Cancer of the Gastrointestinal Tract and Neuroendocrine Tumors




Esophageal Cancers


The prevalence of esophageal cancer varies over 20-fold throughout the world. Esophageal cancer is most common in central Asia and remains relatively rare in the United States. Approximately 14,000 new cases of esophageal cancer occur annually in the United States, where 75% of esophageal cancers develop in men and only 25% in women.


HISTOLOGY OF ESOPHAGEAL CANCER


Worldwide, 90% of esophageal cancers are squamous cell carcinomas. The risk of esophageal squamous cell carcinoma is related closely to excessive alcohol consumption and chronic cigarette smoking. The squamous cell carcinomas, including spindle cell and verrucous variants, are most prevalent in the upper esophagus. Interestingly, in the past two decades the relative incidence of squamous cell carcinoma and adenocarcinoma of the esophagus has shifted markedly in both the United States and Europe. In these regions squamous cell carcinoma has become somewhat less common, whereas the incidence of esophageal adenocarcinoma has increased to a considerable degree. In Caucasian males in the United States, for example, the incidence of adenocarcinoma now exceeds the incidence of squamous cell carcinoma. Adenocarcinomas of the esophagus generally occur in the distal third of the esophagus and are particularly common at the gastroesophageal junction. The risk of esophageal adenocarcinoma has been closely linked to the presence of chronic gastroesophageal reflux and Barrett’s esophagus.


In addition to tobacco and alcohol, other risk factors for squamous cell esophageal cancer include achalasia, history of cancer treated with radiation therapy in the mid- to upper chest region (e.g., breast cancer), tylosis, caustic injury to the esophagus, and Plummer-Vinson syndrome. In contrast, risk factors for the development of adenocarcinoma of the esophagus include gastroesophageal reflux disease, Barrett’s esophagus, obesity, prior radiation exposure to the mid- to upper chest, and smoking. Rare undifferentiated small cell carcinomas occur in the lower and middle esophagus. Risk factors for these unusual lesions have not been established. These highly malignant tumors behave like small cell lung cancers, occasionally producing paraneoplastic syndromes.


STAGING OF ESOPHAGEAL CANCERS


The unique structure of the esophagus is significant to the biologic understanding and clinical management of malignant disease. There is a rich lymphatic drainage throughout the length of the esophagus and a discontinuous serosa. Therefore, “skip areas” of micrometastases occur that necessitate wide surgical resection of operable tumors. Lymph node drainage varies within the esophagus (cervical vs thoracic). Nodal metastases frequently develop in mediastinal, para-aortic, and celiac lymph nodes.


In the TNM staging system (tumor, node, metastasis) commonly used for esophageal carcinoma, stages I and II represent operable disease, stage III denotes marginally resectable disease, and stage IV signifies inoperable cancer. The last stage is characterized by metastases (M1). About 15% of cancers originate in the upper third of the esophagus (cervical and upper thoracic esophagus), 50% in the middle third, and 35% in the lower third. The site of the primary tumor is critically important, because it relates to clinical behavior (adjacent organ involvement, nodal metastases) and technical resectability. Primary surgical resection is possible in about 40% to 50% of cases. About one third of patients are candidates for palliative surgery, and 20% to 30% present with unresectable stage III or IV disease. The 5-year survival rate is less than 5% for stage IV disease but is about 70% for stage I cancers.


Staging procedures involve triple endoscopy, including detailed ear-nose-throat examination as well as bronchoscopy and esophagoscopy, because there is a high potential for development of other aerodigestive cancers because of similar risk factors. Mediastinoscopy, laparoscopy, and computed tomography (CT) scans of the chest, liver, and upper abdomen are important to determine the presence of nodal or visceral metastases. Endoscopic ultrasound is helpful to determine the extent of invasion through the esophageal wall and involvement of regional lymph nodes. Positron emission tomography (PET) scanning has been shown to be highly sensitive in detecting occult metastases from esophageal cancer and is being increasingly used as a staging procedure.


CLINICAL MANIFESTATIONS


About 90% of patients present with dysphagia and weight loss, often accompanied by pain on swallowing (odynophagia). These symptoms characteristically appear with advanced disease, because difficulty in swallowing arises when at least 60% of the esophageal circumference is infiltrated by cancer. Other symptoms include regurgitation or emesis and discomfort in the throat, substernal area, or epigastrium. In advanced disease, local invasion of the trachea, bronchi, lung, or even aorta may result in aspiration pneumonia, massive hemorrhage, pleural effusion, or superior vena cava syndrome. Moreover, the development of one or more tracheo- or bronchoesophageal fistulae may also occur, as well as esophageal perforation and mediastinitis. Occasionally patients present with supraclavicular lymph node, bone, or liver metastases.


