IgG4-Related Disease — SAQ

Stem

A 66-year-old man presents to the surgical outpatient department with three months of painless, progressive jaundice, pale stools, dark urine, fatigue and a 5 kg weight loss. He has no abdominal pain and no fever. On examination he is deeply jaundiced with a palpable, non-tender, firm mass-like fullness in the right upper quadrant; he also has bilateral, painless enlargement of both submandibular glands. Bloods show a cholestatic/obstructive picture (bilirubin 180 micromol/L, ALP 540 U/L), a mildly raised CA 19-9, and a markedly elevated serum IgG4 of 410 mg/dL. Contrast CT shows a diffusely enlarged, 'sausage-shaped' pancreas with a capsule-like rim but no vascular invasion, an upstream biliary stricture, and a periaortic soft-tissue plaque encasing the ureters with mild left hydronephrosis. He has been listed for a pancreaticoduodenectomy for presumed pancreatic cancer.

Questions

a) What is the most likely diagnosis and what two features argue most strongly against pancreatic adenocarcinoma? (2 marks)

The most likely diagnosis is IgG4-related disease presenting with type 1 autoimmune pancreatitis, IgG4-related sclerosing cholangitis and retroperitoneal fibrosis. The two features arguing most strongly against pancreatic adenocarcinoma are: (1) the diffusely enlarged 'sausage-shaped' pancreas with a capsule-like rim rather than a discrete, vascularly invasive mass — a classic imaging signature of type 1 autoimmune pancreatitis; and (2) the multifocal, multi-organ pattern (submandibular sialadenitis and a periaortic/periureteric plaque) together with the markedly elevated serum IgG4, none of which is typical of pancreatic cancer. The mildly raised CA 19-9 is non-specific and occurs with biliary obstruction of any cause.

b) Before any surgery, what is the single most important next investigation and why? (2 marks)

Obtain tissue for histology and cytology (core biopsy or, if accessible, endoscopic ultrasound-guided fine-needle biopsy of the pancreatic mass) before proceeding to resection. The cardinal rule in IgG4-related disease is that it mimics malignancy, and IgG4-RD is dramatically steroid-responsive — so a lesion presumed to be resectable 'cancer' occasionally proves to be IgG4-RD, making a Whipple an avoidable operation. Histology (the gold standard) looks for storiform fibrosis, obliterative phlebitis and a dense IgG4-positive-plasma-cell-rich infiltrate, while cytology excludes adenocarcinoma. A normal serum IgG4 would not have excluded the disease (it is normal in 30 to 40 percent of biopsy-proven cases), so tissue is decisive.

c) List four investigations you would arrange to stage the disease and exclude mimics. (2 marks)

• Histopathology of biopsied tissue with IgG4 immunostaining — confirm the diagnosis (IgG4+/IgG+ plasma-cell ratio above 40 percent and more than 10 IgG4-positive cells per high-power field) and exclude malignancy.
• PET-CT (or contrast CT of chest, abdomen and pelvis) — to map multi-organ involvement (renal, pulmonary, aortic, meningeal) and guide further biopsy.
• MRCP and/or ERCP with brush cytology — to characterise the biliary stricture, distinguish IgG4-related sclerosing cholangitis from cholangiocarcinoma and primary sclerosing cholangitis, and place a stent to relieve obstruction.
• Bloods and serology — FBC (eosinophilia), renal function and eGFR, liver tests, glucose, and autoantibodies (ANA, ANCA, RF, anti-Ro/La) which are typically negative and help exclude Sjogren syndrome, ANCA-associated vasculitis and other mimics.

d) Outline the management of this patient. (4 marks)

1. Relieve obstruction first — ERCP with biliary stenting for the obstructive jaundice (and cholangitis risk); nephrostomy or ureteric stenting if the hydronephrosis or renal function worsens.
2. Glucocorticoid induction — prednisolone 30 to 40 mg daily for 2 to 4 weeks, then a gradual taper over 3 to 6 months. The dramatic response (shrinkage of the pancreatic mass, resolution of the biliary stricture and retroperitoneal plaque, fall in serum IgG4) is characteristic and near-diagnostic.
3. Steroid-sparing therapy — because relapse is common on steroid withdrawal, start a steroid-sparing agent: rituximab (anti-CD20) is the preferred first-line choice for relapsing, steroid-dependent or organ-threatening disease, with conventional DMARDs (azathioprine, mycophenolate, methotrexate) as weaker alternatives.
4. Multidisciplinary care and harm prevention — coordinate rheumatology with gastroenterology/hepatology, nephrology and surgery; give bone protection and PJP prophylaxis for prolonged steroids; vaccinate before rituximab; and arrange imaging plus serum IgG4 surveillance, recognising that relapse may occur without a rise in IgG4.

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