Clin J Gastroenterol (2009) 2:59–63 DOI 10.1007/s12328-008-0045-9
CASE REPORT
A case of pancreatic carcinoma with suspected autoimmune pancreatitis Hiroyuki Matsubayashi Æ Kazuya Matsunaga Æ Katsuhiko Uesaka Æ Akira Fukutomi Æ Keiko Sasaki Æ Hiroyoshi Furukawa Æ Hiroyuki Ono
Received: 29 July 2008 / Accepted: 29 September 2008 / Published online: 2 December 2008 Ó Springer 2008
Abstract We present a case of pancreatic carcinoma with strongly suspected coexisting autoimmune pancreatitis (AIP). The patient presented with a chief complaint of icterus and weight loss, and was referred to our institution after a pancreatic lesion was found. Blood test showed elevation of serum bilirubin, hepato-biliary enzyme, glucose and tumor markers, and also high levels of serum IgG4 (344 mg/dl, normal 4.8–105 mg/dl) and anti-DNA antibody (14 IU/ml, normal \6.0 IU/ml). Ultrasonography demonstrated an enlarged pancreas with smooth borders and low internal echo density. Enhanced computed tomography (CT) showed a sausage-shaped pancreas
H. Matsubayashi (&) H. Ono Division of Endoscopy, Shizuoka Cancer Center, 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan e-mail: [email protected] K. Matsunaga K. Uesaka Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan A. Fukutomi Division of GI Oncology, Shizuoka Cancer Center, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan K. Sasaki Division of Pathology, Shizuoka Cancer Center, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan H. Furukawa Division of Diagnostic Radiology, Shizuoka Cancer Center, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan
without definitive metastasis to the surrounding lymph nodes and liver. Imaging of the pancreatic duct, including endoscopic retrograde pancreatography (ERP) and magnetic resonance cholangiopancreatography (MRCP), showed stenosis of the main pancreatic duct at the pancreatic head as well as a long segment of narrowing at the body and no dilatation at the tail. Tissues from these stenotic sites and open biopsy from pancreatic body showed infiltrating adenocarcinoma and dense fibrosis. To date, only a small number of reports have described pancreatic carcinoma accompanied with AIP. It is important to confirm diagnosis with histology in cases of suspicious autoimmune pancreatitis, even when the clinical images are compatible with AIP. Keywords Pancreatic carcinoma Autoimmune pancreatitis IgG4 Auto-antibody
Introduction Autoimmune pancreatitis (AIP) is characterized by enlargement of the pancreas (confirmed by US, CT and/ or MRI) with narrowing of the main pancreatic duct (ERCP), elevated serum markers, particularly IgG4, and distinctive histological changes of a mixed inflammatory infiltrate centered on the pancreatic ducts and a sclerosing pancreatitis [1]. The differential diagnosis between AIP and pancreatic carcinoma is critical, yet the two entities sometimes have similar clinical findings [2, 3]. Recent case reports have documented cases of AIP that resemble pancreatic carcinoma [4, 5]. We report a case of pancreatic carcinoma with characteristics of autoimmune pancreatitis both by clinical imaging and serum markers.