TREATMENT CONSIDERATIONS


Treatment of esophageal cancers is dependent on the stage of disease as well as whether the health of the patient allows him or her to undergo surgery. For patients with resectable cancers, options would include surgery alone, combined-modality chemotherapy and radiation therapy followed by surgery, or chemoradiation alone. Despite lack of definitive data supporting this approach, for tumors with at least moderate invasion into the esophageal wall and/or regional lymph node involvement, most patients in the United States are treated with chemoradiation followed by surgery. For patients not deemed operative candidates, who refuse surgery, or who have nonresectable disease but lack distant metastases, combined-modality chemotherapy and radiation therapy is the treatment of choice and can lead to a cure in select patients. Finally, patients with metastatic disease should be considered for palliative therapies, including chemotherapy, radiation therapy, and/or esophageal stenting.


FIGURE 7.1


STAGING OF ESOPHAGEAL CARCINOMA. Graph shows survival according to stage of disease. Data from 5071 patients.

(From Greene FL, Page D, Fleming I, et al, editors, for the American Joint Committee on Cancer: AJCC cancer staging handbook , ed 6, New York, 2002, Springer.)



FIGURE 7.2


Trends in age-adjusted incidence rates for esophageal carcinoma among U.S. males by race and cell type, 1974–1976 to 1992–1994.

(From Devesa SS, Blot WJ, Fraumeni J: Changing patterns in the incidence of esophageal and gastric carcinoma in the United States, Cancer 83(10): 2049–2063, 1998.)



FIGURE 7.3


SQUAMOUS CELL CARCINOMA. Endoscopic view of the esophagus shows a tiny, early ulcer that proved on biopsy to be malignant.



FIGURE 7.4


SQUAMOUS CELL CARCINOMA.(A) An esophageal lesion in situ shows full-thickness nuclear atypia but no invasion. (B) An early invasive tumor is marked by downgrowth of malignant epithelium encroaching on the submucosa. (C) An established, infiltrating, well-differentiated lesion shows islands of malignant epithelium invading deep into esophageal muscle.



FIGURE 7.5


SQUAMOUS CELL CARCINOMA. Endoscopic view shows circumferential involvement of the esophagus with friable tumor. Note the narrowed lumen.



FIGURE 7.6


SQUAMOUS CELL CARCINOMA. Endoscopy shows a tracheoesophageal fistula caused by an ulcerating esophageal squamous cancer. The orifice of the fistula tract is clearly visible.



FIGURE 7.7


SQUAMOUS CELL CARCINOMA. A 62-year-old man with progressive dysphagia and marked weight loss was found on endoscopy to have a poorly differentiated tumor of the middle third of the esophagus. (A) Barium swallow film shows narrowing of the esophagus with mucosal destruction, consistent with esophageal cancer. (B) CT scan reveals regional metastases and a large primary mass obstructing the esophagus. Complete clinical remission was achieved in 3 months after combination chemotherapy plus radiation therapy. Unfortunately, liver metastases subsequently occurred.



FIGURE 7.8


SQUAMOUS CELL CARCINOMA. This sagittal section through the larynx, trachea, and anterior wall of the esophagus (on the right) was obtained at autopsy of a 57-year-old man who presented with a short history of dysphagia. A barium swallow revealed neoplastic obstruction of the esophagus; the patient died soon afterward from bronchopneumonia. A solid, raised, pale tumor (6 × 2 × 2 cm), arising in the esophagus, has infiltrated the posterior wall of the trachea, forming a nodular projection into the tracheal lumen. Anthracotic paratracheal lymph nodes are extensively infiltrated by pale tumor. This case clearly demonstrates the spread of esophageal carcinoma.



FIGURE 7.9


ADENOCARCINOMA. Weight loss and right upper abdominal pain, with minimal dysphagia, developed in a 58-year-old man. Esophagoscopy showed a constricting, poorly differentiated lesion of the lower third of the esophagus. (A) Barium swallow film defines the extent of the lesion ( arrowheads ). On CT scan, (B) a large liver metastasis and (C) early pulmonary metastases are noted.



FIGURE 7.10


ADENOCARCINOMA. This ulcerating tumor arose at the gastroesophageal junction where, as in this case, it is often impossible to distinguish an esophageal carcinoma from one arising in the gastric fundus and growing upward to involve the distal esophagus.



