To illustrate the spectrum of abdominal and pelvic manifestations of IgG4-RD, multimodality imaging features will be discussed, including ultrasound (USG), computed tomography (CT), magnetic resonance imaging (MRI) and 18F-FDG positron emission tomography (PET)-CT.

Key diagnostic clues are highlighted to differentiate IgG4-RD from other malignant conditions through companion case comparison.

Selected cases are also included to demonstrate post-treatment response, in terms of morphological, functional or metabolic assessment with 18F-FDG PET-CT.

PANCREAS AND HEPATOBILIARY SYSTEM

IgG4-related Autoimmune Pancreatitis (AIP)

• Manifests as Type 1 AIP^{1-2, 7}. Not associated with Type 2 AIP^{1, 7} 
• Primarily affect middle-aged and elderly men (6th decade)^{2, 6-7} with higher recurrence rate than Type 2 AIP⁷
• Associated autoimmune disorders: Sjogren, SLE, primary sclerosing cholangitis (PSC), primary biliary cirrhosis, etc. ¹⁰
• Pancreatic morphologic change depends on extent of inflammatory response and fibrosis^{1, 4} 
  • Diffuse involvement (most common)^{1-2, 4, 7, 10}
    • Diffusely enlarged pancreas, loss of normal pancreatic clefts
  • Focal lesions^{1-2, 4, 7, 10}
    • Mass-like hypoattenuating lesion often at pancreatic head
    • Can progress to diffuse involvement⁴
• USG : Enlarged pancreas with hypoechoic parenchyma^{6, 10}
• CT
  • Enhancement reduced in pancreatic phase, near-normal in porto-venous phase^{1, 6}
  • Peripancreatic hypoattenuating halo^{1-2, 5-6} 
  • Minimal peripancreatic fat stranding¹⁰
  • Rare: Lymphadenopathy, calcifications, and pseudocyst⁶
  • Features favouring AIP over adenocarcinoma⁷
    • Homogeneous enhancement, persistent delayed phase enhancement (c.f. Pancreatic adenocarcinoma minimally enhances^{1, 7})
    • +/- Pancreatic ductal wall enhancement⁷
•  MRI
  • T1 hypointense/ T2 hyperintense parenchymal change^{1, 6-7} 
  • Restricted diffusion^{1, 7} 
  • Delayed enhancement^{1, 7}
• MR cholangiopancreatography (MRCP)²
  • Pancreatic ductal strictures^{1, 6}
  • Duct-penetrating sign through AIP involved areas^{1, 6}
• 18F-FDG PET-CT
  • Intense FDG tracer uptake of affected segment^{1, 7}
• Usually corticosteroid responsive^{2, 4, 7, 10}
  • Improved pancreatic morphology and function within 4-6 weeks^{2, 6}
  • Predicting treatment outcome from imaging features⁴
    • Features predicting favourable response: related to early inflammatory changes - Diffuse pancreatic swelling; hypoattenuating halo in CT
    • Features predicting suboptimal response: findings that signify fibrosis or late disease stage - Focal mass-like swelling without peripancreatic changes; persistent ductal strictures

Fig 1: IgG4-related autoimmune pancreatitis in 71-year-old woman who presented with epigastric pain and mixed pattern of deranged liver function test. (A) Transabdominal transverse ultrasound (USG) image shows enlarged pancreatic head and proximal body with hypo-echoic echotexture (star). Proximal common bile duct is dilated to 1.1cm (arrow). (B) Axial 18F-FDG PET-CT image shows diffuse sausage-like enlargement of pancreas (loss of lobular contours and pancreatic clefts) (star) with diffusely increased tracer avidity (arrow). No focal lesion detected in pancreas, distal common bile duct and ampulla of Vater. (C) Frontal endoscopic retrograde cholangiopancreatographic (ERCP) image shows lower common bile duct stricture (arrow) with negative cytology for malignancy. Endoscopic ultrasound (not shown) shows diffuse hypo-echoic pancreatic parenchyma with thin rim of peri-pancreatic fluid.

Fig 2: IgG4-related autoimmune pancreatitis in 71-year-old woman who presented with epigastric pain and mixed pattern of deranged liver function test. (A) Transabdominal transverse ultrasound (USG) image shows enlarged pancreatic head and proximal body with hypo-echoic echotexture (star). Proximal common bile duct is dilated to 1.1cm (arrow). (B) Axial 18F-FDG PET-CT image shows diffuse sausage-like enlargement of pancreas (loss of lobular contours and pancreatic clefts) (star) with diffusely increased tracer avidity (arrow). No focal lesion detected in pancreas, distal common bile duct and ampulla of Vater. (C) Frontal endoscopic retrograde cholangiopancreatographic (ERCP) image shows lower common bile duct stricture (arrow) with negative cytology for malignancy. Endoscopic ultrasound (not shown) shows diffuse hypo-echoic pancreatic parenchyma with thin rim of peri-pancreatic fluid.

Fig 3: IgG4-related autoimmune pancreatitis in 71-year-old woman who presented with epigastric pain and mixed pattern of deranged liver function test. (A) Transabdominal transverse ultrasound (USG) image shows enlarged pancreatic head and proximal body with hypo-echoic echotexture (star). Proximal common bile duct is dilated to 1.1cm (arrow). (B) Axial 18F-FDG PET-CT image shows diffuse sausage-like enlargement of pancreas (loss of lobular contours and pancreatic clefts) (star) with diffusely increased tracer avidity (arrow). No focal lesion detected in pancreas, distal common bile duct and ampulla of Vater. (C) Frontal endoscopic retrograde cholangiopancreatographic (ERCP) image shows lower common bile duct stricture (arrow) with negative cytology for malignancy. Endoscopic ultrasound (not shown) shows diffuse hypo-echoic pancreatic parenchyma with thin rim of peri-pancreatic fluid.

