Radiol med DOI 10.1007/s11547-013-0373-9
ABDOMINAL RADIOLOGY
Autoimmune pancreatitis: multidetector-row computed tomography (MDCT) and magnetic resonance (MR) findings in the Italian experience Rossella Graziani • Simona Mautone • Maria Chiara Ambrosetti Riccardo Manfredi • Thomas J. Re • Lucia Calculli • Luca Frulloni • Roberto Pozzi Mucelli
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Received: 9 August 2012 / Accepted: 30 July 2013 Ó Italian Society of Medical Radiology 2014
Abstract Multidetector-row computed tomography (MDCT) and magnetic resonance (MR) imaging are currently the most frequently performed imaging modalities for the study of pancreatic disease. In cases of suspected autoimmune pancreatitis (AIP), a dynamic quadriphasic (precontrast, contrast-enhanced pancreatic, venous and late phases) study is recommended in both techniques. In the diffuse form of autoimmune pancreatitis (DAIP), the pancreatic parenchyma shows diffuse enlargement and appears, during the MDCT and MR contrast-enhanced pancreatic phase, diffusely hypodense and hypointense, respectively, compared to the spleen because of lymphoplasmacytic infiltration and pancreatic fibrosis. During the venous phase of MDCT and MR imaging, the parenchyma appears hyperdense and hyperintense, respectively, in comparison to the pancreatic phase. In the delayed phase of both imaging modalities, it shows retention of contrast media. A ‘‘capsule-like rim’’ may be recognised as a peripancreatic MDCT hyperdense and MR hypointense halo in the T2-weighted images, compared to the parenchyma. DAIP must be differentiated from non-necrotizing acute pancreatitis (NNAP) and lymphoma since both diseases show diffuse enlargement of the pancreatic R. Graziani (&) S. Mautone M. C. Ambrosetti R. Manfredi T. J. Re R. P. Mucelli Department of Radiology, ‘‘G.B. Rossi’’ Hospital, University of Verona, P.le L.A. Scuro 11, 37134 Verona, Italy e-mail: [email protected] L. Calculli Department of Radiology, Sant’Orsola-Malpighi Hospital, University of Bologna, 9 Via Massarenti, Bologna, Italy L. Frulloni Department of Medicine, ‘‘G.B. Rossi’’ Hospital, University of Verona, P.le L.A. Scuro 10, Verona, Italy
parenchyma. The differential diagnosis is clinically difficult, and dynamic contrast-enhanced MDCT has an important role. In the focal form of autoimmune pancreatitis (FAIP), the parenchyma shows segmental enlargement involving the head, the body-tail or the tail, with the same contrast pattern as the diffuse form on both modalities. FAIP needs to be differentiated from pancreatic adenocarcinoma to avoid unnecessary surgical procedures, since both diseases have similar clinical and imaging presentation. The differential diagnosis is clinically difficult, and dynamic contrast-enhanced MDCT and MR imaging both have an important role. MR cholangiopancreatography helps in the differential diagnosis. Furthermore, MDCT and MR imaging can identify the extrapancreatic manifestations of AIP, most commonly biliary, renal and retroperitoneal. Finally, in all cases of uncertain diagnosis, MDCT and/or MR follow-up after short-term treatment (2–3 weeks) with high-dose steroids can identify a significant reduction in size of the pancreatic parenchyma and, in FAIP, normalisation of the calibre of the upstream main pancreatic duct. Keywords Chronic pancreatitis Autoimmune pancreatitis Acute pancreatitis Computed tomography Magnetic resonance Steroid treatment
Autoimmune pancreatitis (AIP): definition and classification Autoimmune pancreatitis (AIP) is a form of chronic pancreatitis associated with autoimmune processes. Distinct histological and clinical profiles reveal two subtypes of AIP, indistinguishable on the basis of imaging alone: type 1, or lymphoplasmacytic sclerosing pancreatitis (LPSP),
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and type 2, or idiopathic duct-centric pancreatitis (IDCP) [1]. Type 1, LPSP, or AIP without granulocyte epithelial lesions, seems to be an IgG4-related multiorgan disease, characterised by elevated serum IgG4 levels, multiple extrapancreatic organ involvement and IgG4-rich lymphoplasmacytic infiltrate on histology in all the affected organs [2, 3]. This form characteristically responds to steroid treatment, though relapse in the pancreas or other affected organs is common. In type 2 AIP, IDCP or AIP with granulocyte epithelial lesions, there is no extrapancreatic organ involvement or IgG4-rich infiltrate on histology, and serum IgG4 elevation is unlikely. This form appears to be a pancreas-specific disorder and is histologically characterised by the presence of neutrophils with typical granulocyte epithelial lesions. The diagnosis of AIP is challenging even at expert centres and many different diagnostic criteria have been developed. Recently, the International Consensus Diagnostic Criteria (ICDC) have unified these diagnostic criteria accommodating regional differences in practice. The comprehensive criteria that must be fulfilled for the diagnosis include pancreatic imaging of the parenchyma and ductal system, serological and histopathological findings, other organ involvement and response to steroid treatment [1]. The clinical presentation overlaps with other forms of acute and chronic pancreatitis, but without a history of alcohol or tobacco abuse or biliary stone disease. AIP may vary in its clinical presentation depending on the pancreatic distribution of disease (focal or diffuse) and on the specific site involved (head, body or tail of the pancreas) [4–21]. In the case of focal distribution in the pancreatic head, patients frequently present painless jaundice. In diffuse forms or in focal distribution in the pancreatic body-tail, patients may present pancreatic abdominal pain in the epigastric region, irradiating to the back with or without jaundice [8–21]. Therefore, the clinical presentation of AIP may mimic pancreatic adenocarcinoma in the focal forms and pancreatic lymphoma or non-necrotizing acute pancreatitis (NNAP) in the diffuse forms [22–26]. In evaluating patients with suspected pancreatic disease, acute or chronic pancreatitis or pancreatic neoplasms, multidetector-row computed tomography (MDCT) and magnetic resonance (MR) are the imaging modalities of choice [15–17, 27–33]. In the specific case of suspected AIP, a dynamic quadriphasic study (precontrast, contrastenhanced arterial, pancreatic, venous and late phases) is recommended for both techniques. Technically, in MDCT of the pancreas, contrast medium administration typically involves the use of bolus tracking software with a region of interest (ROI) placed over the aorta and a predetermined attenuation threshold of 100 HU. Pancreatic arterial and portal venous phase images are
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acquired 20–30 and 60–70 s after bolus tracking, respectively, and the delayed phase images 180 s after the beginning of the injection. A collimation value between a maximum of 2.5 mm and a minimum of 0.625 mm is recommended. The standard reconstruction thickness used during the pancreatic and portal venous phase is 1 mm, with an interval of 0.5 mm, whereas during the late phase it is 2–1 mm, with a range of 1–0.5 mm. Postprocessed coronal and curved MDCT multiplanar reconstruction (MPR) images are recommended in cases of suspected AIP. Pancreatic MR and MR cholangiopancreatography (MRCP) imaging must be performed on a 1.5 T scanner using a surface phased-array body coil. Patients are asked to fast for 4–6 h before the MR examination. To eliminate overlapping fluid-containing organs on T2-weighted MRCP images, 50–150 ml of superparamagnetic iron oxide particles is administered 10–20 min before the MR examination. Pancreatic MR imaging includes the following sequences: axial T1-weighted gradient echo, axial T1-weighted fatsaturated, axial T2-weighted fat-saturated rapid acquisition with relaxation enhancement (RARE), T2-weighted halfFourier RARE, coronal true fast imaging in the steady-state precession (true-FISP), axial and coronal, coronal oblique 2D half-Fourier RARE cholangiopancreatography, axial fat-saturated 3D volumetric gradient echo. The dynamic study, during gadolinium-chelate injection, is obtained by means of a 3D volumetric gradient-echo pulse sequence using parallel imaging. A quadriphasic dynamic study is performed during injection of 0.1 mmol/kg body weight of gadolinium chelates by means of a power injector at 2–2.5 ml/s, by acquiring the precontrast-phase, late arterial/ pancreatic phase (35–45 s), portal venous phase (75–80 s), and delayed phase ([180 s). For diffusion-weighted imaging (DWI), a spin-echo echoplanar sequence is performed with a b value of 0, 50, 600 s/mm2. An apparent diffusion coefficient (ADC) map is automatically calculated for each section by the system’s software.
