Pancreatic cancer differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sudarshana Datta, MD [2]

Overview

Pancreatic cancer must be distinguished from other pancreatobiliary pathologies that cause abdominal pain and jaundice such as acute suppurative cholangitis, acute cholecystitis, cholelithiasis, chronic pancreatitis, primary biliary cirrhosis and primary sclerosing cholangitis. Pancreatic cancer must also be differentiated from other pancreatic pathologies such as autoimmune pancreatitis, pancreatic pseudocyst, and neuroendocrine tumors of the pancreas. Pathologies of the bile duct and duodenum such as Choledocholithiasis, gallstones (cholelithiasis), choledochal cysts, Cholangiocarcinoma, Bile duct strictures and ampullary cancer should be differentiated from pancreatic cancer based on imaging and biopsy findings. Metastasis from different sites and vascular causes such as abdominal aortic aneurysms may also mimic pancreatic cancer.

Differentiating Pancreatic Cancer from other Diseases

Pancreatic cancer may also be distinguished from other causes of abdominal pain and jaundice as depicted in the table below:

Classification of pain in the abdomen based on etiology Disease Clinical manifestations Diagnosis Comments Symptoms Signs Fever Rigors and chills Abdominal Pain Jaundice Hypo- tension Guarding Rebound Tenderness Bowel sounds Lab Findings Imaging Abdominal causes Inflammatory causes Pancreato-biliary disorders Acute suppurative cholangitis + + RUQ + + + + N Abnormal LFT WBC >10,000 Ultrasound shows biliary dilatation/stents/tumor Septic shock occurs with features of SIRS Acute cholangitis + − RUQ + − − − N Abnormal LFT Ultrasound shows biliary dilatation/stents/tumor Biliary drainage (ERCP) + IV antibiotics Acute cholecystitis + − RUQ + − − − Hypoactive Hyperbilirubinemia Leukocytosis Ultrasound shows gallstone and evidence of inflammation Murphy’s sign Acute pancreatitis + − Epigastric ± ± − − N Increased amylase / lipase Ultrasound shows evidence of inflammation Pain radiation to back Primary biliary cirrhosis − − RUQ/Epigastric + − − − N Increased AMA level, abnormal LFTs Primary sclerosing cholangitis + − RUQ + − − − N Increased liver enzymes Increased IgM, IgG4 Anti-neutrophil cytoplasmic antibody (p-ANCA) Anti-nuclear antibody (ANA) Anti-smooth muscle antibody (Anti-Sm) Anti-endothelial antibody Anti-cardiolipin antibody Cholelithiasis ± − RUQ/Epigastric ± − + + N to hyperactive for dislodged stone Leukocytosis Ultrasound shows gallstone Murphy’s sign Pancreatic cancer − − Epigastric ± − − − N Elevated serum bilirubin (conjugated and total) Elevated alkaline phosphatase levels Elevated gamma-glutamyl transpeptidase levels Normal/elevated aspartate aminotransferase and alanine aminotransferase Serum amylase and/or lipase levels are normal/elevated mild normocytic normochromic anemia Thrombocytosis CT shows morphological changes of the gland Destruction of the peripancreatic fat and loss of the sharp margins with surrounding structures Involvement of the regional lymph nodes and adjacent vasculature Pancreatic ductal dilatation Pancreatic atrophy Obstruction of the common bile duct (CBD) USG shows:  ill defined hypoechoic mass is seen infiltrating into a bright pancreatic parenchyma  EUS-guided fine needle aspiration biopsy (FNA) is the best modality for obtaining a tissue diagnosis. Signs of metastatic disease include:  Left supraclavicular lymphadenopathy (Virchow's node) Palpable periumbilical mass (Sister Mary Joseph's node) Metastatic palpable mass in the rectal pouch (Blumer's shelf) Involvement of other nodes in the cervical area Gastric causes Gastrointestinal perforation + ± Diffuse ± + + ± WBC> 10,000 Air under diaphragm in upright CXR Intestinal causes Whipple's disease ± − Diffuse ± ± − − N Thrombocytopenia Hypoalbuminemia Small intestinal biopsy for Tropheryma whipplei *Endoscopy is used to confirm diagnosis. Images used to find complications Chest and joint x-ray CT MRI Echocardiography Extra intestinal findings: Uveitis Endocarditis Encephalitis Dementia Hepatosplenomegaly Arthritis Ascites Celiac disease − − Diffuse ±, also dermatitis herpetiformis − − − Hyperactive (increased sounds) IgA endomysial antibody IgA tissue transglutaminase antibody Anti-gliadin antibody Hepatic causes Viral hepatitis + − RUQ + − + Liver masses + + in Liver abscess RUQ ± + in sepsis Budd-Chiari syndrome ± − RUQ − Hemochromatosis − − RUQ ± + in cirrhotic patients may be in cardicmyopathy − − >60% TS >240 μg/L SF Raised LFT Hyperglycemia Ultrasound shows evidence of cirrhosis Extra intestinal findings: hyperpigmentation Diabetes mellitus Arthralgia Impotence in males Cardiomyopathy Atherosclerosis Hypopituitarism Hypothyroidism Extrahepatic cancer Prone to specific infections Cirrhosis + − RUQ + − Peritoneal causes Spontaneous bacterial peritonitis + − Diffuse + in cirrhotic patients ± − − Hypoactive Ascitic fluid PMN>250 cells/mm³ Culture: Positive for single organism Ultrasound for evaluation of liver cirrhosis Hollow Viscous Obstruction Biliary colic − − RUQ + − − − N Increased bilirubin and alkaline phosphatase Ultrasound Nausea & vomiting

