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Female Reproductive System. Early Embryology. Gonad Development. Week 1: Beginning of Development.
Week After a positive PPD test, a year-old male begins isoniazid therapy. One month later he presents complaining of fever, anorexia and nausea. What is the most likely cause of his current symptoms?
Peripheral nerve damage B. Hepatocyte damage C. Initial laboratory studies show the following: A year-old man with a prior history of blood transfusion pres- ents with jaundice and ascites, along with mildly elevated transaminases as well as evidence of impaired hepatic synthetic function hypoalbuminemia and coagulopathy.
Most commonly caused by chronic toxin exposure alcohol or chronic viral infection; sometimes chronic hepatitis may be caused by inherited metabolic disorders such as hemochromatosis.
Hepatitis virus serologies and possibly a liver biopsy. Hepatic failure, gastrointestinal bleeding, hepatocellular carcinoma. He had a long asymp- tomatic period and now has signs of advanced liver disease. His firm nodular liver probably represents cirrhosis, with scarring of the liver parenchyma along with regenerative nodules.
His transaminases ALT and AST are only mildly elevated but these tests may be within normal limits, particularly early in the course of disease. The fact that he has impaired hepatic synthesis of albumin and coagulation factors indicates that he has very advanced disease, especially in light of the enormous reserve and regenerative capacity of the liver.
The accumulation of ascitic fluid in the peritoneum usually represents portal hypertension, an increase in pressure in the portal venous system that typically results from increased intrahepatic resistance to portal blood flow because of perisinusoidal deposition of collagen. Although often used as a clinical description, cirrhosis is really a pathologic diagnosis that is characterized by disruption of normal liver architecture by interconnecting fibrous scars and the creation of parenchymal nodules by regenerative activity and the network of scars.
This pathologic process can be thought of as the final common pathway of many causes of chronic hepatic injury. The inciting factor causes hepatocyte necrosis and deposition of collagen. At some point the fibro- sis becomes irreversible, and cirrhosis then develops. Cirrhosis can be classified according to morphologic features micronodular, most often caused by alcohol, or macronodular, most often resulting from viral hepatitis or according to the etiology: However, a single cause of hepatic injury can produce a variety of pathologic patterns, and any given morphology can result from a vari- ety of causes.
See Figure Acute hepatitis: The influx of acute inflammatory cells, which may follow or precede hepatocyte necrosis. The morphologic changes in both acute and chronic hepatitis are common to the hepatitis viruses and can be mimicked by drug reactions.
Chronic hepatitis: It can be due to numerous causes, all of which result in hepatic inflammation and necrosis for at least 6 months, but without the nodular regeneration and architectural distortion of cirrhosis.
Hepatic steatosis: Later, the vacuoles coalesce into macrovesicles, compressing and displacing the nucleus so that the hepatocyte resembles a lipocyte.
Grossly, the liver becomes enlarged with a yellow, greasy appearance. Steatosis is usually reversible with discontinuation of the underlying cause, but it may lead to the develop- ment of fibrosis around the central veins and sinusoids and ultimately to cirrhosis.
The liver is organized into 1- to 2-mm hexagonal lobules, with cords or plates of hepatocytes radiat- ing out from the central vein, the terminal venules of the hepatic vein. At each corner of the hexagon are the portal tracts, composed of the terminal branches of the portal vein and the hepatic artery, as well as the bile duct. Arterial and portal venous blood flows through sinusoids, between the cords of hepatocytes, giving them a rich vascular supply 25 percent of cardiac output before draining into the central vein.
Bile is secreted into bile canaliculi between adjacent hepatocytes and flows into the canals of Herring and then to the lobular bile ducts. The organization of a lobule is shown in Figure The liver serves many functions, including maintenance of carbohydrate, lipid, and amino acid metabolism; synthesis of nearly all serum proteins; and detoxification and excretion of noxious substances in the bile. One such sub- stance is bilirubin, a waste product that is the metabolite of the breakdown of heme from senescent red blood cells.
