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ECR 2019 / C-0763
Pancreatic and Biliary Involvement in IgG4-Related Disease: What the Radiologist Needs to Know
Congress: ECR 2019
Poster No.: C-0763
Type: Educational Exhibit
Keywords: Education and training, Diagnostic procedure, MR-Cholangiography, MR, CT, Pancreas, Biliary Tract / Gallbladder, Abdomen
Authors: J. Miguez Gonzalez, P. LOZANO ARRANZ, R. Oliveira Caiafa, F. Calaf Forn, A. Thomas, J. Catala Forteza; Barcelona/ES
DOI:10.26044/ecr2019/C-0763

Findings and procedure details

AUTOIMMUNE PANCREATITIS

 

- Autoinmune Pancreatitis (AIP) is a fibroinflammatory disease of the pancreas with two histologic subtypes that share similar imaging features (Fig. 3): 

 

a) Type I. Most frequent subtype. Associated with­ elevated serum levels of IgG4 and biliary disease (IgG4-SC is present in up to 80-90% of cases), and less frequently with fibrosing diseases in other organs. In this exhibit we will focus on this type of AIP.

 

b) Type II. Only involves the pancreas and there is no association with IgG4.

 

- Serology: In AIP type I analysis show increase in serum levels of IgG4 (>140 mg/dl) in 70% of cases, as well as elevation of bilirrubin and tumoral marker CA 19.9. It is important to point out that normal levels of IgG4 can be seen in up to 30% of cases, and therefore do not exclude the diagnosis.

- Epidemiology: The higher incidence is seen in males between fourth and sixth decades of life.

- Clinical Presentation: Painless jaundice is the main symptom, but mild pain in the upper abdomen and weight loss may also be present.

- Histology: Infiltrate of IgG4-positive plasma cells in the pancreas that causes periductal fibrosis with acinar atrophy.

- Treatment: Steroids is the first option with good and quick response in 4 weeks (there is analitical, clinical and radiological improvement with frequent pancreatic atrophy). Rituximab and Immune-modulators such as Azathioprine can also be used in relapses and as manteinance treatment.

  

Fig. 3
References: Radiology, Hospital Sant Joan Despi Moises Broggi - Barcelona/ES

 

 

There are three classic patterns of presentation in AIP (Fig. 4):  

  1. Diffuse AIP
  2. Focal AIP 
  3. Multifocal AIP
Fig. 4: Scheme illustrating the different patterns of presentation of AIP (based on a previous scheme by Vlachou et al. IgG4-related sclerosing disease: autoimmune pancreatitis and extrapancreatic manifestations. RadioGraphics 2011; 31:1379–1402)
References: Radiology, Hospital Sant Joan Despi Moises Broggi - Barcelona/ES

 

 

Diffuse AIP

Most frequent pattern of presentation with typical imaging features on CT and MRI (Fig. 5, Fig. 6):

  • Sausage-shaped pancreas with diffuse enlargement, loss of lobular contours and absence of pancreatic clefts.
  • Low attenuation peripancreatic rim with delayed enhancement, known as the "halo sign" (very specific of AIP but only present in 30% of cases).
  • Irregular and diffuse narrowing of main pancreatic duct and stenosis of distal common bile duct in its intrapancreatic portion.
  • Restricted diffusion of the whole pancreas with low ADC values.
Fig. 5: Illustrative example of diffuse AIP in a 42-year-old man who presented with painless jaundice, coluria, acolia and elevated serum levels of bilirrubin and transaminases. (a) Contrast-enhanced CT image in pancreatographic phase shows a "sausage-shaped" pancreas with diffuse enlargement and loss of pancreatic clefts (red arrows). (b) Axial T2-weighted image shows mild and diffuse increase in pancreas signal due to edematous changes and a hypointense peripancreatic halo (yellow arrow). The main pancreatic duct can not be identified due to diffuse stenosis. (c) ADC map shows diffuse hypointensity of pancreatic parenchyma due to restricted diffusion (orange arrows).
References: Radiology, Hospital Sant Joan Despi Moises Broggi - Barcelona/ES
Fig. 6: Diffuse AIP in 79-year-old man with painless jaundice and cholestatic pattern. (a) Contrast-enhanced CT image in portal phase showed a "sausage-shaped" pancreas with diffuse enlargement and loss of pancreatic clefts (red arrows). (b) Axial T2-weighted image showed mild and diffuse increase in pancreas signal due to edematous changes (red arrows). The main pancreatic duct can not be identified due to diffuse stenosis. (c) Axial T1-weighted image showed a hypointense peripancreatic halo (blue arrows). (d) ADC map showed diffuse hypointensity of pancreatic parenchyma due to restricted diffusion (green arrows). (e) MR cholangiography showed diffuse and irregular stenosis of the main pancreatic duct (yellow arrows) and the distal common bile duct (blue arrow) with moderate upstream dilatation.
References: Radiology, Hospital Sant Joan Despi Moises Broggi - Barcelona/ES

