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Too Much Pancreas Pathology

Too Much Pancreas Pathology. Normal Pancreas. 15 cm long, 60-140g Shape is compared to letter J turned sideways, with loop of J around the duodenum

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Too Much Pancreas Pathology

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  1. Too Much Pancreas Pathology

  2. Normal Pancreas • 15 cm long, 60-140g • Shape is compared to letter J turned sideways, with loop of J around the duodenum • Divided into head (right of left border of superior mesenteric vein; contains uncinate process), body (between left border of superior mesenteric vein and left border of aorta) and tail • A retroperitoneal organ, lies within duodenal curve, close to superior mesenteric artery and portal vein • Anterior body of pancreas touches posterior wall of stomach; posterior of pancreas touches aorta, splenic vein and left kidney • Pancreatic tail extends to the splenichilum • Has large functional reserve of cells

  3. Normal Pancreas

  4. Exocrine Pancreas • Pancreatic enzymes:trypsin, chymotrypsin, aminopeptidases, elastase, amylases, lipase, phospholipases, nucleases • Trypsin: catalyzes activation of the other enzymes • Pancreatic self-digestion is prevented by: • packaging of most proteins as inactive proenzymes, enzyme sequestration in zymogengranules • proenzymesactivated only by trypsin which is activated only by duodenal enterokinase • trypsininhibitors are present in ductal and acinarsecretions • intrapancreaticrelease of trypsin activates enzymes which degrade other digestive enzymes before they can destroy pancreas • lysosomalhydrolases can degrade zymogen granules to prevent auto destruction if acinar secretion is impaired • acinarcells themselves are highly resistant to trypsin, chymotrypsin and phospholipase A2

  5. Endocrine Pancreas • Consists of islets of Langerhans, represents 1% of pancreas (percentage higher at birth) • Round, compact, highly vascularized with scanty connective tissue; more irregular outline and trabecular arrangement in posterior head of pancreas with cells producing pancreatic polypeptide • Size of islets usually 0.1 to 0.2 mm, endodermal origin, one million islets present in pancreas • Islet composition: beta cells (68%), alpha cells (20%), delta cells (10%), D1 cells (2%), Enterochromaffincells (rare) • Alpha cells: produce glucagon; peripheral dense and round on EM • Beta cells: produce insulin and islet cell amyloid polypeptide (amylin), crystalline appearance on EM with surrounding halo • Delta cells: produce somatostatin (represses release of insulin and glucagon), large pale granules on EM • D1 cells: produce HPP, stimulates GI fluid secretion and excess causes secretory diarrhea • Enterochromaffin cells: synthesize serotonin, excess produces carcinoid syndrome

  6. Congenital Abnormalities • Agenesis • Annular pancreas • Incidence 1 per 7000 • Head of pancreas circles duodenum as a collar and may constrict lumen due to failure of ventral bud to rotate properly • Associated with Down’s syndrome • Associated with pancreatitis, duct obstruction, peptic ulcer • Ectopic Pancreas • Often in gastric antrum, duodenum, jejunum, Meckel’sdiverticulum, gastroesophagealjunction • Case report of pancreatic cyst in anterior mediastinum • Usually incidental findings but may cause ulceration, obstruction, intussusception • Vulnerable to same diseases as normal pancreas (2% of islet cell tumors arise in ectopic pancreatic tissue), may undergo malignant transformation • Pancreatic Divisum • 3-10% of population with incomplete fusion of dorsal and ventral pancreatic buds / ducts • Duct of Santorini(accessory duct) and separate pancreatic duct drain into the distal duodenum. • May predispose to recurrent acute pancreatitis if minor papilla is obstructed

  7. Complete & Partial Pancreatic Divisum

  8. Acute Pancreatitis • Acute onset of abdominal pain due to enzymatic necrosis and inflammation • 80% associated with biliary tract disease or alcoholism • 1/3 to 2/3 of patients have gallstones, but only 5% with gallstones develop pancreatitis • 75% of gallstone related cases occur in women • 86% of alcohol related cases occur in men • Alcoholism associated: 2/3 of all cases in US

  9. Acute Pancreatitis • Less common causes: • trauma (including post-operative), • infection (mumps, coxsackievirus, Mycoplasma pneumonia, adenovirus in immunocompromised, AIDS related toxoplasmosis • Acute ischemia (thromboemboli, vasculitis, shock) • Drugs (thiazides, azathioprine, estrogen, sulfa, frusemide, methyldopa) • Hyperlipidemia, hyperparathyroidism or other causes of hypercalcemia, hyperthyroidism • 10% idiopathic