It undergoes conjugation with glu- curonic acid in the hepatocyte to form conjugated or direct bilirubin, which is water-soluble and nontoxic, and then is excreted into the bile canaliculus. When liver disease causes jaundice, affected individuals usually have reflux of conjugated bilirubin into the blood, which causes the visible icterus when deposited in tissues, as well as the dark urine resulting from urinary excretion of elevated levels of water-soluble conjugated bilirubin.
Figure Microscopic image of liver cirrhosis. Each virus can produce virtually indistinguishable clinical syndromes. Affected individuals often present with a prodrome of nonspecific constitu- tional symptoms, including fever, nausea, fatigue, arthralgias, myalgias, headache, and sometimes pharyngitis and coryza.
This is followed by the onset of visible jaundice caused by hyperbilirubinemia, tenderness and enlargement of the liver, and dark urine caused by bilirubinuria. The clinical course, out- comes, and possible complications vary with the type of virus causing the hep- atitis. A comparison of features of these five viruses is shown in Table Hepatitis A and hepatitis E are very contagious and are transmitted by the fecal-oral route, usually by contaminated food or water in areas where sani- tation is poor, and in day-care situations by children.
Hepatitis A is found worldwide and is the most common cause of acute viral hepatitis in the United States. Both hepatitis A and hepatitis E infections usually lead to self-limited illnesses and generally resolve within weeks. Almost all patients with hepatitis A recover completely and have no long-term complica- tions. Most patients with hepatitis E also have uncomplicated courses, but some patients, particularly pregnant women, have been reported to develop severe hepatic necrosis and fatal liver failure.
Hepatitis B is the second most common type of viral hepatitis in the United States, and it is usually sexually transmitted. It also may be acquired parenterally, for example, through intravenous drug use, and during birth, from chronically infected mothers. The outcome then depends on the age at which the infection was acquired. Up to 90 percent of infected newborns develop chronic hepatitis B infection, which places an affected infant at signifi- cant risk of hepatocellular carcinoma later in adulthood.
Among individuals infected later in life, approximately 95 percent recover completely without sequelae. Between 5 and 10 percent of patients will develop chronic hepatitis and may progress to cirrhosis. Also, a chronic carrier state may be seen in which the virus continues to replicate but does not cause hepatic damage in the host.
Hepatitis C is transmitted parenterally by blood transfusions or intra- venous drug use and rarely by sexual contact. It uncommonly is diagnosed as a cause of acute hepatitis, often producing subclinical infection, but frequently is diagnosed later as a cause of chronic hepatitis.
The natural history of infec- tion is not completely understood, but 50 to 85 percent of patients with hep- atitis C will develop chronic infection. Hepatitis D is a defective RNA virus that requires the presence of the hepatitis B virus to replicate. It can be acquired as a coinfection simultane- ously with acute hepatitis B or as a later superinfection in a person with a chronic hepatitis B infection.
Hepatitis Serologies Clinical presentation does not reliably establish the viral etiology, and so sero- logic studies are used to establish a diagnosis. If anti-hepatitis C antibody is present, acute hepatitis C is diagnosed, but the test may be nega- tive for several months. The hepatitis C polymerase chain reaction PCR assay, which becomes positive earlier in the disease course, often aids in the diagnosis.
Acute hepatitis B infection is diagnosed by the presence of hepati- tis B surface antigen HBsAg in the clinical context of elevated serum transaminase levels and jaundice. There is often an interval of a few weeks between the disappearance of HBsAg and the appearance of anti-HBsAb, which is referred to as the window period. Hepatitis B pre- core antigen HBeAg represents a high level of viral replication. It is almost always present during acute infection, but its persistence after 6 weeks of ill- ness is a sign of chronic infection and high infectivity.