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Case report In May 2006, a 65-year-old Japanese man developed icterus, diarrhea and weight loss (-10 kg/month) and was admitted to our institution after he was found to have obstructive jaundice due to a pancreatic lesion on computed tomography (CT). He noted a history of urethro-renal stones 35 years before and a rectal cancer 14 years before, but he had not been diagnosed with diabetes mellitus. His family history was not remarkable. He denied habitual alcohol intake and tobacco smoking. On admission, he had bilirubinemia, elevated serum hepatobiliary enzymes, glucose level 209 mg/dl, HbA1c 11.5% and tumor markers, including CEA (9.9 ng/ml, normal \5.0 mg/ml) and CA19-9 (1,618 U/ml, normal \37 U/ml). His serum IgG level was within normal range (1,503 mg/dl), but IgG3 (345 mg/dl, normal 6.6–88.3 mg/ dl) and IgG4 (344 mg/dl, normal 4.8–105 mg/dl) were both high. Moreover, serum DNA antibody (14 IU/ml, normal \6.0 IU/ml) was positive. Abdominal ultrasonography (Fig. 1) showed a diffusely enlarged pancreas, with low internal echo, focal calcification and small cyst formation in the body of the pancreas. Enhanced CT (Fig. 2) showed a low-dense, sausage-like, enlarged pancreas from head to tail without obvious lymphadenopathy, and the liver was normal. Magnetic resonance imaging (MRI) and magnetic resonance cholangiopancreatography Fig. 1 Abdominal ultrasonography. Ultrasonography showed diffusely enlarged pancreas, with low internal echo with focal calcification and small cystic formation at the pancreatic body
Fig. 2 Computed tomography. CT scan showed a diffusely enlarged, low-dense pancreas. No lymphadenopathy or nodules suspicious of liver metastasis are present
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(MRCP) showed a diffusely swollen pancreas with a nonvisualized main pancreatic duct from the pancreatic head to the body and no dilatation upstream [6] (Fig. 3c). Positron emission tomography (PET) (Fig. 4) showed diffuse intake of FDG in the pancreas with a maximum SUV value of 7.50. Endoscopic retrograde cholangiopancreatography (ERCP) showed stenosis of the lower bile duct and of the main pancreatic duct at the pancreatic head; it also showed a long segment of narrowing from the pancreatic head to body and no dilatation upstream of the narrowing (Fig. 5). Brushing cytology (Fig. 5a) from the stenotic site of the lower bile duct showed cells suspicious of adenocarcinoma. Forceps biopsy from stenotic sites of the bile duct and main pancreatic duct showed invasive ductal carcinoma (Fig. 6a). IgG4-positive cells were rare in the biopsy specimen. Our preoperative diagnosis was pancreatic carcinoma of the pancreatic head to tail, T3N0M0 (stage III), accompanied by suspected autoimmune pancreatitis. At surgery, the pancreas was diffusely swollen from the body to tail. Multiple tiny whitish nodules of cancer metastasis were recognized in the abdominal cavity and on the surface of the liver, and pancreatic resection was not performed. Lavage fluid cytology was positive for adenocarcinoma. Open biopsy from the pancreatic body to tail (Fig. 6b) revealed invasive adenocarcinoma surrounded by dense fibrous tissue in which IgG4-positive plasma cells
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Fig. 3 Magnetic resonance image. MRI also demonstrated enlarged, sausage-like pancreas from head to tail (a, b). The lower bile duct and main pancreatic duct at the pancreatic head to body were not visualized by MRCP. However, no dilatation of the main pancreatic duct was recognized at the pancreatic body to tail (c)
Fig. 4 Positron emission tomography. FDG is diffusely accumulated in the pancreas
were scarcely recognized. At 6 months from diagnosis, the patient succumbed after systemic chemotherapy using gemcitabine followed by irinotecan combined with cisplatin.
Discussion This report presents a case of diffuse pancreatic carcinoma in which serum markers and clinical images mimicked
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Fig. 5 Endoscopic retrograde cholangiopancreatography. Severe stenosis was present in the distal bile duct with leftsided deviation. Brush cytology was performed, and cells suspicious of adenocarcinoma were obtained from the stenotic site (a). The main pancreatic duct was stenotic at the pancreatic head. However, faint contrast medium was recognized along with the main pancreatic duct at the body (small arrows) and in the upstream duct without obvious dilatation (arrowheads) (b)
