Autoimmune Pancreatitis and Concurrent Small Lymphocytic Lymphoma: Not Just a Coincidence?

Case

A 76-year-old gentleman presented with painless jaundice, weight loss, and anorexia. Computed tomography imaging revealed fullness of the pancreatic head and multiple enlarged retroperitoneal lymph nodes. Cholangiogram revealed a distal common bile duct stricture. Due to concerns of malignancy, the patient underwent operative exploration. Several enlarged lymph nodes in the aortocaval region and a firm hard mass in the pancreatic head were found. Frozen section from one of the lymph nodes was suspicious for low-grade lymphoma. A pancreaticoduodenectomy was performed. Histologic analysis of the pancreatic head revealed a lymphoplasmacytic infiltrate with stromal fibrosis consistent with autoimmune pancreatitis. The retroperitoneal lymph nodes were involved by small lymphocytic lymphoma.

Discussion

Autoimmune pancreatitis is the most common benign diagnosis after pancreatic resection for presumed malignancy. It has a well-documented association with autoimmune conditions, such as Sjögren’s syndrome, inflammatory bowel disease, and sclerosing cholangitis. Additionally, chronic lymphocytic leukemia–small lymphocytic lymphoma is often associated with autoimmune phenomena, most notably autoimmune hemolytic anemia. However, an association between autoimmune pancreatitis and small lymphocytic lymphoma has not been previously described. To our knowledge, this is the first reported case of a patient with concurrent autoimmune pancreatitis and small lymphocytic lymphoma.     

Complete obstruction of the lower common bile duct caused by autoimmune pancreatitis: is biliary reconstruction really necessary?

Recent observations suggest that an immune response is involved in the development of chronic pancreatitis. We report a case of autoimmune pancreatitis in a patient who showed complete obstruction of the lower common bile duct. A 63-year-old man was admitted to a local hospital, complaining of appetite loss and back pain. The patient had obstructive jaundice, and percutaneous transhepatic gallbladder drainage was performed. Fluorography through the biliary drainage catheter showed complete obstruction of the lower common bile duct. The patient had no history of alcohol consumption and no family history of pancreatic disease. Physical examination revealed an elastic hard mass palpable in the upper abdomen. Abdominal ultrasound and abdominal computed tomography (CT) scans showed enlargement of the pancreas head. While autoimmune pancreatitis was highly likely, due to the patients high serum immunoglobulin level, the possibility of carcinoma of the pancreas and/or lower common bile duct could not be ruled out. Laparotomy was performed, and wedge biopsy samples from the pancreas head and body revealed severe chronic pancreatitis with infiltration of reactive lymphocytes, a finding which was compatible with autoimmune pancreatitis. Cholecystectomy and biliary reconstruction, using choledochojejunostomy, were performed, because the complete bile duct obstruction was considered to be irreversible, due to severe fibrosis. After the operation, prednisolone (30mg/day) was given orally for 1 month, and the entire pancreas regressed to a normal size. Complete obstruction of the common bile duct caused by autoimmune pancreatitis has not been reported previously; this phenomenon provides an insight into autoimmune pancreatitis and provokes a controversy regarding whether biliary reconstruction is needed for the treatment of complete biliary obstruction caused by autoimmune pancreatitis.     

自身免疫性胰腺炎临床研究进展

近年来,自身免疫性胰腺炎(AIP)研究逐渐进展.AIP是由自身免疫机制介导的,以淋巴细胞、浆细胞浸润伴有胰腺纤维化及功能障碍为特征的特殊的慢性胰腺炎,可累及胆管、涎腺、肾等胰外器官.常见的临床表现包括梗阻性黄疸、腹痛、体重减轻等,类似于胰腺癌.本病采用类固醇类药物治疗效果显著.目前,各国的AIP诊断标准尚未达成一致.对其病理学分型、影像学表现、血清学标志、活检技术均有各种新进展,而AIP与胰腺癌的鉴别诊断则是研究热点.     

自身免疫性胰腺炎的诊治现状与进展

自身免疫性胰腺炎从1995年其概念被提出,作为慢性胰腺炎的一种,逐渐受到重视,具有自身免疫性的特点.尽管,近年来国外报道较多,其诊断标准并不统一,不易与胰腺癌鉴别;但结果显示,激素治疗效果显著.     

