Lymphoplasmacytic Sclerosing Pancreatitis Research Articles

Autoimmune pancreatitis: the clinicopathological characteristics of the subtype with granulocytic epithelial lesions

Autoimmune pancreatitis (AIP) has been established as a distinct form of chronic pancreatitis that is distinguishable from other types such as alcoholic, hereditary or obstructive chronic pancreatitis. AIP seems to be a global disease, since it has been reported in many different countries, especially from Japan, USA and Europe (Germany, Italy, United Kingdom). Typical histopathological findings in the pancreas in AIP include a periductal lymphoplasmacytic infiltration with fibrosis, causing narrowing of the involved ducts. The typical clinical features include presentation with obstructive jaundice/pancreatic mass and a dramatic response to steroids. However, while the reports from Japan describe uniform changes called lymphoplasmacytic sclerosing pancreatitis (LPSP) in the pancreas from AIP patients, the reports from Europe and USA distinguish two histopathologic patterns in AIP patients: one with the characteristics of LPSP and another with slightly different histological features, called idiopathic duct centric pancreatitis (IDCP) or AIP with granulocytic epithelial lesions (GELs). This article reviews the evidence that GEL-positive AIP or IDCP is a second type of AIP, distinct from LPSP, in regard to pancreatic pathology, immunology and epidemiology.

Incidence and characteristics of chronic and lymphoplasmacytic sclerosing pancreatitis in patients scheduled to undergo a pancreatoduodenectomy

BackgroundThe determination of the exact nature of a pancreatic head mass in a patient scheduled to undergo a pancreatoduodenectomy can be very difficult. This is important as patients who suffer from benign disease such as pancreatitis do not always require surgery. The aim of the present study was to analyse the incidence of pancreatitis and the signs and symptoms associated with these tumours mistaken for pancreatic cancer and the diagnostic procedures performed. MethodsA consecutive group of patients who underwent a pancreatoduodenectomy between 1992 and 2005 with histopathologically proven pancreatic adenocarcinoma (PCA) and pancreatitis were analysed. ResultsThe incidence of pancreatitis after pancreatoduodenectomy is 63 out of 639 patients who underwent a pancreaticoduodenectomy (9.9%). Of these patients, 24 patients (38%) had lymphoplasmacytic sclerosing pancreatitis (LPSP) and 31 patients (49%) had focal chronic pancreatitis. Eight patients (13%) had an intermediate form with characteristics of both. Pancreatic adenocarcinoma occurred in 227 patients (36%). The presence of pancreatitis without a discrete mass on endoscopic ultrasonography (EUS) seemed to have clinical relevance with a positive likelihood ratio of 5.1. Mortality after resection was nil in both groups. ConclusionThe incidence of pancreatitis is 9.9% for patients scheduled to undergo a pancreatoduodenectomy. Of these patients, 38% had LPSP, 13% had a intermediate form and 49% had focal chronic pancreatitis. The determination of the exact nature of a pancreatic head mass remains difficult.

Idiopathic Duct-Centric Pancreatitis (IDCP) with Immunological Studies

A 65-year-old woman with elevated serum levels of pancreatic enzymes was referred to our hospital for further examinations. Abdominal US and contrast-enhanced CT demonstrated swelling of the pancreas body and tail. MRCP and ERCP revealed abrupt ending of the MPD in the pancreas body. Under the suspicion of malignancy, distal pancreatectomy and splenectomy were performed. The histopathological findings showed idiopathic duct-centric pancreatitis (IDCP) with granulocytic epithelial lesions (GEL). As most cases of Japanese autoimmune pancreatitis (AIP) are lymphoplasmacytic sclerosing pancreatitis (LPSP), the present case seems to be helpful to clarify the clinical findings of IDCP in Japan.

Small invasive ductal adenocarcinoma of the pancreas associated with lymphoplasmacytic sclerosing pancreatitis

An asymptomatic 59-year-old man underwent pancreatoduodenectomy for a pancreatic mass that was discovered during a health check-up. Histopathology indicated typical features of lymphoplasmacytic sclerosing pancreatitis (LPSP) or autoimmune pancreatitis along with the presence of abundant IgG4-positive plasma cells throughout the mass. A small invasive ductal adenocarcinoma was observed in the center of the area affected by LPSP. The present case suggests that LPSP may be closely related to carcinogenesis of the pancreas.