FIGURE 7.11


ADENOCARCINOMA IN BARRETT’S METAPLASIA. Endoscopic view demonstrates an extensive lesion arising in an area of Barrett’s metaplasia; the lumen is obstructed by a bleeding and polypoid exophytic mass.



FIGURE 7.12


ADENOCARCINOMA IN BARRETT’S METAPLASIA. (A) Low-power photomicrograph shows esophageal tissue with metaplastic Barrett’s epithelium, with columnar cells and villous changes. There is some residual esophageal squamous mucosa adjacent to an area of ulcerated adenocarcinoma. (B) High-power view shows glands of tumor encroaching on the squamous epithelium.






Gastric Cancers


There is a marked variation in the incidence of gastric cancer worldwide. Death rates are highest in Costa Rica and Japan, about 10-fold greater than those in the United States. Nonetheless, both the incidence and the mortality rate of gastric cancer have decreased worldwide over the past 50 years. In 1930 gastric cancer was the leading cause of cancer-related deaths in men, with a rate of 37 per 100,000 in the United States, as compared with the current U.S. rate of less than 6 per 100,000. The incidence of gastric cancer increases after age 50 and is highest in lower socioeconomic groups. The male-to-female ratio of 3:2 is less than observed in esophageal cancer.


Many etiologic influences have been proposed to explain the decreasing incidence of gastric cancer, mostly concerning dietary and environmental factors and the increased availability of refrigeration, which reduces the growth of nitrate-producing bacteria in food. Another factor, loss of gastric acidity, may predispose to stomach cancer. This condition can be caused by partial gastrectomy, atrophic gastritis, or achlorhydria with subsequent pernicious anemia. Chronic gastritis is frequently associated with gastric cancer, and the presence of intestinal metaplasia further elevates the risk of gastric cancer. Recent studies suggest that infection with Helicobacter pylori is associated with gastric cancer, leading some to postulate a pathogenic role. Other premalignant lesions include adenomas, 40% of which may progress to carcinoma. Hereditary diffuse gastric cancer is associated with mutations in the E-cadherin gene.


HISTOLOGY


About 90% of gastric malignancies are adenocarcinomas, with the remainder comprising malignant gastrointestinal (GI) stromal tumors (GISTs; leiomyosarcomas) and lymphomas. Histologically, adenocarcinomas are classified as intestinal or diffuse. Intestinal-type cancers are characterized by cohesive neoplastic cells that form glandlike tubular structures resembling colonic adenocarcinomas. They are often preceded by premalignant changes (chronic atrophic gastritis and intestinal metaplasia) and may result in ulcerative lesions, particularly in the antrum or the lesser curvature. Diffuse-type cancers are composed of infiltrating gastric mucous or “signet-ring” cells that infrequently form masses or ulcers. They tend to occur throughout the stomach, often resulting in a linitis plastica (“leather bottle”) appearance. Much of the decline in gastric cancer rates has been due to decreases in the intestinal type. Consequently, the diffuse-type adenocarcinomas have become relatively more common, accounting for up to one third of cases. Diffuse-type malignancies are associated with a very poor prognosis, with a survival rate of less than 2%. Much of the pale “tumor” tissue in this variant actually represents fibrosis of the submucosa and muscle.


Macroscopically, gastric cancers are classified into five categories. The ulcerative variant (25% of cases) may resemble a benign gastric ulcer. About 7% and 36% are polypoid and fungating tumors, respectively, and are nodular tumors that can reach a large size. The remaining 26% of gastric cancers show a scirrhous pattern caused by thickening and rigidity of the gastric wall due to diffuse infiltration by signet-ring cells. The marked fibrous reaction results in the appearance of linitis plastica. The least common gross appearance is the superficial type, representing less than 6% of cases. The normal mucosa is replaced by sheetlike collections of malignant cells that do not invade beyond the submucosa. This type is categorized as early gastric cancer and represents potentially resectable (for cure) cancers.


STAGING OF GASTRIC CANCERS


A TNM staging system is used for gastric cancers. Prognosis is dependent both on stage of disease and location within the stomach. Proximal tumors (within the cardia and fundus) have a worse prognosis than distal tumors (antrum and pylorus). The 5-year survival rate is 45% to 80% for the uncommon cases that are detected in stage I of the disease, 25% to 40% for stage II, less than 20% for stage III, and 5% for stage IV.


