CASE 01 LA Path Slide Seminar 13 March, 08 Deepti Dhall, MD Department of Pathology and Laboratory Medicine Cedars-Sinai Medical Center
Clinical History 60 year old male presented with obstructive jaundice CT scan showed an ill-defined 4cm mass in the head of the pancreas FNA was inconclusive The patient underwent whipple resection
Lymphoplasmacytic sclerosing Pancreatitis (LPSP) Autoimmune pancreatitis
First described by Sarles in 1961 as primary inflammatory sclerosing pancreatitis Yoshida in 1995 used the term autoimmune pancreatitis Association with autoimmune diseases (30% of cases) Supporting laboratory finding Sarles et al. Am J Dig Dis. 1961 Jul;6:688-98 Yoshida et al. Dig Dis Sci. 1995 Jul;40(7):1561-8.
Distinct clinicopathological features: Clinical presentation is misleading, mimics pancreatic carcinoma Characteristic histological features May respond to steroids True incidence is not known 5% to 11% of all patients with chronic pancreatitis
Clinical Features Typically affects middle aged patients No history of alcohol abuse Associated with autoimmune diseases Usually presents with jaundice and abdominal pain Severe abdominal pain of acute pancreatitis is lacking
Radiological findings ERCP, ultrasound and CT reveal segmental stenosis of the pancreatic ducts distal bile duct stricture diffuse pancreatic enlargement ill-defined mass
LPSP Adenocarcinoma
Histological features Dense periductal lymphoplasmacytic infiltrate Interstitial and periductal fibrosis
Vein Histological features Venulitis NO Fat necrosis Calcifications Pseudocysts Vein
Diagnostic criteria for autoimmune pancreatitis proposed by Japanese Pancreas Society (2002) 1. Pancreatic imaging studies show diffuse narrowing of the main pancreatic duct with irregular wall (more than 1/3 of length of the entire pancreas) 2. Laboratory data demonstrate abnormally elevated levels of serum gamma globulin and/or IgG 4, or the presence of autoantibodies 3. Histopathologic examination of the pancreas shows fibrotic changes with lymphocyte and plasma cell infiltrate.
Subtypes of LPSP LPSP, classical type LPSP with granulocytic epithelial lesions (GELs) / Idiopathic ductcentric chronic pancreatitis (IDCP). Notahara et al. Am J Surg Pathol. 27: 1119-27, 2003 Zamboni et al. Virchows Arch. 445; 552-63, 2004
Histological subtypes Type of LPSP Age Sex Associated autoimmune disease Recurrence After resection LPSP, classical 60 s M>F Sjogren s syndrome More common LPSP with GELs Mid 40 s M=F Inflammatory bowel disease Less common
LPSP vs. Alcoholic Chronic Pancreatitis Histological Finding Involved ducts Inflammation Venulitis Calculi Pseudocysts LPSP Medium sized interlobular ducts Dense, periductal Present No No Alcoholic chronic pancreatitis Large interlobular ducts Sparse, scattered Absent Yes Yes Modified from: Ectors et al. Gut 41:263-8, 1997
LPSP Peri-tumoral pancreatitis
High serum IgG4 concentrations in patients with sclerosing pancreatitis. Hamano et al. N Engl J Med. 2001 Mar 8;344(10):732-8. Sensitivity 95% Specificity 97%
LPSP, CLASSICAL
Non-specific Adenocarcinoma
Endoscopic ultrasound guided fine needle aspiration biopsy of autoimmune pancreatitis: diagnostic criteria and pitfalls. 16 patients with AIP (11 pts with resection) Compared with 16 PDA cases and 19 NOS CP 3 false positive diagnosis Stromal fragments with embedded lymphocytes (greater than 30 per 60x) were seen in 37.5% of AIP cases and only rarely with adenocarcinoma (12.5%) and pancreatitis, NOS (0%). - The cellularity of stromal fragments was significantly higher in AIP than in the control group Deshpande V - Am J Surg Pathol - 01-NOV-2005; 29(11): 1464-71
Is autoimmune pancreatitis a systemic disease? Involves lung, biliary system, renal tubules, gall bladder and salivary glands Kamisawa. Am J Gastroenterology 2003 Deshpande V at al. Arch Pathol Lab Med. 2005 Sep;129(9):1148-54.
Summary Autoimmune pancreatitis is a distinct clinicopathological entity Easily confused with pancreatic carcinoma Serological markers including serum IgG4 may be very helpful The histological pattern in the pancreatic biopsy and IgG4 stain may contribute to the diagnosis Since most cases respond to steroids, an unnecessary pancreatic resection can be avoided
Questions? Is AP more common than previously thought and whether more cases will be diagnosed through increased clinical awareness? Does AP represents a systemic disease as apposed to a primary disease? Natural history of the disease after treatment or without treatment, needs to be better understood