Differentials based on weight loss, nausea, vomiting, diarrhea, fatigue and abdominal pain

Pancreatic carcinoma should be differentiated from other diseases presenting with weight loss, nausea, vomiting, diarrhea, fatigue and abdominal pain. The differentials include the following:

Disease	Clinical manifestations													Diagnosis		Comments
	Symptoms									Signs
	Abdominal Pain	Fever	Rigors and chills	Nausea or vomiting	Jaundice	Constipation	Diarrhea	Weight loss	GI bleeding	Hypo- tension	Guarding	Rebound Tenderness	Bowel sounds	Lab Findings	Imaging
Chronic pancreatitis	Epigastric	−	−	±	±	−	+	+	−	−	−	−	N	Increased amylase / lipase Increased stool fat content Pancreatic function test	CT scan Calcification Pseudocyst Dilation of main pancreatic duct	Predisposes to pancreatic cancer
Pancreatic carcinoma	Epigastric	−	−	+	+	−	+	+	−	−	−	−	N	↑ Alkaline phosphatase ↑ serum bilirubin ↑ gamma-glutamyl transpeptidase ↑ CA 19-9	MDCT with  PET/CT MRI	Skin manifestations may include: Bullous pemphigoid Cicatricial pemphigoid Migratory superficial thrombophlebitis (classic Trousseau's syndrome) Pancreatic panniculitis
Dumping syndrome	Lower and then diffuse	−	−	+	−	−	+	+	−	+	−	−	Hyperactive	Glucose challenge test Hydrogen breath test	Upper GI series Gastric emptying study	Postgastrectomy

Abbreviations: RUQ= Right upper quadrant of the abdomen, LUQ= Left upper quadrant, LLQ= Left lower quadrant, RLQ= Right lower quadrant, LFT= Liver function test, SIRS= Systemic inflammatory response syndrome, ERCP= Endoscopic retrograde cholangiopancreatography, IV= Intravenous, N= Normal, AMA= Anti mitochondrial antibodies, LDH= Lactate dehydrogenase, GI= Gastrointestinal, CXR= Chest X ray, IgA= Immunoglobulin A, IgG= Immunoglobulin G, IgM= Immunoglobulin M, CT= Computed tomography, PMN= Polymorphonuclear cells, ESR= Erythrocyte sedimentation rate, CRP= C-reactive protein, TS= Transferrin saturation, SF= Serum Ferritin, SMA= Superior mesenteric artery, SMV= Superior mesenteric vein, ECG= Electrocardiogram

To review a comprehensive differential diagnosis of diseases presenting with abdominal pain, click here.

Differentiating Pancreatic Carcinoma on the basis of involved Organ

The differentials for pancreatic cancer mainly involve pathologies of the pancreas, bile duct, duodenum, lymphovascular tissue or metastasis from other sites. It is difficult to differentiate pancreatic cancer from other neoplasms as they all present with non specific constitutional symptoms. Hence, differentiation is primarily based on anatomic location:

Origin	Disease	Diagnostic study of choice
Pancreas	Chronic pancreatitis Autoimmune pancreatitis Pseudocyst of pancreas Pancreatic cyst Neuroendocrine tumors of pancreas Gastrinoma VIPoma Somatostatinoma Insulinoma	Imaging: Non-contrast helical CT Biopsy findings Serum IgG4 levels for autoimmune pancreatitis For pancreatic NETs: Gastrin levels Somatostatin levels Insulin levels Serum electrolytes
Bile duct	Choledocholithiasis Gallstones (Cholelithiasis) Choledochal Cysts Cholangiocarcinoma Bile duct strictures Cholangitis Cholecystitis	Imaging: MRI MRCP USG bile duct ERCP Biopsy findings
Duodenum	Ampullary cancer Duodenal cancer	Imaging: MRI ERCP Upper GI Endoscopy Biopsy findings
Lymphovascular tissue	Abdominal aortic aneurysm Intestinal ischemia Lymphomas Gastric Pancreatic	Imaging: MRI MR Angiography CT Angiography Biopsy for lymphoma
Metastasis	Skin(Melanoma) Kidney Breast Colon Liver(Hepatocellular carcinoma) Stomach	Imaging: MRI PET scan CT Biopsy Specific markers for different cancers: HCC: AFP Breast: BRCA 1 and 2 Colon cancer: CEA Melanoma: S100