Extensive local invasion by gastric cancer is common and most often involves the pancreas, omentum, transverse colon, liver, or spleen; direct contiguous spread into the esophagus or duodenum is also common. Moreover, because gastric cancer so often penetrates the serosa, it is particularly prone to transperitoneal dissemination. Spread also occurs via lymphatics and blood vessels. Gastric cancer can lead to drop metastases to the large and small bowel, pelvic floor, and ovary. Staging studies include endoscopy with or without endoscopic ultrasound, chest imaging; CT scans of liver, abdomen, and pelvis should be obtained.


CLINICAL MANIFESTATIONS


Because early gastric cancer is asymptomatic, many patients present with advanced disease. Symptoms include ulcer-related pain, anorexia, weight loss, and vague epigastric distress. Development of left supraclavicular adenopathy (Virchow’s node), an ovarian mass (Krukenberg tumor), hepatomegaly, ascites, or anemia may be the initial manifestation. Gastric carcinoma is also a well-recognized cause of secondary pyloric stenosis in adulthood.


TREATMENT CONSIDERATIONS


Up to 50% of patients diagnosed with gastric cancer are considered inoperable, and treatment should be directed toward palliation. Options for palliation include best supportive care only, systemic chemotherapy, radiation therapy (usually limited to control bleeding and obstructive systems), and endoscopic stenting. For patients with resectable disease, growing evidence supports the role of either postoperative adjuvant therapy (with combination of chemotherapy and chemoradiotherapy) or neoadjuvant chemotherapy followed by surgery followed by further adjuvant chemotherapy.


FIGURE 7.13


Anatomic subdivisions of the stomach.



FIGURE 7.14


STAGING OF GASTRIC CARCINOMA. Graph of disease-specific survival data taken from the Commission on Cancer Patient Care Evaluation Study (Wanebo HJ, Kennedy BJ, Chmiel J, et al: Cancer of the stomach: a patient care study by the American College of Surgeons, Ann Surg 218:583–592, 1993).

(From Greene FL, Page D, Fleming I, et al, editors, for the American Joint Committee on Cancer: AJCC cancer staging handbook , ed 6, New York, 2002, Springer.)



FIGURE 7.15


EARLY ADENOCARCINOMA. Endoscopic view shows an early gastric lesion arising between the lesser curvature and antrum. Note the irregular area of elevation and scarring.



FIGURE 7.16


EARLY ADENOCARCINOMA. An intestinal-type lesion extends throughout the mucosa and submucosa but not through the muscularis mucosa.



FIGURE 7.17


ADENOCARCINOMA. Endoscopic view shows a lesion extending from the cardia into the distal esophagus.




Table 7.1

Distribution of Malignancies among Subdivisions of the Stomach






















Subdivision Frequency (%)
Antrum and prepylorus ≥50
Cardia and fundus –25
Lesser curvature 20
Greater curvature 3–5
Entire stomach 5–10

* Approximately 2% of patients may have cancers in multiple sites.

FIGURE 7.18


ADENOCARCINOMA. Infiltrating glands of tumor extend upward from the stomach underneath the esophageal squamous lining.



FIGURE 7.19


ADENOCARCINOMA. Barium swallow study shows a large fundal carcinoma.

(Courtesy of H. Shawdon.)



FIGURE 7.20


MALIGNANT GASTRIC ULCER. This antral lesion shows heaped-up nodular margins, particularly suggestive of malignancy.



FIGURE 7.21


MALIGNANT GASTRIC ULCER. Partial gastrectomy specimen shows a large malignant ulcer of the lesser curvature, with raised, rolled margins.



FIGURE 7.22


ADENOCARCINOMA. This intestinal-type tumor shows well-formed malignant glandular elements.



FIGURE 7.23


ADENOCARCINOMA (POLYPOID TYPE). Barium swallow study reveals a large polypoid lesion in the body of the stomach, causing a filling defect.



FIGURE 7.24


ADENOCARCINOMA (FUNGATING TYPE). Endoscopic view reveals a hemorrhagic tumor near the lesser curvature, with ulceration and necrosis.



FIGURE 7.25


ADENOCARCINOMA (FUNGATING TYPE). This specimen, opened along the greater curvature of the stomach, shows a large, fungating tumor occupying the lesser curvature.