AIP: MDCT findings Diffuse forms (DAIP) The pancreatic parenchyma shows [15, 34–36] diffuse enlargement (Fig. 1) and appears isodense compared to the spleen on precontrast MDCT images (Fig. 1a); pancreatic ductal stones are almost always absent at onset but they may be present in advanced stages [37, 38]. Dynamic contrast-enhanced MDCT study is helpful in the diagnosis: during the pancreatic phase, the parenchyma is diffusely hypodense compared to the spleen because of the lymphoplasmacytic infiltration and pancreatic fibrosis (Fig. 1b, e). During the venous phase, the parenchyma
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Fig. 1 Diffuse autoimmune pancreatitis (DAIP) before and after short-term high-dose steroid treatment. Multidetector computed tomography (MDCT) imaging. Precontrast (a), contrast-enhanced pancreatic (b, e), venous (c, f) and late (d) phases. Axial (a–d) and multiplanar curved reconstructions (e, f) MDCT images. Diffuse pancreatic enlargement is present (a–e). The pancreatic parenchyma is homogeneously isodense compared to the spleen on the precontrast MDCT image (a); pancreatic stones are absent. The pancreatic parenchyma appears hypodense compared to the spleen during contrast-enhanced MDCT pancreatic phase (b, e). During the portal venous phase, it becomes more dense, appearing hyperdense compared to the previous pancreatic phase (c). During the late phase
(d), the pancreatic parenchyma shows retention of contrast medium: it is hyperdense compared to the previous venous phase. In the delayed phase (d), a peripancreatic hyperdense halo is visible (‘‘capsule-like rim’’: arrow). The intrapancreatic segment of the common bile duct is slightly dilated (arrow head); the intrahepatic bile ducts are normal. In the left kidney, a solid cortical lesion is present which later proved to be chronic autoimmune pyelonephritis on biopsy (black arrows); the right kidney shows a cystic lesion. Retroperitoneal fluid film, peripancreatic stranding and enlarged lymphonodes are absent. Three weeks after high-dose steroid treatment (f), the pancreatic parenchyma shows normal thickness and parenchymal vascularisation has become normal during the contrast-enhanced pancreatic phase
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appears hyperdense in comparison to the previous pancreatic phase (Fig. 1c) and it shows retention of contrast media during the delayed phase, becoming more hyperdense compared to the previous venous phase (Fig. 1d) [37–43]. The pancreatic margins are smooth and well defined in all phases of the dynamic contrast-enhanced MDCT study (Fig. 1), probably due to peripancreatic tissue inflammation [12, 13]. A capsule-like rim, appearing as a peripancreatic hyperdense halo compared to the parenchyma, may be present in the delayed phase (Fig. 1d). According to some authors, this peripheral rim of delayed contrast enhancement is due to the presence of a chronic inflammatory process and fibrous tissue involving the peripancreatic fat [15, 20, 21, 44]. The periductal inflammatory cell infiltration and fibrous tissue centred around the pancreatic ducts [12, 13, 44–49] produce diffuse narrowing of the main pancreatic duct (MPD). The MPD is frequently not visible within a DAIP lesion in axial and MPR MDCT images (Fig. 1a–e). If local MPD stenosis is present, the upstream duct is dilated. Patients with AIP often demonstrate enhancement of the MPD wall on CT imaging (the ‘‘enhanced duct sign’’) [42, 43] and this could reflect periductal inflammatory changes. The enhanced duct sign is strongly associated with the abnormal enhancement area of the pancreas in AIP and, although relatively uncommon, this finding may be useful for the diagnosis of AIP. Both the enhanced duct sign and the inability to visualise the MPD lumen within a DAIP lesion can aid in the diagnosis of AIP. Furthermore, the side branches are not visible in axial and MPR images. The intrapancreatic segment of the common bile duct (CBD) may be normal or stenotic in DAIP. Retroperitoneal fluid film, recorded at MDCT images as thickening of the anterior pararenal fascial plane, is never present in DAIP. Also peripancreatic stranding, represented by inflammatory changes of peripancreatic fat in mild acute non-necrotizing pancreatitis, recorded as a hypodense peripancreatic halo in all phases of CT examination [32, 37] is absent in DAIP [50]. DAIP must be differentiated from NNAP and lymphoma since both these pathological conditions show diffuse enlargement of the pancreatic parenchyma [19, 25, 51, 52]. In both DAIP and NNAP, pancreatic abdominal pain with epigastric location irradiating to the back, increase of serum amylase and lipase and diffuse pancreatic enlargement are frequently present [28–31]. The clinical differentiation of DAIP from NNAP at onset is useful since only DAIP responds to steroid treatment because of its autoimmune pathogenesis [32–38, 45] (Fig. 2). Dynamic contrast-enhanced MDCT is helpful in differentiating DAIP from NNAP because the parenchymal vascularisation is significantly different in the two diseases [50, 53]. During the pancreatic phase, the glandular parenchyma is
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hypodense in DAIP (Fig. 1b, e) due to lymphoplasmacytic infiltrates and pancreatic fibrosis, and isodense compared to the spleen in NNAP, due to interstitial oedema without areas of necrosis (Fig. 2b, d). During the portal venous phase, DAIP appears hyperdense compared to the previous pancreatic phase (Fig. 1c), while in NNAP the parenchyma most frequently becomes hypodense during the portal venous phase (Fig. 2c). DAIP shows retention of the contrast medium in the delayed phase (Fig. 1d) while NNAP shows parenchymal wash-out. Recently, this vascularisation pattern of DAIP has been assessed using the rate of relative variation in enhancement from the previous phase or Relative Enhancement Rate across all phases of the MDCT study [50]. Evaluation of the Relative Enhancement Rate confirmed the particular vascularisation pattern of DAIP, different from that of NNAP. The presence of a peripheral rim of contrast enhancement in the delayed MDCT phase, due to chronic inflammatory processes and fibrosis involving the fatty peripancreatic tissue, is highly suggestive of AIP (Fig. 1d) and absent in NNAP. A retroperitoneal fluid film, a typical finding in NNAP (Fig. 2a– d) due to retroperitoneal inflammation with peripancreatic oedema, is absent in DAIP. Peripancreatic stranding, appearing as a hypodense peripancreatic halo in all phases of the MDCT examination, is due to mild inflammatory changes of the fat surrounding the pancreas and is frequently present in NNAP (Fig. 2a–d), whereas it is absent in DAIP. A statistically significant difference in the two groups of patients (DAIP and NNAP) regarding the presentation of peripancreatic stranding and retroperitoneal fluid has been demonstrated [50]. In conclusion, the pattern of MDCT contrast enhancement of DAIP and NNAP, particularly considering the Relative Enhancement Rate parameters [50], provides qualitative and quantitative clues for differentiating the diseases. The retroperitoneal findings of peripancreatic stranding and retroperitoneal fluid film, characteristic of NNAP, and the late-phase peripheral rim enhancement, characteristic of DAIP, can also assist in the differential diagnoses. Both in DAIP and in pancreatic lymphoma (Fig. 2e, f), glandular enlargement and reduced parenchymal enhancement in the pancreatic phase are present. In DAIP, the pancreatic parenchyma becomes more dense in the venous and delayed phases, while in lymphoma it remains hypodense in all MDCT phases. A late enhancing capsule-like rim is suggestive of DAIP, whereas the presence of peripancreatic and periaortic lymphadenopathy and/or focal solid splenic lesions suggests the presence of lymphoma [54–56]. Focal forms (FAIP) Focal parenchymal enlargement may be present exclusively in the pancreatic head (Fig. 3a–d), in the body and
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Fig. 2 Diffuse autoimmune pancreatitis (DAIP): differential diagnosis with non-necrotizing acute pancreatitis (NNAP) and pancreatic lymphoma. MDCT imaging. Precontrast (a), contrast-enhanced pancreatic (b, d), venous (c, e, f) phases. Axial (a–c, e, f) and multiplanar curved reconstructions (d) MDCT images. NNAP (a–d). Diffuse pancreatic enlargement is present. Pancreatic parenchyma is homogeneously isodense compared to the spleen on the precontrast MDCT image (a); pancreatic stones are absent. The pancreatic parenchyma appears isodense compared to the spleen during the contrast-enhanced pancreatic phase (b, d). Areas of pancreatic necrosis are not recognisable because of the mild inflammatory
pancreatic process and oedema. During the portal venous phase, the pancreatic parenchyma becomes hypodense compared to the previous pancreatic phase (c). A retroperitoneal fluid film is present in the pararenal anterior space (arrow). The pancreatic gland is surrounded by a hypodense halo in all MDCT phases (peripancreatic stranding: arrow head) due to mild inflammatory changes of peripancreatic fat. Pancreatic lymphoma (e, f). The pancreatic parenchyma appears enlarged (especially in the pancreatic head) and hypodense during the portal venous phase compared to the spleen. Diffuse intra- and extrahepatic bile duct dilatation (black arrow) is present. Pancreatic core biopsies confirmed the diagnosis of non-Hodgkin lymphoma