Fig 4: Pre- and 5-month Post-treatment axial contrast CT of IgG4-related autoimmune pancreatitis in 76-year-old woman. (A) Pre-treatment axial plain and contrast-enhanced CT shows diffuse enlargement of pancreas with no discrete hypo-enhancing lesion. Note characteristic peripancreatic hypoattenuating halo (arrow). (B) Axial pre-treatment contrast-enhanced CT (left) and follow-up CT 5 months later after corticosteroid administration (right) shows favourable treatment response. Pancreas is no longer swollen (star) with resolved hypoattenuating peripancreatic halo.

Fig 5: Pre- and 5-month Post-treatment axial contrast CT of IgG4-related autoimmune pancreatitis in 76-year-old woman. (A) Pre-treatment axial plain and contrast-enhanced CT shows diffuse enlargement of pancreas with no discrete hypo-enhancing lesion. Note characteristic peripancreatic hypoattenuating halo (arrow). (B) Axial pre-treatment contrast-enhanced CT (left) and follow-up CT 5 months later after corticosteroid administration (right) shows favourable treatment response. Pancreas is no longer swollen (star) with resolved hypoattenuating peripancreatic halo.

Fig 6: Companion case for IgG4-related autoimmune pancreatitis. Exocrine pancreatic adenocarcinoma in a 50-year-old woman who presented with obstructive jaundice. (A) Axial (left) and coronal (right) contrast-enhanced CT shows double duct sign - simultaneously dilated common bile duct (arrow) and pancreatic duct (star), due to malignant biliary obstruction. (B) Follow-up axial plain, axial and coronal contrast-enhanced CT 4 months later clearly shows hypo-vascular nature of tumor with minimal contrast enhancement (arrow).

Fig 7: Companion case for IgG4-related autoimmune pancreatitis. Exocrine pancreatic adenocarcinoma in a 50-year-old woman who presented with obstructive jaundice. (A) Axial (left) and coronal (right) contrast-enhanced CT shows double duct sign - simultaneously dilated common bile duct (arrow) and pancreatic duct (star), due to malignant biliary obstruction. (B) Follow-up axial plain, axial and coronal contrast-enhanced CT 4 months later clearly shows hypo-vascular nature of tumor with minimal contrast enhancement (arrow).

IgG4-related Sclerosing Cholangitis (ISC)

• Second most affected organ after pancreas^1-2 
• Most frequently affected organ within hepatobiliary system¹ 
• Commonly associated with IgG4-related autoimmune pancreatitis (60 – 80%)^{1-2, 7}
• Diagnostic challenges
  • ISC can occur independently without pancreatic involvement^{1-2, 6} 
  • Overlap with PSC^{1-2, 6-7, 9} and cholangiocarcinoma^{2, 9} 
    • ISC typically occur in elderly patient, accompanied by pancreatic or extra-pancreatic lesions, with characteristic long and continuous strictures at ERCP, absent hepatic capsular retraction
• Imaging features
  • Thickened bile duct wall with smooth margins^{1-2, 6-7}. Homogeneous enhancement in delayed phase^{2, 7}
  • Can affect both intrahepatic and extrahepatic segments of bile ducts causing stenosis and upstream dilatation +/- gallbladder involvement^{1-2, 6-7} 
    • Most common: common bile duct intrapancreatic portion^{1, 6}
  • 18F-FDG PET-CT
    • Moderate tracer uptake in involved biliary ducts¹
• Usually corticosteroid responsive^{2, 7, 9}
  • Biopsy before treatment necessary to exclude potential malignant lesions²
  • May experience relapses despite maintenance corticosteroid therapy²

Fig 8: IgG4-related sclerosing cholangitis in a 73-year-old man who presented with tea colour urine and deranged liver function test. (A) Magnetic resonance cholangiopancreatography (MRCP) axial T2 (left) and coronal T2 (right) fat-saturated images show mildly dilated common duct (1cm) (arrow) and prominent intrahepatic ducts (not shown). (B) Similar findings (arrow) are also demonstrated on axial and coronal contrast-enhanced CT images. (C) Coronal MRCP maximum intensity projection (MIP) image (left) and frontal endoscopic retrograde cholangiopancreatographic image (ERCP) (right) shows common bile duct stricture (arrow). Biliary cytology shows cytologic atypia with suspected common duct cholangiocarcinoma. Excision of extrahepatic common bile duct was performed with pathology report revealing IgG4-related sclerosing cholangitis.

Fig 9: IgG4-related sclerosing cholangitis in a 73-year-old man who presented with tea colour urine and deranged liver function test. (A) Magnetic resonance cholangiopancreatography (MRCP) axial T2 (left) and coronal T2 (right) fat-saturated images show mildly dilated common duct (1cm) (arrow) and prominent intrahepatic ducts (not shown). (B) Similar findings (arrow) are also demonstrated on axial and coronal contrast-enhanced CT images. (C) Coronal MRCP maximum intensity projection (MIP) image (left) and frontal endoscopic retrograde cholangiopancreatographic image (ERCP) (right) shows common bile duct stricture (arrow). Biliary cytology shows cytologic atypia with suspected common duct cholangiocarcinoma. Excision of extrahepatic common bile duct was performed with pathology report revealing IgG4-related sclerosing cholangitis.