FIGURE 7.26


STENOSING PYLORIC CARCINOMA. This postmortem specimen, showing the distal stomach and pylorus, is from an 84-year-old woman who presented with severe anemia and a 3-month history of weight loss. Palliative gastroenterostomy was performed 4 days before death. A localized, nodular, stenosing tumor, measuring 6 cm in diameter, can be seen in the pyloric canal. There is obvious deep mural invasion, but the proximal duodenum is completely unaffected. The gastroenterostomy, 2 cm proximal to the tumor, is patent.



FIGURE 7.27


DIFFUSE ADENOCARCINOMA (LINITIS PLASTICA). Barium study (erect view) shows the typical appearance of an extensive linitis plastica involving the entire stomach, which appears fixed and narrowed. No peristalsis was observed, and barium flowed out of the stomach quickly. The mucosal edge is only slightly irregular; ulceration of the mucosa may be minimal or absent in this type of carcinoma. ( Arrow indicates the gastric fundus.)



FIGURE 7.28


DIFFUSE ADENOCARCINOMA (LINITIS PLASTICA). This gastrectomy specimen, opened anteriorly, is from a 64-year-old man who had a 3-year history of dyspepsia. Barium swallow and endoscopy revealed a gastric carcinoma. There is diffuse infiltration of the pylorus and body of the stomach by pale tumor, as well as marked luminal narrowing, although the tumor has no exophytic component. Note the irregular infiltration of the muscle coat.



FIGURE 7.29


DIFFUSE ADENOCARCINOMA. (A) No tubular pattern can be seen in the low-power view. (B) Higher magnification reveals the discrete nature of the mucin-laden tumor cells (signet-ring cells) in contrast to the residual benign pyloric gland.



FIGURE 7.30


LIVER INVASION. This specimen, showing the stomach opened anteriorly, is from a 62-year-old man who presented with a 6-month history of epigastric pain, vomiting, and weight loss, as well as a palpable epigastric mass. Total gastrectomy with partial hepatic lobectomy was performed. An ulcerating neoplasm of the lesser curvature has spread extensively into the adherent hepatic parenchyma. Extensive local invasion by gastric cancer is common.



FIGURE 7.31


BONE MARROW METASTASES. A 60-year-old man presented with microangiopathic hemolytic anemia (MAHA). (A) Bone marrow biopsy specimen shows metastatic mucin-producing adenocarcinoma. (B) High-power view of a bone marrow aspirate demonstrates a clump of malignant cells. Further evaluation revealed a primary gastric cancer. Chemotherapy led to a complete clinical remission lasting 9 months. Cancer-related MAHA is most commonly seen with gastric carcinoma. Fragmentation of red blood cells is due to many factors, including the shearing effect of fibrin strands secondary to disseminated intravascular coagulation (associated with mucin-producing adenocarcinomas) or shearing by direct contact with intravascular tumor cells or with secondary proliferation of pulmonary arterioles.






Pancreatic Cancers


The increasing incidence of exocrine pancreatic cancers in the United States reflects the aging of the population. About 32,000 new cases are diagnosed each year, with nearly as many deaths. It is the fourth most common cause of cancer-related mortality in adults in the United States. The median age of patients with these tumors is approximately 70 years, with one third of cases occurring in persons aged 75 years or older. About one quarter of patients are younger than 60 years. The etiology remains obscure, except for a known association with cigarette smoking; pancreatic cancer is two to four times more common in heavy smokers than in nonsmokers. Other risk factors include diabetes mellitus and rare hereditary syndromes (e.g., ataxia-telangiectasia, Peutz-Jeghers syndrome, and hereditary chronic pancreatitis). Data are mixed regarding the risk of alcohol abuse and chronic pancreatitis in the development of pancreatic cancer.


HISTOLOGY


About 75% of pancreatic malignancies are ductal adenocarcinomas, of which approximately 70% occur in the head of the pancreas. A variety of uncommon types of pancreatic carcinoma have been described, including acinar, adenosquamous, anaplastic, papillary, mucous, and microadenocarcinomas, each of which composes less than 5% of the total. All of these have similarly poor prognoses and are treated in a similar fashion. Also uncommon are mucinous cystic neoplasms (cystadenoma/cystadenocarcinoma) of the pancreas, which occur most frequently in middle-aged women. These are typically located in the tail of the pancreas. Clinical behavior can be difficult to predict pathologically, leading some to conclude that all mucinous cystic neoplasms of the pancreas have malignant potential. Complete surgical resection results in cure rates of 30% to 60%. The remaining 5% to 10% of pancreatic neoplasms are predominantly islet cell–derived (see Chapter 10 ). Other rare neoplasms include pancreatoblastomas, most of which occur in children, and the solid and cystic neoplasms. The latter occurs most frequently in young women and carries an excellent prognosis following resection.


