■
Non-neoplastic diseases
Developmental anomalies
The three most commonly encountered developmental anomalies of the pancreas in routine surgical pathology practice are pancreatic divisum, annular pancreas, and ectopic pancreas.
Pancreatic divisum
Clinical features
Pancreatic divisum occurs in 3% to 7% of the population and is the result of failure of the duct systems of the embryonic dorsal and ventral pancreatic buds to properly fuse. As a result, the ducts produced by the two pancreatic buds remain separate. The duct of Santorini becomes the major ductal system of the pancreas, and it drains into the duodenum through the diminutive minor papilla. It is believed that the small size of the minor papilla relative to the substantial flow of pancreatic secretions passing through it impedes the flow of pancreatic secretions and, in some patients, produces pancreatitis.
Definition
- ■
A developmental anomaly characterized by an embryologic failure of the duct systems of the dorsal and ventral pancreatic buds to fuse
Incidence and location
- ■
Relatively common, 3% to 5% of the general population
Gender, race, and age distribution
- ■
No gender predilection, both genders equally involved
- ■
Present at birth, but there is a wide range of age at clinical presentation from less than a year to 90 years; mean age 57 years
Clinical features
- ■
Mostly asymptomatic, incidental finding
- ■
Pancreatitis
Radiologic features
- ■
Abnormal ductal anatomy
Prognosis and therapy
- ■
Sphincterotomy of the minor papilla with mixed results
- ■
Patients may develop chronic pancreatitis.
Radiologic features
Endoscopic retrograde cholangiopancreatography can be used to demonstrate the abnormal ductal anatomy and to exclude other causes of the patient’s symptoms.
Pathologic features
Pancreatic divisum can best be appreciated through careful gross dissection of the duct system. A probe placed in the minor papilla will pass into a pancreatic duct that drains the full length of the gland. By contrast, a probe placed into the major papilla, that is, the papilla that also drains the bile duct, will enter a short duct only 1 to 2 cm in length. Pancreatic divisum is often associated with chronic pancreatitis; the microscopic appearance of this pancreatitis is etiologically nonspecific.
Gross findings
- ■
The pancreatic duct that opens at the minor papilla drains the bulk of the gland
- ■
The duct that drains at the major papilla goes only a short distance
Microscopic findings
- ■
Nonspecific, may show acute and chronic pancreatitis
Ultrastructural findings
- ■
Not applicable
Fine needle aspiration biopsy findings
- ■
Not applicable
Immunohistochemistry
- ■
Not applicable
Differential diagnosis
- ■
Other lesions associated with pancreatitis (see section on Pancreatitis)
Ancillary studies
As discussed earlier, careful gross dissection of the pancreatic duct system is the best way to establish the diagnosis of pancreatic divisum in a surgically resected specimen. Imaging of a resected pancreas following the injection of a radiopaque dye into the duct system can also be used to establish the diagnosis.
Differential diagnosis
The differential diagnosis includes other causes of pancreatitis (see section on Pancreatitis).
Prognosis and therapy
Sphincterotomy of the minor papilla has been used to treat some patients with mixed results. Some patients with longstanding pancreatic divisum develop chronic pancreatitis, and their prognosis will be determined by the severity of their pancreatitis.
Annular pancreas
Clinical features
Annular pancreas is a rare malformation in which the dorsal and ventral buds of the pancreas abnormally fuse, forming a ring of pancreatic parenchyma around the duodenum. This ring can cause duodenal obstruction later in life. Most patients present clinically at a young age (about 1 year), but some patients do not develop symptoms until adulthood. Children with annular pancreas can present with vomiting after meals and even abdominal distention. Abdominal radiographs sometimes reveal a classic “double-bubble” sign of intestinal obstruction.