Fig 10: IgG4-related sclerosing cholangitis in a 73-year-old man who presented with tea colour urine and deranged liver function test. (A) Magnetic resonance cholangiopancreatography (MRCP) axial T2 (left) and coronal T2 (right) fat-saturated images show mildly dilated common duct (1cm) (arrow) and prominent intrahepatic ducts (not shown). (B) Similar findings (arrow) are also demonstrated on axial and coronal contrast-enhanced CT images. (C) Coronal MRCP maximum intensity projection (MIP) image (left) and frontal endoscopic retrograde cholangiopancreatographic image (ERCP) (right) shows common bile duct stricture (arrow). Biliary cytology shows cytologic atypia with suspected common duct cholangiocarcinoma. Excision of extrahepatic common bile duct was performed with pathology report revealing IgG4-related sclerosing cholangitis.

IgG4-related Hepatopathy^{3, 9, 11}

• Hepatic parenchymal disease involvement, manifests as portal inflammation and lobular hepatitis
• Relative new disease entity with limited documentations on pathogenesis and radiological findings
• Can present as infiltrative enhancing mass in periportal location. Potential misdiagnosed as malignant tumour

Fig 11: IgG4-related lymphadenopathy in a 57-year-old woman who presented with deranged liver function test, with subsequent development of IgG4-related sclerosing cholangitis and hepatopathy. (A) Axial plain and contrast-enhanced CT image demonstrates clusters of multiple portal, para-aortic and gastro-hepatic lymphadenopathy (star). Mildly prominent intrahepatic ducts seen (not shown). (B) Axial 18F-FDG PET-CT shows FDG-avidity of the lymph nodes (star), with no suspicious adjacent primary tumour. Endoscopic ultrasound guided biopsy of lymph node confirms the diagnosis of IgG4-related lymphadenopathy. Concurrent biopsy of liver shows chronic cholangitis with no evidence of primary sclerosing cholangitis, primary biliary cirrhosis or IgG4-related cholangitis. Patient was treated with corticosteroid and subsequent liver function test normalized. (C) Interval follow-up and laboratory tests revealed acutely deranged liver function. MR cholangiogram (left) and ERCP (right) shows mildly dilated bilateral intrahepatic ducts with focal irregular tapering (star) towards porta hepatis. Right intrahepatic duct stricture also seen in ERCP (arrow). Histology studies revealed IgG4-related sclerosing cholangitis. (D) Serial axial plain CTs at presentation (left), 2 years (middle) and 3 years (right) after diagnosis of IgG4-related sclerosing cholangitis, shows progressive right hepatic lobe atrophy with widened fissure (star). USG-guided biopsy of right hepatic lobe shows IgG4-related hepatopathy.

Fig 12: IgG4-related lymphadenopathy in a 57-year-old woman who presented with deranged liver function test, with subsequent development of IgG4-related sclerosing cholangitis and hepatopathy. (A) Axial plain and contrast-enhanced CT image demonstrates clusters of multiple portal, para-aortic and gastro-hepatic lymphadenopathy (star). Mildly prominent intrahepatic ducts seen (not shown). (B) Axial 18F-FDG PET-CT shows FDG-avidity of the lymph nodes (star), with no suspicious adjacent primary tumour. Endoscopic ultrasound guided biopsy of lymph node confirms the diagnosis of IgG4-related lymphadenopathy. Concurrent biopsy of liver shows chronic cholangitis with no evidence of primary sclerosing cholangitis, primary biliary cirrhosis or IgG4-related cholangitis. Patient was treated with corticosteroid and subsequent liver function test normalized. (C) Interval follow-up and laboratory tests revealed acutely deranged liver function. MR cholangiogram (left) and ERCP (right) shows mildly dilated bilateral intrahepatic ducts with focal irregular tapering (star) towards porta hepatis. Right intrahepatic duct stricture also seen in ERCP (arrow). Histology studies revealed IgG4-related sclerosing cholangitis. (D) Serial axial plain CTs at presentation (left), 2 years (middle) and 3 years (right) after diagnosis of IgG4-related sclerosing cholangitis, shows progressive right hepatic lobe atrophy with widened fissure (star). USG-guided biopsy of right hepatic lobe shows IgG4-related hepatopathy.

Fig 13: IgG4-related lymphadenopathy in a 57-year-old woman who presented with deranged liver function test, with subsequent development of IgG4-related sclerosing cholangitis and hepatopathy. (A) Axial plain and contrast-enhanced CT image demonstrates clusters of multiple portal, para-aortic and gastro-hepatic lymphadenopathy (star). Mildly prominent intrahepatic ducts seen (not shown). (B) Axial 18F-FDG PET-CT shows FDG-avidity of the lymph nodes (star), with no suspicious adjacent primary tumour. Endoscopic ultrasound guided biopsy of lymph node confirms the diagnosis of IgG4-related lymphadenopathy. Concurrent biopsy of liver shows chronic cholangitis with no evidence of primary sclerosing cholangitis, primary biliary cirrhosis or IgG4-related cholangitis. Patient was treated with corticosteroid and subsequent liver function test normalized. (C) Interval follow-up and laboratory tests revealed acutely deranged liver function. MR cholangiogram (left) and ERCP (right) shows mildly dilated bilateral intrahepatic ducts with focal irregular tapering (star) towards porta hepatis. Right intrahepatic duct stricture also seen in ERCP (arrow). Histology studies revealed IgG4-related sclerosing cholangitis. (D) Serial axial plain CTs at presentation (left), 2 years (middle) and 3 years (right) after diagnosis of IgG4-related sclerosing cholangitis, shows progressive right hepatic lobe atrophy with widened fissure (star). USG-guided biopsy of right hepatic lobe shows IgG4-related hepatopathy.

