4. Pancreatic neoplasm

Question 1

Types of pancreatic neoplasms

Answer 1

1. Benign pancreatic epithelial tumours
   - Serous cystademonas
   - Mucinous cystic neoplasms
   - Intraductal papillary mucinous neoplasm
2. Pancreatic carcinoma
3. Pancreatic endocrine neoplasm
   - Insulinoma
   - Glucagonoma
   - Gastrinoma aka Zollinger-Ellison Syndrome
   - Somatostainoma
   - VIPoma
   - Carcinoid tumour

Question 2

Benign pancreatic epithelial tumours

Answer 2

1. Serous cystadenomas
2. Mucinous cystic neoplasms
3. Intraductal papillary mucinous neoplasm

Question 3

Serous Cystadenomas

Answer 3

1. Almost always benign

2. Glycogen-rich cuboidal cells surrounding small cysts with clear, thin, straw-coloured fluid

Question 4

Mucinous cystic neoplasms

Answer 4

1. May become malignant
2. Usually found in body or tail of pancreas
3. Cysts larger than those found in serous cystsadenomas, filled with thick tenacious mucin

Question 5

Intraductal Papillary Mucinous Neoplasm

Answer 5

1. May become malignant
2. Usually found in head of pancreas
3. Papillary growth pattern, mucin-producing, involves or connected to normal pancreatic ductal system

Question 6

Etiologies & Associations with pancreatic carcinoma

Answer 6

1. Smoking
2. Fat-rich diet
3. Diabetes mellitus (hard to ascertain cause-&-effect)
4. Chronic pancreatitis (hard to ascertain cause-&-effect)

Question 7

Pathogenesis of pancreatic carcinoma

Answer 7

1. Pancreatic intraepithelial neoplasm → invasive pancreatic carcinoma sequence
2. Progressive mutations:
   - Telomere shortening
   - K-RAS mutation
   - p16 tumour suppressor gene inactivation
   - p53, SMAD4, BRCA2 gene inactivation

Question 8

Histological subtypes of pancreatic carcinoma

Answer 8

1. Adenocarcinoma (usual form)
2. Squamous cell carcinoma
3. Cystadenocarcinoma
4. Acinar cell carcinoma
   - Prominent acinar cell differentiation
   - Production of exocrine enzymes
   - May cause metastatic fat necrosis due to lipases released into circulation
5. Undifferentiated carcinoma
   - May have osteoclast-like giant multinucleated cells
6. Pancreatoblastoma
   - Rare, found in children age 1-15 years
   - Squamous islands admixed with acinar cells

Question 9

Sites of pancreatic carcinoma

Answer 9

1. Head of pancreas (60%)
   - Better prognosis in general due to earlier detection due to obstruction of bile duct which passes through the head of the pancreas
2. Body of pancreas (15%)
3. Tail of pancreas (5%)
4. Entire pancreas (20%)

Question 10

Pathological Effects & Complications of pancreatic carcinoma

Answer 10

1. Generally poor prognosis (one of the highest mortality rates amongst all cancers)
2. Biliary obstruction (for tumours of head of pancreas)
   - Obstructive jaundice
   - Ascending cholangitis
   - Cholecystitis
3. Gastrointestinal bleeding
4. Migratory thrombophlebitis (Trousseau’s sign)
   - Due to tumour-elaborated procoagulants & platelet aggregating factors

Question 11

Definition of pancreatic endocrine neoplasms

Answer 11

Islet cell tumours

Question 12

Insulinoma (beta cell tumour)

Answer 12

1. Most common pancreatic endocrine neoplasm
2. Tumour elaborating insulin
3. Clinical features: Whipple’s triad
   - Attacks of hypoglycemia occurring with glucose levels < 50mg/dL
   - CNS manifestation (confusion, stupor, loss of consciousness) related to fasting or exercise
   - Prompt relief of symptoms with glucose administration
4. Other differentials for hypoglycaemia:
   - Islet hyperplasia (e.g. in maternal diabetes)
   - Ectopic insulin production by fibromas
   - Inherited glycogenoses
   - Diffuse liver disease

Question 13

Glucagonoma (alpha cell tumour)

Answer 13

1. Tumour elaborating glucagon
2. Occurs mostly in peri- & postmenopausal women
3. Clinical features:
   - Increased serum glucagon levels
   - Mild diabetes mellitus
   - Migratory necrotizing skin erythema (often presents at groin/perineal region, lower extremities)
   - Anemia

Question 14

Gastrinoma (G cell tumour) aka Zollinger-Ellison Syndrome

Answer 14

1. Tumour elaborating gastrin
2. Clinical features:
   - Gastric hypersecretion/hyperacidity
   - Intractable peptic ulceration (gastric, duodenal & even jejuna)
   - Diarrhoea
3. Note: gastrinomas can arise within the ‘gastrinoma triangle” which comprises:
   - Pancreas
   - Duodenum
   - Peripancreatic soft tissue

Question 15

Somatostatinoma (delta cell tumour)

Answer 15

1. Tumour elaborating somatostatin
2. Clinical features
   - Increased serum somatostatin levels
   - Diabetes mellitus (due to suppressed insulin)
   - Cholelithiasis (due decreased gallbladder motility)
   - Steatorrhea (due to decreased exocrine pancreas enzymatic secretions)
   - Hypochlorhydria (due to decreased parietal cell HCl secretion)

Question 16

VIPoma (WDHA syndrome)

Answer 16

1. Tumour elaborating vasoactive intestinal peptide
2. Clinical features:
   - Watery diarrhea
   - Hypokalemia
   - Achlorhydria

Question 17

Carcinoid tumour

Answer 17

1. Tumour elaborating vasoactive substances (e.g. serotonin)
2. Clinical features: Carcinoid syndrome
   - Cutaneous flushing
   - Diarrhoea
   - Bronchospasm
   - Right sided heart valve lesions