Definition
- ■
A developmental anomaly of the pancreas resulting from abnormal fusion of dorsal and ventral pancreatic buds and the formation of a ring of pancreatic tissue around the duodenum, which may result in intestinal obstruction
Incidence and location
- ■
Rare
Gender, race, and age distribution
- ■
Younger age, mostly around 1 year
Clinical features
- ■
Vomiting after meals
- ■
Abdominal distention
Radiologic features
- ■
“Double-bubble” sign of duodenal obstruction
Prognosis and therapy
- ■
Surgical resection
- ■
Excellent prognosis
Pathologic features
The pathology of annular pancreas is straightforward. A bandlike ring of otherwise normal pancreatic parenchyma encircles the duodenum.
Gross findings
- ■
A bandlike ring of pancreatic parenchyma encircling the duodenum
Microscopic findings
- ■
Nonspecific
Ultrastructural findings
- ■
Not applicable
Fine needle aspiration biopsy findings
- ■
Not applicable
Immunohistochemistry
- ■
Not applicable
Differential diagnosis
- ■
Pyloric stenosis
- ■
Ectopic pancreas
- ■
Duodenal atresia
Ancillary studies
A careful gross dissection of resected specimens is the best way to establish the diagnosis. Clinical correlation with preoperative imaging studies and the finding at surgery are usually necessary to establish the diagnosis.
Differential diagnosis
The differential diagnosis would include other causes of obstruction such as pyloric stenosis, ectopic pancreas, and duodenal atresia.
Prognosis and therapy
Surgery resection of the obstruction is the treatment of choice. The prognosis following successful surgery is excellent.
Ectopic pancreas
Clinical features
Pancreatic parenchyma located outside of the normal pancreas is referred to as ectopic pancreas. Ectopic pancreas is found in 2% of the population. Although ectopic pancreas is usually an incidental finding, it can cause bleeding, and in rare instances, intestinal obstruction.
Definition
- ■
A developmental anomaly characterized by pancreatic parenchyma located outside of the normal anatomic location
Incidence and location
- ■
2% of the population
Clinical features
- ■
Usually incidental
- ■
May cause bleeding
- ■
May cause intestinal obstruction
Radiologic features
- ■
Mass lesion (rare)
Prognosis and therapy
- ■
Surgical resection
- ■
Excellent prognosis
Radiologic features
Ectopic pancreas only rarely forms a mass large enough to be detected radiographically.
Pathologic features
The duodenum is the most common location of ectopic pancreas. Other sites include the jejunum, Meckel’s diverticulum, and the ileum. By light microscopy, these foci are composed of collections of normal acini and ducts and frequently islets of Langerhans.
Gross findings
- ■
Abnormal mass in the duodenum, jejunum, Meckel’s diverticulum, or ileum
Microscopic findings
- ■
Collections of normal acini, ducts, and often islets of Langerhans
Ultrastructural findings
- ■
Not applicable
Fine needle aspiration biopsy findings
- ■
Nonspecific
Immunohistochemistry
- ■
Not applicable
Differential diagnosis
- ■
Metastases from a pancreatic primary tumor
Ancillary studies
Ancillary studies are not necessary to establish the diagnosis.
Differential diagnosis
A metastasis from a pancreatic primary tops the list for the differential diagnosis of ectopic pancreas. The absence of nuclear atypia and a mixed cell phenotype (acini, ducts, and islets) establish the diagnosis of ectopic pancreas.
Prognosis and therapy
Surgical resection is the treatment of choice and is usually curative.
Acute pancreatitis
Clinical features
Acute pancreatitis is a reversible inflammatory injury to the pancreas. It strikes approximately 20 per 100,000 population each year in Western nations. Most cases are caused by alcoholism or biliary tract disease. Patients present with epigastric pain that radiates to the back, and the diagnosis can be confirmed by demonstrating elevated serum amylase levels.
Definition
- ■
A reversible inflammatory process of the pancreas
Incidence and location
- ■
20 per 100,000 people each year in Western nations
Gender, race, and age distribution
- ■
Male-to-female ratio, 2.5:1
- ■
Mean age 52.5 years (range 9 to 100 years)
Clinical features
- ■
Epigastric pain that often radiates to the back
- ■
Elevated serum amylase
Radiologic features
- ■
Diffuse pancreatic enlargement
Prognosis and therapy
- ■
Supportive care
- ■
Prognosis varies, worse in older patients
Radiologic features
Ultrasonography and computed tomography (CT) reveal diffuse enlargement of the gland.