Persistence of HBsAg or HBeAg is a marker for chronic hepatitis or a chronic carrier state; elevated or normal serum transaminase levels distinguish these two entities see Table Hepatitis B serology. There may be hepatocyte swelling called ballooning degeneration, as well as liver cell necrosis, including frag- mentation and condensation of hepatocytes, forming intensely eosinophilic Councilman bodies, which are characteristic of viral hepatitis.
Formation of ropelike eosinophilic structures within hepatocytes, called Mallory bodies, is typical of alcoholic hepatitis. Another finding in acute hepatitis is an inflam- matory infiltrate in the portal tracts. Chronic hepatitis C is characterized by the formation of lymphoid aggregates in the portal tracts as well as fatty changes in hepatocytes. Ground glass cells often are seen in chronic hepatitis B. If inflammation is limited to the portal tracts, the disease is milder and the prognosis is better.
When it spills over into the peri- portal parenchyma, destroying the limiting plate piecemeal necrosis or extend- ing across lobules, such as the portal area to the central vein, which is termed bridging necrosis, the disease is more progressive and the prognosis is poorer. Complications of Chronic Hepatitis Many patients with chronic hepatitis have stable disease, but a significant fraction develops ongoing fibrosis and ultimately cirrhosis, as was described previously.
The fibrosis causes increased intrahepatic resistance to portal venous blood flow and thus increased pressure in this venous system. Portal hypertension in turn leads to the development of ascites, or the accumulation of intraperitoneal fluid, and the formation of collateral venous circulation, such as esophageal varices, which often produce life-threatening hemorrhages.
Finally, patients with chronic hepatitis and cirrhosis of almost any cause, especially hepatitis B or hepatitis C, are at increased risk for developing hepatocellular carcinoma.
The pathologic fea- tures of these conditions were described previously. The major points to note here are that fat begins to accumulate within hepatocytes after even a moder- ate intake of alcohol and, with continued exposure, continues to accumulate until the liver may be 3 to 4 times its normal mass.
Up to the point where fibro- sis appears, the fatty change is reversible with abstention from alcohol. Alcoholic hepatitis is characterized by acute hepatocyte necrosis, particularly after bouts of heavy drinking, and is usually reversible.
It typically includes some sinusoidal and perivenular fibrosis and, if superimposed on fatty liver, often progresses to cirrhosis. Acetaminophen Toxicity A relatively common and treatable form of hepatotoxic exposure that other- wise may lead to hepatic failure and death is acetaminophen poisoning. A minor metabolite of acetaminophen is produced by cytochrome P 2E1 in the form of a hepatotoxin, which normally is detoxified by binding to glu- tathione. Hepatotoxicity is most likely to develop in patients with single very large ingestions such as suicide attempts or patients with enhanced activity of this cytochrome, as well as those with depleted levels of glutathione, such as chronic alcoholics.
Blood levels of acetaminophen correlate with the severity of hepatic injury. Patients with toxic levels of acetaminophen may be treated with doses of N-acetylcysteine, which replaces glutathione stores, allowing detoxification of the metabolite. The disease classically was referred to as bronze diabetes because of the deposition of iron causing skin pigmenta- tion, diabetes, as well as micronodular cirrhosis, with increased levels of fer- ritin and hemosiderin within hepatocytes.
It now can be diagnosed before the occurrence of end-organ damage resulting from iron deposition by screening for transferrin saturation greater than 45 percent and confirmed by HFE genotyping.
In some patients, the abnormal A1AT is synthesized in the liver but cannot be secreted, and so it accumulates in cytoplasmic globules. The spectrum of liver diseases ranges from neonatal hepatitis, to childhood cirrhosis, to adult cirrhosis.
Thus, patients with A1AT deficiency will often develop emphysema due to increased levels of elastase in the lungs in addition to cirrhosis. Wilson Disease Wilson disease is an inherited disorder of copper metabolism in which there is accumulation of copper in multiple tissues, including liver, brain, and eye.
