Diffuse Pancreatic Disease

Etiology

Cystic fibrosis is a life-threatening disorder caused by mutation in the cystic fibrosis transmembrane conductance regulator gene (CFTR) on chromosome 7.

Prevalence and Epidemiology

Cystic fibrosis is an autosomal recessive disorder that is more prevalent in whites, with an incidence of approximately 1 in 2500 (in this population).

Clinical Presentation

Although predominantly characterized by chronic obstructive lung disease and pancreatic insufficiency, cystic fibrosis is a multiorgan disease affecting the liver, gallbladder, bile ducts, intestines, and the reproductive tract. The clinical and imaging findings vary with severity and duration of disease process in all age groups. Nearly 85% to 90% of patients will present with clinical signs within 1 year of life. Significant loss of pancreatic exocrine cells must be present before development of typical clinical symptoms of insufficiency such as steatorrhea, fat intolerance, failure to thrive, bloating, flatulence, and abdominal pain. Pancreatic function may be preserved in 10% to 15% of patients, and when residual exocrine function is present, patients may present with acute pancreatitis. Endocrine dysfunction is less commonly encountered.

Pathophysiology

The defective transmembrane ion transport in cystic fibrosis leads to accumulation of thick, viscous pancreatic secretions in the pancreatic ducts, leading to ductal ectasia and acinar atrophy. Inflammatory reaction, progressive fatty replacement, fibrosis, and calcification result, with extensive atrophic change occurring in severe long-standing disease. Cyst formation can occur secondary to inspissated secretions obstructing the small pancreatic ducts.

Imaging

The patterns of pancreatic involvement include (1) partial fibrofatty replacement of the pancreas, (2) complete fibrofatty replacement with enlargement of pancreas (lipomatous pseudohypertrophy), (3) pancreatic atrophy without evidence of fatty replacement, (4) diffuse pancreatic fibrosis, and (5) pancreatic cystosis. In pancreatic cystosis, cysts are usually multiloculated with individual cysts measuring 0.5 to 12 cm in diameter. Complete fatty replacement of the pancreas is commonly seen, with fat replacement maintaining the shape of the pancreas. This morphologic finding may be evident in older patients and represents late stage of disease, but it also can be seen earlier with severe involvement.

Ultrasonography.

On ultrasonography, the involved pancreas reveals homogeneously or heterogeneously increased echogenicity ( Figure 51-6, A ). The pancreas may be normal or small in size, and the typical fine lobular echotexture of the pancreas is gradually lost. Pancreatic cystosis is seen as multiple, thin-walled, anechoic, multiloculated cysts scattered throughout the pancreas with interspersed hyperechoic pancreatic parenchyma (see Figure 51-6, B ). Ultrasonography is not sensitive for detecting and estimating the extent of pancreatic involvement.

Computed Tomography.

Fatty replacement of the pancreas ( Figure 51-7 ) and fibrosis appears hypodense on computed tomography (CT); measurement of Hounsfield units will differentiate the two processes. A small atrophic pancreas can be seen ( Figure 51-8 ). Calcification, when present, is better appreciated on CT. The cystic lesions appear as well-defined low-attenuation structures without any solid portions or excrescences ( Figure 51-9 ).

Magnetic Resonance Imaging and Magnetic Resonance Cholangiopancreatography.

Fatty changes reveal hyperintense signal Figure 51-10 ), whereas areas of fibrosis show as hypointense signal on T1- and T2-weighted images. Cysts appear as hypointense on T1-weighted images and hyperintense on T2-weighted images. Although magnetic resonance imaging (MRI) is more sensitive in detection of additional small cysts compared to CT or ultrasound, no additional clinically important information is added. Exocrine dysfunction and appearance on MR may not correlate, and a normal-appearing pancreas can be seen in patients with dysfunction. Beading, strictures, poststenotic dilatation, and obstruction of pancreatic duct also may be present and are best characterized on magnetic resonance cholangiopancreatography (MRCP).

Classic Signs

Cystic Fibrosis

• Fatty replacement

• Cystic changes

• Calcifications

• Fibrosis

• Atrophy

• Ductal stenosis and beading

Differential Diagnosis

With cystic changes, differential diagnosis may include cystic pancreatic neoplasms, polycystic kidney disease, and von Hippel-Lindau syndrome. With diffuse fatty change, lipomatosis may be indistinguishable, although clinical findings of recurrent respiratory infections, age, exocrine and endocrine dysfunction, family history, and positive sweat chloride test can aid in diagnosis.

Treatment

Etiology

Fatty replacement of the pancreas is commonly seen with obesity and aging. Metabolic syndrome, characterized by obesity, dyslipidemia, glucose intolerance, hypertension, and proinflammatory or prothrombotic state, is thought to have high association with fatty replacement. Other associated conditions include Cushing's syndrome, adult-onset diabetes mellitus, chronic pancreatitis, hereditary pancreatitis, alcoholic hepatitis, malnutrition, Shwachman-Diamond syndrome, and long-term use of corticosteroids.

Clinical Presentation

Fatty replacement does not cause clinical symptoms. Clinical presentation is according to the primary disease process.