Pathologic features
The pancreas is usually enlarged and soft, and the pancreatic and peripancreatic fat contains chalky white foci of fat necrosis. In severe cases, there can be hemorrhage into the gland. Microscopic findings range from mild edema with scattered inflammatory cells, to extensive necrosis and hemorrhage ( Fig. 17-1 ).
Gross findings
- ■
Enlarged and soft pancreas
- ■
Chalky white foci of fat necrosis
- ■
Hemorrhage in more severe cases
Microscopic findings
- ■
Edema
- ■
Acute inflammation
- ■
Fat necrosis
Ultrastructural findings
- ■
Not needed
Fine needle aspiration biopsy findings
- ■
Not needed
Immunohistochemistry
- ■
Not needed
Differential diagnosis
- ■
Chronic pancreatitis
Ancillary studies
Elevated serum amylase levels support the diagnosis.
Differential diagnosis
The differential diagnosis for acute pancreatitis is narrow and includes chronic pancreatitis. Reversibility of the injury to the pancreas distinguishes acute pancreatitis from chronic pancreatitis. In chronic pancreatitis the injured pancreatic parenchyma has been replaced by scar tissue and therefore cannot resume normal function after the inflammatory process abates.
Prognosis and therapy
Ranson and colleagues have developed a list of clinical and laboratory factors that can be used to predict the prognosis of patients with pancreatitis. Adverse prognostic features include older age, elevated white blood cell count, and hyperglycemia. The treatment of acute pancreatitis primarily consists of “resting” the pancreas and supportive care.
Chronic pancreatitis
Chronic pancreatitis is defined as inflammatory injury to the pancreas associated with irreversible loss of exocrine or endocrine function. Most cases in the United States are caused by chronic alcohol abuse.
Clinical features
Patients present with exocrine and endocrine insufficiency, including diabetes mellitus and malabsorption with steatorrhea and weight loss.
Definition
- ■
An inflammatory process of the pancreas characterized by an irreversible loss of exocrine and endocrine function
Incidence and location
- ■
Not uncommon, 4 to 6 per 100,000 population
Gender, race, and age distribution
- ■
Males > females
- ■
Alcoholism is the most common cause in the United States
Clinical features
- ■
Diabetes mellitus
- ■
Malabsorption with steatorrhea
- ■
Weight loss
Radiologic features
- ■
Calcifications within the pancreas
- ■
Ductal dilatation
- ■
Small cysts
Prognosis and therapy
- ■
Mostly supportive with exocrine enzyme replacement and management of diabetes
- ■
Steroid therapy (for lymphoplasmacytic sclerosing subtype)
- ■
Poor long-term prognosis
Radiologic features
Calcifications within the pancreas can be visualized on plain abdominal radiographs. Ultrasonography demonstrates ductal dilatation; CT shows an atrophic pancreas with calcifications and small cysts.
Pathologic features
Chronic pancreatitis is characterized by an inflammatory cell infiltrate associated with replacement of the normal pancreatic parenchyma with fibrous connective tissue ( Fig. 17-2 ). This loss of acinar tissue can be associated with dilation of the pancreatic ducts. The islets of Langerhans are relatively spared, but in severe cases there is also a substantial loss of endocrine cells. The inflammatory cell infiltrate is usually composed of a mixture of lymphocytes, plasma cells, and scattered neutrophils.