Fig 14: IgG4-related lymphadenopathy in a 57-year-old woman who presented with deranged liver function test, with subsequent development of IgG4-related sclerosing cholangitis and hepatopathy. (A) Axial plain and contrast-enhanced CT image demonstrates clusters of multiple portal, para-aortic and gastro-hepatic lymphadenopathy (star). Mildly prominent intrahepatic ducts seen (not shown). (B) Axial 18F-FDG PET-CT shows FDG-avidity of the lymph nodes (star), with no suspicious adjacent primary tumour. Endoscopic ultrasound guided biopsy of lymph node confirms the diagnosis of IgG4-related lymphadenopathy. Concurrent biopsy of liver shows chronic cholangitis with no evidence of primary sclerosing cholangitis, primary biliary cirrhosis or IgG4-related cholangitis. Patient was treated with corticosteroid and subsequent liver function test normalized. (C) Interval follow-up and laboratory tests revealed acutely deranged liver function. MR cholangiogram (left) and ERCP (right) shows mildly dilated bilateral intrahepatic ducts with focal irregular tapering (star) towards porta hepatis. Right intrahepatic duct stricture also seen in ERCP (arrow). Histology studies revealed IgG4-related sclerosing cholangitis. (D) Serial axial plain CTs at presentation (left), 2 years (middle) and 3 years (right) after diagnosis of IgG4-related sclerosing cholangitis, shows progressive right hepatic lobe atrophy with widened fissure (star). USG-guided biopsy of right hepatic lobe shows IgG4-related hepatopathy.

MESENTERY AND ALIMENTARY TRACT

IgG4-related Sclerosing Mesenteritis

• Previously considered idiopathic cases are recently recognized as part of IgG4-RD spectrum¹
• Characterized by fibrosis and inflammation of mesentery^{2, 6} 
• Associated with AIP, ISC, and RPF²
• Imaging features
  • Present as soft-tissue mass in small-bowel mesentery, typically located at root and encasing mesenteric vessels^{1-2, 6}
  • CT
    • Internal calcification is common¹
    • "Fat ring sign", indicating fibrotic process primarily at the mesentery. Preserved perivascular fat around mesenteric vessels^1-2
    • Tumoral pseudo-capsule (soft-tissue band at mesenteric borders of mass)¹
    • Can cause small bowel obstruction due to fibrous tissue mass effect²
  • MRI: T1/T2 hypointense mass due to fibrotic tissue¹
  • 18F-FDG PET-CT: Mild tracer uptake¹
• Important differentials to consider^1-2
  • Carcinoid, lymphoma, mesenteric fibromatosis, carcinomatosis and inflammatory myofibroblastic tumour

Fig 15: IgG4-related sclerosing mesenteritis in 49-year-old female with lower abdominal pain. (A) Axial plain and contrast-enhanced CT shows ill-defined mesenteric soft tissue mass in lower abdomen (star). Note preservation of fat around the superior mesenteric vessels (fat ring sign) (arrow). (B) Axial 18F-FGD PET-CT shows FDG hypermetabolism of mesenteric soft tissue mass (star). No otherwise definite primary site for malignancy identified. (C) Patient was later re-admitted due to abdominal pain and vomiting. Axial (left) and coronal (right) contrast-enhanced CT shows mechanical small bowel obstruction (star) with transition zone at distal ileum, which is infiltrated by soft tissue mass (arrow). Exploratory laparotomy with resection shows IgG4-related sclerosing mesenteritis.

Fig 16: IgG4-related sclerosing mesenteritis in 49-year-old female with lower abdominal pain. (A) Axial plain and contrast-enhanced CT shows ill-defined mesenteric soft tissue mass in lower abdomen (star). Note preservation of fat around the superior mesenteric vessels (fat ring sign) (arrow). (B) Axial 18F-FGD PET-CT shows FDG hypermetabolism of mesenteric soft tissue mass (star). No otherwise definite primary site for malignancy identified. (C) Patient was later re-admitted due to abdominal pain and vomiting. Axial (left) and coronal (right) contrast-enhanced CT shows mechanical small bowel obstruction (star) with transition zone at distal ileum, which is infiltrated by soft tissue mass (arrow). Exploratory laparotomy with resection shows IgG4-related sclerosing mesenteritis.

Fig 17: IgG4-related sclerosing mesenteritis in 49-year-old female with lower abdominal pain. (A) Axial plain and contrast-enhanced CT shows ill-defined mesenteric soft tissue mass in lower abdomen (star). Note preservation of fat around the superior mesenteric vessels (fat ring sign) (arrow). (B) Axial 18F-FGD PET-CT shows FDG hypermetabolism of mesenteric soft tissue mass (star). No otherwise definite primary site for malignancy identified. (C) Patient was later re-admitted due to abdominal pain and vomiting. Axial (left) and coronal (right) contrast-enhanced CT shows mechanical small bowel obstruction (star) with transition zone at distal ileum, which is infiltrated by soft tissue mass (arrow). Exploratory laparotomy with resection shows IgG4-related sclerosing mesenteritis.

IgG4-related Alimentary Tract Sclerosing Disease^{3, 8, 12}

• Relative new disease entity
• Characterized by increased IgG4-positive plasma cell infiltration to glandular tissues or vascular system of gastrointestinal tract, resulting in ulcers, polypoid lesions, submucosal masses and wall thickening
• Radiological features : Submucosal oedema, mural thickening of affected bowel segment, mimic malignancy

Fig 18: IgG4-related alimentary tract sclerosing disease in 64-year-old man who presented with tender right lower abdomen mass and one-week history of absent bowel opening. (A) Axial (left) and coronal (right) contrast-enhanced CT shows significant mural thickening at terminal ileum, right sided colon involving cecum and ascending colon, with content stasis in upstream small bowel leading to small bowel faeces sign at distal ileum (arrow). Intestines are otherwise not dilated. Right hemicolectomy with end-to-end ileocolic anastomosis performed with tumour suspicion. Intra-operative finding of 5cm caecal mass with adhesion to terminal ileum and retroperitoneum. Pathology confirms IgG4-related sclerosing disease. (B) Axial plain and contrast-enhanced CT status 1-month post-operation shows ileocolic anastomotic leakage with extra-luminal gas (arrow) and fluid. Intra-operative finding of 1cm dehiscence at anastomosis with small bowel resection and exteriorization performed. Pathology reveals IgG4-related disease infiltration to anastomosis.