Histological diagnosis of autoimmune pancreatitis using EUS-guided trucut biopsy: a comparison study with EUS-FNA

The aim of this study was to evaluate the feasibility and safety of endoscopic ultrasonography (EUS)-guided trucut biopsy (TCB) for diagnosis of autoimmune pancreatitis (AIP). Fourteen patients with suspected AIP based on imaging studies underwent both EUS-guided fine-needle aspiration (FNA) and EUS-TCB for diagnosis of AIP and exclusion of pancreatic cancer (PC). According to the revised Japanese clinical diagnostic criteria, AIP was diagnosed in eight while the remaining six patients had pancreatitis of other etiologies. Pathologically, AIP was defined as lymphoplasmacytic sclerosing pancreatitis (LPSP), and sub-divided into two types: definite LPSP (d-LPSP) showing fulspectrum of LPSP and probable LPSP (p-LPSP) without obliterative phlebitis or abundant (>10 cells/hpf) IgG4-positive plasmacytes infiltration. PC was excluded in all patients. EUS-FNA resulted in three of eight patients with AIP were reported as p-LPSP, one was reported as normal, and 4 were inconclusive. One of six with non-autoimmune pancreatitis was diagnosed as p-LPSP on EUS-FNA, one as idiopathic chronic pancreatitis (ICP) and four were inconclusive. By using EUS-TCB, all AIP patients were diagnosed as LPSP (4 d-LPSP and 4 p-LPSP). Of the six patients with non-autoimmune pancreatitis, three were diagnosed as LPSP (1 d-LPSP and 2 p-LPSP) and three showed ICP on TCB. No complications were identified in any patient with either EUS-FNA or TCB. EUS-TCB is a safe and accurate procedure for obtaining a histological diagnosis in patients with suspected AIP. EUS-TCB can serve as a rescue technique in cases of AIP lacking typical findings.

Autoimmune pancreatitis in Japan: overview and perspective

Since the rediscovery and definition of autoimmune pancreatitis (AIP) by Yoshida et al. in 1995, the disease has been attracting attention because of its unique clinical features and practical issues. This disease shows very impressive imaging findings, serological changes, and characteristic histopathology. It occurs most commonly in elderly males with painless jaundice or mild abdominal pain; resemblance in imaging findings between AIP and pancreatobiliary cancers poses an important practical issue of differentiation. With increasing recognition of AIP and accumulation of cases, another important feature of this disease has been revealed, i.e., association of extrapancreatic organ involvements. Initially misunderstood because it can be accompanied by other autoimmune disorders, such as Sjögren's syndrome or primary sclerosing cholangitis (PSC), AIP is now known to be associated with unique types of sialadenitis and cholangitis distinct from Sjögren's syndrome or PSC. Now the concept of "IgG4-related sclerosing disease" has become widely accepted and the list of organs involved continues to increase. With worldwide recognition, an emerging issue is the clinical definition of other possible types of autoimmune-related pancreatitis called "idiopathic duct-centric chronic pancreatitis (IDCP)" and "AIP with granulocyte epithelial lesion (GEL)" and their relation to AIP with lymphoplasmacytic sclerosing pancreatitis (LPSP). The time has arrived to establish clinical diagnostic criteria of AIP based on international consensus and to discuss regional and racial differences in the clinicopathological features of AIP. Consensus guidelines are also required for the ideal use of steroids in the treatment of AIP to suppress recurrence efficiently with minimal side effects. There are many issues to be settled in AIP; international collaboration of experts in the pancreas field is necessary to clarify the entire picture of this unique and important disease.