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tail (Fig. 3e, f), or only in the pancreatic tail. Enlarged glandular portions of the pancreas appear isodense compared to the spleen on precontrast MDCT images (Fig. 3a). Pancreatic ductal stones are always absent. During the contrast-enhanced pancreatic phase of MDCT, the enlarged parenchyma appears hypodense (Fig. 3b, e) compared to the spleen and the unaffected adjacent parenchyma, due to inflammatory cell infiltration and glandular fibrosis [50]. During the venous phase (Fig. 3c), the parenchyma in FAIP becomes more dense, and appears hyperdense compared to its attenuation during the previous pancreatic phase. During the delayed phase, FAIP shows retention of contrast medium: the parenchyma becomes more hyperdense compared to its attenuation in the previous venous phase and to the adjacent unaffected glandular portions. As in DAIP, the pancreatic margins are smooth and well defined in all phases of dynamic contrast-enhanced MDCT (Fig. 3), probably due to the peripancreatic tissue inflammatory process. A capsule-like-rim appearing as a hyperdense halo compared to the parenchyma surrounding the areas involved by FAIP may be present in the delayed phase. This is probably due to chronic inflammatory and fibrotic processes of the peripancreatic fat. When this peripheral rim is present, it is highly suggestive of AIP [15, 40, 57]. The MPD is not visible within FAIP or it may present a focal short stenosis with a short segment of upstream dilatation in the axial and MPR MDCT images, reflecting inflammatory cell infiltrates and fibrosis centred around the pancreatic ducts (Fig. 3). The upstream MPD may be dilated (Fig. 3), as it is in patients with adenocarcinoma, or may be normal. Patients with FAIP also often demonstrate enhancement of the MPD walls on MDCT imaging [42, 43]. This ductal enhancement may reflect periductal inflammatory changes and, although relatively uncommon, this finding may be useful for the diagnosis of AIP (Fig. 3e, f). The enhanced duct sign is strongly associated with the abnormal enhancement area of the pancreas in AIP. The side branches are also not visible in the axial and MPR MDCT images. The intrapancreatic segment of the CBD may be normal or stenotic (Fig. 3) in FAIP of the pancreatic head. If CBD stenosis is present, suprapancreatic CBD has an enlarged calibre. FAIP needs to be differentiated from pancreatic adenocarcinoma (Fig. 4) since both these diseases show focal enlargement, frequently in the pancreatic head, bile duct dilation and a similar clinical presentation at onset [58–61]. Differentiating FAIP from adenocarcinoma is important to avoid unnecessary surgical procedures. In both diseases, the affected parenchyma appears hypovascular, hypodense in the pancreatic phase (Figs. 3, 4) of the dynamic contrastenhanced MDCT study. The upstream MPD is frequently
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dilated in adenocarcinoma. In FAIP, the upstream MPD may be dilated, as in adenocarcinoma, but it may also be normal. The latter finding is uncommon in patients with adenocarcinoma. Therefore, in patients with enlarged pancreatic head and normal size of upstream MPD, FAIP should be considered in the differential diagnosis. In FAIP, however, the hypodensity of the affected parenchyma decreases in the venous and late phases (Fig. 3), unlike in the case of adenocarcinoma (Fig. 4). The margins in FAIP are more sharply defined than in adenocarcinoma, without any extrapancreatic extension. The peripancreatic vessels are normal. The presence of a capsule-like rim excludes adenocarcinoma. Sometimes, the final diagnosis can only be confirmed by a fine-needle aspiration biopsy [62].
AIP: MR and MRCP findings MR imaging, especially completed by MRCP, with or without secretin stimulation, is recommended for the identification and characterisation of parenchymal and ductal change in AIP. At MR imaging, the pancreatic parenchyma shows diffuse (Fig. 5) or focal (Fig. 6) enlargement with sharp borders. It presents an abnormal signal intensity, usually hypointense on T1-weighted images (Fig. 6a) and hyperintense on T2-weighted images, compared to the liver [63, 64]. On T2-weighted images, an hypointense capsule-like rim may be present. During the pancreatic phase of the dynamic study, the parenchyma affected by AIP appears hypointense compared to the spleen in diffuse forms (Fig. 5a, d) and to the unaffected parenchyma in focal forms (Fig. 6b) [63]. In both diffuse and focal forms of AIP, the affected parenchyma usually appears hyperintense during the portal venous phase (Figs. 5b, 6c) compared with the previous pancreatic phase and it appears hyperintense in the delayed phase (Figs. 5c, 6d) compared with the venous phase, due to the contrast medium retention, as in the MDCT study [63]. MRCP best depicts the pancreatic and biliary ductal systems and it has a good correlation with the endoscopic retrograde cholangiopancreatography (ERCP). The MPD is typically not dilated and generally not visible within the affected pancreatic parenchyma because of extrinsic compression by the periductal cell infiltrate (Figs. 5, 6e). In the focal forms, the MPD may present an upstream dilation (Fig. 6e). MRCP after secretin stimulation can be useful to better visualise the MPD. It is particularly important in the focal forms, when a short ductal stricture can mimic a malignant process. Secretin is a polypeptide hormone that induces pancreatic bicarbonate-rich fluid secretion into the duodenum and increases the tone of the sphincter of Oddi with a temporary distension of the pancreatic ducts. If the
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Fig. 3 Focal autoimmune pancreatitis (FAIP). MDCT imaging. Precontrast (a), contrast-enhanced pancreatic (b, d, e), venous (c, f) phases. Axial (a–c, e) and multiplanar curved reconstruction (d, f) MDCT images. Two cases (a–d, e, f). In the first case (a–d), the MDCT images show focal enlargement of the pancreatic head. The pancreatic parenchyma of the enlarged glandular portion (short arrow) is homogeneously isodense to the spleen on precontrast MDCT image (a). Pancreatic stones are absent. The pancreatic parenchyma appears hypodense compared to the spleen and unaffected adjacent parenchyma of the body-tail during the contrastenhanced MDCT pancreatic phase (b, d). During the portal venous phase, the pancreatic parenchyma becomes more dense appearing hyperdense compared to the attenuation of the previous pancreatic
phase (c). The intrahepatic bile ducts are dilated. The main pancreatic duct is not visible within FAIP. Stenting of the upstream main pancreatic duct was performed (arrows) to treat duct stenosis. A nasogastric tube is present (arrow head). In the second case (e, f), the MDCT images show focal enlargement of the pancreatic body and tail. The parenchyma appears hypodense during the contrastenhanced MDCT pancreatic phase (e). The main pancreatic duct is partially invisible because of focal ductal stenosis due to lymphoplasmacytic infiltration and areas of fibrosis in the pancreatic body and head, with upstream main duct dilatation. Enhancement of the main duct walls is present (the enhanced duct sign: arrows). The intrapancreatic segment of the common bile duct is slightly dilated (arrow head)
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Fig. 4 Focal autoimmune pancreatitis (FAIP): differential diagnosis with pancreatic adenocarcinoma. MDCT imaging. Precontrast (a), contrast-enhanced pancreatic (b), venous (c) and late (d) phases. Axial MDCT images. MDCT images show focal enlargement of the pancreatic head. The pancreatic head parenchyma is hypodense compared to the spleen on precontrast MDCT images (a). The
pancreatic head lesion (short arrow) appears more hypodense compared to the spleen and to the body-tail during pancreatic (b), venous (c) and late (d) phases. The main pancreatic duct of the bodytail (arrow) is dilated. The mesenteric vein lumen (arrow head) near the solid lesion in the pancreatic head has a reduced diameter (vascular infiltration)
MPD stricture resolves after secretin stimulation, this rules out a malignancy and is suggestive of AIP (the so-called ‘‘duct penetrating sign’’) [61]. Finally, MRCP is important for evaluating the involvement of the biliary ducts, which is frequently associated because the periductal infiltration can extend to the intrapancreatic CBD and even to its suprapancreatic segment. Recently, some authors [65–68] have reported that the affected pancreatic parenchyma in both diffuse and focal forms of AIP appears slightly hyperintense in the axial MR DW images with b value = 600 s/mm2 and the baseline ADC value is lower than the normal pancreatic parenchyma of patients without chronic pancreatitis (Fig. 5e, f). It is possible that replacement of normal pancreatic parenchyma with a severe inflammatory cellular infiltration of lymphocytes, plasma cells and granulocytes, fibrous tissue and/or reduced exocrine pancreatic function may reduce diffusible tissue water and result in decreased measured ADCs. Thus, in diffuse forms there is a diffusion restriction at DWI and the ADC is low. In most instances,
diffusion restriction is not discernible because the entire pancreatic gland is involved. When only a focal region is involved this finding is more indicative. On the other hand, DWI and ADC values are variable in pancreatic cancer, allowing for this modality to differentiate between massforming focal AIP and pancreatic carcinoma. The final differential diagnosis between focal DAIP and pancreatic cancer can only be confirmed by a fine-needle aspiration biopsy [62, 69, 70].