 

Focal AIP

This pattern of presentation mimics pancreatic carcinoma and shows the following imaging features on CT and MRI (Fig. 7, Fig. 8):

  • Focal mass/pseudomass usually located in the pancreatic head.
  • Segmental narrowing of main pancreatic duct often associated to stricture of the intrapancreatic common bile duct without marked upstream dilatation.
  • "Halo sign" surrounding the affected pancreatic segment.
  • Focal restricted diffusion of the pancreatic mass/pseudomass.

 

Fig. 7: Focal AIP in a 60-year-old man with mild pain in the upper abdomen and jaundice. (a, b, c) Axial slices from contrast-enhanced CT in pancreatographic and equilibrium phases and coronal slice in portal phase. A globular pancreatic head can be seen with pseudonodular uptake and increased density of adjacent fat with late enhancement, suggestive of focal AIP (red arrows). It causes a marked concentric stenosis of intrapancreatic common bile duct with mural enhancement (yellow arrow).
References: Radiology, Hospital Sant Joan Despi Moises Broggi - Barcelona/ES

 

Fig. 8: Focal AIP with associated mesenteric inflammatory pseudotumor in a 73-year-old woman who presented with painless jaundice and fever. (a,b,c) Coronal and axial slices from contrast-enhanced CT in portal phase showed a globular pancreatic head with an image of pseudomass and mild stranding of the peripancreatic fat (red arrow), as well as stenosis of the intrapancreatic common bile duct with mild upstream dilatation (blue arrow). As an additional finding a mesenteric mass was identified (yellow arrows) compressing the right ureter and producing a delay in the right nephrogram (green arrow). (d,e,f) Control CT after two months of steroid treatment showed significant decrease in size of the pancreatic head (red arrow) with resolution of the biliary dilatation. There was also a significant decrease of the mesenteric mass (yellow arrows) with resolution of the ureteral entrapment and the functional delay of the right kidney (green arrow). A choledochal biliary prosthesis is also visualized (it was placed initially due to suspicion of neoplastic origin but was withdrawn after confirming the autoimmune etiology).
References: Radiology, Hospital Sant Joan Despi Moises Broggi - Barcelona/ES

 

Multifocal AIP

Involves different portions of the pancreas and is the less frequent pattern, showing these imaging features on CT and MRI (Fig. 9):

  • Multifocal pancreatic masses or pseudomasses.
  • Multiple strictures of the main pancreatic duct.
  • Irregular "halo sign" in the affected pancreatic segments.
  • Multifocal restricted diffusion in the affected segments.
Fig. 9: Multifocal AIP confirmed after biopsy performed by endoscopic ultrasonography in a 49-year-old man with recurrent pancreatitis without cholelithiasis. (a,b) Contrast-enhanced CT in portal phase showed a pseudonodular enhancing focal area in the pancreatic head and a second more extensive enhancing area in the body and tail with loss of pancreatic clefts (red arrows). Between both areas, at the level of the pancreatic neck, there is a spared segment of pancreas with normal morphology and density (white arrow). (c,d) T2-weighted MR sequences with fat saturation showed increased signal of the affected pancreatic segments in relation to inflammatory changes (red arrows) with normal signal of the pancreatic neck (white arrow). (e) ADC map showed low values at the pancreatic head due to focal restriction (green arrow). (f) MR cholangiography showed marked narrowing of the main pancreatic duct in the pancreatic head (blue arrow) and multifocal strictures in the body and tail (yellow arrows).
References: Radiology, Hospital Sant Joan Despi Moises Broggi - Barcelona/ES