自身免疫性胰腺炎的诊断

自身免疫性胰腺炎（AIP）是由自身免疫介导,以梗阻性黄疸、胰腺肿大、胰管不规则狭窄、淋巴浆细胞浸润并纤维化、伴或不伴胰外器官受累为特征．对激素治疗敏感的一种特殊类型的慢性胰腺炎。临床上AIP诊断十分困难,且临床及病理医师对其亦认识不足,误诊率较高。因AIP常以梗阻性黄疸、胰腺肿大为特征,故易误诊为胰腺肿瘤而采取不必要的手术切除。增加对AIP的认识,提高诊断正确率,对改善AIP的诊断现状和治疗水平尤为重要。     

T cell lymphoplasmacellular and eosinophilic infiltration of the pancreas with involvement of the gallbladder and duodenum in non-alcoholic duct-destructive chronic pancreatitis

Background Non-alcoholic duct destructive chronic pancreatitis is a rare entity with specific pathological features. The majority of the patients are from Japan. We report a case with involvement of the distal bile duct, the gallbladder, the duodenum and the ampulla, and present a review of patients from Europe and the USA since 1997.Case presentation A 56-year-old man presented with a 3-month history of mild acute pancreatitis and obstructive jaundice, followed by increasing weight loss, lethargy and epigastric pain. CT showed a mass in the head of the pancreas. ERCP demonstrated a smooth stricture of the intra-pancreatic main bile duct and an irregular, incomplete, stricture in the main pancreatic duct. A pancreatic cancer could not be reliably excluded, and, therefore, he underwent a pylorus-preserving Kausch–Whipples pancreatoduodenectomy.Results Histopathology showed typical peri-ductal T cell-rich lymphoplasmacellular and eosinophilic infiltration of the pancreas, with involvement of the distal bile duct but, also, unusual inflammatory infiltration of the gallbladder, the duodenum and the ampulla.Conclusion The inflammatory process in non-alcoholic duct-destructive chronic pancreatitis can affect the entire pancreato-biliary region and mimics pancreatic cancer. Currently, there are no definitive criteria for pre-operative diagnosis, so it is very difficult for one to avoid resection.     

Elevation of Serum IgG4 in Western Patients With Autoimmune Sclerosing Pancreatocholangitis: A Word of Caution

Background Autoimmune pancreatocholangitis is characterized by sclerosing inflammation of the biliary tree or pancreatic duct and can mimic pancreaticobiliary malignancy. Serum immunoglobin (Ig) G4 values seem to be helpful in distinguishing autoimmune pancreatocholangitis from pancreatic malignancy in the Japanese population; however, its significance in the Western population has not been well studied. Methods We report a retrospective analysis of 7 consecutive patients with autoimmune pancreatocholangitis and compare them to 23 patients with pancreatic malignancy. Clinical presentation, diagnostic tests, and preoperative IgG4 levels were reviewed in all patients. Presence of autoimmune pancreatocholangitis or pancreatic malignancy was determined by pathologic analysis in all patients and reviewed by a single pathologist. Results In all patients, autoimmune pancreatocholangitis manifested in a similar fashion to pancreatic malignancy. Median IgG4 levels were far lower in pancreatic cancer patients with localized, resectable disease (24 mg/dL), locally advanced disease (24 mg/dL), and metastatic disease (28 mg/dL) as compared with patients with autoimmune pancreatocholangitis (142 mg/dL, P < .05). Only one patient with pancreatic cancer had an IgG4 level that was >100 mg/dL. In contrast, all patients with autoimmune pancreatitis or cholangitis had levels >100 mg/dL. However, in five of these seven patients, IgG4 levels were below the upper limits of normal. Conclusions Autoimmune pancreatocholangitis mimics pancreatobiliary malignancy. Serum IgG4 values seem to be helpful in distinguishing autoimmune pancreatocholangitis from malignancy in the Western population. However, absolute values seem to be lower in the United States compared with Japan. The upper limit of normal as reported in laboratories in the United States may not be useful in identifying abnormally high IgG4 values. A new upper limit of normal may need to be defined because IgG subclass determinations are being used more frequently in Western patients with biliary obstruction.     

