Pancreatic ductal adenocarcinoma, frequently referred to as pancreatic cancer, makes up the vast majority (~90%) of all pancreatic neoplasms and remains a disease with a very poor prognosis and high morbidity.

Epidemiology

Pancreatic cancer accounts for 22% of all deaths due to gastrointestinal malignancy, and 5% of all cancer deaths ¹. In general, it is a malignancy of the elderly with over 80% of cases occurring after the age of 60 ¹.

Risk factors

Risk factors include:

• cigarette smoking: the strongest environmental risk factor

• chronic pancreatitis ¹²

• a diet rich in animal fats and protein

• obesity

• diabetes mellitus

• family history: three or more first-order relatives with pancreatic cancer results in ~20x increase in risk ⁸

• hereditary syndromes ⁶

  • BRCA2 mutations are the most frequent cause of familial pancreatic cancer ¹²

  • HNPCC

  • familial breast cancer

  • familial atypical multiple mole melanoma (FAMMM) 

  • hereditary pancreatitis

  • ataxia-telangiectasia

  • Peutz-Jeghers syndrome

There is only a weak association, if at all, with heavy alcohol consumption alone, though chronic pancreatitis is a risk factor ¹.

Clinical presentation

• pain (most common)

• Courvoisier gallbladder: painless jaundice and enlarged gallbladder

• Trousseau syndrome: migratory thrombophlebitis 

• new-onset diabetes mellitus

• lipase hypersecretion syndrome (10-15%) ⁹

  • polyarthralgia and subcutaneous fat necrosis +/- lytic bone lesions

  • elevated serum lipase and eosinophilia

Pathology 

Three precursor lesions for pancreatic adenocarcinoma have been identified ⁸:

• pancreatic intraepithelial neoplasia (PanIN): responsible for more than 90% of pancreatic cancers ¹² 

• intraductal papillary mucinous neoplasm (IPMN)

• mucinous cystic neoplasm

Cancerous cells arise from the pancreatic ductal epithelium. The tumour's histologic spectrum ranges from well-formed glandular/ductal structures in well-differentiated carcinoma to abortive tubular structures in poorly differentiated carcinoma in the background of desmoplastic stroma. Most glands in well-differentiated carcinoma produce mucin.

Two characteristic appearances of pancreatic adenocarcinoma are:

• highly invasive behaviour of tumoural cells leads to infiltrating perineural spaces and blood vessels ¹²

• explicit desmoplastic reaction, which causes hard consistency of tumour ¹²

Because of this tumour's aggressiveness, tumoural cells often directly extend into the spleen, adrenals, stomach, and transverse colon ¹².

Location

• head and uncinate process: two-thirds of cases

• body and tail: one-third of cases ¹

Subtypes

Histological subtypes include:

• adenocarcinoma: majority

• acinar cell carcinoma of the pancreas

• adenosquamous carcinoma of the pancreas

• colloid carcinoma of the pancreas

• hepatoid carcinoma of the pancreas

• medullary carcinoma of the pancreas

• signet-ring cell carcinoma of the pancreas

• undifferentiated carcinoma and undifferentiated with osteoclast-like giant cells ¹²

Markers

• CA19-9

• CEA (carcinoembryonic antigen)

The serum levels of these antigens are frequently raised in people with pancreatic cancer and can be used to track a patient's response to treatment. However, these markers cannot be used for population screening due to a lack of sensitivity and specificity ¹².

Genetics

The most prevalent molecular changes responsible for pancreatic carcinoma are:

• KRAS: the most commonly mutated oncogene (>90%) 

• TP53: alterations in 70-75%

• SMAD4: inactivated in 55%

• CKN2A: altered in 30% ¹²

Staging 

Please see pancreatic ductal adenocarcinoma staging. Recurrence is probably better estimated by a risk score than by staging ¹⁰.

Radiographic features

As the majority of tumours (90%) ¹ are not resectable, diagnosis is usually achieved with imaging (typically CT) although laparoscopy is often required to confirm resectability ^1,2. The key to accurate staging is the assessment of the superior mesenteric artery and coeliac axis, which if involved exclude the patient from any attempted resection ^1,2.

Fluoroscopy 

Barium meal / small bowel follow-through

If large enough, may demonstrate a reverse impression on the duodenum: Frostburg inverted 3 sign or a wide duodenal sweep.

Ultrasound

Findings are non-specific and include:

• hypoechoic mass

• double duct sign may be seen

CT

• role in imaging:

  • CT is the primary imaging modality ("workhorse") for pancreatic evaluation

• ductal adenocarcinoma appearance:

  • poorly defined masses with extensive surrounding desmoplastic reaction

  • typically hypoattenuating on arterial phase scans in 75-90% of cases, with possible isoattenuation on delayed scans (necessitating multiphase imaging when pancreatic cancer is suspected)

  • double duct sign may be present

  • calcifications are rare and, when present, are more likely secondary to pre-existing conditions (e.g., chronic pancreatitis)

  • an enlarged pancreatic duct calibre to AP gland width ratio of ~0.5 may be present, reflecting ductal dilatation and parenchymal atrophy

• assessment of resectability:

  • CT correlates well with surgical findings for predicting unresectability (positive predictive value: 89-100%)

  • the key feature is the tumour's relationship with surrounding vessels:

    • superior mesenteric artery and coeliac axis involvement: Tumour encasement of >180 degrees is classified as T4 disease, indicating unresectability

MRI

Signal characteristics include:

• T1/T1FS: hypointense to normal pancreas ⁵

• T1 C+ (Gd): slower enhancement than the normal pancreas, therefore dynamic injection with fat saturation with arterial phase imaging is ideal

• T2/FLAIR: variable (therefore not very useful), depending on the amount of reactive desmoplastic reaction ^1,5

• MRCP: double duct sign may be seen

Treatment and prognosis

• resectability:

  • the majority of pancreatic ductal adenocarcinomas are not resectable at the time of diagnosis

  • unresectability is primarily determined by the presence of metastasis and/or vascular invasion, particularly encasement of the coeliac trunk and superior mesenteric artery

• surgical intervention:

  • surgical resection is potentially curative in stage I and II disease (see staging of pancreatic cancer); however, it is associated with significant morbidity (20-30%) and mortality (5%)³

  • resection of pancreatic head tumours is typically performed using the Whipple procedure

• prognosis:

  • despite surgical resection, recurrence remains common, with only a modest improvement in overall survival (from 5% to 10% at 5 years)⁴

  • the approximate 12 month survival rate of pancreatic ductal adenocarcinoma is 25% from time of diagnosis

Differential diagnosis

General imaging differential considerations include:

• acute pancreatitis

• chronic pancreatitis

  • the "duct penetrating sign" is an important sign to differentiate between chronic focal pancreatitis and pancreatic malignancy

  • pancreatic duct : parenchyma ratio is usually < 0.5

• other pancreatic neoplasms

• lymphoma

• fatty infiltration of the pancreatic head

  • usually involving the anterior portion

  • no secondary signs (e.g. pancreatic duct or common bile duct dilatation)

  • high signal on T1 and signal drop on chemical shift sequences

• cholangiocarcinoma

• periampullary tumours

• pancreatic metastases