 

 

DIFFERENTIAL DIAGNOSIS OF AUTOIMMUNE PANCREATITIS 

 

Pancreatic Carcinoma                                                      

- Aggresive cancer with poor prognosis most frequently located in the pancreatic head that requires differential diagnosis with focal AIP.
- Serology: Elevation of bilirrubine and CA 19.9
- Clinical presentation: Obstructive jaundice usually painless, weight loss.

- Histology: More than 90% are invasive ductal adenocarcinomas with intense stromal desmoplasia and variable necrosis.

- Treatment: Surgery is the first option but usually the tumor can not be resected at the time of diagnosis. In this cases the patient can be treated with a combination of radiation therapy and chemotherapy.

- CT and MRI findings (Fig. 10):

  • Infiltrating and poorly defined hypovascular solid lesion.
  • Abrupt cutoff of the main pancreatic duct +/- the intrapancreatic common bile duct with marked upstream dilatation (more severe than in AIP) and distal pancreatic atrophy (not present in AIP).
  • Infiltration +/- thrombosis of adjacent vessels.
  • Common visceral and peritoneal metastases at diagnosis.
Fig. 10: Contrast-enhanced CTs in axial and coronal planes illustrating three different examples of pancreatic cancer: (a,b) Pancreatic head neoplasm that infiltrates superior mesenteric-portal vein confluence (red arrows). It causes abrupt cut off of the main pancreatic duct with significant upstream dilatation and distal pancreatic atrophy of body and tail. (c,d) Pancreatic body neoplasm that causes narrowing of distal common bile duct and thrombosis of the spleno-mesenteric-portal confluence (yellow arrows). (e,f) Pancreatic tail neoplasm (orange arrows) with thrombosis of splenic vein and infiltration of splenic artery. It is associated with multiple hepatic metastases and perihepatic ascites.
References: Radiology, Hospital Sant Joan Despi Moises Broggi - Barcelona/ES


 

Acute Pancreatitis

- Acute focal or diffuse inflammation of the pancreas, usually of biliary etiology. 
- Serology: Elevation of lipase and amylase.  
- Clinical presentation: Epigastric pain radiating to the back, nausea and vomiting.

- CT and MRI findings (Fig. 11):

  • Enlargement of the pancreas with edema and restricted diffusion.
  • Glandular necrosis and/or peripancreatic fat necrosis.
  • Ill-defined stranding of peripancreatic fat.
  • Peripancreatic exudates and free fluid.
Fig. 11: Three examples of acute pancreatitis: (a,b,c) Contrast-enhanced CT in portal phase, T2-weighted image with fat saturation and diffusion-weighted image. There is an acute focal pancreatitis involving the pancreatic head with edematous changes consisting in mild hyperintensity and restricted diffusion (red arrows), associated with stranding of the adjacent fat and right anterior pararenal fluid. (d) Contrast-enhanced CT in portal phase shows diffuse acute pancreatitis with hypodensity of the glandular parenchyma in relation to edema and necrosis (yellow arrows), associated with stranding of adjacent fat and fluid that extends to anterior pararenal spaces. (e) Control of the previous case one month later shows sequelae of necrotizing pancreatitis with partial replacement of the glandular parenchyma by pseudocysts (yellow arrows). (f) Acute diffuse edematous pancreatitis (blue arrows) with exudates and stranding of the peripancreatic fat, without areas of necrosis.
References: Radiology, Hospital Sant Joan Despi Moises Broggi - Barcelona/ES

 

Chronic Pancreatitis

- Chronic inflammatory disease of the pancreas with parenchymal fibrosis.

- Generally diffuse and associated with chronic enolism.