  10. Pathophys of Acute Pancreatitis • Obstruction from gallstones or alcohol associated concretions increases intraductal pressure, causing enzyme-rich interstitial fluid to accumulate, which causes fat necrosis, which attracts neutrophils that release cytokines and cause interstitial edema, which impairs blood flow and causes ischemia and acinar cell injury • Acinar cell injury also caused by infections, drugs, trauma, shock, premature release of proenzymes and lysosomalhydrolases • Obstruction or alcohol cause proenzymes to be delivered in an intracellular compartment with lysosomalhydrolases, which may activate them prematurely • Alcohol may also reactivate chronic pancreatitis due to secretion of protein-rich pancreatic fluid, which causes deposition of protein plugs, causing obstruction of small pancreatic ducts

  11. Acute Pancreatitis - Clinical • Symptoms: abdominal pain, high white blood count, DIC, ARDS, diffuse fat necrosis, peripheral vascular collapse, acute tubular necrosis, shock (blood loss, electrolyte disturbances, endotoxemia, release of cytokines), hypocalcemia, hyperglycemia • DD: acute abdomen (appendicitis, perforated peptic ulcer, acute cholecystitis with rupture, occlusion of mesenteric vessels with bowel infarction) • Diagnosis: elevated amylase (also seen in duodenal ulcer, volvulus, gangrenous cholecystitis, ruptured abdominal aortic aneurysm, mesenteric thrombosis), elevated lipase, elevated CRP • Xray(pancreas large and inflamed) • Outcome: 5% die of shock during first week; overall mortality is 20% (10% if swollen/edematous) vs. 50% if hemorrhagic/necrotic • Acute respiratory distress syndrome or acute renal failure are poor prognostic factors • Gross: swollen, edematous or hemorrhagic/necrotic, yellow nodules represent fat necrosis in pancreas, mesenteric and peritoneal fat; may spread to colon and cause ileus, stenosis, perforation, fistulas

  12. Chronic Pancreatitis • Men, 40+, often alcoholics; biliary disease usually not a factor in chronic pancreatitis • Repeated attacks of inflammation with loss of parenchyma and replacement with fibrosis • Causes variable pain and symptoms of pancreatic insufficiency (malabsorption, steatorrhoea, diabetes) • May coexist with pancreatic carcinoma or intraductalpapillary mucinous neoplasm (IPMN) • Attacks precipitated by alcohol, overeating, opiates, other drugs • Other risk factors:hypercalcemia, hyperparathyroidism, hyperlipoproteinemia, pancreas divisum (seen in 12%), pancreatic neoplasm or IPMN, cystic fibrosis but no known risk factor in 30% • Also associated with mumps, polyarteritisnodosa, sarcoidosis, malakoplakia, primary sclerosingcholangitis, HIV (mild changes)

  13. Other Subtypes of Chronic Pancreatitis • Autoimmune pancreatitis (IgG, mass formed by dense periductal infiltrate compressing the bile duct) • Herpes simplex (parenchymal necrosis, hemorrhage, minimal fat necrosis, many multinucleated giant cells with ground-glass appearance • Very rare: CMV and eosinophilic pancreatitis

  14. Chronic Pancreatitis - Clinical • Diagnosis:mildly elevated amylase during attacks; CT scan shows calcifications; weight loss, intractable abdominal pain, hypoalbuminaemiaand associated oedemadue to pancreatic insufficiency • Treatment: pancreatic duct drainage, Whipple resection (relieves pain in 50% of patients with pain) • Gross: hard, dilated ducts, visible calcified concretions (protein plugs), pseudocysts; 5% have obstruction due to tumor or stones • Micro: loss of acini with relative sparing of islets, irregularly distributed periductalfibrosis, obstruction of pancreatic ducts of all sizes; chronic inflammation (including mast cells) around lobules and ducts; dilated ducts with concretions; ductal epithelium is atrophic, hyperplastic or undergoes squamousmetaplasia; islets may become sclerotic and disappear; may have islet cell proliferation with invasive-like pattern

  15. Fibrosis due to Chronic Pancreatitis

  16. Congenital Cysts • Polycystic disease affecting liver and kidney • Von HippelLindausyndrome (rare autosomal dominant mutation of VHL TS gene – found in inbred feuding hillbillies made angry by phaeochromocytomas) • Pancreatic cystic dysplasia • Cysts of Cystic Fibrosis The very angry Hatfield clan in 1897

  17. Acquired Cysts & Tumours

  18. Serous Cystadenoma • Serous cystadenomas are characterized by a circumscribed, sponge-like gross appearance with a central stellate scarm Microscopically: characterized by clear glycogen-rich ells

  19. Mucinous Cystic Neoplasm • Almost always women, mean age 45 (young), if malignant then better prognosis than ductaladenocarcinoma • Present with abdominal pain or mass • Can be benign, borderline or malignant • Metastases usually restricted to abdominal cavity; metastases to ovary may simulate primary ovarian tumors • Gross: large (mean 10 cm); usually in body/tail, multilocular (occasionally unilocular) megacysts that don’t communicate with ductal system unless fistula are present; cyst wall is papillary, trabecular or thickened; has mucoid/watery cyst contents • Micro: lined by tall mucin-producing cells, often forming papillae; supported by ovarian-type stroma; endocrine cells often scattered among columnar lining cells.