Gross findings
- ■
Firm, often atrophic gland
- ■
Calcifications
- ■
Ductal dilatation
Microscopic findings
- ■
Inflammatory cell infiltrate (predominantly chronic inflammation)
- ■
Fibrosis
- ■
Loss of acinar tissue
- ■
Relative sparing of the islets of Langerhans
Ultrastructural findings
- ■
Not needed
Fine needle aspiration biopsy findings
- ■
Paucicellularity, mixed inflammatory cells with predominance of lymphocytes and plasma cells
- ■
Degenerated cellular debris
- ■
Fibroblastic cells, epithelial cells with reactive atypia
Genetics
- ■
Can be caused by germline mutations in the cationic trypsinogen gene (PRSS1)
Immunohistochemistry
- ■
Not needed
Differential diagnosis
- ■
Well-differentiated infiltrating ductal adenocarcinoma
Ancillary studies
Fine-needle aspiration (FNA) reveals paucicellular smears with mixed inflammatory cells showing a predominance of lymphocytes and plasma cells. Background may depict degenerated cellular debris and occasional discohesive fibroblastic mesenchymal cells and naked fusiform nuclei. Rarely, partially intact islets of Langerhans may be noticed. Epithelial fragments are scanty and may disclose a range of reactive cellular changes ( Fig. 17-3 ). Quite often, the cytopathologic diagnosis in chronic pancreatitis is descriptive and not definitive on FNA.
Differential diagnosis
The atrophic glands of chronic pancreatitis can mimic a well-differentiated infiltrating adenocarcinoma. Features that favor a reactive process over a neoplastic process include retention of the normal branching growth pattern of the ducts, glands with complete lumina, the absence of luminal necrosis, and only mild nuclear pleomorphism (the cross-sectional areas of the nuclei in a single gland vary by < 4:1). If present, perineural and vascular invasion would obviously strongly support the diagnosis of a carcinoma.
Prognosis and therapy
The prognosis for patients with chronic pancreatitis is surprisingly poor. Mortality rates of 50% at 20 years have been reported. Treatment is mostly supportive, with pancreatic exocrine enzyme replacement and careful management of diabetes. As noted below, some patients with lymphoplasmacytic sclerosing chronic pancreatitis respond to steroid therapy.
Lymphoplasmacytic sclerosing pancreatitis
Clinical features
Lymphoplasmacytic sclerosing pancreatitis, also known as autoimmune pancreatitis, is a distinctive form of pancreatitis characterized by a mixed inflammatory cell infiltrate, composed of lymphocytes and plasma cells, centered around and within the epithelium of the pancreatic ducts. A venulitis is also often present. The disease strikes men more often than women, with a male-to-female ratio of approximately 8:3. The mean age at diagnosis is 57 years, and patients typically do not have conventional risk factors for pancreatitis such as alcoholism. Some patients have other autoimmune diseases such as Sjögren’s syndrome and inflammatory bowel disease.
Definition
- ■
A form of chronic pancreatitis characterized by a mixed inflammatory cell infiltrate centered on the pancreatic ducts, and venulitis.
Incidence and location
- ■
Rare, but being recognized with increasing frequency
Gender, race, and age distribution
- ■
Unlike most autoimmune diseases, lymphoplasmacytic sclerosing pancreatitis is more common in men than it is in women.
- ■
Most patients are between the ages of 40 and 60
Clinical features
- ■
Can mimic pancreatic cancer with abdominal pain, weight loss, and jaundice
- ■
Some have other autoimmune disorders such as inflammatory bowel disease and sclerosing cholangitis
- ■
Elevated serum IgG4 levels
Radiologic features
- ■
Diffuse or focal enlargement of the pancreas
Prognosis and therapy
- ■
Although many patients respond to steroid therapy, many also undergo surgery because the disease so closely mimics pancreatic cancer
- ■
The prognosis is excellent, but patients should be monitored for other autoimmune diseases
Radiologic features
The typical finding on CT is an ill-defined mass lesion with diffuse enlargement of the gland.
Pathologic features
Three features characterize lymphoplasmacytic sclerosing pancreatitis. First, the inflammatory cell infiltrate is mixed, with lymphocytes, plasma cells, and a few polymorphonuclear leukocytes. Second, the inflammatory cell infiltrate is centered on the pancreatic ducts ( Fig. 17-4 ). This is often best appreciated at low power. Third, there is a venulitis (see Fig. 17-4 B). This venulitis is often best appreciated at the interface between diseased and normal tissues. In some, but not all, cases small aggregates of neutrophils, called granulocytic epithelial lesions (GELs), collect within the ductal epithelium. Immunolabeling for IgG4 will reveal increased numbers of IgG4 expressing plasma cells in most cases.