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Extrapancreatic AIP: MDCT and MR findings CT and MR can identify some of the many extrapancreatic manifestations of AIP, most commonly biliary, renal and retroperitoneal [17, 71]. Biliary involvement, present in up to 80 % of AIP patients, is the most common extrapancreatic involvement. Both intrahepatic and extrahepatic bile ducts can be involved, showing multifocal stenosis and wall thickening
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Fig. 5 Diffuse autoimmune pancreatitis (DAIP). MR imaging. Axial 3D volumetric T1-weighted fat-suppressed gradient-echo images after intravenous contrast medium administration during pancreatic (a), venous (b) and delayed phase (c). Coronal true fast imaging in the steady-state precession (true-FIST) (d). Diffusion-weighted MR imaging (DWI): axial spin-echo echoplanar DW image with b value = 600 s/mm2 (e); axial apparent diffusion coefficient (ADC) map calculated from baseline images obtained with b value
of 0, 50, 600 (f). The overall pancreatic gland is enlarged with sharp borders (a–d) and presents decreased enhancement in the arterial pancreatic phase (a, d) compared to the spleen, with an increased progressive contrast uptake during the venous (b) and the delayed (c) phases. The affected pancreatic parenchyma appears slightly hyperintense in the DW images (e) with lower ADC value (f) than patients without pancreatitis due to a severe inflammatory cellular infiltration (lymphocytes, plasma cells and granulocytes)
resembling primary sclerosing cholangitis. [72]. MDCT shows only focal or diffuse thickening and enhancement of bile duct wall. If the gallbladder is involved, it shows diffuse wall thickening. Biliary involvement by AIP is, therefore, best evaluated by MRCP. This is an important technique to evaluate involvement of the biliary ducts, which is frequently associated because the periductal infiltration can extend to the intrapancreatic CBD and even to its suprapancreatic
segment. This causes thickening and enhancement of the CBD walls, a pattern similar to primary sclerosing cholangitis [73]. Renal involvement (Figs. 1, 6) is more rare than biliary involvement (35 %). Renal lesions in AIP patients are often multiple, bilateral cortex solid nodular lesions frequently well circumscribed and well shaped. At MDCT (Fig. 1) and MR imaging (Fig. 6), they appear as cortical solid lesions, which are hypovascular during the pancreatic
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Fig. 6 Focal autoimmune pancreatitis (FAIP). MR imaging. Axial 3D volumetric T1-weighted fat-suppressed gradient-echo images before (a) and after intravenous contrast medium administration during the pancreatic (b), venous (c) and delayed phases (d, f). MR cholangio-pancreatography (e). The parenchyma of the pancreatic body-tail shows focal enlargement (arrows) with sharp borders and abnormal signal intensity: it appears hypointense in the T1-weighted images (a) compared to the unaffected parenchyma. In the dynamic
study, the AIP-affected parenchyma shows decreased enhancement during the pancreatic phase (b), with a homogeneous and progressive contrast uptake during the venous (c) and delayed phases (d). The main pancreatic duct is not visible within the FAIP (e: arrowhead), compressed by the crowded cellularity all around, with an upstream dilation (e). This patient also presents renal involvement (f) with multiple, bilateral, cortical solid lesions (black arrows: autoimmune pyelonephritis)
phase of both modalities (Fig. 1b), with enhancement in the venous (Fig. 1c) and delayed phases (Figs. 1d, 6f). These lesions respond to steroid treatment with a reduction in size.
Retroperitoneal involvement in AIP is represented by retroperitoneal fibrosis. MDCT and MR identify a soft tissue mass surrounding peripancreatic (Fig. 7a, b) and retroperitoneal (Fig. 7d) vessels.
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Fig. 7 Extrapancreatic AIP findings. MDCT imaging. Contrastenhanced pancreatic (a–c, e), venous (d, f) phases. Axial (a, c– f) and multiplanar coronal reconstruction (b). Two cases (a, b, c–f). In both cases (a, b, c–f), diffuse pancreatic enlargement and hypodense pancreatic parenchyma are present during the pancreatic phase. MDCT also shows a retroperitoneal soft tissue mass surrounding
peripancreatic vessels (a, b: arrows) and right side pelvic vessels (d: arrow). Histological analysis of pancreatic, retroperitoneal and pelvic soft tissue mass showed lymphoplasmacytic infiltrate and fibrosis. In the second case, the pancreatic parenchyma (e) and pelvic soft tissue mass (f: arrow) are reduced in size at follow-up CT 3 weeks after high-dose steroid treatment
Post-treatment focal and diffuse AIP: MDCT and MR findings
both in the diffuse and focal forms, as well as normalisation of the calibre of the upstream MPD in the pancreatic head or body of focal AIP [71]. Pancreatic enhancement during MDCT and MR dynamic studies also becomes normal in AIP. Both in diffuse and focal AIP, the pancreatic parenchyma appears isovascular to the spleen in the enhanced
After a short-term treatment (2–3 weeks) with high-dose steroid (Figs. 1f, 7e, f), MDCT and MR imaging can identify a significant reduction in size of the pancreatic parenchyma
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pancreatic phase and hypovascular in the venous phase, with wash-out in the delayed phase. Finally, MDCT and MR imaging can easily identify normalisation of the calibre of the intra- and suprapancreatic common bile duct [19, 20, 37]. The Japan Pancreas Society has proposed diagnostic criteria for the diagnosis of AIP [74–78]. These criteria include: the finding of typical pancreatic imaging results (enlargement of the pancreatic parenchyma and MPD narrowing), positive laboratory tests (autoantibodies and elevated serum levels of immunoglobulin G4) and positive histopathologic al findings (lymphoplasmacytic infiltrate and pancreatic fibrosis). When all three diagnostic criteria proposed by the Japan Pancreas Society are present, AIP diagnosis is easy. However, there are clinical conditions in which AIP diagnosis and the differential diagnosis with other pancreatic diseases may be difficult. The differential diagnosis of AIP is difficult when a patient with typical clinical findings has other associated autoimmune disorders with only non-specific imaging and/or histopathological findings. In all the cases in which AIP is strongly suspected but the diagnosis is uncertain, MDCT and MR are useful imaging modalities to suggest the correct diagnosis. Repeated MDCT and/or MR examinations after short-term treatment (2–3 weeks) with high-dose steroids can identify a significant reduction in the size of pancreatic parenchyma, and the normalisation of the calibre of the MPD and bile ducts. The results of this short-term follow-up are obviously present in AIP and absent in the case of pancreatic adenocarcinoma. The response at short-term imaging follow-up after steroid treatment was recently considered a diagnostic criterion of AIP [1]. Conflict of interest RGraziani, S. Mautone, M.C. Ambrosetti, R. Manfredi, T.J. Re, L. Calculli, L. Frulloni, R. Pozzi Mucelli declare no conflict of interest.