Isolated Lymphoplasmacytic Sclerosing Pancreatitis Involving the Pancreatic Tail

We present an interesting case of a 62-year-old woman with a 3-month history of vague, left-sided abdominal pain. CT imaging revealed a hypodense lesion in the tail of the pancreas. The patient had no history of pancreatitis or autoimmune diseases. Laboratory testing revealed a normal CA19-9 (33 U/mL) and an elevated IgG4 (133 mg/dL). Due to concerns of pancreatic malignancy, she underwent operation. We found a dense, inflammatory mass in the tail of the pancreas, which was removed via an open distal pancreatectomy with splenectomy. Histologic analysis revealed a pancreas with sclerotic ducts and surrounding lymphoplasmacytic inflammation most consistent with lymphoplasmacytic sclerosing pancreatitis (LPSP). LPSP, also termed autoimmune pancreatitis, is a benign disease of the pancreas, which can mimic pancreatic adenocarcinoma. It is the most common benign finding diagnosed on pathology after pancreatic resection for presumed malignancy. LPSP most commonly involves the head and, more uncommonly, the tail of the pancreas. It can be successfully treated with steroids obviating the need for resection. IgG4 levels may assist in recognition of this disease. As our experience with utilization of IgG4 testing and knowledge of the systemic nature of LPSP increase, patients with this disease may be spared unnecessary resection.

Lymphoplasmacytic Sclerosing Pancreatitis and Retroperitoneal Fibrosis

Although cases of lymphoplasmacytic sclerosing pancreatitis (LSP) associated with idiopathic retroperitoneal fibrosis have been reported, the association is rare. We describe a 74-year-old man who presented with obstructive jaundice and weight loss. Nineteen months earlier, he had been diagnosed with idiopathic retroperitoneal fibrosis and treated with bilateral ureteric stents. Initial investigations were suggestive of a diagnosis of LSP, however, a malignant cause could not be ruled out. He underwent an exploratory laparotomy and frozen sections confirmed the diagnosis of LSP. An internal biliary bypass was performed using a Roux loop of jejunum, and the patient made an uneventful recovery. This case illustrates the difficulty in distinguishing LSP from pancreatic carcinoma preoperatively.

Is Pancreatic Core Biopsy Sufficient to Diagnose Autoimmune Chronic Pancreatitis?

This study aimed to evaluate the adequacy of pancreatic core biopsy in histological diagnosis of autoimmune chronic pancreatitis (AIP). Histopathologic study as well as immunohistochemical staining using anti-IgG4 antibody was done with pancreatic tissue specimens of 26 AIP patients (19 transabdominal ultrasound (US)-guided core biopsies, 3 intraoperative wedge biopsies, and 4 surgical resections). Eight patients with alcoholic chronic pancreatitis and 10 patients with pancreatic cancer served as controls. Lymphoplasmacytic sclerosing pancreatitis (LPSP) histology was observed in 26% (5/19) of US-guided core biopsy specimens, 33% (1/3) of open biopsy specimens, and all 4 resection specimens in AIP patients. None of the patients in the control group showed the full spectrum of changes of LPSP. Abundant IgG4-positive cells (>10 cells/high-power field) in the pancreas were observed in 21% (4/19) of AIP patients with US-guided core biopsy specimen. Abundant IgG4-positive cells in the pancreas were also observed in 2 of 8 patients with chronic alcoholic pancreatitis and 1 of 10 patients with pancreatic cancer. Transabdominal US-guided pancreatic core biopsy may not provide enough tissue to evaluate characteristic histopathologic features of AIP that include LPSP or abundant IgG4-positive cell infiltration. The LPSP histology may be specific to AIP, but abundant IgG4-positive cells in the pancreas may not.

Diagnostic criteria for autoimmune pancreatitis in Japan

Autoimmune pancreatitis (AIP) is a particular type of pancreatitis of presumed autoimmune etiology. Currently, AIP should be diagnosed based on combination of clinical, serological, morphological, and histopathological features. When diagnosing AIP, it is most important to differentiate it from pancreatic cancer. Diagnostic criteria for AIP, proposed by the Japan Pancreas Society in 2002 first in the world, were revised in 2006. The criteria are based on the minimum consensus of AIP and aim to avoid misdiagnosing pancreatic cancer as far as possible, but not for screening AIP. The criteria consist of the following radiological, serological, and histopathological items: (1) radiological imaging showing narrowing of the main pancreatic duct and enlargement of the pancreas, which are characteristic of the disease; (2) laboratory data showing abnormally elevated levels of serum gamma-globulin, IgG or IgG4, or the presence of autoantibodies; (3) histopathological examination of the pancreas demonstrating marked fibrosis and prominent infiltration of lymphocytes and plasma cells, which is called lymphoplasmacytic sclerosing pancreatitis (LPSP). For a diagnosis of AIP, criterion 1 must be present, together with criterion 2 and/or criterion 3. However, it is necessary to exclude malignant diseases such as pancreatic or biliary cancer.