- A focal variant can be seen usually located in the pancreatic head and duodenal-pancreatic groove, which sometimes causes chronic stenosis of the intrapancreatic common bile duct.

- Serology: Not very useful except in case of exacerbation.

- Clinical Presentation: Dyspepsia, chronic diarrhea, occasional episodes of epigastralgia radiating to the back.

- CT and MRI findings (Fig. 12):

  • Increase in size of the pancreas (atrophy in late stages).
  • Parenchymal and intraductal calcifications.
  • Pseudocysts.
  • Irregular dilatation of the main pancreatic duct with intermittent strictures.

 

Fig. 12: Two examples of chronic pancreatitis: (a,b,c) Contrast-enhanced CT slices in axial and coronal planes in pancreatographic phase and coronal T2-weighted image show changes of chronic groove pancreatitis with calcifications (red arrow), cystic duodenal wall dystrophy (yellow arrow) and marked narrowing of intrapancreatic common bile duct (blue arrow). Stranding of adjacent fat is also present, suggesting exacerbation. (d,e,f) Contrast-enhanced CT in portal phase, T2-weighted image and MR cholangiography with MIP reconstruction show diffuse chronic pancreatitis with parenchymal atrophy, intraductal calcifications and lithiasis (red arrows). There is also an irregular dilatation of the main pancreatic duct with intermittent strictures (blue arrows).
References: Radiology, Hospital Sant Joan Despi Moises Broggi - Barcelona/ES

 

 

IgG4-RELATED SCLEROSING CHOLANGITIS

 

- IgG4-Related Sclerosing Cholangitis (IgG4-SC) is a biliary disease of unknown etiology associated to elevated serum levels of IgG4 (>140 mg/dl).

- Association with AIP is very frequent and it can be seen in up to 80-90% of cases. Relation with fibrosing diseases in other organs like the kidneys (IgG4-Related Tubulointerstitial Nephritis) has also been reported, but there is no association with inflammatory bowel disease.

- Epidemiology: 80% of cases are males with a mean age of 65 years.

- Serology: Cholestatic pattern with elevation of bilirrubin, IgG4 and CA 19.9. As it was commented previously on AIP, normal levels of IgG4 can be seen in up to 30% of cases and do not exclude the diagnosis.

- Clinical presentation: Relatively acute with marked jaundice that quite often is associated with mild or moderate upper abdominal pain and weight loss.

Histology: IgG4-positive plasma cell infiltration in bile ducts with obliterative phlebitis and fibrosis that cause sclerosis with important periluminal inflammation (but biliary epithelium is not usually affected).

- Treatment: Steroids (Rituximab and Inmune-modulators can also be used as an alternative treatment in relapses and as maintenance therapy).

- CT and MRI findings (Fig. 13, Fig. 14, Fig. 15, Fig. 16):

  • Long segmental band-like strictures of the bile ducts (most frequently involving the common bile duct) with significant circumferential thickening and prestenotic ductal dilatation.
Fig. 13
References: Radiology, Hospital Sant Joan Despi Moises Broggi - Barcelona/ES

 

Fig. 14: IgG4-Related Sclerosing Cholangitis and synchronous diffuse AIP in a 72-year-old woman with painless jaundice and elevation of bilirubin and CA 19.9. (a,b) Contrast-enhanced CT in portal phase in axial and coronal planes showed long narrowing of the common bile duct with marked circumferential thickening (red arrows) and upstream dilatation of intrahepatic bile ducts. (c,d,e,f) MR cholangiography was performed afterwards with T1-weighted images, T2-weighted images, MIP reconstruction of the biliary tree in coronal plane and ADC map, confirming the irregular and stenosing thickening of the common bile duct seen on CT (blue arrows) and the irregular dilatation of intrahepatic bile ducts. There were also signs of diffuse AIP with a “sausage-shaped” pancreas that showed a hypointense peripancreatic halo (orange arrows), irregular stenosis of the main pancreatic duct (yellow arrows) and low values on ADC map (green arrows). (g,h,i) Control MR cholangiography performed after two months of steroid treatment showed practical resolution of the circumferential thickening and narrowing of the common bile duct (blue arrows) and resolution of the intrahepatic bile ducts dilatation, as well as significant improvement of the irregular stenosis of the main pancreatic duct (yellow arrows). There is also a decreased volume of the pancreas showing a post-treatment atrophic appearance (orange arrows) with higher values on ADC map (green arrows).
References: Radiology, Hospital Sant Joan Despi Moises Broggi - Barcelona/ES