Fig. 6 Histology. Biopsy sample from the stenotic portion of the main pancreatic duct was diagnostic of adenocarcinoma (a). Open biopsy from pancreatic body demonstrated dense fibrous tissue and abundant inflammatory cells surrounding invasive carcinoma (b)
autoimmune pancreatitis (AIP). To date, only a few case reports have demonstrated a pancreatic carcinoma with a high level of serum IgG4 [7] and positive autoantibodies [8], and only a few have reported on pancreatic carcinoma accompanied by definitive AIP [9–11]. These reports emphasize the difficulty of distinguishing definitively between pancreatic carcinoma and AIP, and the possibility of a malignant neoplasm masked by AIP. In our case, the clinical images of a sausage-like, enlarged pancreas and the positive serum markers were compatible with AIP. Adding to these findings, the long segment of narrowing of the main pancreatic duct from the pancreatic head to body without obvious dilatation at upstream recognized by both ERCP and MRCP [6] was also very suggestive of AIP [1]. The diffuse and multifocal intake of FDG was also compatible with AIP [12]. One finding that was not compatible with AIP was the severe stenosis of the main pancreatic duct at the pancreatic head (Fig. 5b), where we determined invasive carcinoma by perampullary forceps biopsy (Fig. 6a). We strongly suspect this type of stenosis, not simple narrowing, can be used to
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distinguish between AIP and PC accompanied by AIP. Open biopsy from the swollen pancreatic body to tail (Fig. 6b) in this case showed abundant fibrosis with moderate to severe inflammation surrounding the invasive adenocarcinoma. It was not clear if this inflammation was caused by obstructive pancreatitis or desmoplastic reaction caused by the invasive cancer [13], or fibroblast-prominent, lymphpoplasmacytic sclerotic-type AIP [14]. It can be difficult to distinguish between the histology of background AIP in the presence of an invasive cancer unless significant amounts of IgG4-positive plasma are present [7]. We finally diagnosed this case as pancreatic carcinoma accompanied with ‘‘suspected AIP.’’ From biopsy tissue obtained endoscopically and surgically, the pancreatic cancer in this case extended at least from the pancreatic head to the body. From the clinical images of sausage-like pancreas, we suspect that the AIP affected the tail of the pancreas. The most important clue or objective data supporting the diagnosis of AIP were the level of serum IgG4 (344 mg/dl). Hamano et al. [15] reported that a cutoff value of serum
Clin J Gastroenterol (2009) 2:59–63
IgG4 of 135 mg/dl resulted in 97% accuracy, 95% sensitivity and 97% sensitivity for the diagnosis of AIP versus pancreatic cancer. Raina et al. [16] also showed that serum IgG4 levels [135 mg/dl were present in 7% (5 of 71) of pancreatic carcinoma cases and 1% (1 of 103) of healthy controls, and the serum IgG4 level in the five pancreatic cancer cases with[135 mg/dl was 160.9 mg/dl on average, ranging from 144.1 to 194.0 mg/dl. Ghazale et al. [17] reported that IgG4 levels[280 mg/dl are found only in 1% of pancreatic cancer patients, but in 53% of patients with AIP. Hence, in the case presented, we strongly suspect that pancreatic cancer co-existed with AIP. To date, clinicians have made tremendous efforts to accurately diagnose mass-forming pancreatic lesions. In the case presented, we obtained a number of imaging tests and biopsy and brush cytology from the areas of stenosis of the pancreaticobiliary duct, and we were able to confirm the diagnosis of adenocarcinoma in a patient with several features of AIP. Endoscopic-ultraonography-guided fineneedle aspiration biopsy (EUS-FNAB) is an another option having superior sensitivity for carcinoma (82% [18] to 93% [19]) than the ERCP approach (47% [19] to 76% [20]). Although the sampling size is limited and sometimes not large enough to make a diagnosis, the typical histology of AIP is sometimes obtained by EUS-FNA [21]. Clinicians must keep in mind that some carcinoma cases may be associated with AIP, and exclusion of carcinoma with histological evidence is necessary. Acknowledgments The authors thank Dr. Ralph H. Hruban of Johns Hopkins Medical Institutions in the USA for his assistance with reviewing the English of the manuscript and providing beneficial comments.
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10. 11.
