Isolated Lymphoplasmacytic Sclerosing Pancreatitis Involving the Pancreatic Tail

Written By: Sam Savage

Published Date: August 29, 2008 Last Edited: August 29, 2008

By Kim, Tad Grobmyer, Stephen R; Dixon, Lisa R; Hochwald, Steven N

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 (LPSP), also referred to as autoimmune pancreatitis, is a unique form of pancreatitis characterized by irregular narrowing of the main pancreatic duct, enlargement of the pancreas, lymphoplasmacytic inflammation, and responsiveness to steroid therapy.1 LPSP presents most commonly with obstructive jaundice and can clinically mimic pancreatic adenocarcinoma or cholangiocarcinoma.2, 3 It has previously been shown that approximately 2.5 per cent of pancreaticoduodenectomies performed for presumed malignancy were in fact cases of LPSP.4 Most cases are diagnosed after resection and subsequent pathologic examination due to the difficulty in distinguishing LPSP from pancreatic or biliary adenocarcinoma.

Several different sets of criteria exist for the diagnosis of LPSP.5 Commonly cited criteria include: 1) imaging to demonstrate narrowing of the main pancreatic duct, 2) elevated IgG4 levels or autoantibodies, 3) histopathology revealing lymphoplasmacytic infiltration and fibrosis, and 4) response to steroids.6, 7 Although imaging is important, it is by itself not sufficiently sensitive enough to preoperatively diagnose LPSP and distinguish this from malignancy. Demonstration of serum IgG4 elevations can help confirm the diagnosis and possibly help avoid unnecessary surgery.8, 9

We recently reported a retrospective analysis of seven consecutive patients with LPSP compared with 23 patients with pancreatic malignancy. Six of the seven LPSP patients presented with obstructive jaundice, and five of the seven LPSP patients were found to have a discrete pancreatic mass on imaging-all but one of which were in the head of the pancreas. We found that the median IgG4 levels were significantly higher in patients with LPSP compared with those with carcinoma and that, interestingly, these levels in our Western population were not elevated to the extent seen in Japan.10

Thus, consistent with other published reports, our experience has shown us that pancreatic lesions in LPSP most commonly occur in the head of the pancreas, and these patients can present identically to pancreatic adenocarcinoma or cholangiocarcinoma.11, 12 Also, we found that serum IgG4 determination may help us avoid unnecessary operation in patients who may respond to steroid treatment. However, the typical imaging features of the narrowing of the pancreatic duct and/or diffuse pancreatic enlargement are not present in all cases of LPSP. There are also atypical imaging criteria, as described by Chari et al.,11 and these include pancreatitis, focal pancreatic mass, focal pancreatic duct stricture, pancreatic atrophy, and pancreatic calcification. In concordance with this, we present an unusual case of a patient with LPSP who presented with a pancreatic tail mass.

Case

Clinical Information

A 62-year-old type II diabetic female presented with a 3-month history of intermittent, vague, left-sided abdominal pain. She had no symptoms of jaundice, weight loss, or anorexia. She reported no past history of pancreatitis or autoimmune conditions. Past medical history consisted of diabetes, hypertension, and gastroesophageal reflux disease. Physical examination was unremarkable overall with a soft, nontender abdomen and no palpable lymphadenopamy. An extensive work-up was initiated, including a computed tomography (CT) scan of the abdomen and pelvis, which revealed a hypodense mass in the tail of the pancreas most consistent with pancreatic adenocarcinoma. She was consented for and underwent an open distal pancreatectomy and splenectomy.

Radiological Findings

Contrasted CT scan of the abdomen revealed a 3.3 cm x 2.4 cm hypodense mass in the tail of the pancreas with minimal enhancement on the delayed phase and no arterial enhancement. There was no evidence of calcification within the pancreas. The intra and extrahepatic bile ducts and pancreatic duct were not dilated. There was no evidence of local invasion or metastatic disease. The findings were most consistent with adenocarcinoma of the tail of the pancreas (Fig. 1).

Laboratory Findings

The serum IgG4 level was 133 mg/dL, above the upper threshold of normal (range 6-89 mg/dL). Her serum cancer antigen (CA) 19-9 level was normal (33 mg/dL).

Intraoperative Details

We initially performed an exploratory laparoscopy, and there was no evidence of liver metastases or peritoneal disease. We proceeded with an open exploration and identified a hard, gritty mass in the tail of the pancreas. The pancreas proximal to this mass was soft and normal in appearance. Our differential diagnosis at this point was malignancy versus focal pancreatitis. We proceeded with a distal pancreatectomy and splenectomy.

FIG. 1. CT scan demonstrating hypodense mass in the tail of the pancreas (arrow).

Macroscopic Findings

Grossly, there was a firm, well circumscribed nodule measuring 1.4 cm x 2.2 cm x 2.9 cm in the tail of the pancreas with no evidence of invasion into surrounding tissue. The remaining pancreas was finely lobulated and appeared normal.

Microscopic Findings

Histologically, this lesion showed dense fibrosis surrounding pancreatic ductal structures and a predominantly plasmacytic inflammatory infiltrate. Venulitis and reactive ductal changes were present, and the surrounding uninvolved parenchyma was atrophic. Areas of necrosis with surrounding inflammation were noted. Immunohistochemical (CD20 and CD3) and in situ hybridization studies were performed, confirming that this was not a lymphoproliferative process. The final diagnosis was autoimmune pancreatitis or LPSP (Fig. 2).