Gross findings
- ■
Diffuse or segmental enlargement of the pancreas
Microscopic findings
- ■
Mixed inflammatory infiltrate composed of lymphocytes, plasma cells, and eosinophils
- ■
Inflammation centered on the pancreatic ducts and ductules
- ■
Venulitis
- ■
Intraepithelial collections of polymorphonuclear leukocytes (GELs) in some cases
Ultrastructural findings
- ■
Not applicable
Fine needle aspiration biopsy findings
- ■
Nonspecific with a mixed inflammatory cell infiltrate
Immunohistochemistry
- ■
Increased numbers of IgG4 expressing plasma cells
Differential diagnosis
- ■
Other forms of chronic pancreatitis
Ancillary studies
Serum IgG4 levels are elevated in most patients, and this finding can be used to support a preoperative diagnosis.
Differential diagnosis
The differential diagnosis includes other forms of pancreatitis.
Prognosis and therapy
This form of pancreatitis is important to recognize because it can clinically mimic pancreatic cancer and because it may respond to steroid therapy.
Paraduodenal wall cyst
Clinical features
Paraduodenal wall cyst is a non-neoplastic cyst with an associated inflammatory reaction occurring in the “groove” region—the region demarcated by the superior aspect of the pancreas, the common bile duct and the minor papilla. It is thought that the cysts are caused by a small calculus obstructing a small duct associated with the minor papilla. Most patients are young males with a history of alcohol abuse.
Definition
- ■
Non-neoplastic inflammatory cystic dilatation of small ducts in the “groove region”—the area demarcated by the superior aspect of the pancreatic head, the common bile duct, and the duodenum
Incidence and location
- ■
Rare
- ■
By definition, located in the “groove” region
Gender, race, and age distribution
- ■
Strong male predominance
- ■
Most patients are in their 50s
Clinical features
- ■
A history of alcohol abuse is common
- ■
Common symptoms include abdominal pain and weight loss
Radiologic features
- ■
May produce a solid or a cystic mass lesion in the head of the pancreas/duodenum
Prognosis and therapy
- ■
Prognosis is excellent because these are non-neoplastic lesions
Radiologic features
Computed tomography scanning usually reveals a thickened duodenum associated with cyst formation in the duodenal wall or subjacent pancreas.
Pathologic features
Paraduodenal wall cysts, in addition to arising in a very specific region, have a characteristic microscopic appearance. The cysts, which may contain inspissated secretions, are lined by partially denuded ductal epithelium. Often there is an associated reactive spindle cell proliferation.
Gross findings
- ■
Cyst or a solid mass lesion located in the groove region of the pancreas
Microscopic findings
- ■
Cyst lined by partially denuded ductal epithelium
- ■
Associated inflammatory cell infiltrate
- ■
A prominent reactive spindle cell proliferation is present in some cases
Ultrastructural findings
- ■
Not applicable
Fine needle aspiration biopsy findings
- ■
Not well defined
Immunohistochemistry
- ■
Not applicable
Differential diagnosis
- ■
Cystic neoplasms of the pancreas
- ■
Spindle cell neoplasms
Ancillary studies
A careful gross dissection documenting the distinctive location of the lesion is critical to establishing the correct diagnosis.
Differential diagnosis
The differential diagnosis includes cystic neoplasms of the pancreas (see later), as well as mesenchymal neoplasms. The characteristic location of the lesion and the presence of a partially denuded but otherwise unremarkable epithelium lining the cyst both help establish the diagnosis.
Prognosis and therapy
These are entirely benign lesions.
Pseudocysts
Clinical features
Pseudocysts are localized collections of necrotic material rich in pancreatic enzymes. Pseudocysts lack an epithelial lining and are often extrapancreatic. Pseudocysts account for 75% of all “pancreatic” cysts. Pseudocysts usually develop after an episode of acute pancreatitis or following trauma to the pancreas. Patients often have a severe epigastric pain that radiates to the back. In the United States most patients have a history of heavy alcohol consumption.