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ABDOMINAL RADIOLOGY
Autoimmune pancreatitis: multidetector-row computed tomography (MDCT) and magnetic resonance (MR) findings in the Italian experience Rossella Graziani • Simona Mautone • Maria Chiara Ambrosetti Riccardo Manfredi • Thomas J. Re • Lucia Calculli • Luca Frulloni • Roberto Pozzi Mucelli
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Received: 9 August 2012 / Accepted: 30 July 2013 Ó Italian Society of Medical Radiology 2014
Abstract Multidetector-row computed tomography (MDCT) and magnetic resonance (MR) imaging are currently the most frequently performed imaging modalities for the study of pancreatic disease. In cases of suspected autoimmune pancreatitis (AIP), a dynamic quadriphasic (precontrast, contrast-enhanced pancreatic, venous and late phases) study is recommended in both techniques. In the diffuse form of autoimmune pancreatitis (DAIP), the pancreatic parenchyma shows diffuse enlargement and appears, during the MDCT and MR contrast-enhanced pancreatic phase, diffusely hypodense and hypointense, respectively, compared to the spleen because of lymphoplasmacytic infiltration and pancreatic fibrosis. During the venous phase of MDCT and MR imaging, the parenchyma appears hyperdense and hyperintense, respectively, in comparison to the pancreatic phase. In the delayed phase of both imaging modalities, it shows retention of contrast media. A ‘‘capsule-like rim’’ may be recognised as a peripancreatic MDCT hyperdense and MR hypointense halo in the T2-weighted images, compared to the parenchyma. DAIP must be differentiated from non-necrotizing acute pancreatitis (NNAP) and lymphoma since both diseases show diffuse enlargement of the pancreatic R. Graziani (&) S. Mautone M. C. Ambrosetti R. Manfredi T. J. Re R. P. Mucelli Department of Radiology, ‘‘G.B. Rossi’’ Hospital, University of Verona, P.le L.A. Scuro 11, 37134 Verona, Italy e-mail: [email protected] L. Calculli Department of Radiology, Sant’Orsola-Malpighi Hospital, University of Bologna, 9 Via Massarenti, Bologna, Italy L. Frulloni Department of Medicine, ‘‘G.B. Rossi’’ Hospital, University of Verona, P.le L.A. Scuro 10, Verona, Italy
parenchyma. The differential diagnosis is clinically difficult, and dynamic contrast-enhanced MDCT has an important role. In the focal form of autoimmune pancreatitis (FAIP), the parenchyma shows segmental enlargement involving the head, the body-tail or the tail, with the same contrast pattern as the diffuse form on both modalities. FAIP needs to be differentiated from pancreatic adenocarcinoma to avoid unnecessary surgical procedures, since both diseases have similar clinical and imaging presentation. The differential diagnosis is clinically difficult, and dynamic contrast-enhanced MDCT and MR imaging both have an important role. MR cholangiopancreatography helps in the differential diagnosis. Furthermore, MDCT and MR imaging can identify the extrapancreatic manifestations of AIP, most commonly biliary, renal and retroperitoneal. Finally, in all cases of uncertain diagnosis, MDCT and/or MR follow-up after short-term treatment (2–3 weeks) with high-dose steroids can identify a significant reduction in size of the pancreatic parenchyma and, in FAIP, normalisation of the calibre of the upstream main pancreatic duct. Keywords Chronic pancreatitis Autoimmune pancreatitis Acute pancreatitis Computed tomography Magnetic resonance Steroid treatment
Autoimmune pancreatitis (AIP): definition and classification Autoimmune pancreatitis (AIP) is a form of chronic pancreatitis associated with autoimmune processes. Distinct histological and clinical profiles reveal two subtypes of AIP, indistinguishable on the basis of imaging alone: type 1, or lymphoplasmacytic sclerosing pancreatitis (LPSP),
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and type 2, or idiopathic duct-centric pancreatitis (IDCP) [1]. Type 1, LPSP, or AIP without granulocyte epithelial lesions, seems to be an IgG4-related multiorgan disease, characterised by elevated serum IgG4 levels, multiple extrapancreatic organ involvement and IgG4-rich lymphoplasmacytic infiltrate on histology in all the affected organs [2, 3]. This form characteristically responds to steroid treatment, though relapse in the pancreas or other affected organs is common. In type 2 AIP, IDCP or AIP with granulocyte epithelial lesions, there is no extrapancreatic organ involvement or IgG4-rich infiltrate on histology, and serum IgG4 elevation is unlikely. This form appears to be a pancreas-specific disorder and is histologically characterised by the presence of neutrophils with typical granulocyte epithelial lesions. The diagnosis of AIP is challenging even at expert centres and many different diagnostic criteria have been developed. Recently, the International Consensus Diagnostic Criteria (ICDC) have unified these diagnostic criteria accommodating regional differences in practice. The comprehensive criteria that must be fulfilled for the diagnosis include pancreatic imaging of the parenchyma and ductal system, serological and histopathological findings, other organ involvement and response to steroid treatment [1]. The clinical presentation overlaps with other forms of acute and chronic pancreatitis, but without a history of alcohol or tobacco abuse or biliary stone disease. AIP may vary in its clinical presentation depending on the pancreatic distribution of disease (focal or diffuse) and on the specific site involved (head, body or tail of the pancreas) [4–21]. In the case of focal distribution in the pancreatic head, patients frequently present painless jaundice. In diffuse forms or in focal distribution in the pancreatic body-tail, patients may present pancreatic abdominal pain in the epigastric region, irradiating to the back with or without jaundice [8–21]. Therefore, the clinical presentation of AIP may mimic pancreatic adenocarcinoma in the focal forms and pancreatic lymphoma or non-necrotizing acute pancreatitis (NNAP) in the diffuse forms [22–26]. In evaluating patients with suspected pancreatic disease, acute or chronic pancreatitis or pancreatic neoplasms, multidetector-row computed tomography (MDCT) and magnetic resonance (MR) are the imaging modalities of choice [15–17, 27–33]. In the specific case of suspected AIP, a dynamic quadriphasic study (precontrast, contrastenhanced arterial, pancreatic, venous and late phases) is recommended for both techniques. Technically, in MDCT of the pancreas, contrast medium administration typically involves the use of bolus tracking software with a region of interest (ROI) placed over the aorta and a predetermined attenuation threshold of 100 HU. Pancreatic arterial and portal venous phase images are
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acquired 20–30 and 60–70 s after bolus tracking, respectively, and the delayed phase images 180 s after the beginning of the injection. A collimation value between a maximum of 2.5 mm and a minimum of 0.625 mm is recommended. The standard reconstruction thickness used during the pancreatic and portal venous phase is 1 mm, with an interval of 0.5 mm, whereas during the late phase it is 2–1 mm, with a range of 1–0.5 mm. Postprocessed coronal and curved MDCT multiplanar reconstruction (MPR) images are recommended in cases of suspected AIP. Pancreatic MR and MR cholangiopancreatography (MRCP) imaging must be performed on a 1.5 T scanner using a surface phased-array body coil. Patients are asked to fast for 4–6 h before the MR examination. To eliminate overlapping fluid-containing organs on T2-weighted MRCP images, 50–150 ml of superparamagnetic iron oxide particles is administered 10–20 min before the MR examination. Pancreatic MR imaging includes the following sequences: axial T1-weighted gradient echo, axial T1-weighted fatsaturated, axial T2-weighted fat-saturated rapid acquisition with relaxation enhancement (RARE), T2-weighted halfFourier RARE, coronal true fast imaging in the steady-state precession (true-FISP), axial and coronal, coronal oblique 2D half-Fourier RARE cholangiopancreatography, axial fat-saturated 3D volumetric gradient echo. The dynamic study, during gadolinium-chelate injection, is obtained by means of a 3D volumetric gradient-echo pulse sequence using parallel imaging. A quadriphasic dynamic study is performed during injection of 0.1 mmol/kg body weight of gadolinium chelates by means of a power injector at 2–2.5 ml/s, by acquiring the precontrast-phase, late arterial/ pancreatic phase (35–45 s), portal venous phase (75–80 s), and delayed phase ([180 s). For diffusion-weighted imaging (DWI), a spin-echo echoplanar sequence is performed with a b value of 0, 50, 600 s/mm2. An apparent diffusion coefficient (ADC) map is automatically calculated for each section by the system’s software.
