Differentiation

Well/moderate/poor/undifferentiated, or, Grade 1 /2/3/4.

Pancreatic ductal and ampullary adenocarcinoma can be graded according to the percentage tumour gland formation (well/G1 >95%: moderate/G2 50-95%: poor/G3 <50%).

By convention and definition signet ring cell adenocarcinoma and undifferentiated carcinoma (no glandular differentiation) are grade 3 and grade 4, respectively. Well-differentiated pancreatic adenocarcinoma can be difficult to distinguish from non-neoplastic ducts. Malignant glands are of variable size, shape and angularity with atypical nuclear/nucleolar features. Cell cytoplasm is tall and pale to clear in character. Perineural invasion is diagnostically helpful. Intraduct papillary lesions are:

Low-grade mild nuclear atypia no mitoses Intermediate moderate nuclear atypia

<5 mitoses/10hpfs High-grade severe cellular atypia mitoses >5/10hpfs

Endocrine tumours are not graded because of poor correlation of cyto-logical features and growth pattern with biological behaviour.

4. EXTENT OF LOCAL TUMOUR SPREAD

Border: pushing/infiltrative. Lymphocytic reaction: prominent/sparse.

The TNM classification applies to carcinomas of the ampulla of Vater and exocrine pancreas.

Ampulla pTis carcinoma in situ pT1 tumour limited to the ampulla or sphincter of Oddi pT2 tumour invades duodenal wall pT3 tumour invades pancreas pT4 tumour invades peripancreatic soft tissues or other adjacent organs or structures.

Tumour limited to ampulla of Vater or sphincter of Oddi

Figure 3.1. Ampulla of Vater carcinoma.

Tumour limited to ampulla of Vater or sphincter of Oddi

Figure 3.1. Ampulla of Vater carcinoma.

Figure 3.3. Ampulla of Vater carcinoma. |W Pancreas pTis carcinoma in situ pT1 tumour limited to the pancreas, <2 cm maximum dimension pT2 tumour limited to the pancreas, >2 cm dimension pT3 tumour extends beyond pancreas*, but without involvement of coeliac axis or superior mesenteric artery pT4 tumour involves coeliac axis or superior mesenteric artery.

Figure 3.3. Ampulla of Vater carcinoma. |W Pancreas pTis carcinoma in situ pT1 tumour limited to the pancreas, <2 cm maximum dimension pT2 tumour limited to the pancreas, >2 cm dimension pT3 tumour extends beyond pancreas*, but without involvement of coeliac axis or superior mesenteric artery pT4 tumour involves coeliac axis or superior mesenteric artery.

*Beyond pancreas includes the retroperitoneal fat and space, mesenteric fat, meso-colon, greater and lesser omenta and peritoneum. Direct invasion to bile ducts and duodenum includes involvement of the ampulla of Vater. Peripancreatic soft tissue involvement is an adverse prognostic indicator.

Tumour invades peripancreatic soft tissues, or other adjacent organs or structures

Figure 3.4. Ampulla of Vater carcinoma.

Tumour invades peripancreatic soft tissues, or other adjacent organs or structures

Figure 3.4. Ampulla of Vater carcinoma.

5. LYMPHOVASCULAR INVASION

Present/absent. Intra-/extratumoral.

Perineural space involvement is common in pancreatic carcinoma and lymphovascular invasion is present in up to 50% of cases with spread to local regional nodes at the time of diagnosis. Invasion of portal vein has adverse independent prognostic significance. Sites of distant metastases are liver, peritoneum, lung, adrenal, bone, skin and CNS. Regional node involvement is also present in 35-50% of ampullary carcinomas.

6. LYMPH NODES

Site/number/size/number involved/limit node/extracapsular spread. Regional nodes: peripancreatic, pancreaticoduodenal, common bile duct, pyloric and proximal mesenteric. A regional lymphadenectomy will ordinarily include a minimum of 10 lymph nodes.

pN0 no regional lymph node metastasis pN1 metastasis in regional lymph node(s).

7. EXCISION MARGINS

Distances (mm) to the following margins; proximal (gastric/duodenal), distal (duodenal), common bile duct, distal pancreatic, posterior pancreatic surface (deep radial).

The commonest site for local recurrence of invasive carcinoma after a Whipple's procedure is the posterior pancreatic soft tissue margin. This should be inked accordingly and the distance of tumour to it measured. Similarly for the non-peritonealized margin of the uncinate process. Local recurrence from intraductal tumour is more likely at a ductal resection margin.

8. OTHER PATHOLOGY

Cholestatic jaundice—carcinoma head of pancreas and ampulla. Ampulla

— duodenal adenoma(s), familial adenomatous polyposis coli (ampullary carcinoma is one of the commonest causes of death in FAPC).

Pancreas

— 3-10% of pancreatic carcinoma are familial—hereditary, BRCA2,

— disseminated intravascular coagulation, thrombophlebitis migrans (25% of cases, particularly with mucin-secreting tumours).

— gastrointestinal neuroendocrine syndromes, e.g. Zollinger-Ellison syndrome (diarrhoea, gastric hyperacidity with gastric/duodenal/ jejunal ulcers), Werner-Morrison syndrome, WDHA syndrome (watery diarrhoea, hypokalaemia, alkalosis).

— chronic pancreatitis shows acinar atrophy, distortion and regenerative changes with stromal fibrosis and residual islet tissue and can mimic pancreatic carcinoma. Similar changes are also seen upstream and adjacent to pancreatic carcinoma due to duct obstruction indicating that interpretation and sampling can be problematic. Ductules in chronic pancreatitis tend to retain their lobular architecture, lack significant malignant cytological change and show no invasion of nerve sheaths or peripancreatic fat. Jaundice of short duration in a patient older than 60 years is suspicious of malignancy. Other indicators are elevated serum CA19-9 (usually in cancers >3 cm diame-

HNPCC.

Portal

Aorta

Portal

Aorta

Superior Head mesenteric

Body

Tail

Figure 3.5. Pancreas. |W

Superior Head mesenteric

Body

Tail

Figure 3.5. Pancreas. |W

ter), duct stricture at ERCP or a mass lesion on CT/ELUS. Imaging is important in establishing contraindications to surgery (distant nodal/major vessel involvement) or other potentially operable diagnoses, e.g. serous or mucinous cystic tumours. A tissue diagnosis may be obtained by positive duct cytology brushings or transduodenal/per-cutaneous FNA or needle core biopsy. This is important to exclude other treatable malignancies, e.g. lymphoma in peripancreatic nodes. In a proportion of cases a firm diagnosis will not be obtained and must be assumed on the basis of clinical probability. Thus pancreati-coduodenectomy has a 5% false negative rate on the basis of benign disease.

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