INTRODUCTION
A 57-year-old man complains of severe upper abdominal pain extending to his midback. He also has had fatigue and a loss in appetite over the last several weeks. Physical examination reveals generalized jaundice but no other significant findings. An upper endoscopy does not identify any mucosal ulcerations or masses. A CT scan of the abdomen shows a large mass in the head and body of the pancreas.
· What is the most likely
diagnosis?
· What is the likely
prognosis of this condition?
Summary: A 57-year-old man has severe upper
abdominal pain radiating to his midback, fatigue, loss of appetite, and
generalized jaundice. A large mass in the head and body of the pancreas is noted
on CT imaging.
· Most likely diagnosis:
Pancreatic carcinoma.
· Likely prognosis of this
condition: Poor prognosis with 5-year survival less than 5
percent.
CLINICAL
CORRELATION
Introduction
The vast majority of pancreatic carcinomas involve
exocrine glands and are known as adenocarcinomas. The etiology is largely
unknown. However, point mutations of the K-ras gene have been observed in
over 90 percent of the tumors, suggesting abnormalities at the genetic level.
Pain and nonspecific systemic symptoms such as weakness and weight loss are the
usual first signs of malignancy. Obstructive jaundice is seen commonly because
of the preference for tumors to occur in the head of the pancreas. The
symptomatic course of pancreatic carcinoma is typically brief and progressive.
Radiologic workups, including abdominal CT and ultrasound, are diagnostic for
the cancer and are used for staging. No specific biological tests are available
for screening or early detection. Cancer of the pancreas is now the fifth most
common cause of cancer-related death in the United States. The median survival
period from the time of diagnosis to demise is arguably the worst of any of the
cancers. The median survival for untreated advanced cases is about 3.5 months;
with good treatment this increases to about 6 months. The 5-year relative
survival rate of patients with this cancer is only 3 to 5 percent. Even though a
Whipple operation is considered the treatment of choice for localized and early
disease, fewer than 15 percent of pancreatic tumors overall are resectable at
the time of diagnosis. The prognosis of pancreatic carcinoma is one of the most
dismal among any malignancies ever known.
Approach to
Pancreatic Cancer
Definitions
Jaundice: A yellow discoloring of the skin,
mucous membranes, and eyes caused by excess bilirubin in the blood. Common
causes of jaundice in adults include prehepatic causes such as intravascular
hemolysis, hepatic causes such as hepatitis A and hepatic tumors, and
posthepatic causes, including obstruction of the bile duct as a result of
infection, tumor, or gallstones.
Exocrine gland: A gland that secretes its
products through ducts or canals, such as sweat glands or mammary glands. The
secretion products produce their biological effects locally.
Endocrine gland:A gland, such as the pituitary
or thyroid, that secretes its products, called hormones, directly into the
bloodstream. Hormones generate their biological effects at distant
locations.
Pancreatic cancer and adenocarcinoma of the
pancreas: By definition, pancreatic cancer includes all malignant neoplasms
of the pancreas. It includes the tumors arising from the exocrine portion of
pancreas such as gland-forming adenocarcinoma of the pancreas, those of ductal
origin, and tumors from endocrine components. Adenocarcinoma is the most common
form of cancer, accounting for over 75 percent of all pancreatic
cancers.
Discussion
Normal
Pancreatic Histology
The pancreas is a small, spongy gland that lies just
under the curvature of the stomach and deep within the abdomen. The majority of
the pancreas is composed of exocrine glands, which produce enzymes
necessary for food digestion. The secretions from acinar cells, the
structural unit throughout the pancreas, containing salts and enzymes, are
called pancreatic fluid, which eventually drains into the pancreatic duct. The
pancreatic duct usually joins the bile duct and empties its combined digestive
contents into the duodenum. Additionally, the pancreas has an endocrine,
or hormonal, function. Inside specialized groupings of cells called the
islets of Langerhans, the pancreas produces hormones such as insulin
and glucagons, among other hormones. These molecules are secreted directly
into the bloodstream, eliciting numerous biological effects throughout the
body.
Epidemiology
Each year about 30,000 people in the United States are
diagnosed with adenocarcinoma of the pancreas. Most of them will have passed
away by the end of the first year. Most patients are between the ages of 60 and
80. Men tend to be affected more often than women. The median survival period
from the time of diagnosis until demise is extremely short, with a mean of 3.5
months. It has been approximated that about 30 percent of the changes that
initiate cancer of the pancreas are caused by smoking and that about 8 percent
are "secondary to a hereditary genetic predisposition. There does not appear to
be a strong correlation between the onset of pancreatic adenocarcinoma and the
drinking of alcohol or coffee.
Biochemical
Tests
Laboratory results often reveal nonspecific elevated
bilirubin and elevated liver function enzymes as a result of biliary
obstruction. The CA 19-9 marker, a Lewis blood group-related mucin,
frequently is elevated in adenocarcinoma of the pancreas, but its use in
screening for or diagnosis of the cancer is not accepted in general practice.
High CA 19-9 levels may be associated with but do not always indicate larger
tumors and with a decreased likelihood of surgical resectability. The use of
this marker is accepted more widely as a running measure in a particular
individual to help reflect the stability or progression of the cancer. Point
mutation of K-ras is observed in 90 percent of pancreatic cancer
patients. However, the utility of a screening test for K-ras mutation
is not proven clinically.