 

Fig. 15: Same patient of the previous case, a 72 year-old-woman with known IgG4-Related Sclerosing Cholangitis and diffuse AIP, that presented one year later with a new episode of painless obstructive jaundice and with mild impairment of renal function due to IgG4-Related Tubulointerstitial Nephritis. (a,b,c,d,e,f) MR cholangiography was performed with T2-weighted images, MIP reconstruction of the biliary tree in coronal plane, diffusion-weighted images and ADC map. We can see a new severe stricture of the distal common bile duct with circumferential thickening (blue arrows) causing upstream biliary dilatation, as well as an atrophic pancreas (orange arrows) with irregular strictures and dilatations of the main pancreatic duct (yellow arrows). The interesting finding in this case was the apparition of bilateral renal cortical lesions, hypointense on T2-weighted images (red arrows) and with marked restricted diffusion (green arrows), that in the clinical context were highly suggestive of IgG4-Related Tubulointerstitial Nephritis. (g,h,i,j,k,l) Control MR cholangiography performed after one month of steroid treatment showed dramatic response with resolution of the circumferential thickening and narrowing of the distal common bile duct (blue arrows) and the upstream dilatation, as well as significant improvement of the irregular stenosis of the main pancreatic duct (yellow arrows). There was also a significant decrease in size of the renal lesions (red arrows) with mild restricted diffusion (green arrows), confirming the radiological suspicion of IgG4-Related Tubulointerstitial Nephritis. Post-treatment pancreatic atrophy was also seen, more severe than in previous MR (orange arrows).
References: Radiology, Hospital Sant Joan Despi Moises Broggi - Barcelona/ES

 

Fig. 16: IgG4-Related Sclerosing Cholangitis and diffuse AIP in a 69-year-old man with weight loss and epigastralgia. (a,b) Contrast-enhanced CT in portal phase showed marked wall thickening of the common bile duct (red arrows) and signs of diffuse AIP in relation to pancreas enlargement with loss of lobulated contours and hypodense halo (orange arrows). (c,d,e) MR Cholangiography showed a hypointense peripancreatic halo and mild hyperintensity of pancreatic parenchyma on T2-weighted images in relation to inflammatory changes (blue arrows), with narrowing of intrapancreatic common bile duct and main pancreatic duct. Coronal reconstruction of the biliary tree showed segmental stenosis of the biliary confluence and the intrapancreatic common bile duct (yellow arrows) with upstream dilatation, while the Wirsung could not be clearly identified due to diffuse narrowing. (f,g,h) A new MR Cholangiography was performed after two months of steroid treatment, showing decreased volume of the pancreas with resolution of the inflammatory changes on T2-weighted images (blue arrows). Coronal reconstruction of the biliary tree showed significant improvement of the stenosing thickenings at the level of the biliary confluence and the intrapancreatic common bile duct (yellow arrows) and resolution of the diffuse narrowing of the main pancreatic duct with clear visualization of the Wirsung (green arrows).
References: Radiology, Hospital Sant Joan Despi Moises Broggi - Barcelona/ES

 

DIFFERENTIAL DIAGNOSIS OF IgG4-SC

 

Primary Sclerosing Cholangitis

- Chronic cholestatic disease of unknown etiology characterized by inflammation and fibrosis of intra and extrahepatic bile ducts.

Associated with inflammatory bowel disease (IBD), usually in the form of Ulcerative Colitis.             

Epidemiology: More frequent in males (65% cases) with a mean age of 40 years.    

Serology: Cholestatic pattern with no elevation of IgG4.

- Clinical Presentation: Less acute than in IgG4-SC, quite often is an incidental finding during the study of IBD. Occasionally cholestatic pruritus can be present but jaundice is not frequent in early stages.

