Case 4 -
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Autoimmune pancreatitis, Fine-needle aspiration, Autoimmune
disease, Chronic pancreatitis
This 77-year old African American woman presented to her
physician complaining of a 25 pound weight loss, abdominal discomfort and a skin rash. The rash was
present on her back, hands, and legs, most prominently on the extensor surfaces. An abdominal CT scan
showed a 5.5 cm lobulated pancreatic mass. The virtual slide is a Papanicolaou-stained smear of the
pancreatic mass ultrasound-guided fine needle aspirate specimen.
Case 4 - Slide 1
Negative for malignant cells. Lymphocytes present.
Chronic pancreatitis with fibrosis.
The fine needle aspirate specimen is moderately
cellular and consists of cellular stromal fragments in a lymphocytic background. At higher
magnification, the stromal fragments contain bland spindled mesenchymal cells with a lymphocytic
infiltrate. Rare plasma cells are also present in the stromal fragments. Of note, there is an absence
of normal benign pancreatic ductal and acinar epithelium. No granulomas are seen.
Autoimmune pancreatitis, though a more recently described
entity, is important to recognize whenever possible in fine needle aspirate specimens from endoscopic
ultrasound guided fine-needle aspirate biopsies. This cytologic diagnosis can be quite challenging,
given that the clinical and radiologic impression often suggest a diagnosis of pancreatic adenocarcinoma.
However, this distinction from both pancreatic adenocarcinoma and a chronic pancreatitis, not otherwise
specified, is particularly important, since resolution of symptoms occur following administration of
corticosteroid therapy. In addition, patients with autoimmune pancreatitis can be spared a surgical
procedure when the disease presents as a mass lesion.
Patients with autoimmune pancreatitis usually present as adults during the middle of the sixth decade
and are predominantly males (1.7-2.1:1). Preceding a diagnosis of autoimmune pancreatitis, patients may
a have concurrent autoimmune disease including Sjögren's syndrome, rheumatoid arthritis, retroperitoneal
fibrosis, inflammatory bowel disease or primary sclerosing cholangitis. Similar to patients with
pancreatic adenocarcinoma, patients with autoimmune pancreatitis often present to their physicians with
jaundice and weight loss. In addition, they may complain of a mild vague abdominal pain. Notably absent
are acute attacks of pain which are associated more commonly with acute pancreatitis.
Imaging modalities are crucial in contributing to the diagnosis of this entity. Computed tomography
(CT) scan may show either focal or diffuse enlargement of the entire pancreas. Focal enlargement, when
present, is most often in the pancreatic head. The presence of a mass-like lesion leads to a
consideration of pancreatic carcinoma in the differential diagnostic possibilities. When the pancreas is
diffusely enlarged, the findings are considered "sausage-like" or "bulky". This diffuse pancreatic
enlargement correlates with diffuse edema on gross examination. With the use of endoscopic retrograde
cholangiopancreatography (ERCP), the main pancreatic duct shows either focal or diffuse irregular
narrowing with concomitant strictures of the distal common bile duct. This narrowing of the ductal lumen
is attributed to the histologic findings of diffuse periductal inflammation. This bile duct narrowing
can lead to the jaundice seen in the majority of these patients. Similar to CT scans, endoscopic
ultrasonography (EUS) demonstrates a hypoechoic pancreas with either focal or diffuse enlargement.
Following visualization of the lesion by EUS, fine-needle aspiration can be accurately performed and
assist in the cytologic diagnosis of this entity.
Fine-needle aspiration biopsy of autoimmune pancreatitis demonstrates cytologic features which may
closely mimic those of chronic pancreatitis. Both ductal and acinar epithelium is usually inconspicuous
due to the paucity of cells present in a background of fibrosis. The most notable feature is the
presence of cellular stromal fragments with embedded lymphocytes (greater than 30 per 600x field). The
ERCP and serologic features are also useful in differentiating autoimmune pancreatitis from chronic
pancreatitis. Patients will have elevated serum levels of IgG4. Immunoglobulin G4 is the least common
of the IgG subtypes and accounts for approximately 3 – 6% of the total IgG in the serum of normal
subjects. It has an intermediate affinity for Fc, its target antigen, and is unique in that it does not
It is also important to distinguish a well-differentiated pancreatic adenocarcinoma from autoimmune
pancreatitis, due to their overlapping clinical and radiologic features. In addition, autoimmune
pancreatitis can be successfully treated with a course of corticosteroids, thereby avoiding a pancreatic
surgical procedure. Maintenance of a normal "honeycomb" pattern in any ductal epithelium on the slide,
as well as a lack of nuclear membrane irregularities, anisonucleosis and increased nuclear:cytoplasmic
ratios in any ductal epithelial cells favor a non-neoplastic etiology. It has been reported that in
cases of pancreatic adenocarcinoma in which stromal fragments are present within the fine-needle aspirate
specimen, frankly malignant epithelial cells can usually be identified adjacent to the stroma.
The diagnosis of autoimmune pancreatitis by core biopsy can likewise be difficult. Focal to diffuse
fibrosis of the pancreatic stroma with acinar atrophy and a diffuse lymphoplasmacytic infiltrate support
the diagnosis of autoimmune pancreatitis, though they are not pathognomonic of it. Further excisional
pancreatic biopsy or pancreatoduodenectomy of autoimmune pancreatitis histologically show a collar of
periductal lymphoplasmacytic inflammation with occasional eosinophils along with periphlebitis or
obliterative phlebitis. Of note, granulomas may also be present. However, unlike the granulomas present
in sarcoidosis or those with an infectious etiology, these granulomas have a periductal distribution and
do not involve lymph nodes. Immunostaining for IgG4 demonstrates staining of plasma cells, often present
in a periductal distribution. The lymphoplasmacytic infiltrate is present within a myofibroblastic-like
stroma surrounding both large and small interlobular pancreatic ducts. The myofibroblastic proliferation
may extend into the peripancreatic soft tissue and coalesce to form a tumor-like lesion (pseudotumor).
It is also important to exclude features of chronic alcoholic pancreatitis in these cases. These
features include pseudocysts, calcifications, autodigestive necrosis and ductal dilation with mucous
Fine-needle aspiration of the pancreas can help to exclude a pancreatic adenocarcinoma and suggest
autoimmune pancreatitis. This is of great clinical benefit to the patient, as autoimmune pancreatitis
will respond well to corticosteroid therapy and the patient can be spared a pancreaticoduodenectomy.
Associated conditions such as Sjögren's syndrome, rheumatoid arthritis and ulcerative colitis, as well as
an elevated serum IgG4 level may assist in the differential diagnosis. Also, core biopsy and resection
specimens often show IgG4 immunostaining of the cytoplasm of plasma cells in a ductulocentric
distribution. However, the utility of immunostaining of IgG4 in fine-needle aspirate biopsy specimens
has not been described. The presence of IgG4-positive plasma cells outside the pancreas, including the
common bile duct, liver, salivary glands, and ampulla of Vater has been documented and supports the
hypothesis that autoimmune pancreatitis is part of a multisystem disease.
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