Fig 19: IgG4-related alimentary tract sclerosing disease in 64-year-old man who presented with tender right lower abdomen mass and one-week history of absent bowel opening. (A) Axial (left) and coronal (right) contrast-enhanced CT shows significant mural thickening at terminal ileum, right sided colon involving cecum and ascending colon, with content stasis in upstream small bowel leading to small bowel faeces sign at distal ileum (arrow). Intestines are otherwise not dilated. Right hemicolectomy with end-to-end ileocolic anastomosis performed with tumour suspicion. Intra-operative finding of 5cm caecal mass with adhesion to terminal ileum and retroperitoneum. Pathology confirms IgG4-related sclerosing disease. (B) Axial plain and contrast-enhanced CT status 1-month post-operation shows ileocolic anastomotic leakage with extra-luminal gas (arrow) and fluid. Intra-operative finding of 1cm dehiscence at anastomosis with small bowel resection and exteriorization performed. Pathology reveals IgG4-related disease infiltration to anastomosis.

GENITOURINARY SYSTEM AND RETROPERITONEUM

IgG4-related Renal Disease

• Kidney: Most frequently involved genitourinary organ⁵
• More commonly manifested as tubulointerstitial nephritis than membranous glomerulonephropathy^{1, 5} 
• Obstructive nephropathy possible due to post-renal obstruction^{1-2, 5-7} 
• Commonly presented as acute or progressive renal failure¹
• Prompt diagnosis and treatment to prevent chronic kidney disease^1. Usually corticosteroid responsive^{2, 5, 7}
• Tubulointerstitial Nephritis classified into
  • Parenchymal involvement (most common)
    • CT: Present as small round or wedge-shaped peripheral hypo-enhancing cortical lesions^{1-2, 5, 7}
      • Differentials: Multifocal pyelonephritis, metastasis, lymphoma^{2, 5, 7}
    • MRI: T1/T2 hypointense. Gradual progressive enhancement, +/- diffusion restriction^{1-2, 5, 7}
  • Renal pelvic involvement
    • Present as masses in renal pelvis or diffuse pelvic wall thickening^{1, 5, 7}
    • Mimic renal cell carcinoma and urothelial cell carcinoma⁵
  • Perinephric involvement
    • Present as a diffuse rind of soft tissue surrounding the kidney^{1, 5, 7}
    • Excretory phase CT urography may show extrinsically compressed collecting systems^{1-2, 5-7} without intraluminal defect, aiding differentiation from urothelial tumours
  • 18F-FDG PET-CT
    • Limited use for initial evaluation due to physiologic renal radiotracer excretion¹
    • Monitor treatment response in known cases to guide treatment duration⁵

Fig 20: IgG4-related renal pelvic disease in a 72-year-old man. Tapering of immunosuppressive therapy based on FDG inactivity and lack of active inflammation on repeat biopsy post-treatment. (A) Pre-treatment axial (left) and coronal (right) contrast-enhanced CT image at presentation shows ill-defined mildly enhancing soft tissue mass (star) encasing renal pelvises or sinuses, causing hydronephroses. (B) Post-treatment axial contrast-enhanced CT 5 years later shows partial resolution of bilateral peri-pelvic soft tissue lesions with residue (arrows). (C) Subsequent 18F-FDG PET-CT shows no significant FDG metabolism of soft tissue lesion (star). Biopsy of the lesion shows fibrous tissue with no significant inflammation. In view of inactive disease with predominant fibrosis, immunosuppressive treatment was gradually tapered down. (D) Another similar biopsy-proven case of IgG4-related renal pelvic disease. Excretory phase of coronal maximum intensity projection (MIP) (left) and axial (right) images of contrast-enhanced CT Urography shows soft tissue thickening with smooth outer border, encasing left renal pelvis (arrow). Note the compressed upper collecting system also retains smooth inner surface with no discrete intra-luminal filling defect, rendering urothelial tumour origin unlikely.

Fig 21: IgG4-related renal pelvic disease in a 72-year-old man. Tapering of immunosuppressive therapy based on FDG inactivity and lack of active inflammation on repeat biopsy post-treatment. (A) Pre-treatment axial (left) and coronal (right) contrast-enhanced CT image at presentation shows ill-defined mildly enhancing soft tissue mass (star) encasing renal pelvises or sinuses, causing hydronephroses. (B) Post-treatment axial contrast-enhanced CT 5 years later shows partial resolution of bilateral peri-pelvic soft tissue lesions with residue (arrows). (C) Subsequent 18F-FDG PET-CT shows no significant FDG metabolism of soft tissue lesion (star). Biopsy of the lesion shows fibrous tissue with no significant inflammation. In view of inactive disease with predominant fibrosis, immunosuppressive treatment was gradually tapered down. (D) Another similar biopsy-proven case of IgG4-related renal pelvic disease. Excretory phase of coronal maximum intensity projection (MIP) (left) and axial (right) images of contrast-enhanced CT Urography shows soft tissue thickening with smooth outer border, encasing left renal pelvis (arrow). Note the compressed upper collecting system also retains smooth inner surface with no discrete intra-luminal filling defect, rendering urothelial tumour origin unlikely.