Focal Lymphoplasmacytic Sclerosing Pancreatitis

To correlate cross-sectional imaging findings with histological results in patients with histopathologically proven lymphoplasmacytic sclerosing pancreatitis (LSP) after surgery. Four cases of resectable pancreatic lesions that were proven to represent LSP are presented in our study. All patients were thought to harbor malignancy. A detailed research in patients' records was retrospectively done concerning clinical presentation and imaging studies. Characteristic imaging findings consistent with fibrotic changes were evident in only one case on magnetic resonance imaging. A discrete mass was evident on imaging in 2 patients that correlated well with pathology results. In the other patients, the extent of inflammatory changes on microscopic examination correlated well with the degree of pancreatic head enlargement on imaging studies. Lymphoplasmacytic sclerosing pancreatitis is a particular form of benign inflammatory pancreatic disease that is extremely difficult to diagnose preoperatively. Familiarization with the variable imaging findings is essential and may result in the reduction of the number of patients with LSP who undergo surgical resection.

Clinical and Radiologic Resolution of IgG 4 Normal, Nonoperatively Diagnosed Lymphoplasmacytic Sclerosing Pancreatitis (LPSP) after Initiation of Steroid Therapy

Clinical and Radiologic Resolution of IgG 4 Normal, Nonoperatively Diagnosed Lymphoplasmacytic Sclerosing Pancreatitis (LPSP) after Initiation of Steroid Therapy

Clinical diagnostic criteria of autoimmune pancreatitis: revised proposal

In 1961, Sarles et al.1 asked the following question regarding the particular cases of pancreatitis with hypergammaglobulinemia: “Chronic inflammatory sclerosis of the pancreas—an autoimmune pancreatic disease?” As similar cases were rarely observed, a relationship between such pancreatitis and autoimmunity was viewed skeptically during the following several decades. In 1992, Toki et al.2 have reported 4 cases with unusual diffuse irregular narrowing of the main pancreatic duct and diffuse enlargement of the entire pancreas due to lymphocyte infiltration. In 1995, Japanese investigators3 firstly proposed a concept of “autoimmune pancreatitis (AIP)”, in which the patients showed diffusely enlarged pancreas, narrowing pancreatogram, increased serum IgG, presence of autoantibodies, fibrotic changes with lymphocytic infiltration and steroidal efficacy. Thereafter, many AIP cases have been reported from Japan, and AIP has been accepted as a new clinical entity.4,5 The histopathological findings of AIP show massive infiltration of lymphoplasmacytes with fibrosis, which is consistent with lymphoplasmacytic sclerosing pancreatitis (LPSP).6 Many Japanese investigators have paid great attention to AIP, especially with regard to its unique pancreatic images,2 IgG4,7 disease-associated autoantibodies,8 extrapancreatic lesions,6,9–14 and steroidal efficacy.14,15 Currently in Japan, diagnosis of AIP is based on the “diagnostic criteria 2002 of autoimmune pancreatitis”16 proposed by the Japan Pancreas Society. However, the accumulation of many AIP cases shows that the concept of AIP has changed slightly to include extrapancreatic lesions and associated disorders, which suggests that the current diagnostic criteria are becoming inadequate. In 2003, the Research Committee of Intractable Diseases of the Pancreas, supported by the Japanese Ministry of Health, Labour and Welfare (Chairman, M. Otsuki), began to review the current diagnostic criteria in light of recently acquired information and knowledge. The team organized a working group (WG), consisting of the team members and researchers specializing in autoimmune pancreatitis, to develop a proposal for the revision of the current diagnostic criteria. On 7 October 2005 and 22 April 2006, the Research Committee of Intractable Diseases of the Pancreas and the Japan Pancreas Society jointly held open forums to discuss the proposed amendments. This report describes the background of the proposed amendments and the final proposal for the revised version of the clinical diagnostic criteria of AIP.