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References 18. 1. Okazaki K, Uchida K, Fukui T. Recent advances in autoimmune pancreatitis: concept, diagnosis, and pathogenesis. J Gastroenterol. 2008;43(6):409–18. 2. Kamisawa T, Egawa N, Nakajima H, Tsuruta K, Okamoto A, Kamata N. Clinical difficulties in the differentiation of autoimmune pancreatitis and pancreatic carcinoma. Am J Gastroenterol. 2003;98(12):2694–9. 3. Nakazawa T, Ohara H, Sano H, Ando T, Imai H, Takada H, et al. Difficulty in diagnosing autoimmune pancreatitis by imaging findings. Gastrointest Endosc. 2007;65(1):99–108. 4. Matsubayashi H, Furukawa H, Uesaka K, Sasaki K, Ono H, Hruban RH. Autoimmune pancreatitis accompanied with cholecystistis, periaortitis and pseudotumors of the liver. Case Rep Gastroenterol. 2008;1(2):155–61. 5. Kajiwara M, Gotohda N, Konishi M, Nakagohri T, Takahashi S, Kojima M, et al. Incidence of the focal type of autoimmune pancreatitis in chronic pancreatitis suspected to be pancreatic
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carcinoma: experience of a single tertiary cancer center. Scand J Gastroenterol. 2008;43(1):110–6. Kamisawa T, Tu Y, Egawa N, Tsuruta K, Okamoto A, Kodama M, et al. Can MRCP replace ERCP for the diagnosis of autoimmune pancreatitis? Abdom Imaging 2008 (in press). Kamisawa T, Chen PY, Tu Y, Nakajima H, Egawa N, Tsuruta K, et al. Pancreatic cancer with a high serum IgG4 concentration. World J Gastroenterol. 2006;12(38):6225–8. Ohtsubo K, Watanabe H, Okada G, Tsuchiyama T, Mouri H, Yamaguchi Y, et al. A case of pancreatic cancer with formation of a mass mimicking alcoholic or autoimmune pancreatitis in a young man. Possibility of diagnosis by hypermethylation of pure pancreatic juice. JOP. 2008;9(1):37–45. Fukui T, Mitsuyama T, Takaoka M, Uchida K, Matsushita M, Okazaki K. Pancreatic cancer associated with autoimmune pancreatitis in remission. Intern Med. 2008;47(3):151–5. Inoue H, Miyatani H, Sawada Y, Yoshida Y. A case of pancreas cancer with autoimmune pancreatitis. Pancreas. 2006;33(2):208–9. Witkiewicz AK, Kennedy EP, Kennyon L, Yeo CJ, Hruban RH. Synchronous autoimmune pancreatitis and infiltrating pancreatic ductal adenocarcinoma: case report and review of the literature. Hum Pathol. 2008;39(10):1548–51. Ozaki Y, Oguchi K, Hamano H, Arakura N, Muraki T, Kiyosawa K, et al. Differentiation of autoimmune pancreatitis from suspected pancreatic cancer by fluorine-18 fluorodeoxyglucose positron emission tomography. J Gastroenterol. 2008;43(2):144–51. Infante JR, Matsubayashi H, Sato N, Tonascia J, Klein AP, Riall TA, et al. Peritumoral fibroblast SPARC expression and patient outcome with resectable pancreatic adenocarcinoma. J Clin Oncol. 2007;25(3):319–25. Adsay NV, Basturk O, Thirabanjasak D. Diagnostic features and differential diagnosis of autoimmune pancreatitis. Semin Diagn Pathol. 2005;22(4):309–17. Hamano H, Kawa S, Horiuchi A, Unno H, Furuya N, Akamatsu T, et al. High serum IgG4 concentrations in patients with sclerosing pancreatitis. N Engl J Med. 2001;344(10):732–8. Raina A, Krasinskas AM, Greer JB, Lamb J, Fink E, Moser AJ, et al. Serum immunoglobulin G fraction 4 levels in pancreatic cancer: elevations not associated with autoimmune pancreatitis. Arch Pathol Lab Med. 2008;132(1):48–53. Ghazale A, Chari ST, Smyrk TC, Levy MJ, Topazian MD, Takahashi N, et al. Value of serum IgG4 in the diagnosis of autoimmune pancreatitis and in distinguishing it from pancreatic cancer. Am J Gastroenterol. 2007;102(8):1646–53. Takahashi K, Yamao K, Okubo K, Sawaki A, Mizuno N, Ashida R, et al. Differential diagnosis of pancreatic cancer and focal pancreatitis by using EUS-guided FNA. Gastrointest Endosc. 2005;61(1):76–9. Wakatsuki T, Irisawa A, Bhutani MS, Hikichi T, Shibukawa G, Takagi T, et al. Comparative study of diagnostic value of cytologic sampling by endoscopic ultrasonography-guided fineneedle aspiration and that by endoscopic retrograde pancreatography for the management of pancreatic mass without biliary stricture. J Gastroenterol Hepatol. 2005;20(11):1707–11. Uchida N, Kamada H, Tsutsui K, Ono M, Aritomo Y, Masaki T, et al. Utility of pancreatic duct brushing for diagnosis of pancreatic carcinoma. J Gastroenterol. 2007;42(8):657–62. Levy MJ. Endoscopic ultrasound-guided trucut biopsy of the pancreas: prospects and problems. Pancreatology. 2007;7(2–3): 163–6.