Fig 22: IgG4-related renal pelvic disease in a 72-year-old man. Tapering of immunosuppressive therapy based on FDG inactivity and lack of active inflammation on repeat biopsy post-treatment. (A) Pre-treatment axial (left) and coronal (right) contrast-enhanced CT image at presentation shows ill-defined mildly enhancing soft tissue mass (star) encasing renal pelvises or sinuses, causing hydronephroses. (B) Post-treatment axial contrast-enhanced CT 5 years later shows partial resolution of bilateral peri-pelvic soft tissue lesions with residue (arrows). (C) Subsequent 18F-FDG PET-CT shows no significant FDG metabolism of soft tissue lesion (star). Biopsy of the lesion shows fibrous tissue with no significant inflammation. In view of inactive disease with predominant fibrosis, immunosuppressive treatment was gradually tapered down. (D) Another similar biopsy-proven case of IgG4-related renal pelvic disease. Excretory phase of coronal maximum intensity projection (MIP) (left) and axial (right) images of contrast-enhanced CT Urography shows soft tissue thickening with smooth outer border, encasing left renal pelvis (arrow). Note the compressed upper collecting system also retains smooth inner surface with no discrete intra-luminal filling defect, rendering urothelial tumour origin unlikely.

Fig 23: IgG4-related renal pelvic disease in a 72-year-old man. Tapering of immunosuppressive therapy based on FDG inactivity and lack of active inflammation on repeat biopsy post-treatment. (A) Pre-treatment axial (left) and coronal (right) contrast-enhanced CT image at presentation shows ill-defined mildly enhancing soft tissue mass (star) encasing renal pelvises or sinuses, causing hydronephroses. (B) Post-treatment axial contrast-enhanced CT 5 years later shows partial resolution of bilateral peri-pelvic soft tissue lesions with residue (arrows). (C) Subsequent 18F-FDG PET-CT shows no significant FDG metabolism of soft tissue lesion (star). Biopsy of the lesion shows fibrous tissue with no significant inflammation. In view of inactive disease with predominant fibrosis, immunosuppressive treatment was gradually tapered down. (D) Another similar biopsy-proven case of IgG4-related renal pelvic disease. Excretory phase of coronal maximum intensity projection (MIP) (left) and axial (right) images of contrast-enhanced CT Urography shows soft tissue thickening with smooth outer border, encasing left renal pelvis (arrow). Note the compressed upper collecting system also retains smooth inner surface with no discrete intra-luminal filling defect, rendering urothelial tumour origin unlikely.

Fig 24: Companion case for IgG4-related renal pelvic disease. Incidental finding of B-cell right renal sinus lymphoma in a hepatitis-B infected 52-year-old man who underwent routine screening for hepatocellular carcinoma. Axial plain and contrast-enhanced CT shows abnormal enhancing soft tissue lesion with ill-defined infiltrative border that involves the right renal sinus (arrow) and upper ureter (not shown). Subsequent biopsy showed extra-nodal marginal zone B-cell lymphoma of MALT type.

IgG4-related Retroperitoneal Fibrosis (RPF)

• Chronic inflammation with IgG4-positive plasma cells retroperitoneal infiltration, leading to fibrotic tissue formation around infra-renal abdominal aorta, commonly extending to iliac vessels^{1-2, 5-7}
• Entrapped ureters resulting in obstructive uropathy^{1-2, 5-7}
• Imaging features
  • Soft tissue lesion hypoechoic on USG, homogenously attenuating on CT, T1 hypointense/variable T2 signal intensity on MRI depending on inflammation and fibrosis^{1, 5-7}
  • Enhancement pattern on CT and MRI indicate disease activity and treatment response^{1, 5-6}
    • Active inflammatory RPF: Early enhancement
    • Chronic non-active RPF: Delayed enhancement
• 18F-FDG PET-CT
  • Assess disease activity and residual disease^1,5,7
  • Predict treatment prognosis¹
• Important differentials to consider^{1-2, 5}
  • Lymphoma, large-vessel vasculitis (e.g. giant cell arteritis or Takayasu arteritis), aortitis associated with syphilis or sarcoidosis
• Usually corticosteroid responsive^6-7

Fig 25: IgG4-related retroperitoneal fibrosis in 75-year-old man who presented with acute on chronic renal failure. (A) Axial 18F-FDG PET-CT shows FDG-avid retroperitoneal soft tissue lesion infiltrating left renal hilum (star), right ureter (not shown) and encasing abdominal aorta (arrow). Upstream obstructive uropathy with bilateral hydronephroses are seen, worse on right. (B) MR Urography axial T1 (upper left) and axial T2 (upper right) images show heterogenous intermediate T1 and low T2 signal retroperitoneal soft tissue (arrow). Coronal T2 (lower left) and Maximum intensity projection (MIP) images (lower right) demonstrates bilateral hydronephroses with tapering at upper ureters, in keeping with urinary obstruction due to bilateral ureteric encasement by retroperitoneal tissues. (C) Subsequent CT-guided percutaneous biopsy confirms IgG4-related retroperitoneal fibrosis.

Fig 26: IgG4-related retroperitoneal fibrosis in 75-year-old man who presented with acute on chronic renal failure. (A) Axial 18F-FDG PET-CT shows FDG-avid retroperitoneal soft tissue lesion infiltrating left renal hilum (star), right ureter (not shown) and encasing abdominal aorta (arrow). Upstream obstructive uropathy with bilateral hydronephroses are seen, worse on right. (B) MR Urography axial T1 (upper left) and axial T2 (upper right) images show heterogenous intermediate T1 and low T2 signal retroperitoneal soft tissue (arrow). Coronal T2 (lower left) and Maximum intensity projection (MIP) images (lower right) demonstrates bilateral hydronephroses with tapering at upper ureters, in keeping with urinary obstruction due to bilateral ureteric encasement by retroperitoneal tissues. (C) Subsequent CT-guided percutaneous biopsy confirms IgG4-related retroperitoneal fibrosis.