Lymphoplasmacytic sclerosing pancreatitis presenting as a pancreatic head mass in a child: case report and management recommendations

Lymphoplasmacytic sclerosing pancreatitis (LPSP) is an autoimmune form of chronic pancreatitis found most commonly in elderly men and only rarely in children. A 10-year-old boy presented with a 3-week history of obstructive jaundice. Imaging studies showed a pancreatic head mass, hepatic ductal dilatation, and involvement of the portal vein. A preliminary diagnosis of malignancy was based on endoscopic ultrasound characteristics and fine-needle aspiration cytology. The patient underwent a pancreaticoduodenectomy. The patient recovered uneventfully and was discharged home on postoperative day 6. The final pathological diagnosis was LPSP. Lymphoplasmacytic sclerosing pancreatitis is a rare form of chronic pancreatitis in children that is difficult to distinguish from malignancy preoperatively. We discuss the diagnosis and treatment of LPSP. Determination of elevated IgG4 levels in children with pancreatic head masses may allow for the medical treatment of LPSP.

Lymphoplasmacytic sclerosing (autoimmune) pancreatitis

Lymphoplasmacytic sclerosing pancreatitis (LPSP), also known as autoimmune pancreatitis or nonalcoholic, duct destructive chronic pancreatitis, has been increasingly recognized in the past decade as a histologically distinctive type of pancreatitis that affects middle-aged patients who lack the typical risk factors for chronic pancreatitis (alcohol abuse in particular). LPSP is sometimes associated with other autoimmune diseases or fibroinflammatory lesions, although in some patients, pancreatic and biliary involvement represent the only known disease process. Many patients present with pancreatic masses clinically and radiographically simulating pancreatic carcinoma, and associated bile duct strictures enhance the resemblance. Elevated serum IgG4 levels have been described in patients with LPSP and have been used to distinguish LPSP from pancreatic carcinoma preoperatively. Although there is some heterogeneity of pathologic findings, resected cases of LPSP typically demonstrate dense periductal lymphoplasmacytic inflammation, periductal and parenchymal fibrosis, and obliterative venulitis; neutrophilic infiltration of the ductal epithelium ("granulocytic epithelial lesions") may also occur. Large tumor-like masses of fibroinflammatory tissue ("reactive fibroinflammatory pseudotumors") may develop and extend beyond the pancreas. Following surgical resection, a few patients suffer recurrence of fibroinflammatory lesions in the pancreatobiliary tree, or they may develop other manifestations of autoimmune disease elsewhere in the body. However, the overall prognosis is excellent. Response to steroid therapy has been noted. Current studies are focusing on identifying additional preoperative diagnostic tests and on characterizing possible variants of LPSP. This review presents the defining clinical and pathologic features of LPSP and discusses the ongoing efforts to understand the pathogenesis of this disease.

Lymphoplasmacytic sclerosing pancreatitis with obstructive jaundice: CT and pathology features.

The clinical presentation of lymphoplasmacytic sclerosing pancreatitis (LPSP) can be very similar to that of pancreatic cancer, with no statistically significant differences in the rates of abdominal pain, weight loss, jaundice, or levels of carcinoembryonic agent or cancer antigen 19-9. The purpose of this study is to describe and illustrate the CT features of LPSP presenting with obstructive jaundice and to correlate CT and pathology findings. Five patients with LPSP were evaluated. Morphologic features of the pancreas on CT scans, including the size of the pancreas, presence or absence of a mass, segmental difference of contrast enhancement, pancreatic duct, major pancreatic vasculature, and biliary tract, were retrospectively evaluated and correlated with histopathology. The degree of contrast enhancement of the pancreas was compared in 10 patients without LPSP, who were scanned with the same protocol. CT scans showed diffuse (n = 2) or focal (n = 3) enlargement of the pancreatic head. The normal lobular appearance of the pancreas was effaced, and the gland appeared featureless in the involved region. Enlarged areas showed an enhancement pattern similar to that of the rest of the pancreas, and no segmental difference of contrast enhancement was identified. Pancreatic duct dilatation was not seen in any patient. Thickening and contrast enhancement of the common bile duct wall (n = 4) and gallbladder wall (n = 3) were observed and were pathologically correlated with inflammatory infiltrate and fibrosis of the common bile duct (n = 3) and gallbladder (n = 1). When these findings are encountered, further evaluation with serologic tests or biopsy may aid in the diagnosis of LPSP.