Definition
- ■
A localized collection of necrotic material rich in pancreatic enzymes and lacking an epithelial lining
Incidence and location
- ■
75% of all pancreatic cysts
- ■
Often extrapancreatic
Gender, race, and age distribution
- ■
Older males, especially alcoholics
Clinical features
- ■
Severe epigastric pain often radiating to the back
Radiologic features
- ■
Unilocular cystic mass
Prognosis and therapy
- ■
Supportive care
- ■
Surgical drainage
- ■
Excellent prognosis
Radiologic features
Abdominal imaging will reveal a unilocular cystic mass.
Pathologic features
Pseudocysts are usually solitary, usually extrapancreatic, and typically filled with necrotic/hemorrhagic material. Pseudocysts do not have an epithelial lining. Instead, pseudocysts are lined by granulation tissue, fibrous connective tissue, or simply by necrotic debris ( Fig. 17-5 ).
Gross findings
- ■
Solitary cysts, intrapancreatic or extrapancreatic
- ■
Necrotic/hemorrhagic contents
Microscopic findings
- ■
Cyst without lining epithelium
- ■
Wall composed of granulation tissue or fibrous connective tissue
Ultrastructural findings
- ■
Not needed
Fine needle aspiration biopsy findings
- ■
Nonspecific findings, degenerated cystic debris, lymphomononuclear cells, and histiocytes
- ■
Macrophages and fibroblastic cells may mimic cellular atypia
- ■
Lack of epithelial component
- ■
Aspirated fluid with a low CEA level and high in lipase and amylase
Immunohistochemistry
- ■
Not applicable
Differential diagnosis
- ■
Retention cysts
- ■
Serous cystadenoma
- ■
Mucinous cystic neoplasms
- ■
Intraductal pancreatic mucinous neoplasms
- ■
Solid-pseudopapillary neoplasm
- ■
Cystically degenerated carcinoma
Ancillary studies
Two aspects of the FNA biopsy can be highly informative. First, a morphologic analysis of the cellular component can help determine if the cyst has an epithelial lining. Second, the aspirated fluid can be analyzed biochemically to determine if the cyst contents contain high concentrations of pancreatic enzymes. Aspirates of pseudocysts show abundant thin and watery, turbid fluid, which may appear hemorrhagic. The cytomorphology is often nonspecific and consists mostly of degenerated cellular debris, fibroblastic cells, macrophages, and lymphomononuclear cells ( Fig. 17-6 ). Aspirates typically lack an epithelial component. Reactive/reparative changes in the mesenchymal cells and macrophages may raise suspicion for a neoplastic cyst. The fluid aspirated from pseudocysts is rich in lipase and amylase and has low carcinoembryonic antigen (CEA) levels. By contrast, most neoplastic cysts have low to normal amylase levels, and some have elevated CEA levels. In one study, the diagnosis of neoplastic cysts based on a CEA level greater than 10 ng/mL had a sensitivity of 100% and a specificity of 81%.
Differential diagnosis
The differential diagnosis of pancreatic cysts includes retention cysts, serous cystadenoma, mucinous cystic neoplasms, intraductal papillary mucinous neoplasms (IPMNs), the solid-pseudopapillary neoplasm, and cystic change in a usually solid pancreatic neoplasm. The absence of an epithelial lining combined with necrotic/hemorrhagic cyst contents rich in lipase and amylase establish the diagnosis of a pseudocyst.
Prognosis and therapy
Most pseudocysts resolve with supportive care, although some require surgical drainage. Superinfection of a pseudocyst is a serious complication.
■
Exocrine neoplasms
Solid neoplasms
Solid neoplasms of the pancreas showing predominantly exocrine differentiation include infiltrating ductal adenocarcinoma and its variants, pancreatoblastoma, and acinar cell carcinoma.