Autoimmune pancreatitis misdiagnosed as a tumor of the head of the pancreas

Autoimmune pancreatitis can mimic pancreatic cancer in its clinical presentation, imaging features and laboratory parameters. Differentiating between those two entities requires implementation of clinical judgment and experience along with objective parameters that may suggest either condition. Few strategies have been proposed for the surgeon to implement when facing borderline cases. The following case is an example of a clinical scenario compatible with an accepted algorithm for diagnosis of pancreatic cancer, which eventually proved wrong. We present a 75-year-old patient who was admitted for obstructive jaundice. Imaging features were highly suggestive for pancreatic cancer as was the carbohydrate antigen 19-9 (CA 19-9) level, leading to a decision for surgery. Pathological examination revealedautoimmune pancreatitis. Though no frank carcinoma was found, premalignant ductal changes of pancreatic intraepithelial neoplasia (PanIN)Ⅰand PanIN Ⅱ were discovered throughout the pancreatic duct. Caution is advised when relying on the combination of highly suggestive radiology features and elevated levels of CA 19-9 in the diagnosis of pancreatic cancer. When the tissue diagnosis is not conclusive, obtaining IgG4 and antinuclear Ab levels is advised, to rule out the rare possibility of autoimmune pancreatitis. Patients with autoimmune pancreatitis should be followed carefully as precancerous lesions may accompany the benign disease and the correlation of these two entities has not been ruled out.     

Autoimmune pancreatitis diagnosed after pancreatoduodenectomy and successfully treated with low-dose steroid

A 69-year-old woman presented with obstructive jaundice and a 30-mm hypoechoic mass in the pancreatic head on ultrasonography. Magnetic resonance imaging (MRI) revealed enlargement of the pancreatic head with dilatation of the upstream main pancreatic duct and no dilatation of the proximal biliary tree. Endoscopic retrograde pancreatography showed a localized irregular narrowing of the main pancreatic duct in the head of the pancreas. Pylorus-preserving pancreatoduodenectomy (PPPD) was performed under the diagnosis of pancreatic head cancer. Histopathological examination showed fibrosis with lymphoplasmacytic infiltration, suggesting the diagnosis of autoimmune pancreatitis (AIP). Serum IgG concentration was within normal limits immediately after the operation but was elevated 4 months later, when MRI showed enlargement of the remnant pancreas, with a peripheral rim of low intensity. Oral administration of prednisolone was initiated, at a dose of 5 mg/day. The serum IgG concentration declined and MRI showed improvement of the pancreatic enlargement and the disappearance of the peripheral rim. AIP has not relapsed for 1 year so far, with the patient being kept on 5 mg/day prednisolone. This communication reports a patient with AIP showing an interesting clinical course.     

CT与MRI检查对自身免疫性胰腺炎的诊断价值

目的 探讨CT与MRI检查对自身免疫性胰腺炎（AIP）的诊断价值。方法 回顾性分析2011年 6月至2013年12月期间眉山市中医医院收治的14例AIP患者的临床和影像学资料。结果 CT和MRI检查示AIP患者的胰腺弥漫性肿大呈腊肠状,T1WI示胰腺实质信号明显减低,扩散加权成像（DWI）示胰腺实质信号明显增高;增强扫描后动脉期胰腺实质强化幅度明显降低,延迟期呈持续性延迟强化伴包膜征,胆总管胰腺段呈鸟嘴样狭窄。结论 AIP的影像学表现具有一定的特征性,结合临床表现及实验室检查可早期诊断,对选择治疗方案具有重要意义。     

Lymphoplasmacytic sclerosing pancreatitis: Inflammatory mimic of pancreatic carcinoma

