New study may help distinguish rare IgG4 gallbladder disease from cancer
Study highlights imaging and tissue features that may improve diagnosis
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Researchers in Japan have described the clinical and tissue features of localized-type IgG4-related cholecystitis, a rare form of IgG4-related disease (IgG4-RD) that affects the gallbladder, which may help distinguish it from gallbladder cancer.
“Understanding these … features would contribute to a more accurate differential diagnosis from [gallbladder] cancer,” the researchers wrote.
The findings were described in the study “Clinicopathological features of localized-type IgG4-related cholecystitis: a nationwide multicenter study in Japan,” published in the Journal of Gastroenterology.
Rare immune condition can affect multiple organs
IgG4-RD is a rare immune disorder in which immune cells, most commonly plasma cells that produce the antibody IgG4, accumulate in organs throughout the body. This causes inflammation that can lead to tissue scarring (fibrosis) and tumor-like masses.
Symptoms vary depending on which organs are affected, and because they can resemble those of other conditions, including cancer, IgG4-RD can be difficult to diagnose.
IgG4-RD can affect the biliary system, which is responsible for the production, storage, and transport of bile — a fluid made by the liver that helps with digestion. Bile flows to the intestines through tubes called bile ducts and is stored in the gallbladder, a small pear-shaped organ below the liver, when not in use.
Localized-type IgG4-related cholecystitis is a form of IgG4-RD marked by focal, nodule- or mass-like thickening of the gallbladder wall, which can mimic gallbladder cancer. Symptoms can vary but may include abdominal pain, jaundice (yellowing of skin and eyes), fatigue, and weight loss — signs that can overlap with gallbladder disease or cancer.
Because of its rarity, little is known about localized-type IgG4-related cholecystitis. “Only a few case reports or small case series of localized-type IgG4-related cholecystitis have been published, which poses a serious challenge in differentiating this condition from [gallbladder] cancers,” the researchers wrote.
With this in mind, the team conducted a nationwide, multicenter study to better understand the disease’s features and improve its diagnosis. Across 30 Japanese institutions, the team identified 10 men and five women, ages 54-79, with localized-type IgG4-related cholecystitis among 2,560 people with IgG4-related gastroenterological disease.
Many patients had no symptoms at diagnosis
Most patients (67%) experienced no symptoms, while three (20%) reported abdominal pain and two (13%) reported appetite loss. Among those without symptoms, gallbladder abnormalities were detected incidentally during tests for other IgG4-related manifestations (70%) or during routine health checkups (30%).
All participants showed involvement of other organs. Autoimmune pancreatitis, a common IgG4-RD manifestation in which the immune system attacks the pancreas, was present in all but one (93%). IgG4-related sclerosing cholangitis, marked by inflammation and scarring of the bile ducts, was seen in eight (53%). All patients had elevated blood IgG4 levels.
More than half of the cases (53.3%) were correctly diagnosed with IgG4-related cholecystitis, while one-third (33.3%) received an initial diagnosis of gallbladder cancer and 13.3% were initially misdiagnosed with adenomyomatosis, a benign thickening of the gallbladder wall.
Eleven patients (73.3%) underwent surgery to remove the gallbladder, including all of those initially misdiagnosed with gallbladder cancer.
In imaging studies, most participants (80%) showed lesions located in the gallbladder fundus, the rounded end of the gallbladder farthest from the bile ducts. All 15 patients had masses beneath the tissue surface (subepithelial lesions) and gallbladder wall thickening. Features suggestive of adenomyomatosis were also present in 60%.
In tissue analysis, all 11 cases examined showed dense infiltration of IgG4-positive plasma cells. Storiform fibrosis, a hallmark feature of IgG4-RD characterized by scarring in a swirling or “cartwheel” pattern, was observed in nearly all (91%). Most patients (82%) also showed inflammatory pseudotumors, or tumor-like lesions composed of inflammatory cells that mimic cancer.
Obliterative phlebitis, an IgG4-RD hallmark marked by the partial or complete blockage of medium-sized veins, was detected in seven of the nine patients with available data (77%).
Most patients responded well to steroid treatment
Of the four participants who received glucocorticoids, the first-line IgG4-RD treatment, one achieved complete resolution within two weeks. The other three showed partial improvement within two to four weeks and later achieved complete resolution within two months to three years.
During a median follow-up of 68 months (almost six years), one patient experienced a recurrence six months after stopping glucocorticoids and achieved complete resolution again after re-treatment.
Data from “the largest case series to date of localized-type IgG4-related cholecystitis,” the researchers wrote, showed that the condition “is characterized by imaging findings of [subepithelial lesions], [tissue] features common to IgG4-RD, unique lesions centered around ADM, and good responsiveness to [glucocorticoid] therapy.”
These findings may help improve the diagnosis of localized-type IgG4-related cholecystitis, the researchers concluded.