Clinical manifestations may include acute or chronic hepatitis, fatty liver, and cirrhosis, along with extrapyramidal movement disorders or psychiatric dis- turbances. Diagnosis is made by finding Kayser-Fleischer rings in the cornea, which are pathognomonic, or by low levels of serum ceruloplasmin a serum copper-transport protein , as well as increased levels of hepatic or urinary copper. It is nearly always a self-limited infection without a chronic or car- rier state.
It is an RNA virus that usually is acquired from contaminated food and water. It typically is associated with the formation of Mallory bodies on biopsy. When it is acquired in adulthood, more than 85 percent of patients develop chronic hepatitis.
Her liver biopsy shows hepatocyte necrosis and inflam- matory portal tract infiltrate. Which of the following tests is most likely to yield the diagnosis? Staining of liver specimen with Prussian blue B. Ophthalmologic slit-lamp examination E. Serum acetaminophen level [3. A liver biopsy reveals liver cell drop-out along with focal inflammation and ballooning degeneration of hepatocytes.
A few intensely eosinophilic oval bodies are found. What are these microscopic bodies called? Councilman bodies B. Cowdry A bodies C. Mallory bodies D. Psammoma bodies E. Russell bodies Answers [3. Acute hepatitis B infection is characterized by the presence or shedding of HbsAg, followed by a rise in anti-Hbc IgM. Adult infec- tion has a much better prognosis only 5 to 10 percent of patients develop chronic hepatitis compared with perinatal infection more than 90 percent develop chronic infection.
Councilman bodies can be seen in viral hepatitis; Mallory bodies are characteristic of alco- holic hepatitis. The pathologic findings of acute hepatitis are nonspecific. The dis- tinguishing feature in this case is the presence of hemiballism, an extrapyramidal movement disorder, suggesting Wilson disease.
Kayser-Fleischer rings are green to brown deposits of copper in the Descemet membrane near the corneal limbus and are diagnostic. Councilman bodies are intensely eosinophilic bodies that may be seen in liver biopsy specimens from individuals with viral hepatitis. These Councilman bodies are in fact necrotic hepatocytes that have undergone T-cell induced apoptosis.
These apoptotic cells are cleared rapidly, and there may not be as many present in a liver biopsy spec- imen as were originally present. The liver and biliary tract. Crawford JM. Acute viral hepatitis. Braunwald E. Damjanov I, Linder J, eds. Mosby, No invasive carcinomas are identified, but two small pedun- culated tubular adenomas are removed and one villous adenoma measuring 5 mm in diameter is biopsied. A year-old man with a family history of colon cancer underwent colonoscopy for rectal bleeding.
Colonoscopic findings included several small pedunculated polyps in the right colon, all measuring less than 5 mm. Hyperplastic polyps or tubular adenomas. Diets rich in fat and red meat and low in fiber may contribute to the development of colon cancer.
The peak inci- dence is in the seventh decade of life. Recommended screening for colon cancer for patients without increased risk starts at age 50, but for at-risk patients with a positive family history, screening should start at age 40 some recommend 10 years earlier than the age at which the youngest index case presents.
Annual fecal occult blood tests should be performed as well as digital rectal examination and flexible sigmoidoscopy every 5 years. Additional screening can be done by colonoscopy every 10 years, or a double- contrast barium enema can be done every 5 to 10 years. These recommended screening intervals may be maintained after a negative examination. For patients at high risk for cancer or with polyps, rescreening by colonoscopy at 3-year intervals is recommended.
New technologies such as virtual colonog- raphy and genetic testing of stool specimens are being examined for their appropriate clinical settings.
In this patient, the colonic polyps showed prolif- eration of tubular glands, arising from a fibromuscular base with normal colonic epithelium consistent with a polyp stalk.
The polyps showed no evi- dence of malignant transformation i. The diagnosis was multi- ple tubular adenomas of the colon. Neoplastic proliferation of colonic epithelium that results in the formation of a polyp. Usually implies abnormal, often clonal proliferation of cells that results in the formation of a tumor.