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CASE REPORT
A case of pancreatic carcinoma with suspected autoimmune pancreatitis Hiroyuki Matsubayashi Æ Kazuya Matsunaga Æ Katsuhiko Uesaka Æ Akira Fukutomi Æ Keiko Sasaki Æ Hiroyoshi Furukawa Æ Hiroyuki Ono
Received: 29 July 2008 / Accepted: 29 September 2008 / Published online: 2 December 2008 Ó Springer 2008
Abstract We present a case of pancreatic carcinoma with strongly suspected coexisting autoimmune pancreatitis (AIP). The patient presented with a chief complaint of icterus and weight loss, and was referred to our institution after a pancreatic lesion was found. Blood test showed elevation of serum bilirubin, hepato-biliary enzyme, glucose and tumor markers, and also high levels of serum IgG4 (344 mg/dl, normal 4.8–105 mg/dl) and anti-DNA antibody (14 IU/ml, normal \6.0 IU/ml). Ultrasonography demonstrated an enlarged pancreas with smooth borders and low internal echo density. Enhanced computed tomography (CT) showed a sausage-shaped pancreas
H. Matsubayashi (&) H. Ono Division of Endoscopy, Shizuoka Cancer Center, 1007, Shimonagakubo, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan e-mail: [email protected] K. Matsunaga K. Uesaka Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan A. Fukutomi Division of GI Oncology, Shizuoka Cancer Center, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan K. Sasaki Division of Pathology, Shizuoka Cancer Center, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan H. Furukawa Division of Diagnostic Radiology, Shizuoka Cancer Center, Nagaizumi, Suntogun, Shizuoka 411-8777, Japan
without definitive metastasis to the surrounding lymph nodes and liver. Imaging of the pancreatic duct, including endoscopic retrograde pancreatography (ERP) and magnetic resonance cholangiopancreatography (MRCP), showed stenosis of the main pancreatic duct at the pancreatic head as well as a long segment of narrowing at the body and no dilatation at the tail. Tissues from these stenotic sites and open biopsy from pancreatic body showed infiltrating adenocarcinoma and dense fibrosis. To date, only a small number of reports have described pancreatic carcinoma accompanied with AIP. It is important to confirm diagnosis with histology in cases of suspicious autoimmune pancreatitis, even when the clinical images are compatible with AIP. Keywords Pancreatic carcinoma Autoimmune pancreatitis IgG4 Auto-antibody
Introduction Autoimmune pancreatitis (AIP) is characterized by enlargement of the pancreas (confirmed by US, CT and/ or MRI) with narrowing of the main pancreatic duct (ERCP), elevated serum markers, particularly IgG4, and distinctive histological changes of a mixed inflammatory infiltrate centered on the pancreatic ducts and a sclerosing pancreatitis [1]. The differential diagnosis between AIP and pancreatic carcinoma is critical, yet the two entities sometimes have similar clinical findings [2, 3]. Recent case reports have documented cases of AIP that resemble pancreatic carcinoma [4, 5]. We report a case of pancreatic carcinoma with characteristics of autoimmune pancreatitis both by clinical imaging and serum markers.