Postoperative Course and Follow-Up

The patient’s postoperative course was unremarkable and on 2- week follow-up, she reported feeling well without anymore episodes of abdominal pain. She has not developed any other autoimmune diseases in the following 10 months.

Discussion

Lymphoplasmacytic sclerosing pancreatitis is a rare condition that can affect patients of a wide age range, from 14 to 70 years, with most patients being older than 50 years.11 Based on several large series, there seems to be a 2:1 to 4:1 predominance in men.2, 3, 11-13 The clinical presentation is variable, but most commonly includes obstructive jaundice, weight loss, and abdominal pain.11 Radiographic findings are also variable with some patients demonstrating diffuse enlargement of the pancreas, but with other patients demonstrating a focal mass.14, 15

FIG. 2. Histopathologic findings in LPSP: a) Periductal infiltrates composed of lymphocytes and plasma cells; b) Plasma cells and Russell bodies (arrowheads [black right triangle]); and c) Intense lymphoplasmacytic infiltrate surrounding a smaller duct.

Various sets of criteria have been created to improve our diagnosis of this rare condition, and each has its strengths and weaknesses. By the Japan Pancreas Society criteria (Table 1), our patient did not meet the requirements to diagnose LPSP, whereas by the HISORt criteria (Table 2), which accounts for atypical imaging features (i.e., discrete pancreatic lesion), our patient did meet criteria to diagnose LPSP.

When LPSP does present with a discrete pancreatic lesion, it is most commonly in the head of the pancreas.16, 17 In fact, approximately 80 per cent of LPSP involves the head.3, 14 There are series in the literature reporting incidences of LPSP involving the pancreatic tail anywhere from 0 to 22 per cent and only two previous case reports of LPSP presenting with tail masses (Table 3).3, 12, 13, 17-20 Plaza et al.21 reported a case of a patient presenting with left flank pain and thickening of the pancreatic tail found on MRI; the radiographic differential included chronic pancreatitis and pancreatic adenocarcinoma. She underwent distal pancreatectomy and was found to have LPSP on histopathologic examination. Taniguchi et al.22 reported a case of LPSP in a patient who was referred with a 3 cm hypoechoic lesion in the tail of the pancreas. CT imaging demonstrated swelling of the pancreatic tail, with greater enhancement on the delayed phase-a feature uncharacteristic of pancreatic cancer. The patient was treated with and responded well to steroids, avoiding surgery. Serum IgG4 levels can help differentiate LPSP from pancreatic cancer. In 2001, Hamano et al.8 published their seminal findings describing patients with autoimmune pancreatitis who had significantly higher levels of serum IgG4 than patients with pancreatic cancer. The authors reported accuracy, sensitivity, and specificity of 97 per cent, 95 per cent, and 97 per cent, respectively, in using IgG4 levels to diagnose LPSP. The Western experience includes a Mayo Clinic study by Ghazale et al.23 of 45 patients with LPSP, which reported sensitivity, specificity, and positive predictive values of 53 per cent, 99 per cent, and 75 per cent for IgG4 of >280 mg/dL in diagnosing LPSP.

TABLE 1. Diagnostic Criteria of LPSP 2006 by the Japan Pancreas Society

TABLE 2. HISORt Diagnostic Criteria for LPSP

TABLE 3. Reports Describing Location of Pancreatic Involvement with LPSP

We have reported a series of seven cases of LPSP demonstrating IgG4 elevation above 100 mg/dL compared with controls with median IgG4 levels of 24 to 28 mg/dL; however five of these cases had levels below the technical upper limit of normal.10 Interestingly, Deheragoda et al.24 reported a series of 11 patients, six of whom did not demonstrate elevated serum IgG4. Subsequent immunostaining of pancreatic and extrapancreatic tissue showed increased numbers of IgG4-positive plasma cells (>10/high power field) in five of those six patients without serum IgG4 elevation. The diagnostic yield was improved from less than 20 per cent to 73 per cent. Based on the above data, it seems that in LPSP, median IgG4 levels in the United States are elevated but to a smaller extent compared with levels seen in Japan. This would suggest the need for either decreasing the upper limit threshold for serum IgG4, or performing more accurate differentiation of total IgG levels with the subfractions including IgGl, IgG2, IgG3, and IgG4. After biopsy or surgical resection has been performed, adding IgG4 immunostaining to our diagnostic armamentarium may be of assistance.

In conclusion, our one case demonstrates the difficulty of differentiating LPSP from pancreatic cancer, due to both similar clinical presentation and radiographic appearance. Although LPSP most commonly presents with obstructive jaundice and pancreatic head involvement, a discrete, isolated mass in the tail of the pancreas is also possible. Serum IgG4 may be a useful adjunct to increase the accuracy of diagnosing LPSP. Novel strategies are needed to assist in the preoperative diagnosis of LPSP to help reduce otherwise unnecessary operations in this benign condition.

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TAD KIM, M.D.,* STEPHEN R. GROBMYER, M.D.,* LISA R. DIXON, M.D.,[dagger] STEVEN N. HOCHWALD, M.D.*

From the * Division of Surgical Oncology and the [dagger] Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, Florida

Presented at the Annual Scientific Meeting and Postgraduate Course Program, Southeastern Surgical Congress, Birmingham, AL, February 9-12, 2008.

Address correspondence and reprint requests to Steven N. Hochwald, M.D., Division of Surgical Oncology, University of Florida College of Medicine, 1600 SW Archer Road, P.O. Box 100286, Gainesville, FL 32610. E-mail: steven.hochwald@ surgery.ufl.edu.

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