STAGING OF PANCREATIC CANCERS


Pancreatic cancer most commonly presents at an advanced stage. Early or local disease (stage I), with cancer confined to the pancreas, is unusual. Regional disease (stage II or III) is more common and includes tumor invasion into the bile duct, duodenum, adjacent peripancreatic tissue, or adjacent lymph nodes. Extensive disease (stage IV) signifies either invasion of tumor into the stomach, colon, spleen, or blood vessels, or the presence of distant metastases. More practically, pancreatic cancer can be divided into three stages: local/resectable, locally advanced (considered unresectable but without distant metastases), and metastatic. The overall prognosis of pancreatic carcinoma (excluding mucinous cystic neoplasms) is dismal, with a median survival time of 4–6 months and a 5-year survival rate of 2% to 3%.


Staging procedures include ultrasonography, CT scanning, and magnetic resonance imaging (MRI). A diagnostic laparoscopy may also be performed to detect peritoneal disease that is not visible radiologically. Regardless of these studies, an accurate histologic diagnosis is necessary to distinguish benign disease from carcinoma, islet cell tumors, and retroperitoneal lymphomas, because of the major therapeutic and prognostic differences among these disease entities. When liver metastases are present, fine-needle aspiration biopsy is often successful in establishing a diagnosis of metastatic disease. In the case of locally advanced disease, endoscopic retrograde cholangiopancreatography or fine-needle aspiration may be used. In the setting of a resectable pancreatic mass, biopsy may be deferred in favor of proceeding directly with surgical resection. Criteria for surgical resection include absence of metastatic disease and absence of invasion of prominent local blood vessels.


CLINICAL MANIFESTATIONS


Carcinoma of the head of the pancreas leads to jaundice caused by biliary obstruction. The gallbladder is usually distended (Courvoisier sign). Carcinomas of the body and tail are accompanied by severe pain resulting from retroperitoneal invasion and infiltration of the celiac ganglia and splanchnic nerves. However, body and tail lesions are often detected at later stages because symptoms do not occur until the disease has advanced more than pancreatic head tumors. About 75% of patients present with pain and progressive weight loss. Splenomegaly, due to encasement and obstruction of the splenic vein, may also occur. Other features include depression, diabetes mellitus (5% to 10% of cases), alterations in bowel function (particularly obstipation), and venous thrombosis with migratory thrombophlebitis (Trousseau sign; see “Hepatobiliary Cancers” ).


TREATMENT CONSIDERATIONS


Treatment of pancreatic cancer is dependent on the clinical stages described earlier—local/resectable, locally advanced, and metastatic. For resectable disease surgery remains the treatment of choice (although recurrence rates are >80%). The use and choice of adjuvant therapy remain controversial but may include chemotherapy alone or combined-modality chemotherapy and radiation therapy. For patients with locally advanced disease either chemoradiotherapy or chemotherapy alone should be considered. Patients with metastatic disease should be considered for chemotherapy; however, the benefits for most patients remain limited.



FIGURE 7.32


CYSTADENOMA-CYSTADENOCARCINOMA. Cystadenomas and cystadenocarcinomas are often quite large at the time of clinical detection. (A) As their names imply, both tumors contain cystic elements and both frequently show internal calcification, often in a stellate pattern ( arrowheads ). (B, C) The tumor is typically hypervascular; angiography demonstrates hypertrophied pancreatic branches ( arrowheads ) of the splenic artery feeding the lesion in the tail of the pancreas.



FIGURE 7.33


CYSTADENOCARCINOMA. CT scan of a 33-year-old woman who presented with metastatic disease shows one of several large pancreatic cysts and many liver metastases.



FIGURE 7.34


PANCREATIC CARCINOMA. Endoscopic view shows a tumor invading the duodenal wall just above the papilla of the pancreatic duct. The folds are irregular and nodular.



FIGURE 7.35


PANCREATIC CARCINOMA. Barium study shows a tumor mass in the head of the pancreas invading the duodenal loop and producing changes in the fold pattern.



FIGURE 7.36


PANCREATIC CARCINOMA. Percutaneous transhepatic cholangiogram demonstrates obstruction of the common bile duct by tumor, which produced jaundice in this patient.



FIGURE 7.37


PANCREATIC CARCINOMA. Ultrasound scan (sagittal section) shows a lobulated mass in the body of the pancreas.

(Courtesy of Dr W. Lees.)