AIP: MDCT findings Diffuse forms (DAIP) The pancreatic parenchyma shows [15, 34–36] diffuse enlargement (Fig. 1) and appears isodense compared to the spleen on precontrast MDCT images (Fig. 1a); pancreatic ductal stones are almost always absent at onset but they may be present in advanced stages [37, 38]. Dynamic contrast-enhanced MDCT study is helpful in the diagnosis: during the pancreatic phase, the parenchyma is diffusely hypodense compared to the spleen because of the lymphoplasmacytic infiltration and pancreatic fibrosis (Fig. 1b, e). During the venous phase, the parenchyma
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Fig. 1 Diffuse autoimmune pancreatitis (DAIP) before and after short-term high-dose steroid treatment. Multidetector computed tomography (MDCT) imaging. Precontrast (a), contrast-enhanced pancreatic (b, e), venous (c, f) and late (d) phases. Axial (a–d) and multiplanar curved reconstructions (e, f) MDCT images. Diffuse pancreatic enlargement is present (a–e). The pancreatic parenchyma is homogeneously isodense compared to the spleen on the precontrast MDCT image (a); pancreatic stones are absent. The pancreatic parenchyma appears hypodense compared to the spleen during contrast-enhanced MDCT pancreatic phase (b, e). During the portal venous phase, it becomes more dense, appearing hyperdense compared to the previous pancreatic phase (c). During the late phase
(d), the pancreatic parenchyma shows retention of contrast medium: it is hyperdense compared to the previous venous phase. In the delayed phase (d), a peripancreatic hyperdense halo is visible (‘‘capsule-like rim’’: arrow). The intrapancreatic segment of the common bile duct is slightly dilated (arrow head); the intrahepatic bile ducts are normal. In the left kidney, a solid cortical lesion is present which later proved to be chronic autoimmune pyelonephritis on biopsy (black arrows); the right kidney shows a cystic lesion. Retroperitoneal fluid film, peripancreatic stranding and enlarged lymphonodes are absent. Three weeks after high-dose steroid treatment (f), the pancreatic parenchyma shows normal thickness and parenchymal vascularisation has become normal during the contrast-enhanced pancreatic phase
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appears hyperdense in comparison to the previous pancreatic phase (Fig. 1c) and it shows retention of contrast media during the delayed phase, becoming more hyperdense compared to the previous venous phase (Fig. 1d) [37–43]. The pancreatic margins are smooth and well defined in all phases of the dynamic contrast-enhanced MDCT study (Fig. 1), probably due to peripancreatic tissue inflammation [12, 13]. A capsule-like rim, appearing as a peripancreatic hyperdense halo compared to the parenchyma, may be present in the delayed phase (Fig. 1d). According to some authors, this peripheral rim of delayed contrast enhancement is due to the presence of a chronic inflammatory process and fibrous tissue involving the peripancreatic fat [15, 20, 21, 44]. The periductal inflammatory cell infiltration and fibrous tissue centred around the pancreatic ducts [12, 13, 44–49] produce diffuse narrowing of the main pancreatic duct (MPD). The MPD is frequently not visible within a DAIP lesion in axial and MPR MDCT images (Fig. 1a–e). If local MPD stenosis is present, the upstream duct is dilated. Patients with AIP often demonstrate enhancement of the MPD wall on CT imaging (the ‘‘enhanced duct sign’’) [42, 43] and this could reflect periductal inflammatory changes. The enhanced duct sign is strongly associated with the abnormal enhancement area of the pancreas in AIP and, although relatively uncommon, this finding may be useful for the diagnosis of AIP. Both the enhanced duct sign and the inability to visualise the MPD lumen within a DAIP lesion can aid in the diagnosis of AIP. Furthermore, the side branches are not visible in axial and MPR images. The intrapancreatic segment of the common bile duct (CBD) may be normal or stenotic in DAIP. Retroperitoneal fluid film, recorded at MDCT images as thickening of the anterior pararenal fascial plane, is never present in DAIP. Also peripancreatic stranding, represented by inflammatory changes of peripancreatic fat in mild acute non-necrotizing pancreatitis, recorded as a hypodense peripancreatic halo in all phases of CT examination [32, 37] is absent in DAIP [50]. DAIP must be differentiated from NNAP and lymphoma since both these pathological conditions show diffuse enlargement of the pancreatic parenchyma [19, 25, 51, 52]. In both DAIP and NNAP, pancreatic abdominal pain with epigastric location irradiating to the back, increase of serum amylase and lipase and diffuse pancreatic enlargement are frequently present [28–31]. The clinical differentiation of DAIP from NNAP at onset is useful since only DAIP responds to steroid treatment because of its autoimmune pathogenesis [32–38, 45] (Fig. 2). Dynamic contrast-enhanced MDCT is helpful in differentiating DAIP from NNAP because the parenchymal vascularisation is significantly different in the two diseases [50, 53]. During the pancreatic phase, the glandular parenchyma is
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hypodense in DAIP (Fig. 1b, e) due to lymphoplasmacytic infiltrates and pancreatic fibrosis, and isodense compared to the spleen in NNAP, due to interstitial oedema without areas of necrosis (Fig. 2b, d). During the portal venous phase, DAIP appears hyperdense compared to the previous pancreatic phase (Fig. 1c), while in NNAP the parenchyma most frequently becomes hypodense during the portal venous phase (Fig. 2c). DAIP shows retention of the contrast medium in the delayed phase (Fig. 1d) while NNAP shows parenchymal wash-out. Recently, this vascularisation pattern of DAIP has been assessed using the rate of relative variation in enhancement from the previous phase or Relative Enhancement Rate across all phases of the MDCT study [50]. Evaluation of the Relative Enhancement Rate confirmed the particular vascularisation pattern of DAIP, different from that of NNAP. The presence of a peripheral rim of contrast enhancement in the delayed MDCT phase, due to chronic inflammatory processes and fibrosis involving the fatty peripancreatic tissue, is highly suggestive of AIP (Fig. 1d) and absent in NNAP. A retroperitoneal fluid film, a typical finding in NNAP (Fig. 2a– d) due to retroperitoneal inflammation with peripancreatic oedema, is absent in DAIP. Peripancreatic stranding, appearing as a hypodense peripancreatic halo in all phases of the MDCT examination, is due to mild inflammatory changes of the fat surrounding the pancreas and is frequently present in NNAP (Fig. 2a–d), whereas it is absent in DAIP. A statistically significant difference in the two groups of patients (DAIP and NNAP) regarding the presentation of peripancreatic stranding and retroperitoneal fluid has been demonstrated [50]. In conclusion, the pattern of MDCT contrast enhancement of DAIP and NNAP, particularly considering the Relative Enhancement Rate parameters [50], provides qualitative and quantitative clues for differentiating the diseases. The retroperitoneal findings of peripancreatic stranding and retroperitoneal fluid film, characteristic of NNAP, and the late-phase peripheral rim enhancement, characteristic of DAIP, can also assist in the differential diagnoses. Both in DAIP and in pancreatic lymphoma (Fig. 2e, f), glandular enlargement and reduced parenchymal enhancement in the pancreatic phase are present. In DAIP, the pancreatic parenchyma becomes more dense in the venous and delayed phases, while in lymphoma it remains hypodense in all MDCT phases. A late enhancing capsule-like rim is suggestive of DAIP, whereas the presence of peripancreatic and periaortic lymphadenopathy and/or focal solid splenic lesions suggests the presence of lymphoma [54–56]. Focal forms (FAIP) Focal parenchymal enlargement may be present exclusively in the pancreatic head (Fig. 3a–d), in the body and
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Fig. 2 Diffuse autoimmune pancreatitis (DAIP): differential diagnosis with non-necrotizing acute pancreatitis (NNAP) and pancreatic lymphoma. MDCT imaging. Precontrast (a), contrast-enhanced pancreatic (b, d), venous (c, e, f) phases. Axial (a–c, e, f) and multiplanar curved reconstructions (d) MDCT images. NNAP (a–d). Diffuse pancreatic enlargement is present. Pancreatic parenchyma is homogeneously isodense compared to the spleen on the precontrast MDCT image (a); pancreatic stones are absent. The pancreatic parenchyma appears isodense compared to the spleen during the contrast-enhanced pancreatic phase (b, d). Areas of pancreatic necrosis are not recognisable because of the mild inflammatory
pancreatic process and oedema. During the portal venous phase, the pancreatic parenchyma becomes hypodense compared to the previous pancreatic phase (c). A retroperitoneal fluid film is present in the pararenal anterior space (arrow). The pancreatic gland is surrounded by a hypodense halo in all MDCT phases (peripancreatic stranding: arrow head) due to mild inflammatory changes of peripancreatic fat. Pancreatic lymphoma (e, f). The pancreatic parenchyma appears enlarged (especially in the pancreatic head) and hypodense during the portal venous phase compared to the spleen. Diffuse intra- and extrahepatic bile duct dilatation (black arrow) is present. Pancreatic core biopsies confirmed the diagnosis of non-Hodgkin lymphoma