Pathology

Mature adipocytes and bands of fibrous tissue replace the pancreatic tissue with sparing of acini and islets of Langerhans.

Imaging

Computed Tomography.

Uniform or patchy fatty replacement can be readily identified on CT, which reveals separation of pancreatic parenchyma with prominence of lobulations interspersed with fat. With patchy involvement, the spared regions can be mistaken as pseudotumors. Associated atrophy of the pancreas may be seen to a variable degree, particularly in elderly individuals ( Figure 51-11 ). Massive enlargement of the pancreas due to fatty replacement is known as lipomatous pseudohypertrophy.

Differential Diagnosis

Clinical diagnosis gives an insight to the cause of fatty replacement. In the presence of clinical diagnosis and imaging findings, no other diagnostic studies are required.

Treatment

No medical treatment is required or available. Sometimes lipomatous pseudohypertrophy can be mistaken as pancreatic mass and taken for surgical resection. Fatty replacement is reversible in obesity after weight reduction, in treated Cushing's syndrome, and with discontinuation of corticosteroids.

Etiology

Amyloidosis is a systemic disorder characterized by abnormal protein folding and extracellular deposition of insoluble fibrillar proteins. Three forms have been defined, with the primary form representing deposition of light-chain immunoglobulins secondary to plasma cell dyscrasias; the secondary form arising as a result of chronic diseases such as rheumatoid, sarcoid, or diabetes; and the familial form representing the autosomal dominant form of the disease with formation of abnormal proteins.

Clinical Presentation

Patients can present with exocrine or endocrine dysfunction or abdominal pain, in addition to the signs and symptoms of associated systemic illness.

Pathology

The pancreas can be involved in primary amyloidosis or, more commonly, as a part of amyloidosis secondary to chronic systemic disease processes. Affinity to Congo red with apple green birefringence under polarized light microscopy are pathognomonic for all amyloidosis.

Imaging

Although literature on characteristic imaging findings on pancreatic amyloidosis is scarce, pancreatic involvement can be focal or diffuse.

Differential Diagnosis

Differential diagnosis for diffuse involvement of the pancreas includes autoimmune pancreatitis, lymphoma, and acute pancreatitis. Involvement of other organ systems can indicate the diagnosis in secondary amyloidosis. Histopathologic evaluation with Congo red and immunostaining of tissue is required for differentiation from other clinical entities.

Treatment

Medical management involves treatment of the systemic disease process in secondary forms of amyloidosis.

Etiology

Hemochromatosis is a disorder of excessive iron accumulation.

Prevalence and Epidemiology

Hereditary hemochromatosis is prevalent in Northern European descent and is less common in blacks, Hispanics, and Asian-Americans. The disease is five times more common in men, and they usually experience symptoms at an earlier age. Because women lose iron with menstruation and pregnancy, they tend to store less iron than men. After menopause or hysterectomy, the risk for women is the same as that for men.

Clinical Presentation

Pancreatic involvement manifests as abdominal pain, in addition to the other systemic manifestations of hemochromatosis owing to involvement of heart, skin, liver, thyroid, joints, and other organ systems. Patients will typically present with abdominal pain, fatigue, joint pain, and loss of libido, among other symptoms related to iron deposition in multiple organs.

Pathophysiology

Hemochromatosis can be primary/hereditary or secondary. Hereditary hemochromatosis is an autosomal dominant disorder resulting from excessive absorption of iron; secondary hemochromatosis results from excessive ingestion of iron or from multiple transfusions. Hereditary hemochromatosis is mainly caused by a defect in the HFE gene, which helps regulate the amount of iron absorbed from food. The two common mutations involving the HFE gene are C282Y and H63D . Juvenile and neonatal hemochromatosis, two additional forms, are caused by a mutation in a gene called hemojuvelin.

Imaging

Magnetic Resonance Imaging.

Pancreatic involvement is uncommon without cirrhosis. On T2-weighted gradient recalled echo MRI, the liver and pancreas reveal markedly diminished signal intensity compared with that of skeletal muscles ( Figure 51-12 ). Hypointense signal also can be seen on spin echo T2-weighted images, although this sequence is less sensitive. The splenic signal is normal in primary hemochromatosis. On chemical shift in-phase and out-of-phase imaging, reversal of signal drop is seen in comparison to when there is intracytoplasmic fat, with signal drop out seen on in-phase imaging with iron deposition. Quantification of the liver iron content can be performed using T2-weighted gradient recalled echo images. By calculating the ratio of signal intensity of liver to that of fat, mounting iron overload can be serially evaluated.

Classic Signs

Hemochromatosis

• Hyperdense on CT (pancreas and lymph nodes)

• Hypointense on T2-weighted gradient recalled echo MRI

Differential Diagnosis

Systemic involvement of the heart, skin, liver, joints, thyroid, and other organ systems supports the imaging diagnosis. Findings of elevated serum iron concentration, total iron-binding capacity, and transferrin saturation values are characteristic. Liver biopsy is the gold standard for diagnosis.

Treatment