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Case report In May 2006, a 65-year-old Japanese man developed icterus, diarrhea and weight loss (-10 kg/month) and was admitted to our institution after he was found to have obstructive jaundice due to a pancreatic lesion on computed tomography (CT). He noted a history of urethro-renal stones 35 years before and a rectal cancer 14 years before, but he had not been diagnosed with diabetes mellitus. His family history was not remarkable. He denied habitual alcohol intake and tobacco smoking. On admission, he had bilirubinemia, elevated serum hepatobiliary enzymes, glucose level 209 mg/dl, HbA1c 11.5% and tumor markers, including CEA (9.9 ng/ml, normal \5.0 mg/ml) and CA19-9 (1,618 U/ml, normal \37 U/ml). His serum IgG level was within normal range (1,503 mg/dl), but IgG3 (345 mg/dl, normal 6.6–88.3 mg/ dl) and IgG4 (344 mg/dl, normal 4.8–105 mg/dl) were both high. Moreover, serum DNA antibody (14 IU/ml, normal \6.0 IU/ml) was positive. Abdominal ultrasonography (Fig. 1) showed a diffusely enlarged pancreas, with low internal echo, focal calcification and small cyst formation in the body of the pancreas. Enhanced CT (Fig. 2) showed a low-dense, sausage-like, enlarged pancreas from head to tail without obvious lymphadenopathy, and the liver was normal. Magnetic resonance imaging (MRI) and magnetic resonance cholangiopancreatography Fig. 1 Abdominal ultrasonography. Ultrasonography showed diffusely enlarged pancreas, with low internal echo with focal calcification and small cystic formation at the pancreatic body
Fig. 2 Computed tomography. CT scan showed a diffusely enlarged, low-dense pancreas. No lymphadenopathy or nodules suspicious of liver metastasis are present
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(MRCP) showed a diffusely swollen pancreas with a nonvisualized main pancreatic duct from the pancreatic head to the body and no dilatation upstream [6] (Fig. 3c). Positron emission tomography (PET) (Fig. 4) showed diffuse intake of FDG in the pancreas with a maximum SUV value of 7.50. Endoscopic retrograde cholangiopancreatography (ERCP) showed stenosis of the lower bile duct and of the main pancreatic duct at the pancreatic head; it also showed a long segment of narrowing from the pancreatic head to body and no dilatation upstream of the narrowing (Fig. 5). Brushing cytology (Fig. 5a) from the stenotic site of the lower bile duct showed cells suspicious of adenocarcinoma. Forceps biopsy from stenotic sites of the bile duct and main pancreatic duct showed invasive ductal carcinoma (Fig. 6a). IgG4-positive cells were rare in the biopsy specimen. Our preoperative diagnosis was pancreatic carcinoma of the pancreatic head to tail, T3N0M0 (stage III), accompanied by suspected autoimmune pancreatitis. At surgery, the pancreas was diffusely swollen from the body to tail. Multiple tiny whitish nodules of cancer metastasis were recognized in the abdominal cavity and on the surface of the liver, and pancreatic resection was not performed. Lavage fluid cytology was positive for adenocarcinoma. Open biopsy from the pancreatic body to tail (Fig. 6b) revealed invasive adenocarcinoma surrounded by dense fibrous tissue in which IgG4-positive plasma cells
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Fig. 3 Magnetic resonance image. MRI also demonstrated enlarged, sausage-like pancreas from head to tail (a, b). The lower bile duct and main pancreatic duct at the pancreatic head to body were not visualized by MRCP. However, no dilatation of the main pancreatic duct was recognized at the pancreatic body to tail (c)
Fig. 4 Positron emission tomography. FDG is diffusely accumulated in the pancreas
were scarcely recognized. At 6 months from diagnosis, the patient succumbed after systemic chemotherapy using gemcitabine followed by irinotecan combined with cisplatin.
Discussion This report presents a case of diffuse pancreatic carcinoma in which serum markers and clinical images mimicked
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Fig. 5 Endoscopic retrograde cholangiopancreatography. Severe stenosis was present in the distal bile duct with leftsided deviation. Brush cytology was performed, and cells suspicious of adenocarcinoma were obtained from the stenotic site (a). The main pancreatic duct was stenotic at the pancreatic head. However, faint contrast medium was recognized along with the main pancreatic duct at the body (small arrows) and in the upstream duct without obvious dilatation (arrowheads) (b)
Fig. 6 Histology. Biopsy sample from the stenotic portion of the main pancreatic duct was diagnostic of adenocarcinoma (a). Open biopsy from pancreatic body demonstrated dense fibrous tissue and abundant inflammatory cells surrounding invasive carcinoma (b)