FIGURE 7.38


PANCREATIC CARCINOMA. Endoscopic retrograde cholangiopancreatography shows stricture of the pancreatic duct with dilatation upstream due to carcinoma. Shown are examples of carcinoma of the head (A) , body (B) , and tail (C) of the pancreas producing obstruction of the pancreatic duct ( arrow ).



FIGURE 7.39


PANCREATIC CARCINOMA. Abdominal CT scan shows a large focal mass in the tail of the pancreas.



FIGURE 7.40


Staging of pancreatic carcinoma.

(From Greene FL, Page D, Fleming I, et al, editors, for the American Joint Committee on Cancer: AJCC cancer staging handbook , ed 6, New York, 2002, Springer.)



FIGURE 7.41


BENIGN VERSUS MALIGNANT PANCREATIC CYTOLOGY. In contrast to (A) a sheet of benign ductal cells, (B) malignant cells show the usual characteristics of malignancy: an increased nucleus-to-cytoplasm ratio, hyperchromatic nuclei, and irregular nuclear contours. Note the uniform distribution of the benign, as compared with the malignant cells.



FIGURE 7.42


Adenocarcinoma of the pancreas often appears as a diffuse infiltrative, tan/white fibrotic lesion effacing the normal lobular architecture of the pancreatic parenchyma, as shown here in the head of the pancreas (between the pancreatic and common bile ducts) in a Whipple resection specimen. (1) ampulla, (2) common bile duct, (3) cancer, (4) pancreatic duct, (5) duodenal wall.



FIGURE 7.43


PANCREATIC CARCINOMA. Three histologic patterns may be found in pancreatic carcinoma. (A) Well-differentiated tumors are marked by well-formed glands of tumor cells. (B) In this moderately differentiated lesion, nests of tumor cells produce a squamoid configuration. (C) Pancreatic carcinomas typically induce an intense desmoplastic response. Perineural tumor invasion is also a frequent finding. In some cases diagnosis of malignancy from a needle biopsy that samples only the desmoplastic stroma may be difficult to distinguish from dense fibrosis in chronic pancreatitis.



FIGURE 7.44


PANCREATIC CARCINOMA. These autopsy specimens demonstrate (A) a carcinoma invading the head of the pancreas, infiltrating the duodenum, and destroying the pancreatic duct, and tumors (B) of the body ( arrows ) and (C) tail. Note the well-demarcated masses and areas of necrosis.

( A , Courtesy of M. Knight; B , courtesy of Dr J. Newman.)



FIGURE 7.45


LIVER METASTASES. Abdominal CT scan in a patient with pancreatic carcinoma shows an enlarged, abnormal-looking liver, with dilated bile ducts centrally (to which the patient’s jaundice can be ascribed) and widespread metastases more peripherally. Other CT sections showed a mass in the head of the pancreas.



FIGURE 7.46


(A) Solid pseudopapillary tumor of the pancreas, as shown here in the tail of the pancreas abutting the spleen, typically has hemorrhagic/necrotic foci on gross examination; occasionally such foci impart a pseudocystic appearance (not shown). The tumor is classically encountered as an incidental finding or as a cause of abdominal pain in young adult females. The cytologic appearance on direct smears prepared from fine-needle aspirates is characteristic: loosely cohesive tumor cells appear to show off a “pseudopapilla,” that is, a core of myxoid stroma containing a central capillary. Although more than 95% of patients are cured by excision alone, this case showed cytologic atypia (B) , vascular invasion (C) , and frequent mitoses (not shown), warranting designation as the malignant variant of solid pseudopapillary tumor. An isolated metastasis in the lesser sac was identified at the time of resection (not shown).



FIGURE 7.47


(A) Nonbacterial thrombotic endocarditis (NBTE). A 70-year-old man with pancreatic cancer developed fatal pulmonary and cerebral emboli. Autopsy findings included classic features of NBTE, characterized by sterile thrombi without inflammation at the lines of closure of cardiac valve leaflets. This complication is associated with the hypercoaguable state classically referred to as the Trousseau syndrome in patients with mucinous adenocarcinoma. The thrombi may embolize or disseminated intravascular coagulation may supervene, leading to vascular occlusion in end organs such as the spleen, which displays wedge-shaped hemorrhagic infarcts ( B ), or the heart, where microscopy reveals a thrombus in a small muscular artery supplying an organizing, infarcted zone of myocardium (C) .