Lymphoplasmacytic sclerosing pancreatitis (LP) is a rare cause of benign mass lesions of the pancreas that can resemble adenocarcinoma. This study evaluates and classifies a series of patients with LP. Patients with benign pancreatic disease were identified from a prospective pancreatic database, and these cases were reviewed to identify patients with LP. Patients were subdivided into two groups: (1) classic LP, which included those patients who had all four of the characteristic histologic features of LP, including lymphoplasmacytic infiltration of the pancreas, interstitial fibrosis, periductal inflammation, and peri-phlebitis; and (2) intermediate LP, which included patients with at least two of these histologic findings. Patient demographics, pathologic and clinical features, and outcome were analyzed. From 1985 to 2001, a total of 1287 pancreatic resections were performed at our institution, of which 159 were for benign disease. Of these, 31 had pathologic features consistent with LP, and all of these patients had a presumed preoperative diagnosis of pancreatic carcinoma. Most of these patients presented with jaundice (n = 21) or abdominal pain (n = 7). In 29 of 31 patients, curative resection was possible. Of these, 28% (8/29) developed recurrence after resection: seven with jaundice and one with recurrent pancreatitis (median time to recurrence, 11 months; median follow up, 38 months). All patients with recurrent jaundice appeared to have biliary strictures at the time of direct cholangiography and no patient had malignancy. A review of the pathology reports identified 19 patients with classic LP and 12 patients with intermediate LP, and there was no difference between these two groups. LP is a rare cause of pancreatitis that is difficult to differentiate from carcinoma preoperatively. Patients with classic and intermediate LP appear to demonstrate a similar clinical behavior. Nearly one third of patients have a progressive course after resection, with 25% developing recurrent jaundice; thus close follow-up is mandatory for all patients. Presented at the Forty-Third Annual Meeting of The Society for Surgery of the Alimentary Tract, San Francisco, California, May 19–22, 2002 (oral presentation).     

Autoimmune pancreatitis with multifocal lesions

Two cases of a focal type of autoimmune pancreatitis (AIP) with distinct double mass lesions within the pancreas are described. In both patients, computed tomography (CT) showed localized pancreatic masses with delayed enhancement, and magnetic resonance cholangiopancreatography (MRCP) revealed localized stenoses of the main pancreatic duct (MPD) with mild upstream dilatation. Fluorodeoxyglucose positron emission tomography (FDG-PET) examination, performed in one patient, showed intense uptake concordant with tumors. Both patients received pancreatic resection with a presumptive diagnosis of pancreatic carcinoma. Histologic evaluation of the tumors showed marked lymphoplasmacytic infiltration and fibrosis around the large and medium pancreatic ducts, without any evidence of malignancy. Serum IgG4 concentration, measured postoperatively, was elevated in both patients. The characteristic morphological features of AIP are diffuse swelling of the pancreatic parenchyma and diffuse narrowing of the MPD. Recently, a focal type of AIP, which mimics pancreatic carcinoma, has been recognized. Considering the favorable response of AIP to steroid therapy, it is clinically important to differentiate the focal type of AIP from pancreatic carcinoma and to know that AIP sometimes exhibits multiple lesions within the pancreas.     

Pancreatitis autoinmune: un dilema quirúrgico

Autoimmune pancreatitis (AIP) is defined as a particular form of pancreatitis that often manifests as obstructive jaundice associated with a pancreatic mass or an obstructive bile duct lesion, and that has an excellent response to corticosteroid treatment. The prevalence of AIP worldwide is unknown, and it is considered as a rare entity. The clinical and radiological presentation of AIP can mimic bilio-pancreatic cancer, presenting difficulties for diagnosis and obliging the surgeon to balance decision-making between the potential risk presented by the misdiagnosis of a deadly disease against the desire to avoid unnecessary major surgery for a disease that responds effectively to corticosteroid treatment. In this review we detail the current and critical points for the diagnosis, classification and treatment for AIP, with a special emphasis on surgical series and the methods to differentiate between this pathology and bilio-pancreatic cancer.     

肿块型慢性胰腺炎的影像学特征

肿块型慢性胰腺炎包括以纤维化的肉芽组织增生为特征的普通型肿块型慢性胰腺炎和以致密的淋巴浆细胞浸润伴丰富纤维化增生为特征的肿块型自身免疫性胰腺炎两种病理类型,在临床上有时均很难与胰腺癌鉴别。准确的术前诊断与鉴别对于其治疗及预后有着极为重要的意义。肿块型慢性胰腺炎与胰腺癌在CT和MRI上分别具有一定特征性的影像学表现,特别是磁共振动态增强后信号强度-时间（signal intensity-time,SI-T）曲线及弥散加权成像（DWI）更有助于两者的鉴别,肿块型慢性胰腺炎呈慢升慢降型曲线,而胰腺癌呈渐进性升高曲线;肿块型慢性胰腺炎的表现弥漫系数（ADC）值低于胰腺癌的ADC值等。     