ENDOSONOGRAPHIC FEATURES OF LYMPHOPLASMACYTIC SCLEROSING PANCREATITIS

The role of endoscopic ultrasound (EUS) in the evaluation of pancreatic disorders is well established. However, little information on the endosonographic features of uncommon pancreatic diseases is available. We describe the case of a rare form of autoimmune chronic pancreatitis evaluated with EUS. Clinical Vignette: A 31 year-old Mexican male was referred to our institution with jaundice and a common bile duct (CBD) stricture on endoscopic retrograde cholangiopancreatography (ERCP). The patient described a three-month history of malaise, abdominal pain, a forty-pound weight loss, and the recent onset of jaundice; on ERCP he had a 6 cm distal biliary stricture with proximal dilation of the biliary tree. EUS was performed revealing severe changes of chronic pancreatitis including marked lobularity, prominent interlobular septae and a diffusely inhomogeneous echo pattern, features suggestive of diffuse fibrosis. The pancreatic duct was hardly visible. At the level of the pancreatic head, these changes coalesced into a mass-like lesion which involved the distal CBD and produced near-complete biliary obstruction. No lymphadenopathy was present. Concerned for the possibility of an underlying malignancy, no EUS-guided fine needle aspiration (FNA) was performed and the patient was taken for pancreaticoduodenectomy. Histopathologic examination of the surgical specimen demonstrated diffuse lymphoplasmacytic infiltration of the pancreas with marked acinar atrophy, obliterated phlebitis, and extensive fibrosis. The CBD and gallbladder showed marked inflammatory wall thickness. These features were compatible with lymphoplasmacytic sclerosing pancreatitis (LPSP). Serologic markers for autoimmune disease were negative. The patient recovered satisfactorily from the procedure and was discharged home. His follow-up at 21 months has included the development of insulin-requiring diabetes, an episode of acute pancreatitis of the remaining gland, and the need for chronic immunosuppressive therapy. Conclusion: Lymphoplasmacytic sclerosing pancreatitis is a rare form of autoimmune pancreatitis that can only be accurately diagnosed with histopathology. However, the clinical and endosonographic features (including the information obtained with EUS-guided FNA) can provide important clues to consider this disease in the differential diagnosis of patients with chronic pancreatic disorders.

Results of pancreaticoduodenectomy for lymphoplasmacytic sclerosing pancreatitis.

To compare the presentation and short-term results of pancreaticoduodenectomy for lymphoplasmacytic sclerosing pancreatitis (LPSP) and pancreatic adenocarcinoma (PA) and to provide long-term follow-up on patients undergoing resection for LPSP. LPSP is a rare form of chronic pancreatitis characterized by a mixed inflammatory infiltrate centered around pancreatic ducts and ductules, combined with obliterative phlebitis. Its presentation may mimic that of PA. Among 1,648 patients undergoing pancreaticoduodenectomy at the authors' institution from January 1992 to May 2002, 37 with LPSP were identified. The demographics, clinical features, and short- and long-term outcomes of these patients were analyzed. Where applicable, comparisons were made to a consecutive group of 45 patients who underwent pancreaticoduodenectomy for PA from July 2001 to December 2001. Twenty-four percent (9/37) of the LPSP patients and none of the PA patients had a history of either atopic or autoimmune disease. The LPSP patients had a similar clinical presentation to the PA patients, but the LPSP patients were less likely to have a discrete pancreatic mass on CT and more likely to have CT findings suggesting a diffusely enlarged pancreas. The LPSP patients were also less likely to have a discrete pancreatic mass at operation, more likely to have a diffusely firm or hard gland, and more likely to have a difficult portal vein/superior mesenteric vein dissection when compared to the PA patients. Transfusion requirement, operative time, postoperative length of stay, and overall complication rate were similar between groups; however, the LPSP patients had a greater operative blood loss. The median length of follow-up for LPSP patients was 33 months. No patients had recurrent jaundice. One patient with LPSP had clinically evident recurrent pancreatitis. Among LPSP patients available for current telephone interview, 68% subjectively rated their quality of life as better, 18% reported no change, and 14% reported diminished quality of life compared to before surgery. LPSP mimics PA in clinical presentation, though CT findings of a diffusely enlarged pancreas without a discrete mass may suggest a diagnosis of LPSP. Nevertheless, differentiation from pancreatic neoplasia remains difficult. Patients undergoing pancreaticoduodenectomy for LPSP have durable relief of symptoms and a subjectively improved quality of life.

Lymphoplasmacytic chronic cholecystitis and biliary tract disease in patients with lymphoplasmacytic sclerosing pancreatitis.