  20. Mucinous Cystic Neoplasm (LP)

  21. Mucinous Cystic Neoplasm (HP)

  22. Solid Pseudopapillary Neoplasm • Rare, benign or low grade malignant forming cystic structures of epithelial origin containing hemorrhagic debris and usually surrounded by necrotic-hemorrhagic tissue

  23. Intraductalpapillary mucinous neoplasm (IPMN) • Affects mostly older males (> 60 YO) • Papillary proliferation of ductal epithelium of the head with excessive thick mucin production • Somewhat indolent; 30% associated with invasive carcinoma, which is often colloid carcinoma • Gross: May present as multilocular cystic masses • Micro: complex papillary fronds of mucin-producing epithelial cells; ductal fibrosis, acinar atrophy but well preserved islets; associated with chronic pancreatitis

  24. IPMN • (IPMN) grossly involves the main pancreatic ducts

  25. IPMN • The tail of the pancreas contained an intraductal papillary mucinous neoplasm (IPMN) which may be a aprecursor to invasive carcinoma

  26. MCN v IPMN

  27. Exocrine Cancers - Ductal Adenocarcinoma • Ductal adenocarcinoma (85% of pancreatic cancers) • Risk factors:Family Hx, smoking, alcohol abuse, obesity, beta-naphthylamine or benzidine exposure, familial relapsing pancreatitis, oldness (uncommon < 40 YO) • Uncertain risk factors: chronic pancreatitis, diabetes, maleness (M/F = 1.6:1), high consumption of fructose sweetened drinks, high meat/fat – low vegetable diet • Familial syndromes: hereditary nonpolyposis colorectal carcinoma (Lynch Syndrome), familial atypical mole-melanoma syndrome, Peutz-Jeghers syndrome, hereditary pancreatitis • Clinical: 60% of tumors are in head, 15% in body, 5% in tail, 20% diffusely involve pancreas • Symptoms: pain, weight loss, anorexia, malaise, weakness • Trousseau sign: migratory thrombophlebitis, in 10% due to tumor or tumor necrosis producing platelet-aggregating factors and procoagulants; causes arterial and venous thrombi, including pulmonary and portal thromboemboli • Metastases:liver, lung, peritoneum, adrenal, bone, distal nodes; supraclavicular node metastases may be presenting symptom, metastases to ovary may simulate primary mucinous ovarian tumors • Treatment (curative): distal pancreatectomy for body/tail tumors, Whipple resection (subtotal pancreaticoduodenectomy) for head/periampullarytumors • Most (85%) tumors are not amenable to curable surgery • Prognosis: 5 year survival 2-4%, 90% die within 1 year

  28. Ductal Adenocarcinoma

  29. Ductal Adenocarcinoma Infiltrating pancreatic adenocarcinoma – abnormal nuclei, mitotic figures – the usual cancer stuff. Metastasises to peripancreatic lymph nodes.

  30. Adenosquamous carcinoma • You thought ductal adenocarcinoma was bad - worse prognosis (mean survival 6 months) • Malignant squamoid and glandular components • Rare, M/F = 2:1, mean age 65 • Aspirates show extensive necrosis with dense blue globules • Clinical: upper abdominal distension, dyspepsia, jaundice, and significant weight loss over a period of months

  31. Adenosquamous carcinoma • adenosquamous carcinoma of the pancreas characterized by clear cells and rhabdoid cells (eosinic)

  32. Colloid Carcinoma • Tumors composed predominantly (80%+) of scanty malignant epithelial cells floating in nodular extracellular mucin lakes with muconodular invasive component • Mean age 61; M=F, usually in head of pancreas • May have originated from high grade IPMN • 5 year survival 57%

  33. Endocrine Carcinomas • 3-5% of pancreatic neoplasms, 80% occur in MEN1 patients, usually age 50-60 • “Islet cell tumors” is inaccurate, as they are believed to arise from pluripotentialductal cells that have the capacity to differentiate along neuroendocrine lines • Most are malignant; no TNM staging exists for these tumors • Most tumors are functional and secrete multiple hormones, hCGmore common in malignant tumors. Usually produce glucagon, insulin or pancreatic polypeptide; tendency towards multiple tumors in same patient, often microscopic, which often produce different hormones; associated with nesidioblastosis in 30% of cases (B-cell hyperplasia causing hypoglycemia and hyperinsulinemia) • Usually occurs in adults in body/tail • Tumors are either syndromic or not; non-syndromic may produce hormones so are still functional • Tumors are hypervascular and circumscribed • Usually slow growing, metastases to nodes, liver, bone

  34. Pancreatic Endocrine Carcinoma pink (resemble spleen, lymph node), no well defined capsule, variable fibrous tissue, calcium, bone, cysts

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