Adenocarcinoma
of the Pancreas
In up to 95 percent of cases, pancreatic cancer
arises from the exocrine portion of the organ. Most of the exocrine
tumors (approximately 90 percent) are from ductal cells¾those which line the pancreatic ducts. Further, under the
microscope, the appearance and arrangement of these carcinoma cells can appear
as ductlike (or "adeno"), giving the term adenocarcinoma to this most common
form of pancreatic cancer. About three-quarters of exocrine tumors of the
pancreas arise in the head and neck of the pancreas. It is believed that
cancer is caused by the mutations of a gene, which confer increased abnormal
growth potential to cells. Among other abnormalities, an oncogene called
K-ras is found to be altered in up to 95 percent of ductal
adenocarcinomas of the pancreas. The Whipple operation (pancreaticoduodenectomy)
typically is performed in patients with tumors localized in the head of the
pancreas.
Other Malignant
Tumors of the Pancreas
Neuroendocrine tumors of the pancreas (islet
cell tumors) are much less common than tumors arising from the exocrine
pancreas. About 75 percent of these tumors are "functioning," meaning
that they are found to be producing symptoms related to one or more of the
hormone peptides they secrete. The predominant peptide secreted gives the
functioning islet cell tumor its name. The hormones produced by neuroendocrine
tumors include insulin, gastrin, glucagon, somatostatin, neurotensin,
pancreatic polypeptide (PP), vasoactive intestinal peptide (VIP),
growth hormone-releasing factor (GRF), and adronocorticotropic hormone
(ACTH), among others.
Typically, the symptoms produced by the excess
secretion of the predominant hormone in a functioning endocrine tumor lead to
the eventual diagnosis. It is not possible to determine malignancy from the
histologic appearance. Malignancy is determined by finding additional metastatic
sites. The natural history of neuroendocrine carcinoma tends to be favorable
compared with that of pancreatic adenocarcinoma. For example, the median
survival duration from the time of diagnosis for patients with nonfunctioning
metastatic neuroendocrine tumors approaches 5 years. Immediate treatment of the
symptomatic conditions created by the oversecretion of the hormone may be
appropriate. Surgery is generally curative.
COMPREHENSION
QUESTIONS
[5.1] A 51-year-old man presents with slowly
progressive jaundice, weight loss, and upper abdominal pain that radiates to his
midback. Physical examination finds an enlarged gallbladder in the right upper
quadrant of his abdomen, and a CT scan shows an irregular mass involving the
head of the pancreas. Histologic sections from this mass are most likely to
reveal what abnormality?
A. Adenocarcinoma
B. Clear cell carcinoma
C. Medullary carcinoma
D. Signet ring carcinoma
E. Squamous cell carcinoma
[5.2] Which one of the tumor markers listed below is
most likely to be used by a clinician who is following a 64-year-old man after
surgery for pancreatic cancer to look for possible recurrence of the pancreatic
cancer?
A. CA 15-3
B. CA 19-9
C. CA 27-29
D. CA-50
E. CA-125
[5.3] A 44-year-old woman presents with worsening
episodes of feeling "light-headed and dizzy." She says that her symptoms are
relieved if she quickly eats a candy bar. Laboratory evaluation finds that
during one of these episodes her serum glucose level is decreased and her serum
insulin level is increased. What is the most likely cause of her
symptoms?
A. Carcinoid tumor
B. Functional hamartoma
C. Islet cell adenoma
D. Microcystic adenoma
E. Tubulovillous adenoma
ANSWERS
[5.1] A. Adenocarcinoma is the most common type
of pancreatic malignancy arising from the pancreatic ducts. In contrast,
squamous cell carcinomas usually originate from stratified squamous epithelium,
such as the esophagus. Clear cell carcinomas can be found in the kidneys, and
signet cell carcinomas can be found in the stomach. A medullary carcinoma is a
type of carcinoma of the thyroid gland.
[5.2] B. CA 19-9 is currently the best
available tumor marker used clinically to look for possible recurrence of
pancreatic cancer after surgery. Other markers have been studied in patients
with pancreatic cancer, including CA-50, SPAN-1, and DUPAN-1, but these markers
have not been as useful as CA 19-9. In contrast, CA-125 is associated with
ovarian cancer, whereas CA 15-3 and CA 27-29 are associated with breast cancer,
particularly advanced breast cancer.
[5.3] C. Elevated serum levels of insulin that
result in hypoglycemia can be caused by a tumor that secretes insulin; an
insulinoma is a type of islet cell tumor of the pancreas. In contrast, carcinoid
tumors, which are found in the appendix and small intestine, may secrete
vasoactive substances such as serotonin. A microcystic adenoma is a rare type of
benign tumor of the pancreas, and a tubulovillous adenoma is a type of
neoplastic polyp of the colon.
PATHOLOGY
PEARLS
· Pancreatic cancer usually
has a very poor prognosis.
· Adenocarcinoma is the most
common type of primary pancreatic cancer, usually arsing from the exocrine
glands.
· Neuroendocrine tumors of
the pancreas tend to have a better prognosis than do adenocarcinomas.
· Painless obstructive
jaundice is a common presentation of pancreatic cancer.
· Depression can herald an
occult pancreatic cancer.
REFERENCES
Hruban RH, Wilentza RE. The pancreas. In: Kumar V,
Assas AK, Fausto N, eds. Robbins and Cotran pathologic basis of disease, 7th ed.
Philadelphia: Elsevier Saunders, 2004:939-953.
Mayer RJ. Pancreatic cancer. In: Kasper DL, Fauci AS,
Longo DL, et al., eds. Harrison's principles of internal medicine, 16th ed. New
York: McGraw-Hill, 2004:537-538.
Copyright © 2006 by the
McGraw-Hill Companies, Inc. All rights reserved.