Usually the result of additional genetic abnormalities in cells that lead to further dysfunction or abnormal cell maturation.
Adenoma-dysplasia-carcinoma sequence: Model for colon cancer devel- opment that outlines the genetic pathway involved in the progression from a benign neoplastic polyp adenoma to frankly invasive cancer carcinoma.
Familial adenomatous polyposis syndrome: The prototypic inherited colon cancer phenotype; affected patients have hundreds to thousands of polyps and are at high risk for cancer development. Hereditary nonpolyposis colorectal cancer: Also known as Lynch syn- drome.
Often presents as right-sided colon cancer and involves muta- tion in mismatch repair genes. It is inherited in an autosomal dominant fashion, and affected individuals are also at high risk for extracolonic malignancies such as endometrial carcinomas.
Inflammatory polyps can be seen in chronic colitides such as ulcerative colitis and Crohn disease. Hyperplastic polyps are some of the more frequently encountered polyps and are thought to represent nonneoplastic proliferation of colonic epithelium. There is accumulating evi- dence that some hyperplastic polyps may transform to adenomas through a serrated adenoma pathway.
Adenomas are truly neoplastic proliferations and have the potential to transform and progress to carcinomas see Figure With increasing age, there is an increased incidence of adenoma formation. Approximately 50 percent of patients who have one adenoma have additional synchronous adenomas present. Most polyps are present in the rectosigmoid colon, but with increasing age, there is a tendency to see more right-sided involvement by polyps.
Types of Adenomas Adenomas can be classified on the basis of the pattern of growth: Histologically, depending on the extent of tubular gland formation versus fin- gerlike villous projections, they are classified as tubular adenomas, villous adenomas, or tubulovillous adenomas. Colonic polyp: Polyposis and Inherited Colon Cancer Syndromes Syndromes that involve the formation of multiple gastrointestinal polyps occur infrequently.
Some, such as Peutz-Jeghers syndrome and Cowden disease, are autosomal dominant, resulting in the formation of nonneoplastic hamartomatous polyps; others, such as Canada-Cronkhite syndrome, are not hereditary and result in multiple juvenile polyps. Other clinically significant polyposis or colon cancer syndromes include familial adenomatous polypo- sis and hereditary nonpolyposis colorectal cancer.
Affected individuals have hundreds to thousands of polyps, typically presenting in the left colon. Almost all individuals with APC gene mutations eventually develop colon cancer. Hence, carriers usually are candidates for prophylactic colectomy. Recent studies have shown that cyclooxygenase inhibitors can suppress polyp formation and possibly carcinoma development in patients with FAP.
Henry Lynch. The autosomal dominant inherited disease presents early in life, often with right- sided cancer, and can be associated with polyps, although much less numer- ous usually fewer than 10 than what is seen in FAP. CLINICAL CASES 43 There are also less-well-defined familial cancer syndromes involving glan- dular elements adenocarcinomas that are associated with a family history or personal history of breast, ovarian, endometrial, or colon cancer.
The development of colon cancer is a multifactorial process involving not only predisposition genes but also factors such as diet low-fiber foods, red meat, and refined carbohydrates are nonfavorable , obesity, and inactivity. Genetically, it is known that adenomas can progress and transform through additional mutations i.
Additional genes that have been shown to be involved in this process include the K-ras oncogene, the DCC deleted in colon cancer adhe- sion molecule gene, and the p53 tumor suppressor gene. It is noted that several members of his family also developed colon cancer at relatively young ages. Which of the following genes is most likely to be involved?
Hereditary nonpolyposis colorectal cancer gene B. Mismatch repair gene C. K-ras oncogene [4. The lesion is removed and histologic examination reveals a polyp composed of dysplastic stratified epithelial cells having hyperchromatic nuclei and decreased mucin production.
