Abdominal immune-related adverse events: detection on ultrasonography, CT, MRI and 18F-Fluorodeoxyglucose positron emission tomography

Abstract

Immune checkpoint inhibitor and chimeric antigen receptor T-cell therapies are associated with a unique spectrum of complications termed immune-related adverse events (irAEs). The abdomen is the most frequent site of severe irAEs that require hospitalization with life-threatening consequences. Most abdominal irAEs such as enterocolitis, hepatitis, cholangiopathy, cholecystitis, pancreatitis, adrenalitis, and sarcoid-like reaction are initially detected on imaging such as ultrasonography (US), CT, MRI and fusion 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)-CT during routine surveillance of cancer therapy. Early recognition and diagnosis of irAEs and immediate management with cessation of immune modulator cancer therapy and institution of immunosuppressive therapy are necessary to avert morbidity and mortality. Diagnosis of irAEs is confirmed by tissue sampling or by follow-up imaging demonstrating resolution. Abdominal radiologists reviewing imaging on patients being treated with anti-cancer immunomodulators should be familiar with the imaging manifestations of irAEs.

Figure 1.

(a) Chimeric antigen receptor (CAR) T-cell therapy. In patients with B­ cell leukemias or lymphoma, the patient’s own T-cells are engineered ex vivo to express a chimeric antigen receptor (CAR) targeting CD19 expressed on the surface of most malignant B cells. When infused back into the patient, the stimulation of cytotoxic immune response from the reprogrammed T cells kills the B cell tumors. (b) Immune response adverse events (irAEs). irAEs associated with cancer immunotherapy have been reported in almost every major organ and can present as acute or chronic inflammation.

Figure 2.

(a–c) Pancolitis. 76-year-old female undergoing pembrolizumab therapy for metastatic lung cancer presents with new onset diarrhea and elevated white blood cell count. Abdomen CT with contrast axial (a) and coronal reconstruction (b) images show long segment thickening throughout the colon. Coronal reconstruction image from a followup CT 8 months after cessation of immunotherapy. (c) shows a normal-appearing colon (solid arrows) but enlarging hepatic metastases (dashed arrows).

Figure 3.

(a, b) Hepatitis. 54-year-old male with metastatic lung cancer being treated with pembrolizumab presents with transaminitis. Ultrasound (a) shows a thickened gallbladder wall (calipers). Coronal reconstruction CT image (b) shows enlarged lymph nodes in the porta hepatis (arrows) and fat stranding suggesting inflammation. Non-focal liver biopsy showed checkpoint-inhibitor induced hepatitis. (c, d) Hepatic inflammatory pseudotumor. 74-year­-old female with metastatic lung cancer treated with nivolumab. Axial T2-weighed (c) and delayed phase image after gadoxetate disodium (d) shows a nodule in segments 2 and 3 (arrows) with hepatobiliary uptake of contrast. Focal biopsy showed inflammatory pseudotumor consistent with irAE.

Figure 4.

(a–c) Sclerosing cholangitis. 63-year-old female with lung adenocarcinoma being treated with nivolumab presents with abnormal liver function tests. Coronal MRI post contrast (a), MRCP (b), and ERCP (c) images show multifocal strictures and dilatation of the intra-hepatic bile ducts (solid arrows) and hyper­ enhancement of the bile duct wall (dashed arrows).

Figure 5.

(a, b) Pancreatitis. 53-year-old male with Hurthle cell thyroid carcinoma being treated with pembrolizumab presents with abdominal pain and elevated serum amylase and lipase. CT with contrast (a) shows a diffusely enlarged, edematous-appearing pancreas with adjacent fat stranding (arrows). Immune modulator therapy was discontinued. CT 4 months later (b) shows resolution of inflammation and a shrunken pancreas with loss of normal lobulations (arrows) indicating fibrosis.

Figure 6.

(a, b) Adrenalitis. 69-year-old male with melanoma treated with ipilimumab. Coronal reconstruction CT (a) and coronal T ₂-weighted MRI (b) image shows diffuse bilateral adrenal thickening (arrows). Fine needle aspiration diagnosed chronic inflammation consisted with irAE.

Figure 7.

Splenic sarcoid-like granulomas. 78 year-old malewithlung cancer being treated with pembrolizumab presents for surveillance imaging.CT with contrast coronal reconstruction image shows multiple hypoenhancinglesions (arrows) which were non FDG-avid (not shown).

Figure 8.

(a, b) Splenic inflammatory pseudotumor. 33-year-old male with diffuse large B-cell lymphoma on treatment with chimeric antigen receptor (CAR) T-cells. Axial contrast-enhanced CT (a) and fusion PET/CT (b) images shows a new solid heterogeneously enhancing FDG­ avid splenic lesion (arrow) shown to be a granuloma on biopsy. (c, d) Pancreatitis. 64-year-old male with diffuse large B-cell lymphoma after 2 doses of CAR T-cells. Contrast enhanced CT (c) shows enlarged pancreas with adjacent fat stranding (arrow) and ascites. FDG PET/CT fusion (b) image shows avid and diffuse pancreatic tracer uptake. Diagnosis of pancreatitis was confirmed with serum amylase and lipase and follow-up to resolution after cessation of CAR T therapy.

Figure 9.

(a, b) Clostridium difficile pancolitis. 63-year-old female with diarrhea and abdominal pain following antibiotic treatment for urinary tract infection. Abdomen CT with contrast axial (a) and coronal reconstruction (b) images show long segment thickening throughout the colon (solid arrows). Stool Clostridium difficile toxin was positive.

Figure 10.

(a, b) Primary sclerosing cholangitis. 35-year-old male undergoing surveillance imaging for primary sclerosing cholangitis. Coronal MRCP (a) and ERCP (b) images show multifocal strictures and dilatation of the intra-hepatic bile ducts (arrows).

Figure 11.

(a, b) IgG4-related autoimmune pancreatitis. 76-year-old male with right abdominal pain and elevated lipase. CT with contrast axial (a) and coronal reconstruction (b) images show a diffusely enlarged, edematous­ appearing pancreas with adjacent fat stranding and circumferential rind of peripancreatic soft tissue attenuation (arrows). Tissue sampling revealed storiform fibrosis and chronic inflammation with IgG4 staining.

Figure 12.

(a, b) Splenic sarcoid granulomas. 66-year-old male with incidentally detected splenic lesions. CT with contrast axial (a) and coronal reconstruction (b) images shows multiple hypoenhancing lesions (arrows). Biopsy showed granulomatous inflammation consistent with sarcoidosis.