Infiltrating ductal adenocarcinoma
Clinical features
Infiltrating ductal adenocarcinoma (“pancreatic cancer”) is a malignant invasive gland forming epithelial neoplasm. A number of variants have been described, including adenosquamous carcinoma, hepatoid carcinoma, mucinous noncystic adenocarcinoma (colloid carcinoma), signet ring cell carcinoma, undifferentiated (anaplastic) carcinoma, and undifferentiated carcinoma with osteoclast-like giant cells. Infiltrating ductal adenocarcinoma is a disease of the elderly, with most patients being older than the age of 60 years. The disease strikes men slightly more frequently than it does women, and in the United States, African Americans more than whites. Common presenting signs and symptoms include painless jaundice, unexplained weight loss, and epigastric pain radiating to the back. New-onset diabetes mellitus may be the first manifestation of the disease.
Definition
- ■
A malignant invasive epithelial neoplasm with ductal differentiation
Incidence and location
- ■
85% to 90% of all pancreatic neoplasms
- ■
Pancreatic head (> 60%)
Gender, race, and age distribution
- ■
More often in men (M:F ratio, 2:1)
- ■
Increased risk with smoking, family history of pancreatic cancer
- ■
Older age group, usually older than 60 years
Clinical features
- ■
Epigastric pain, often radiating to the back
- ■
Weight loss
- ■
Painless jaundice
- ■
Less often, migratory thrombophlebitis, pancreatitis, new-onset diabetes mellitus
Radiologic features
- ■
Poorly defined infiltrative nonenhancing pancreatic mass
Prognosis and therapy
- ■
Surgical resection
- ■
Palliative bypass procedures
- ■
Radiation and chemotherapy
- ■
Prognosis extremely poor (slightly better for mucinous noncystic adenocarcinoma)
- ■
5-year survival: <2%
Radiologic features
CT is one of the best modalities to image the pancreas. Infiltrating ductal adenocarcinomas typically produce a hypodense mass lesion that distorts the normal architecture of the gland. The pancreatic duct is often dilated secondary to duct obstruction by the cancer.
Pathologic features
Infiltrating ductal adenocarcinomas grossly form poorly defined, firm, white-yellow masses ( Fig. 17-7 ). Most arise in the head of the pancreas, but they can also involve the body, tail, or even the entire gland. Focal cystic degeneration and areas of necrosis are not uncommon. As noted radiologically, the pancreatic duct is often dilated upstream of the cancer. Microscopically, varying degrees of differentiation can be seen, but all infiltrating ductal adenocarcinomas, by definition, show both epithelial and glandular differentiation ( Fig. 17-8 ). Well-differentiated adenocarcinoma is characterized by clearly formed neoplastic glands arranged in a haphazard pattern of growth. This haphazard growth pattern, more than any other feature, helps distinguish well-differentiated adenocarcinomas from non-neoplastic reactive glands. Moderately differentiated adenocarcinomas show the same haphazard growth pattern but, in addition, are characterized by greater architectural and cytologic atypia. The neoplastic cells may form incomplete glands, cribriform structures, or papillae without fibrovascular cores. Significant nuclear pleomorphism can be appreciated, and the nuclei in a single gland often vary in size by more than 4 to 1. Nucleoli may be present and may be prominent. Mitoses, including abnormal mitoses, can be seen. Poorly differentiated adenocarcinoma, as the name implies, is an infiltrating cancer in which it can be difficult to recognize the direction of differentiation of the neoplastic cells. Individual cells, cells forming solid sheets, poorly formed glands, and even single infiltrating neoplastic cells are seen. Significant pleomorphism with bizarre mitotic figures is common. Perineural and vascular invasion, when present, can help establish the diagnosis.