Fingerlike villous projections are not seen. Hyperplastic polyp B. Inflammatory polyp C. Retention polyp D. Tubular adenoma E. Villous adenoma [4. Cowden disease B. Gardner syndrome C. Peutz-Jeghers syndrome D. Rotor syndrome E. Hereditary nonpolyposis colorectal carcinoma, also known as Lynch syndrome, presents as an autosomal dominant disorder charac- terized by the formation of colon cancer, usually early in life.
The dis- order is associated with the hereditary nonpolyposis colorectal cancer gene and with the formation of multiple colonic polyps, although fewer than seen in the family adenomatous polyposis syndrome.
The presence of dysplastic epithelium within a colonic polyp defines adenomas of the colon, the three types of which are tubular adenomas, mixed tubulovillous villoglandular adenomas, and vil- lous adenomas. Tubular adenomas are the smallest adenomatous polyps of the colon and have the least malignant potential. Microscopically these polyps are composed of dysplastic epithelium that forms tubules and glandular structures. If abundant finger-like papillary structures are present, then the polyp is classified as vil- lous adenomas.
These polyps are the largest types of colonic adeno- mas and have the greatest malignant potential. The Peutz-Jeghers syndrome is an autosomal-dominant disorder that is characterized by the combination of hamartomatous polyps of the small intestine and pigmented lesions around the oral cavity.
The most common site for the hamartomatous polyps is the jejunum. This syndrome is associated with a slight increased risk for the develop- ment of colon cancer. One pathway is the adenoma-dysplasia-carcinoma sequence.
Gastrointestinal Pathology, 2nd ed. Lippincott-Raven, He also has had fatigue and a loss in appetite over the past several weeks. Physical examination reveals generalized jaundice but no other signif- icant 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. A 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. The etiology is largely unknown. However, point mutations of the K-ras gene have been observed in over 90 percent of the pancreatic 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 avail- able 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 approximately 3.
The 5-year relative survival rate of patients with this can- cer 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 progno- sis of pancreatic carcinoma is one of the most dismal among any malignancies ever known. 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 pro- duce their biologic 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 biologic 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 ori- gin, and tumors from endocrine components. Adenocarcinoma is the most common form of cancer, accounting for over 75 percent of all pan- creatic cancers.
The majority of the pancreas is com- posed of exocrine glands, which produce enzymes necessary for food diges- tion. 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 biologic effects throughout the body.
Epidemiology Each year approximately 30, 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 Men tend to be affected more often than women. There does not appear to be a strong correlation between the onset of pancreatic adeno- carcinoma 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 marker, a Lewis blood group—related mucin, frequently is elevated in adenocarcinoma of the pan- creas, but its use in screening for or diagnosis of the cancer is not accepted in gen- eral practice. High CA 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 partic- ular 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 cells—those which line the pancreatic ducts. Approximately 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.
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 polypep- tide PP , vasoactive intestinal peptide VIP , growth hormone-releasing factor GRF , and adrenocorticotropic hormone ACTH , among others.
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 neu- roendocrine tumors approaches 5 years.
Immediate treatment of the sympto- matic conditions created by the oversecretion of the hormone may be appropriate. Surgery is generally curative. 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 which of the following abnormalities? Clear cell carcinoma C.
Medullary carcinoma D. Signet ring carcinoma E. Squamous cell carcinoma [5. CA B. CA C. CA D. CA E. CA [5. Laboratory evaluation finds that during one of these episodes her serum glucose level is decreased and her serum insulin level is increased. Which of the following is the most likely cause of her symptoms? Carcinoid tumor B. Functional hamartoma C. Islet cell adenoma D. Microcystic adenoma E. Adenocarcinoma is the most common type of pancreatic malig- nancy 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 kid- neys, and signet cell carcinomas can be found in the stomach. A medullary carcinoma is a type of carcinoma of the thyroid gland. CA is currently the best available tumor marker used clini- cally to look for possible recurrence of pancreatic cancer after sur- gery. In contrast, CA is associated with ovarian cancer, whereas CA and CA are associated with breast cancer, particularly advanced breast cancer.