Fig 27: IgG4-related retroperitoneal fibrosis in 75-year-old man who presented with acute on chronic renal failure. (A) Axial 18F-FDG PET-CT shows FDG-avid retroperitoneal soft tissue lesion infiltrating left renal hilum (star), right ureter (not shown) and encasing abdominal aorta (arrow). Upstream obstructive uropathy with bilateral hydronephroses are seen, worse on right. (B) MR Urography axial T1 (upper left) and axial T2 (upper right) images show heterogenous intermediate T1 and low T2 signal retroperitoneal soft tissue (arrow). Coronal T2 (lower left) and Maximum intensity projection (MIP) images (lower right) demonstrates bilateral hydronephroses with tapering at upper ureters, in keeping with urinary obstruction due to bilateral ureteric encasement by retroperitoneal tissues. (C) Subsequent CT-guided percutaneous biopsy confirms IgG4-related retroperitoneal fibrosis.

IgG4-related Aortitis

• More common in adult male¹³
• Presents as non-stenotic aortic mass with thickened aortic walls and irregular margins^1-2,7
• Typically associated with IgG4-related retroperitoneal fibrosis¹³
• Progress to aortic aneurysm formation^{1-2, 7, 13}
  • Risk of rupture lower than other inflammatory diseases¹
• CT
  • Homogeneous late enhancement of aortic mass^{1-2, 7, 13}
  • Other organ involvement is common¹³
• MRI
  • Low to intermediate T1/ variable T2 signal intensity in aortic mass¹
• 18F-FDG PET-CT
  • Moderate to intense tracer uptake in mass^1,7
• Important differential to consider: Lymphoma¹³
  • Clue: Presence of IgG4-RD in other organs and IgG4 serologic examination
• Usually corticosteroid responsive¹³
  • Steroid therapy may increase rupture risk in aneurysmal IgG4-related peri-aortitis, by promoting arterial wall thinning¹³

Fig 28: IgG4-related aortitis in 64-year-old man who presented with abdominal pain and vomiting. (A) Axial (left) and coronal (right) contrast-enhanced CT image shows circumferential thickening of aortic wall (star) with peri-aortic soft tissue extending to common iliac arteries (arrow). (B) Axial 18F-FDG PET-CT image shows ring of hypermetabolic soft tissue encasing abdominal aorta (arrow). Note smooth outline of soft tissue lesion, in contrast to lobulated nodular contour more commonly seen in retroperitoneal tumours. (C) Comparison of CT at presentation (left) and 4 years after (right) shows interval shrinkage of periaortic soft tissue infiltrate (arrow) , with residual chronic thickening due to multiple disease flares.

Fig 29: IgG4-related aortitis in 64-year-old man who presented with abdominal pain and vomiting. (A) Axial (left) and coronal (right) contrast-enhanced CT image shows circumferential thickening of aortic wall (star) with peri-aortic soft tissue extending to common iliac arteries (arrow). (B) Axial 18F-FDG PET-CT image shows ring of hypermetabolic soft tissue encasing abdominal aorta (arrow). Note smooth outline of soft tissue lesion, in contrast to lobulated nodular contour more commonly seen in retroperitoneal tumours. (C) Comparison of CT at presentation (left) and 4 years after (right) shows interval shrinkage of peri-aortic soft tissue infiltrate (arrow) , with residual chronic thickening due to multiple disease flares.

Fig 30: IgG4-related aortitis in 64-year-old man who presented with abdominal pain and vomiting. (A) Axial (left) and coronal (right) contrast-enhanced CT image shows circumferential thickening of aortic wall (star) with peri-aortic soft tissue extending to common iliac arteries (arrow). (B) Axial 18F-FDG PET-CT image shows ring of hypermetabolic soft tissue encasing abdominal aorta (arrow). Note smooth outline of soft tissue lesion, in contrast to lobulated nodular contour more commonly seen in retroperitoneal tumours. (C) Comparison of CT at presentation (left) and 4 years after (right) shows interval shrinkage of peri-aortic soft tissue infiltrate (arrow) , with residual chronic thickening due to multiple disease flares.

LYMPHATIC SYSTEM

IgG4-related Lymphadenopathy

• Non-specific early sign of IgG4-RD; often recognized after other organ involvement^1-2
• Most common affecting mediastinal and abdominal (especially peripancreatic, periportal and para-aortic) nodes^{1-2, 6}
• Next cervical, axillary, and pulmonary hilar nodes^{1-2, 6}
• Smaller lymph nodes (<2 cm) compared to other diseases, e.g. lymphoma and Castleman disease, and absent systemic symptoms (fever, weight loss)^{1-2, 6}
• Imaging features non-specific
  • USG: Initial imaging modality, diffuse nodal cortical thickening with fatty hilum preservation¹
  • 18F-FDG PET-CT: Avid tracer uptake in affected lymph node¹
• Usually corticosteroid responsive⁶