IgG4-related sclerosing lymphoplasmacytic pancreatitis and cholangitis mimicking carcinoma of pancreas and Klatskin tumour

Background: Autoimmune sclerosing pancreatitis is a well‐known disease entity for years, particularly recognizing the difficulty in distinguishing it from malignancy. Immunohistochemical study showed that immunoglobulin IgG4 staining was positive in plasma cells of some autoimmune pancreatitis or cholangitis. The term ‘autoimmune sclerosing pancreatocholangitis’ was used as it was believed that they belonged to a range of disease involving both pancreas and biliary tree. It may also be part of a systemic fibro‐inflammatory disease. Patients and Methods: All the patients suffering from immunoglobulin G4 (IgG4)‐related pancreatitis and cholangitis from May 2003 to September 2006 in Queen Elizabeth Hospital, Hong Kong were retrospectively studied. Results: A total of five patients with clinical diagnosis of IgG4‐related autoimmune pancreatitis or cholangitis were analysed. All presented with jaundice or abdominal pain, mimicking carcinoma. Two patients had major resection, two patients were diagnosed by intraoperative biopsy and one was based on serum IgG4 level. Conclusion: With the growing awareness of this relatively recently characterized clinical entity and its similar presentation to pancreatic carcinoma or bile duct cholangiocarcinoma, it is important for autoimmune sclerosing pancreatocholangitis to be included in the differential diagnosis of pancreaticobiliary disease. The management strategy has shown to be modified – from major resection to intraoperative biopsy and to the assay of serum IgG4 level without the necessity of histology confirmation.     

Tubulointerstitial nephritis associated with IgG4-related systemic disease

We report three patients with tubulointerstitial nephritis (TIN) with high serum IgG4 concentrations. None of the patients had notable pancreatic lesions when the TIN developed, although one had a history of autoimmune pancreatitis (AIP). Nevertheless, the clinicopathological findings were quite similar to those of AIP. They were all middle-aged to elderly men. Sialadenitis and lymphadenopathy were often evident. Serum total IgG and IgG4 concentrations were elevated and hypocomplementemia was observed. Although antinuclear antibodies were positive, anti-Ro and anti-La antibodies were negative. Renal biopsy showed dense lymphoplasmacytic infiltration with fibrosis in the renal interstitium, and the infiltrated plasma cells had strong immunoreactivity for IgG4. Furthermore, lymphoplasmacytic infiltration and abundant IgG4-positive plasma cells were observed in the salivary glands of a patient. Steroid therapy was effective for TIN in all three patients. The present findings support the recently proposed concept of IgG4-related systemic disease, and suggest that IgG4 is associated not only with AIP but also with other systemic lymphoplasmacytic diseases, including TIN. The conditions responsible for the pathogenesis of TIN need to be considered, irrespective of the presence of AIP.     

Capillary refill time as a guide for operational decision-making process of autoimmune pancreatitis:Preliminary results

AIM: To investigate the efficacy of a novel intraoperative diagnostic technique for patients with preliminary diagnosis of autoimmune pancreatitis(AIP).METHODS: Patients with pancreatic surgery were reviewed to identify those who received a preliminary diagnosis of AIP between January 2010 and January 2014. The following data were collected prospectively for patients with a pathological diagnosis of AIP: clinical and demographic features, radiological and operative findings, treatment procedure, and intraoperative capillary refill time(CRT) in the pancreatic bed.RESULTS: Eight patients(six males, two females; mean age: 51.4 years) met the eligibility criteria of pathologically confirmed diagnosis. The most frequent presenting symptoms were epigastric pain and weight loss. The most commonly conducted preoperative imaging studies were computed tomography and endoscopic retrograde pancreaticodoudenography. The most common intraoperative macroscopic observations were mass formation in the pancreatic head and diffuse hypervascularization in the pancreatic bed. All patients showed decreased CRT(median value: 0.76 s, range: 0.58-1.35). One-half of the patients underwent surgical resection and the other half received medical treatment without any further surgical intervention. CONCLUSION: This preliminary study demonstrates a novel experience with measurement of CRT in the pancreatic bed during the intraoperative evaluation of patients with AIP.     