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.
The pancreas. Mayer RJ. Pancreatic cancer. At first the episodes, which usu- ally last 1 or 2 weeks, were several months apart, but recently they have occurred more frequently. Other symptoms have included mild joint pain and sometimes red skin lesions. On at least one occasion, her stool has been guaiac-positive, indicating the presence of occult blood.
Colonoscopy reveals several sharply delineated areas with thickening of the bowel wall and mucosal ulceration. Areas adjacent to these lesions appear normal. Biopsies of the affected areas show full-thickness inflammation of the bowel wall and several noncaseating granulomas. A year-old woman has a 2-year history of recurrent diarrhea, abdominal pain, slight fever, joint pain, and red skin lesions. Colonoscopy reveals several sharply delineated areas with thickening of the bowel wall and mucosal ulceration, which on biopsy show full-thickness inflammation of the bowel wall and several noncaseating granulomas.
Additionally, the colonoscopy revealing full-thickness inflammation with non- caseating granulomas is consistent with Crohn disease. Crohn disease is a chronic inflammatory condition that is ubiquitous in its distribution in the gas- trointestinal tract. It most commonly manifests in the small intestine, in par- ticular the terminal ileum.
The disease exhibits aggressive activity of the gastrointestinal immune system, but the exact cause is unknown. Published studies in the United States report incidence rates that vary between 1. The con- dition is more common in the cold climates of the northeastern United States than in the south. Those of Jewish ethnicity have a high incidence. The disor- der, which is slightly more common in females, has a bimodal age distribution, peaking in the early twenties and again emerging in the mid-sixties.
Theories regarding pathogenesis have referred to genetics, infection, autoimmune or allergic processes, thromboembolic disorders, and dietary disorders. The principal stimulus for diarrhea is the mucosal immune response in association with cytokine release. If the colon is involved, diarrhea may be more marked and tenesmus may occur. Abdominal pain may be due to local inflammation or obstruction if it is experienced in the central abdomen or right lower quad- rant. Abscesses or fistulae also may produce pain.
Secondary causes of abdominal pain in relation to Crohn disease are gallstones and renal colic. Malabsorption leading to weight loss and failure to thrive may occur in chil- dren.
Fat, protein, mineral, and vitamin deficiencies may be associated with extensive or recurrent disease. About one-third of patients develop perineal symptoms or signs such as anal fistulae or fissures.
Nongastrointestinal symptoms of Crohn disease involve the skin, joints, or eyes. Skin lesions include erythema nodosum, pyoderma gangrenosa, aphthous stomatitis, and finger clubbing. The rheumatologic manifestations often present as a large joint polyarthropathy resembling ankylosing spondyli- tis or a small joint fleeting polyarthropathy that is like rheumatoid arthritis. Inflammatory eye lesions are confined to the anterior chamber, such as uveitis, iritis, episcleritis, and conjunctivitis.
A chronic active hepatitis may develop; more seriously, sclerosing cholangitis can progress to cirrhosis. There is a predisposition to gallstones when terminal ileal disease is present. Physical Examination Physical examination may reveal a nutritional deficiency. The extraintestinal manifestations may be apparent. Abdominal examination may suggest partial bowel obstruction, inflammatory mass, focal areas of tenderness, or ente- rocutaneous fistulae.
Gingivitis and periodontitis 68 6. Major infections of the mouth, jaws and perioral tissues 90 7. Cysts of the jaw 8. Odontogenic tumours and tumour-like lesions of the jaws 9. Non-odontogenic tumours of the jaws Genetic, metabolic and other non-neoplastic bone diseases Diseases of the oral mucosa: Non-infective stomatitis Tongue disorders Benign chronic white mucosal lesions Oral premalignancy Oral cancer Neoplastic and non-neoplastic diseases of salivary glands Common benign mucosal swellings Soft-tissue mesenchymal neoplasms