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tail (Fig. 3e, f), or only in the pancreatic tail. Enlarged glandular portions of the pancreas appear isodense compared to the spleen on precontrast MDCT images (Fig. 3a). Pancreatic ductal stones are always absent. During the contrast-enhanced pancreatic phase of MDCT, the enlarged parenchyma appears hypodense (Fig. 3b, e) compared to the spleen and the unaffected adjacent parenchyma, due to inflammatory cell infiltration and glandular fibrosis [50]. During the venous phase (Fig. 3c), the parenchyma in FAIP becomes more dense, and appears hyperdense compared to its attenuation during the previous pancreatic phase. During the delayed phase, FAIP shows retention of contrast medium: the parenchyma becomes more hyperdense compared to its attenuation in the previous venous phase and to the adjacent unaffected glandular portions. As in DAIP, the pancreatic margins are smooth and well defined in all phases of dynamic contrast-enhanced MDCT (Fig. 3), probably due to the peripancreatic tissue inflammatory process. A capsule-like-rim appearing as a hyperdense halo compared to the parenchyma surrounding the areas involved by FAIP may be present in the delayed phase. This is probably due to chronic inflammatory and fibrotic processes of the peripancreatic fat. When this peripheral rim is present, it is highly suggestive of AIP [15, 40, 57]. The MPD is not visible within FAIP or it may present a focal short stenosis with a short segment of upstream dilatation in the axial and MPR MDCT images, reflecting inflammatory cell infiltrates and fibrosis centred around the pancreatic ducts (Fig. 3). The upstream MPD may be dilated (Fig. 3), as it is in patients with adenocarcinoma, or may be normal. Patients with FAIP also often demonstrate enhancement of the MPD walls on MDCT imaging [42, 43]. This ductal enhancement may reflect periductal inflammatory changes and, although relatively uncommon, this finding may be useful for the diagnosis of AIP (Fig. 3e, f). The enhanced duct sign is strongly associated with the abnormal enhancement area of the pancreas in AIP. The side branches are also not visible in the axial and MPR MDCT images. The intrapancreatic segment of the CBD may be normal or stenotic (Fig. 3) in FAIP of the pancreatic head. If CBD stenosis is present, suprapancreatic CBD has an enlarged calibre. FAIP needs to be differentiated from pancreatic adenocarcinoma (Fig. 4) since both these diseases show focal enlargement, frequently in the pancreatic head, bile duct dilation and a similar clinical presentation at onset [58–61]. Differentiating FAIP from adenocarcinoma is important to avoid unnecessary surgical procedures. In both diseases, the affected parenchyma appears hypovascular, hypodense in the pancreatic phase (Figs. 3, 4) of the dynamic contrastenhanced MDCT study. The upstream MPD is frequently
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dilated in adenocarcinoma. In FAIP, the upstream MPD may be dilated, as in adenocarcinoma, but it may also be normal. The latter finding is uncommon in patients with adenocarcinoma. Therefore, in patients with enlarged pancreatic head and normal size of upstream MPD, FAIP should be considered in the differential diagnosis. In FAIP, however, the hypodensity of the affected parenchyma decreases in the venous and late phases (Fig. 3), unlike in the case of adenocarcinoma (Fig. 4). The margins in FAIP are more sharply defined than in adenocarcinoma, without any extrapancreatic extension. The peripancreatic vessels are normal. The presence of a capsule-like rim excludes adenocarcinoma. Sometimes, the final diagnosis can only be confirmed by a fine-needle aspiration biopsy [62].
AIP: MR and MRCP findings MR imaging, especially completed by MRCP, with or without secretin stimulation, is recommended for the identification and characterisation of parenchymal and ductal change in AIP. At MR imaging, the pancreatic parenchyma shows diffuse (Fig. 5) or focal (Fig. 6) enlargement with sharp borders. It presents an abnormal signal intensity, usually hypointense on T1-weighted images (Fig. 6a) and hyperintense on T2-weighted images, compared to the liver [63, 64]. On T2-weighted images, an hypointense capsule-like rim may be present. During the pancreatic phase of the dynamic study, the parenchyma affected by AIP appears hypointense compared to the spleen in diffuse forms (Fig. 5a, d) and to the unaffected parenchyma in focal forms (Fig. 6b) [63]. In both diffuse and focal forms of AIP, the affected parenchyma usually appears hyperintense during the portal venous phase (Figs. 5b, 6c) compared with the previous pancreatic phase and it appears hyperintense in the delayed phase (Figs. 5c, 6d) compared with the venous phase, due to the contrast medium retention, as in the MDCT study [63]. MRCP best depicts the pancreatic and biliary ductal systems and it has a good correlation with the endoscopic retrograde cholangiopancreatography (ERCP). The MPD is typically not dilated and generally not visible within the affected pancreatic parenchyma because of extrinsic compression by the periductal cell infiltrate (Figs. 5, 6e). In the focal forms, the MPD may present an upstream dilation (Fig. 6e). MRCP after secretin stimulation can be useful to better visualise the MPD. It is particularly important in the focal forms, when a short ductal stricture can mimic a malignant process. Secretin is a polypeptide hormone that induces pancreatic bicarbonate-rich fluid secretion into the duodenum and increases the tone of the sphincter of Oddi with a temporary distension of the pancreatic ducts. If the
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Fig. 3 Focal autoimmune pancreatitis (FAIP). MDCT imaging. Precontrast (a), contrast-enhanced pancreatic (b, d, e), venous (c, f) phases. Axial (a–c, e) and multiplanar curved reconstruction (d, f) MDCT images. Two cases (a–d, e, f). In the first case (a–d), the MDCT images show focal enlargement of the pancreatic head. The pancreatic parenchyma of the enlarged glandular portion (short arrow) is homogeneously isodense to the spleen on precontrast MDCT image (a). Pancreatic stones are absent. The pancreatic parenchyma appears hypodense compared to the spleen and unaffected adjacent parenchyma of the body-tail during the contrastenhanced MDCT pancreatic phase (b, d). During the portal venous phase, the pancreatic parenchyma becomes more dense appearing hyperdense compared to the attenuation of the previous pancreatic
phase (c). The intrahepatic bile ducts are dilated. The main pancreatic duct is not visible within FAIP. Stenting of the upstream main pancreatic duct was performed (arrows) to treat duct stenosis. A nasogastric tube is present (arrow head). In the second case (e, f), the MDCT images show focal enlargement of the pancreatic body and tail. The parenchyma appears hypodense during the contrastenhanced MDCT pancreatic phase (e). The main pancreatic duct is partially invisible because of focal ductal stenosis due to lymphoplasmacytic infiltration and areas of fibrosis in the pancreatic body and head, with upstream main duct dilatation. Enhancement of the main duct walls is present (the enhanced duct sign: arrows). The intrapancreatic segment of the common bile duct is slightly dilated (arrow head)
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Fig. 4 Focal autoimmune pancreatitis (FAIP): differential diagnosis with pancreatic adenocarcinoma. MDCT imaging. Precontrast (a), contrast-enhanced pancreatic (b), venous (c) and late (d) phases. Axial MDCT images. MDCT images show focal enlargement of the pancreatic head. The pancreatic head parenchyma is hypodense compared to the spleen on precontrast MDCT images (a). The
pancreatic head lesion (short arrow) appears more hypodense compared to the spleen and to the body-tail during pancreatic (b), venous (c) and late (d) phases. The main pancreatic duct of the bodytail (arrow) is dilated. The mesenteric vein lumen (arrow head) near the solid lesion in the pancreatic head has a reduced diameter (vascular infiltration)
MPD stricture resolves after secretin stimulation, this rules out a malignancy and is suggestive of AIP (the so-called ‘‘duct penetrating sign’’) [61]. Finally, MRCP is important for evaluating the involvement of the biliary ducts, which is frequently associated because the periductal infiltration can extend to the intrapancreatic CBD and even to its suprapancreatic segment. Recently, some authors [65–68] have reported that the affected pancreatic parenchyma in both diffuse and focal forms of AIP appears slightly hyperintense in the axial MR DW images with b value = 600 s/mm2 and the baseline ADC value is lower than the normal pancreatic parenchyma of patients without chronic pancreatitis (Fig. 5e, f). It is possible that replacement of normal pancreatic parenchyma with a severe inflammatory cellular infiltration of lymphocytes, plasma cells and granulocytes, fibrous tissue and/or reduced exocrine pancreatic function may reduce diffusible tissue water and result in decreased measured ADCs. Thus, in diffuse forms there is a diffusion restriction at DWI and the ADC is low. In most instances,
diffusion restriction is not discernible because the entire pancreatic gland is involved. When only a focal region is involved this finding is more indicative. On the other hand, DWI and ADC values are variable in pancreatic cancer, allowing for this modality to differentiate between massforming focal AIP and pancreatic carcinoma. The final differential diagnosis between focal DAIP and pancreatic cancer can only be confirmed by a fine-needle aspiration biopsy [62, 69, 70].
