Exocrine Pancreas Lectures 3 & 4 2022 PDF

EXOCRINE PANCREAS Lectures 3 and 4 DEPARTMENT OF ANATOMICAL PATHOLOGY 2022 Learning Objectives  Know the four of congenital abnormalities of the pancreas   Know the causes, morphology , pathogenesis and complications of acute and chronic pancreatitis   Know the non-neoplastic...

EXOCRINE PANCREAS Lectures 3 and 4 DEPARTMENT OF ANATOMICAL PATHOLOGY 2022 Learning Objectives  Know the four of congenital abnormalities of the pancreas   Know the causes, morphology , pathogenesis and complications of acute and chronic pancreatitis   Know the non-neoplastic and neoplastic pancreatic cysts  Know the causes, pathogenesis and morphology of pancreatic carcinoma ANATOMY, PHYSIOLOGY & HISTOLOGY  Anatomy  Retroperitoneal organ  Extends : C-loop of the duodenum → hilum of the spleen  Separated: head, neck, body and tail  20cm in length  Anatomy Pancreatic duct system  Main pancreatic duct (duct of Wirsung) drains into duodenum at papilla of Vater  Accessory pancreatic duct (duct of Santorini) drains into duodenum through minor papilla  Main pancreatic duct joins common bile duct – forms ampulla of Vater  Ductal architecture differs significantly amongst people  Physiology  Exocrine portion produces digestive enzymes, constitutes 80-85% of organ  Endocrine portion composed of islets of Langerhans; secrete insulin, glucagon and somatostatin, constitutes 1-2% of organ  Physiology Exocrine pancreas  Secretes 1 – 2 litres of alkaline fluid / day  Fluid contains approx. 20 enzymes : proteases, lipases, elastases, amylases  Epithelium lining duct of pancreas secretes bicarbonate to make secretions alkaline  Histology  Exocrine pancreas composed of acinar cells, which produce enzymes needed for digestion  Acinar cells pyrimidally shaped epithelial cells radially orientated around a central lumen contain zymogen granules rich in digestive enzymes  Series of ductules & ducts convey secretions to duodenum  Non-neoplastic pancreatic cysts Congenital pancreatic cysts Pancreatic pseudocysts Congenital pancreatic cysts  Occurs due to anomalous development of the pancreatic ducts  May be Sporadic Occur Polycystic disease in which cysts occur in the pancreas, kidney and liver Von Hippel-Lindau disease  Congenital pancreatic cysts  Variably sized lesions Microscopic Larger cysts measure up to 5cm  Cysts are lined by cuboidal epithelium or an attenuated cell layer  Thin fibrous capsule surrounds the cyst  Cysts are filled with clear, turbid, serous or mucoid material This is an example of 2 cysts lined by simple cuboidal epithelium and separated by fibrous capsule. Pancreatic pseudocysts  Localised collection of necrotic-haemorrhagic material rich in pancreatic enzymes  Cysts lack a true epithelial lining – PSEUDOcyst  Formed by walling off of areas of peripancreatic haemorrhagic fat necrosis with fibrous tissue  Range in size from 2-30cm  Solitary lesions Pancreatic pseudocysts Location :  In the pancreatic substance  Attached to the surface of the gland : lesser omental sac between stomach and colon between stomach and liver Pancreatic pseudocysts  May follow An episode of acute pancreatitis (Often superimposed on chronic) Trauma ***  Most cysts resolve spontaneously  Complications: Secondary infection – septic shock Compression of adjacent structures Perforation into adjacent structures Pseudocyst does not have an epithelial lining.  Pancreatic Neoplasms Cystic neoplasms Pancreatic carcinoma Cystic neoplasms  5-15 % of cysts are neoplastic  Types Serous cystadenomas Mucinous cystic neoplasms Intraductal papillary mucinous neoplams (IPMNs) Solid pseudopapillary neoplasms  Serous cystadenomas  Multicystic  Often in tail  Simple cuboidal lining  Content: clear/straw-coloured  More common in Females  Rx: Excision Mucinous cystic neoplasms  Can be pre-malignant  Usually in tail  More common in Females  Painless, slow-growing  Filled with mucin  Lined by columner cells Intraductal papillary mucinous neoplams (IPMNs)  Larger ducts  More common in males  Usually in head, 10-20% multifocal  Can progress to invasive cancer Solid pseudopapillary neoplasms  Mainly young women  Malignant  Solid and cystic components Solid pseudopapillary neoplasms Pancreatic carcinoma  Infiltrating ductal adenocarcinomas  Patients 60 – 80 yrs  Risk factors : Smoking ( major ) Diabetes mellitus Chronic pancreatitis  Inherited familial defects (gene mutations) Peutz-Jeghers syndrome Melanoma syndrome Associated with breast and ovarian cancer Precursor to pancreatic cancer  Progression of lesion : Non neoplastic epithelium → Histologically well-defined non-invasive lesions in small ducts and ductules → Invasive carcinoma  Precursor lesions : PanINs Pancreatic intraepithelial neoplasia Molecular Carcinogenesis Postulated that telomere shortening and mutations of the oncogene KRAS occur early Inactivation of the CDKN2A tumor suppressor gene that encodes the cell cycle regulator p16 occurs in intermediate grade lesions Inactivation of the TP53, SMAD4, and BRCA2 tumor suppressor genes occur in higher grade (PanIN-3) lesions. Macroscopic features  Located in the head of the pancreas Hard Grey-white Poorly defined margins The x-section through the tail of the pancreas showing normal pancreatic parenchyma and a normal pancreatic duct (left), an ill-defined mass in the pancreatic substance (centre) with narrowing of the pancreatic duct, and dilatation of the pancreatic upstream (right) from the mass. Microscopic features  Ductal adenocarcinomas forming glands secreting mucin  Widely invasive  Dense desmoplastic stromal response  Lymphovascular invasion is common  Extension to adjacent structures often occurs  Peripancreatic, gastric, mesenteric and omental lymph node involvement Microscopic variants  Adenosquamous carcinoma  Undifferentiated carcinoma with osteoclast-like giant cells  Mucinous non-cystic adenocarcinoma  Signet ring carcinoma  Anaplastic carcinoma  Mixed ductal-endocrine carcinoma Treatment  Curative treatment is surgical excision with the extent depending on site and size of the tumour  Most tumours at time of diagnosis are too extensive for surgical excision and patients receive palliative bypass surgery, chemotherapy or radiotherapy  Prognosis is poor Overall 5-year survival