Histology: Obliterative cholangitis with concentric fibrosis without IgG4-positive cells, involving the biliary epithelium and producing stenosis and saccular dilatations.   

Treatment: There is no approved or proven specific therapy for PSC. Immunosuppressants, bile salts, chelators and steroids are used in an attempt to control the disease, but none of them has shown significant benefit.

CT and MRI findings (Fig. 17, Fig. 18, Fig. 19): 

  • Multifocal short strictures of the intra and extrahepatic bile ducts alternating with normal segments and saccular dilatations that give a pruned-tree appearance.
Fig. 17
References: Radiology, Hospital Sant Joan Despi Moises Broggi - Barcelona/ES

 

Fig. 18: Primary sclerosing cholangitis in a 52-year-old man with Ulcerative Colitis and recurrent episodes of cholangitis. (a, b, c, d, e, f) MR cholangiography with axial and coronal T2-weighted sequences and coronal MIP reconstruction of the biliary tree. There is a circumferential and stenosing thickening of the common hepatic duct and common bile duct (red arrows), as well as multifocal short strictures of the intrahepatic bile ducts alternating with normal segments and saccular dilatations (blue arrows) that give a pruned-tree appearance. The morphology and signal of the pancreas is preserved with main pancreatic duct of normal caliber, without signs of AIP (yellow arrows).
References: Radiology, Hospital Sant Joan Despi Moises Broggi - Barcelona/ES

 

Fig. 19: Table summarizing the main differences between Primary Sclerosing Cholangitis (PSC) and IgG4-Related Sclerosing Cholangitis (IgG4-SC).
References: Radiology, Hospital Sant Joan Despi Moises Broggi - Barcelona/ES

  

 Cholangiocarcinoma

- Related to chronic inflammation of the biliary tract.

Epidemiology: Mean age of 50-70 years with no gender predominance.    - Serology: Elevation of bilirrubin and tumor markers CA 19.9 and CEA.

Clinical Presentation: Jaundice, coluria, pruritus, abdominal pain and weight loss.

- Histology: Adenocarcinomas usually embedded in a desmoplastic stroma.

Treatment: Surgical resection when possible, liver transplant may be an option in selected cases. Unresectable cases can be treated with palliative chemotherapy and biliary drainage.

- There are 3 types of cholangiocarcinoma according to its location:

 

  • Intrahepatic (10-20%): Mass-forming lesion that requires differential diagnosis with Hepatocellular Carcinoma.  
  • Hilar or Klatskin Tumor (50-75%) and Extrahepatic (20-30%): Infiltrating lesions that require differential diagnosis with IgG4-SC.

CT and MRI findings (Fig. 20, Fig. 21):

  • Irregular thickening of the bile duct wall with late enhancement that causes focal or segmental stricture with regular upstream dilatation of intrahepatic ducts.

  • Associated signs of malignancy like enlarged lymph nodes, liver metastases or portal thrombosis.
Fig. 20
References: Radiology, Hospital Sant Joan Despi Moises Broggi - Barcelona/ES

 

Fig. 21: Examples of extrahepatic cholangiocarcinoma and hilar cholangiocarcinomas. (a,b) MR cholangiography sequences of extrahepatic cholangiocarcinoma show short stricture of the common bile duct with abrupt cut off (red arrows) and regular upstream dilatation. (c) Coronal T2-weighted image of hilar cholangiocarcinoma shows a segmental stricture of common hepatic duct and biliary confluence with wall thickening (yellow arrow). (d,e) Contrast-enhanced CT in portal phase and MR cholangiography of Klatskin tumor show an ill-defined pseudonodular area of solid appearance in hepatic hilum that causes severe stenosis of the biliary confluence with significant upstream dilatation (blue arrows). (f) Coronal T2-weighted image shows extensive hilar cholangiocarcinoma that infiltrates common bile duct, biliary confluence and liver parenchyma (orange arrows) and is associated with hepatic metastases (green arrows).
References: Radiology, Hospital Sant Joan Despi Moises Broggi - Barcelona/ES

 

 

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