplasia) B, borderline; C, noninvasive carcinoma (high-grade dysplasia) Benign-borderline Borderline-noninvasive

11 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

12 Materials and Methods  Mucin profiles (Semiquantitative) 1. Extent of staining(extent score)--- 0(no staining), 1( 2/3 positive) 2. intensity of staining (intensity score)---0(no staining), 1(weak), and 2(strong). 3. labeling score--- extent score+ intensity score

13 Results NumberGENDER: M/F MEAN AGE GASTRIC TYPE 5031/1965.5 (47-83) INTESTINAL TYPE 3018/1265.1(37-81) no significant difference between gender and age.

14 Results


16 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)

17 Results

18 A, gastric type, MUC5AC(Foveolar); B, intestinal type, MUC5AC; C, gastric type, MUC2; (+) in scattered goblet cells D, intestinal type, MUC2;

19 E, gastric type, MUC6(pyloric gland); F, intestinal type, MUC6; G, gastric type, MUC1;H, intestinal type, MUC1.

20 Discussion TypeIntra- luminal nodular growth Low grade PanIN complex Pyloric gland- like structure gradeatrophy 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%) low1/50 (2%)

21 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

22 Discussion  Malignant change: intestinal >gastric 1. Mucin pools --- associated with mucinous adenocarcinoma in intestinal-type IPMNs; lead to muconodular infiltration, like occurred in invasive colorectal villous tumors; sign of invasive 2. Gastric-type IPMNs--- conventional type

23 Discussion  Gastric-type IPMNs V.S Low-grade PanIN 1. Both have “pyloric gland-like structures” and “low-grade PanIN-like complex” 2. Both are MUC5AC+/MUC2- 3. Both have genetic alterantions associated with ductal carcinoma, ex: K-ras, p53, DPC4/Smad4, p16 (more common in Low-grade PanIN) 4. Low-grade PanIN  gastric-type IPMNs 5. Further molecular studies still needed

24 Discussion  Two hypothesis 1. Gastric type, which being called “null-type” by Adsay et al, may progress to intestinal type or others 2. 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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