Long-term Results After Surgery for Autoimmune Sclerosing Pancreatitis

Autoimmune sclerosing pancreatitis (ASP) is a recently recognized cause of chronic pancreatitis. The role of operative intervention in this disease is controversial. A single center experience with 161 consecutive pancreatic resections for chronic pancreatitis was retrospectively reviewed. Operative specimens were reanalyzed and assessed for histological features of ASP. Long-term outcome was assessed by patient survey. Eight patients were identified with histological changes consistent with ASP. The pancreatic anatomic configuration according to intraoperative findings and preoperative radiographic evaluation was categorized into (1) diffusely enlarged pancreas (n = 4), (2) localized mass (n = 2), or (3) refractory pancreatic duct disruption without pancreatic enlargement (n = 2). Five patients underwent pancreaticoduodenectomy and three patients underwent distal pancreatectomy. Perioperative morbidity, operative time, and intraoperative estimated blood loss were similar to the same operation for other etiologies of chronic pancreatitis. Biliary obstruction occurred in two patients. Seven patients were alive 5 ± 0.4 years after operation. Good quality of life measured by the SF-36 questionnaire was present in 4 of 7 patients surveyed. Good pain control was achieved with return to work in 5 of 7 patients. Two patients with poor pain control received glucocorticosteroids therapy without improvement in symptoms. Patients with ASP and a mass suspicious for malignancy or refractory duct disruption require operative intervention. Early postoperative outcome, long-term pain control, and improvement in quality of life appear to be good. This study was presented in part at the annual meeting of the American Hepato-Pancreato-Biliary Association, Miami Beach, Florida, March 9–12, 2006.     

Chronic Pancreatitis

Chronic pancreatitis is a debilitating condition often associated with severe abdominal pain and exocrine and endocrine dysfunction. The underlying cause is multifactorial and involves complex interaction of environmental, genetic, and/or other risk factors. The pathology is dependent on the underlying pathogenesis of the disease. This review describes the clinical, gross, and microscopic findings of the main subtypes of chronic pancreatitis: alcoholic chronic pancreatitis, obstructive chronic pancreatitis, paraduodenal (“groove”) pancreatitis, pancreatic divisum, autoimmune pancreatitis, and genetic factors associated with chronic pancreatitis. As pancreatic ductal adenocarcinoma may be confused with chronic pancreatitis, the main distinguishing features between these 2 diseases are discussed.     

Autoimmune pancreatitis: an adolescent case and review of literature

We present a case of a 16-year-old adolescent boy with autoimmune pancreatitis and a review of the related literature.The patient was sent from a peripheral medical center, presenting with jaundice, pruritus, weight loss, and hyperglycemia of 20 days' duration. At admission, the patient was icteric, choluric, and acholic. His abdomen was soft and nontender, and the patient felt no pain in his abdomen. He had skin lesions because of scratching. Laboratory findings showed a blood glucose level of 135 mg%; total serum bilirubin, 29.4 mg%; direct bilirubin, 23 mg%; and alkaline phosphatase, 1100 IU/L. Abdominal ultrasound showed an enlarged head of the pancreas that was 30 × 35 mm. The parenchyma was slightly heterogeneous. Abdominal computed tomography showed an enlarged head of the pancreas with a normal body and tail, thickened duodenal wall, and dilated intra- and extrahepatic biliary tract, and the distal choledochus was not visible. Magnetic resonance imaging showed dilated intra- and extrahepatic biliary tract. The choledochus was not visible, and the cystic duct ended abruptly. The pancreas head was enlarged and homogenous, and there were no changes with contrast. Wirsung's duct was not dilated.Laparotomy was performed with a presumed diagnosis of pancreatic head tumor. The pancreas was diffusely indurated and enlarged; biopsy and intraoperative cholangiography were performed. The biliary tract was dilated with no duodenal passage of contrast, and the Wirsung's duct was not observed. Cholecystectomy was performed, and a transcystic drain was positioned.The histopathology was compatible with autoimmune pancreatitis. Prednisone treatment was started with good response. Autoimmune pancreatitis is a very rare entity among children and adolescents. It should be suspected when characteristic clinical signs and radiographic images are associated with a higher level of IgG4. Autoimmune pancreatitis is confirmed by biopsy. Treatment with prednisone often alleviates all the symptoms, as what happened in this case.