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Extrapancreatic AIP: MDCT and MR findings CT and MR can identify some of the many extrapancreatic manifestations of AIP, most commonly biliary, renal and retroperitoneal [17, 71]. Biliary involvement, present in up to 80 % of AIP patients, is the most common extrapancreatic involvement. Both intrahepatic and extrahepatic bile ducts can be involved, showing multifocal stenosis and wall thickening
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Fig. 5 Diffuse autoimmune pancreatitis (DAIP). MR imaging. Axial 3D volumetric T1-weighted fat-suppressed gradient-echo images after intravenous contrast medium administration during pancreatic (a), venous (b) and delayed phase (c). Coronal true fast imaging in the steady-state precession (true-FIST) (d). Diffusion-weighted MR imaging (DWI): axial spin-echo echoplanar DW image with b value = 600 s/mm2 (e); axial apparent diffusion coefficient (ADC) map calculated from baseline images obtained with b value
of 0, 50, 600 (f). The overall pancreatic gland is enlarged with sharp borders (a–d) and presents decreased enhancement in the arterial pancreatic phase (a, d) compared to the spleen, with an increased progressive contrast uptake during the venous (b) and the delayed (c) phases. The affected pancreatic parenchyma appears slightly hyperintense in the DW images (e) with lower ADC value (f) than patients without pancreatitis due to a severe inflammatory cellular infiltration (lymphocytes, plasma cells and granulocytes)
resembling primary sclerosing cholangitis. [72]. MDCT shows only focal or diffuse thickening and enhancement of bile duct wall. If the gallbladder is involved, it shows diffuse wall thickening. Biliary involvement by AIP is, therefore, best evaluated by MRCP. This is an important technique to evaluate involvement of the biliary ducts, which is frequently associated because the periductal infiltration can extend to the intrapancreatic CBD and even to its suprapancreatic
segment. This causes thickening and enhancement of the CBD walls, a pattern similar to primary sclerosing cholangitis [73]. Renal involvement (Figs. 1, 6) is more rare than biliary involvement (35 %). Renal lesions in AIP patients are often multiple, bilateral cortex solid nodular lesions frequently well circumscribed and well shaped. At MDCT (Fig. 1) and MR imaging (Fig. 6), they appear as cortical solid lesions, which are hypovascular during the pancreatic
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Fig. 6 Focal autoimmune pancreatitis (FAIP). MR imaging. Axial 3D volumetric T1-weighted fat-suppressed gradient-echo images before (a) and after intravenous contrast medium administration during the pancreatic (b), venous (c) and delayed phases (d, f). MR cholangio-pancreatography (e). The parenchyma of the pancreatic body-tail shows focal enlargement (arrows) with sharp borders and abnormal signal intensity: it appears hypointense in the T1-weighted images (a) compared to the unaffected parenchyma. In the dynamic
study, the AIP-affected parenchyma shows decreased enhancement during the pancreatic phase (b), with a homogeneous and progressive contrast uptake during the venous (c) and delayed phases (d). The main pancreatic duct is not visible within the FAIP (e: arrowhead), compressed by the crowded cellularity all around, with an upstream dilation (e). This patient also presents renal involvement (f) with multiple, bilateral, cortical solid lesions (black arrows: autoimmune pyelonephritis)
phase of both modalities (Fig. 1b), with enhancement in the venous (Fig. 1c) and delayed phases (Figs. 1d, 6f). These lesions respond to steroid treatment with a reduction in size.
Retroperitoneal involvement in AIP is represented by retroperitoneal fibrosis. MDCT and MR identify a soft tissue mass surrounding peripancreatic (Fig. 7a, b) and retroperitoneal (Fig. 7d) vessels.
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Fig. 7 Extrapancreatic AIP findings. MDCT imaging. Contrastenhanced pancreatic (a–c, e), venous (d, f) phases. Axial (a, c– f) and multiplanar coronal reconstruction (b). Two cases (a, b, c–f). In both cases (a, b, c–f), diffuse pancreatic enlargement and hypodense pancreatic parenchyma are present during the pancreatic phase. MDCT also shows a retroperitoneal soft tissue mass surrounding
peripancreatic vessels (a, b: arrows) and right side pelvic vessels (d: arrow). Histological analysis of pancreatic, retroperitoneal and pelvic soft tissue mass showed lymphoplasmacytic infiltrate and fibrosis. In the second case, the pancreatic parenchyma (e) and pelvic soft tissue mass (f: arrow) are reduced in size at follow-up CT 3 weeks after high-dose steroid treatment
Post-treatment focal and diffuse AIP: MDCT and MR findings
both in the diffuse and focal forms, as well as normalisation of the calibre of the upstream MPD in the pancreatic head or body of focal AIP [71]. Pancreatic enhancement during MDCT and MR dynamic studies also becomes normal in AIP. Both in diffuse and focal AIP, the pancreatic parenchyma appears isovascular to the spleen in the enhanced
After a short-term treatment (2–3 weeks) with high-dose steroid (Figs. 1f, 7e, f), MDCT and MR imaging can identify a significant reduction in size of the pancreatic parenchyma
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pancreatic phase and hypovascular in the venous phase, with wash-out in the delayed phase. Finally, MDCT and MR imaging can easily identify normalisation of the calibre of the intra- and suprapancreatic common bile duct [19, 20, 37]. The Japan Pancreas Society has proposed diagnostic criteria for the diagnosis of AIP [74–78]. These criteria include: the finding of typical pancreatic imaging results (enlargement of the pancreatic parenchyma and MPD narrowing), positive laboratory tests (autoantibodies and elevated serum levels of immunoglobulin G4) and positive histopathologic al findings (lymphoplasmacytic infiltrate and pancreatic fibrosis). When all three diagnostic criteria proposed by the Japan Pancreas Society are present, AIP diagnosis is easy. However, there are clinical conditions in which AIP diagnosis and the differential diagnosis with other pancreatic diseases may be difficult. The differential diagnosis of AIP is difficult when a patient with typical clinical findings has other associated autoimmune disorders with only non-specific imaging and/or histopathological findings. In all the cases in which AIP is strongly suspected but the diagnosis is uncertain, MDCT and MR are useful imaging modalities to suggest the correct diagnosis. Repeated MDCT and/or MR examinations after short-term treatment (2–3 weeks) with high-dose steroids can identify a significant reduction in the size of pancreatic parenchyma, and the normalisation of the calibre of the MPD and bile ducts. The results of this short-term follow-up are obviously present in AIP and absent in the case of pancreatic adenocarcinoma. The response at short-term imaging follow-up after steroid treatment was recently considered a diagnostic criterion of AIP [1]. Conflict of interest RGraziani, S. Mautone, M.C. Ambrosetti, R. Manfredi, T.J. Re, L. Calculli, L. Frulloni, R. Pozzi Mucelli declare no conflict of interest.
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