Fig 11: IgG4-related lymphadenopathy in a 57-year-old woman who presented with deranged liver function test, with subsequent development of IgG4-related sclerosing cholangitis and hepatopathy. (A) Axial plain and contrast-enhanced CT image demonstrates clusters of multiple portal, para-aortic and gastro-hepatic lymphadenopathy (star). Mildly prominent intrahepatic ducts seen (not shown). (B) Axial 18F-FDG PET-CT shows FDG-avidity of the lymph nodes (star), with no suspicious adjacent primary tumour. Endoscopic ultrasound guided biopsy of lymph node confirms the diagnosis of IgG4-related lymphadenopathy. Concurrent biopsy of liver shows chronic cholangitis with no evidence of primary sclerosing cholangitis, primary biliary cirrhosis or IgG4-related cholangitis. Patient was treated with corticosteroid and subsequent liver function test normalized. (C) Interval follow-up and laboratory tests revealed acutely deranged liver function. MR cholangiogram (left) and ERCP (right) shows mildly dilated bilateral intrahepatic ducts with focal irregular tapering (star) towards porta hepatis. Right intrahepatic duct stricture also seen in ERCP (arrow). Histology studies revealed IgG4-related sclerosing cholangitis. (D) Serial axial plain CTs at presentation (left), 2 years (middle) and 3 years (right) after diagnosis of IgG4-related sclerosing cholangitis, shows progressive right hepatic lobe atrophy with widened fissure (star). USG-guided biopsy of right hepatic lobe shows IgG4-related hepatopathy.

Fig 12: IgG4-related lymphadenopathy in a 57-year-old woman who presented with deranged liver function test, with subsequent development of IgG4-related sclerosing cholangitis and hepatopathy. (A) Axial plain and contrast-enhanced CT image demonstrates clusters of multiple portal, para-aortic and gastro-hepatic lymphadenopathy (star). Mildly prominent intrahepatic ducts seen (not shown). (B) Axial 18F-FDG PET-CT shows FDG-avidity of the lymph nodes (star), with no suspicious adjacent primary tumour. Endoscopic ultrasound guided biopsy of lymph node confirms the diagnosis of IgG4-related lymphadenopathy. Concurrent biopsy of liver shows chronic cholangitis with no evidence of primary sclerosing cholangitis, primary biliary cirrhosis or IgG4-related cholangitis. Patient was treated with corticosteroid and subsequent liver function test normalized. (C) Interval follow-up and laboratory tests revealed acutely deranged liver function. MR cholangiogram (left) and ERCP (right) shows mildly dilated bilateral intrahepatic ducts with focal irregular tapering (star) towards porta hepatis. Right intrahepatic duct stricture also seen in ERCP (arrow). Histology studies revealed IgG4-related sclerosing cholangitis. (D) Serial axial plain CTs at presentation (left), 2 years (middle) and 3 years (right) after diagnosis of IgG4-related sclerosing cholangitis, shows progressive right hepatic lobe atrophy with widened fissure (star). USG-guided biopsy of right hepatic lobe shows IgG4-related hepatopathy.

Fig 13: IgG4-related lymphadenopathy in a 57-year-old woman who presented with deranged liver function test, with subsequent development of IgG4-related sclerosing cholangitis and hepatopathy. (A) Axial plain and contrast-enhanced CT image demonstrates clusters of multiple portal, para-aortic and gastro-hepatic lymphadenopathy (star). Mildly prominent intrahepatic ducts seen (not shown). (B) Axial 18F-FDG PET-CT shows FDG-avidity of the lymph nodes (star), with no suspicious adjacent primary tumour. Endoscopic ultrasound guided biopsy of lymph node confirms the diagnosis of IgG4-related lymphadenopathy. Concurrent biopsy of liver shows chronic cholangitis with no evidence of primary sclerosing cholangitis, primary biliary cirrhosis or IgG4-related cholangitis. Patient was treated with corticosteroid and subsequent liver function test normalized. (C) Interval follow-up and laboratory tests revealed acutely deranged liver function. MR cholangiogram (left) and ERCP (right) shows mildly dilated bilateral intrahepatic ducts with focal irregular tapering (star) towards porta hepatis. Right intrahepatic duct stricture also seen in ERCP (arrow). Histology studies revealed IgG4-related sclerosing cholangitis. (D) Serial axial plain CTs at presentation (left), 2 years (middle) and 3 years (right) after diagnosis of IgG4-related sclerosing cholangitis, shows progressive right hepatic lobe atrophy with widened fissure (star). USG-guided biopsy of right hepatic lobe shows IgG4-related hepatopathy.

Fig 14: IgG4-related lymphadenopathy in a 57-year-old woman who presented with deranged liver function test, with subsequent development of IgG4-related sclerosing cholangitis and hepatopathy. (A) Axial plain and contrast-enhanced CT image demonstrates clusters of multiple portal, para-aortic and gastro-hepatic lymphadenopathy (star). Mildly prominent intrahepatic ducts seen (not shown). (B) Axial 18F-FDG PET-CT shows FDG-avidity of the lymph nodes (star), with no suspicious adjacent primary tumour. Endoscopic ultrasound guided biopsy of lymph node confirms the diagnosis of IgG4-related lymphadenopathy. Concurrent biopsy of liver shows chronic cholangitis with no evidence of primary sclerosing cholangitis, primary biliary cirrhosis or IgG4-related cholangitis. Patient was treated with corticosteroid and subsequent liver function test normalized. (C) Interval follow-up and laboratory tests revealed acutely deranged liver function. MR cholangiogram (left) and ERCP (right) shows mildly dilated bilateral intrahepatic ducts with focal irregular tapering (star) towards porta hepatis. Right intrahepatic duct stricture also seen in ERCP (arrow). Histology studies revealed IgG4-related sclerosing cholangitis. (D) Serial axial plain CTs at presentation (left), 2 years (middle) and 3 years (right) after diagnosis of IgG4-related sclerosing cholangitis, shows progressive right hepatic lobe atrophy with widened fissure (star). USG-guided biopsy of right hepatic lobe shows IgG4-related hepatopathy.