CASE 01LA Path Slide Seminar

13 March, 08

Deepti Dhall, MDDepartment of Pathology and

Laboratory MedicineCedars-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 sclerosingPancreatitis (LPSP)

Autoimmune pancreatitis

• First described by Sarles in 1961 as primary inflammatory sclerosingpancreatitis

• 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

Histological features

• Venulitis

• NO– Fat necrosis – Calcifications – Pseudocysts

Vein

Vein

Diagnostic criteria for autoimmunepancreatitis 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.

– LPSP, classical type– LPSP with

granulocytic epithelial lesions (GELs) / Idiopathic duct-centric chronic pancreatitis (IDCP).

Notahara et al. Am J Surg Pathol. 27: 1119-27, 2003

Zamboni et al. Virchows Arch. 445; 552-63, 2004

Subtypes of LPSP

Histological subtypes

M=F

M>F

Sex

Less commonInflammatory bowel disease

Mid 40’s

LPSP with GELs

More commonSjogren’s syndrome60’sLPSP,

classical

RecurrenceAfter resection

Associated autoimmune

diseaseAgeType of

LPSP

LPSP vs. Alcoholic Chronic Pancreatitis

Modified from: Ectors et al. Gut 41:263-8, 1997

YesNoPseudocysts

YesNoCalculi

AbsentPresentVenulitis

Sparse, scatteredDense, periductalInflammation

Large interlobular ducts

Medium sized interlobular ducts

Involved ducts

Alcoholic chronic pancreatitis

LPSPHistological Finding

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

AdenocarcinomaNon-specific

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