autoimmune pancreatitis (AIP). To date, only a few case reports have demonstrated a pancreatic carcinoma with a high level of serum IgG4 [7] and positive autoantibodies [8], and only a few have reported on pancreatic carcinoma accompanied by definitive AIP [9–11]. These reports emphasize the difficulty of distinguishing definitively between pancreatic carcinoma and AIP, and the possibility of a malignant neoplasm masked by AIP. In our case, the clinical images of a sausage-like, enlarged pancreas and the positive serum markers were compatible with AIP. Adding to these findings, the long segment of narrowing of the main pancreatic duct from the pancreatic head to body without obvious dilatation at upstream recognized by both ERCP and MRCP [6] was also very suggestive of AIP [1]. The diffuse and multifocal intake of FDG was also compatible with AIP [12]. One finding that was not compatible with AIP was the severe stenosis of the main pancreatic duct at the pancreatic head (Fig. 5b), where we determined invasive carcinoma by perampullary forceps biopsy (Fig. 6a). We strongly suspect this type of stenosis, not simple narrowing, can be used to
123
distinguish between AIP and PC accompanied by AIP. Open biopsy from the swollen pancreatic body to tail (Fig. 6b) in this case showed abundant fibrosis with moderate to severe inflammation surrounding the invasive adenocarcinoma. It was not clear if this inflammation was caused by obstructive pancreatitis or desmoplastic reaction caused by the invasive cancer [13], or fibroblast-prominent, lymphpoplasmacytic sclerotic-type AIP [14]. It can be difficult to distinguish between the histology of background AIP in the presence of an invasive cancer unless significant amounts of IgG4-positive plasma are present [7]. We finally diagnosed this case as pancreatic carcinoma accompanied with ‘‘suspected AIP.’’ From biopsy tissue obtained endoscopically and surgically, the pancreatic cancer in this case extended at least from the pancreatic head to the body. From the clinical images of sausage-like pancreas, we suspect that the AIP affected the tail of the pancreas. The most important clue or objective data supporting the diagnosis of AIP were the level of serum IgG4 (344 mg/dl). Hamano et al. [15] reported that a cutoff value of serum
Clin J Gastroenterol (2009) 2:59–63
IgG4 of 135 mg/dl resulted in 97% accuracy, 95% sensitivity and 97% sensitivity for the diagnosis of AIP versus pancreatic cancer. Raina et al. [16] also showed that serum IgG4 levels [135 mg/dl were present in 7% (5 of 71) of pancreatic carcinoma cases and 1% (1 of 103) of healthy controls, and the serum IgG4 level in the five pancreatic cancer cases with[135 mg/dl was 160.9 mg/dl on average, ranging from 144.1 to 194.0 mg/dl. Ghazale et al. [17] reported that IgG4 levels[280 mg/dl are found only in 1% of pancreatic cancer patients, but in 53% of patients with AIP. Hence, in the case presented, we strongly suspect that pancreatic cancer co-existed with AIP. To date, clinicians have made tremendous efforts to accurately diagnose mass-forming pancreatic lesions. In the case presented, we obtained a number of imaging tests and biopsy and brush cytology from the areas of stenosis of the pancreaticobiliary duct, and we were able to confirm the diagnosis of adenocarcinoma in a patient with several features of AIP. Endoscopic-ultraonography-guided fineneedle aspiration biopsy (EUS-FNAB) is an another option having superior sensitivity for carcinoma (82% [18] to 93% [19]) than the ERCP approach (47% [19] to 76% [20]). Although the sampling size is limited and sometimes not large enough to make a diagnosis, the typical histology of AIP is sometimes obtained by EUS-FNA [21]. Clinicians must keep in mind that some carcinoma cases may be associated with AIP, and exclusion of carcinoma with histological evidence is necessary. Acknowledgments The authors thank Dr. Ralph H. Hruban of Johns Hopkins Medical Institutions in the USA for his assistance with reviewing the English of the manuscript and providing beneficial comments.
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10. 11.
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References 18. 1. Okazaki K, Uchida K, Fukui T. Recent advances in autoimmune pancreatitis: concept, diagnosis, and pathogenesis. J Gastroenterol. 2008;43(6):409–18. 2. Kamisawa T, Egawa N, Nakajima H, Tsuruta K, Okamoto A, Kamata N. Clinical difficulties in the differentiation of autoimmune pancreatitis and pancreatic carcinoma. Am J Gastroenterol. 2003;98(12):2694–9. 3. Nakazawa T, Ohara H, Sano H, Ando T, Imai H, Takada H, et al. Difficulty in diagnosing autoimmune pancreatitis by imaging findings. Gastrointest Endosc. 2007;65(1):99–108. 4. Matsubayashi H, Furukawa H, Uesaka K, Sasaki K, Ono H, Hruban RH. Autoimmune pancreatitis accompanied with cholecystistis, periaortitis and pseudotumors of the liver. Case Rep Gastroenterol. 2008;1(2):155–61. 5. Kajiwara M, Gotohda N, Konishi M, Nakagohri T, Takahashi S, Kojima M, et al. Incidence of the focal type of autoimmune pancreatitis in chronic pancreatitis suspected to be pancreatic
19.
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