Several variants of ductal adenocarcinoma are worth discussing. The adenosquamous carcinoma is characterized by the presence of both glandular and squamous differentiation. Adenosquamous carcinomas have a particularly poor prognosis. Hepatoid carcinoma , as the name suggests, has prominent liver differentiation. Metastasis from a liver primary should be ruled out clinically before making this diagnosis. The mucinous noncystic adenocarcinoma is also known as the colloid carcinoma and is characterized by relatively well-differentiated neoplastic mucin-producing epithelial cells “floating” in large pools of extracellular mucin ( Fig. 17-9 ). This variant is also fully malignant but may have a slightly better prognosis than infiltrating ductal adenocarcinoma. Mucinous noncystic adenocarcinoma almost always arises in association with an intraductal papillary mucinous neoplasm (IPMN). The Signet ring cell carcinoma is composed of noncohesive individual neoplastic cells with abundant cytoplasmic mucin that indents the nuclei pushing them toward the periphery. Metastases from a breast or gastric primary should be considered before making this diagnosis. The undifferentiated (anaplastic) carcinoma , as the name suggests, is an extremely aggressive neoplasm composed of highly atypical cells, with significant pleomorphism and frequent, often bizarre, mitoses. These carcinomas can have a significant spindle cell component, or they can be composed of large polygonal cells. Finally, mixed carcinomas, such as the mixed ductal-endocrine carcinoma , have—in addition to an infiltrating ductal adenocarcinoma—significant components with other directions of differentiation. The mixed nature of these neoplasms can usually be demonstrated with immunolabeling.
Gross findings
- ■
Poorly defined, firm mass with irregular boarders
- ■
Cut surface: yellow-white microcystic areas, hemorrhage, and necrosis
Microscopic findings
- ■
Neoplastic glands in haphazard arrangement
- ■
Architectural atypia with incomplete glands, luminal necrosis
- ■
Cytologic atypia with nuclei in a single gland varying by more than 4:1
- ■
Vascular and perineural invasion
- ■
Glands adjacent to muscular vessels
- ■
Mitoses and necrosis
- ■
Solid sheets or single infiltrating cells (poorly differentiated tumors)
- ■
Glandular and squamous differentiation (adenosquamous carcinoma)
- ■
Hepatocellular differentiation (hepatoid carcinoma)
- ■
Mucin-producing cells floating in pools of mucin (mucinous noncystic carcinoma)
- ■
Individual cells with eccentric mucin vacuoles (signet ring cell carcinoma)
- ■
Undifferentiated spindle cell component (undifferentiated/anaplastic carcinoma)
- ■
Endocrine differentiation (mixed ductal-endocrine carcinoma)
Ultrastructural findings
- ■
Ductal epithelial differentiation with microvilli on the luminal surface, cell-cell junctions, and cytoplasmic mucin granules
Fine needle aspiration biopsy findings
- ■
Hypercellularity, fragments and single neoplastic cells with ductal features, relative paucity, or total lack of acinar epithelium
- ■
Nuclear enlargement, nuclear overlap, hyperchromasia, and irregular nuclear contours
- ■
Pleomorphism, lack of polarity, and haphazard arrangement; “drunken honey comb” arrangement
- ■
Bizarre neoplastic cells, multinucleation, squamoid change, mitosis, and necrosis
- ■
Mucinous change with cytoplasmic vacuolization
Genetics
- ■
Mutation of the KRAS oncogene
- ■
Somatic mutations of multiple tumor suppressor genes, particularly TP53 , SMAD4 / DPC4 , and p16 / CDKN2A
- ■
Overexpression of growth factors (epidermal growth factor, transforming growth factor α, and others)
- ■
Familial clustering of pancreatic cancer has been observed
- ■
Germline mutations in the STK11 , BRCA2 , PALB2 , p16 / CDKN2A , and PRSS1 genes predispose to pancreatic cancer
Immunohistochemistry
- ■
Positive for CK7, CK8, CK18, and CK19
- ■
Positive for CEA, CA19-9, Dupan-2, MUC1, MUC4, and MUC5AC
- ■
Most positive for mesothelin, claudin 18, prostate stem cell antigen, and fascin
- ■
Loss of Smad4 protein expression (55%)
- ■
Endocrine markers (such as chromogranin) positive in mixed ductal-endocrine neoplasms
Differential diagnosis
- ■
Chronic pancreatitis
- ■
Ampullary carcinoma
- ■
Other primary and metastatic pancreatic neoplasms
Related posts:
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