Lymphoplasmacytic sclerosing pancreatitis (LPSP) represents a distinctive form of chronic pancreatitis characterized by diffuse fibroinflammatory infiltrates that can involve both the pancreatic ducts and acinar parenchyma. Several cases of inflammatory infiltrates within the gallbladder have been reported in association with LPSP, but the spectrum of gallbladder pathology in patients with LPSP has not been systematically reviewed. Many patients with LPSP have distal CBD fibrosis, strictures, and inflammation, features that overlap somewhat with primary sclerosing cholangitis (PSC). In PSC, a pattern of gallbladder pathology termed "diffuse acalculous lymphoplasmacytic chronic cholecystitis" has been previously described as showing a triad of diffuse, mucosal-based, plasma cell-rich inflammatory infiltrates. We studied 20 gallbladders from patients with LPSP and compared them with 20 gallbladders in PSC, 20 gallbladders with chronic cholelithiasis, and 10 gallbladders from patients with benign (non-LPSP) pancreatic disease. The following features were evaluated: degree and composition of mucosal inflammation and deep (mural) inflammation, lymphoid nodules, metaplasia, dysplasia/neoplasia, fibrosis, muscular hypertrophy, Rokitansky-Aschoff sinuses, and cholesterolosis. The majority (60%) of gallbladders in LPSP contained moderate or marked inflammatory infiltrates and lymphoid nodules, frequencies similar to PSC but significantly higher than in chronic cholelithiasis and benign non-LPSP pancreatic disease. LPSP gallbladders received the highest scores for deep inflammation of all groups, and 35% of LPSP gallbladders showed transmural chronic cholecystitis. Overall, "diffuse lymphoplasmacytic chronic cholecystitis" was present in 50% of PSC cases and 25% of LPSP cases, but in only 5% of chronic cholelithiasis and none of non-LPSP benign pancreatic disease. Mucosal inflammation in LPSP gallbladders correlated significantly with the presence of inflammation in the extrapancreatic portion of the CBD. These findings suggest that inflammatory pathology of the gallbladder is frequently associated with LPSP and that it is part of the spectrum of biliary tract disease in these patients, rather than a simple reflection of the pancreatitis itself.

Idiopathic tumefactive chronic pancreatitis: Clinical profile, histology, and natural history after resection

Background & Aims: Little is known about subjects with idiopathic tumefactive chronic pancreatitis (TCP), that is, chronic pancreatitis whose clinical presentation, usually with a mass or obstructive jaundice, suggests cancer. Methods: We independently reviewed clinical data and histology of 45 TCP (27 idiopathic, 18 alcohol induced) resected at Mayo Clinic (January 1985-March 2001). Follow-up data were obtained from medical records and mailed questionnaires. Results: Compared with alcoholic subjects, idiopathic TCP patients were older (58 ± 2 vs. 48 ± 3 yr, P < 0.001), had shorter symptom duration (median 3 vs. 24 wk, P < 0.001), were more likely to have no or mild abdominal pain (70% vs. 17%, P = 0.001), and were more often jaundiced (67% vs. 33%, P = 0.02). Three distinct histologic patterns were identified in TCP. Typical CP (n = 19) showed lobular atrophy, fat necrosis, and ductal changes (dilatation, protein plugs, and stones). Lymphoplasmacytic sclerosing pancreatitis (LPSP) (n = 14) was characterized by periductal lymphoplasmacytic infiltration, obliterative phlebitis, and cholangitis with edema. Idiopathic duct-centric CP (IDCP) (n = 12) had neutrophil-predominant lobular inflammation, without phlebitis. On correlation of clinical and histologic diagnosis, 17 of 18 (94%) patients with alcohol-induced TCP had typical CP, and 25 of 27 (93%) with idiopathic TCP had LPSP or IDCP. LPSP and IDCP were indistinguishable clinically except for higher incidence of jaundice in LPSP (93% vs. 42%, P = 0.005). In idiopathic TCP no recurrence of symptoms was observed after resection (median follow-up 49 mo). Conclusions: Idiopathic TCP is clinically and histologically distinct from alcohol-induced TCP. It is unclear whether LPSP and IDCP, 2 unique patterns of histologic injury observed in idiopathic TCP, are part of the spectrum of the same disease or represent 2 or more different entities. Resection of mass prevents recurrence of symptoms in idiopathic TCP.