Pancreatic Cancers


The increasing incidence of exocrine pancreatic cancers in the United States reflects the aging of the population. About 32,000 new cases are diagnosed each year, with nearly as many deaths. It is the fourth most common cause of cancer-related mortality in adults in the United States. The median age of patients with these tumors is approximately 70 years, with one third of cases occurring in persons aged 75 years or older. About one quarter of patients are younger than 60 years. The etiology remains obscure, except for a known association with cigarette smoking; pancreatic cancer is two to four times more common in heavy smokers than in nonsmokers. Other risk factors include diabetes mellitus and rare hereditary syndromes (e.g., ataxia-telangiectasia, Peutz-Jeghers syndrome, and hereditary chronic pancreatitis). Data are mixed regarding the risk of alcohol abuse and chronic pancreatitis in the development of pancreatic cancer.


HISTOLOGY


About 75% of pancreatic malignancies are ductal adenocarcinomas, of which approximately 70% occur in the head of the pancreas. A variety of uncommon types of pancreatic carcinoma have been described, including acinar, adenosquamous, anaplastic, papillary, mucous, and microadenocarcinomas, each of which composes less than 5% of the total. All of these have similarly poor prognoses and are treated in a similar fashion. Also uncommon are mucinous cystic neoplasms (cystadenoma/cystadenocarcinoma) of the pancreas, which occur most frequently in middle-aged women. These are typically located in the tail of the pancreas. Clinical behavior can be difficult to predict pathologically, leading some to conclude that all mucinous cystic neoplasms of the pancreas have malignant potential. Complete surgical resection results in cure rates of 30% to 60%. The remaining 5% to 10% of pancreatic neoplasms are predominantly islet cell–derived (see Chapter 10 ). Other rare neoplasms include pancreatoblastomas, most of which occur in children, and the solid and cystic neoplasms. The latter occurs most frequently in young women and carries an excellent prognosis following resection.


STAGING OF PANCREATIC CANCERS


Pancreatic cancer most commonly presents at an advanced stage. Early or local disease (stage I), with cancer confined to the pancreas, is unusual. Regional disease (stage II or III) is more common and includes tumor invasion into the bile duct, duodenum, adjacent peripancreatic tissue, or adjacent lymph nodes. Extensive disease (stage IV) signifies either invasion of tumor into the stomach, colon, spleen, or blood vessels, or the presence of distant metastases. More practically, pancreatic cancer can be divided into three stages: local/resectable, locally advanced (considered unresectable but without distant metastases), and metastatic. The overall prognosis of pancreatic carcinoma (excluding mucinous cystic neoplasms) is dismal, with a median survival time of 4–6 months and a 5-year survival rate of 2% to 3%.


Staging procedures include ultrasonography, CT scanning, and magnetic resonance imaging (MRI). A diagnostic laparoscopy may also be performed to detect peritoneal disease that is not visible radiologically. Regardless of these studies, an accurate histologic diagnosis is necessary to distinguish benign disease from carcinoma, islet cell tumors, and retroperitoneal lymphomas, because of the major therapeutic and prognostic differences among these disease entities. When liver metastases are present, fine-needle aspiration biopsy is often successful in establishing a diagnosis of metastatic disease. In the case of locally advanced disease, endoscopic retrograde cholangiopancreatography or fine-needle aspiration may be used. In the setting of a resectable pancreatic mass, biopsy may be deferred in favor of proceeding directly with surgical resection. Criteria for surgical resection include absence of metastatic disease and absence of invasion of prominent local blood vessels.


CLINICAL MANIFESTATIONS


Carcinoma of the head of the pancreas leads to jaundice caused by biliary obstruction. The gallbladder is usually distended (Courvoisier sign). Carcinomas of the body and tail are accompanied by severe pain resulting from retroperitoneal invasion and infiltration of the celiac ganglia and splanchnic nerves. However, body and tail lesions are often detected at later stages because symptoms do not occur until the disease has advanced more than pancreatic head tumors. About 75% of patients present with pain and progressive weight loss. Splenomegaly, due to encasement and obstruction of the splenic vein, may also occur. Other features include depression, diabetes mellitus (5% to 10% of cases), alterations in bowel function (particularly obstipation), and venous thrombosis with migratory thrombophlebitis (Trousseau sign; see “Hepatobiliary Cancers” ).


TREATMENT CONSIDERATIONS


Treatment of pancreatic cancer is dependent on the clinical stages described earlier—local/resectable, locally advanced, and metastatic. For resectable disease surgery remains the treatment of choice (although recurrence rates are >80%). The use and choice of adjuvant therapy remain controversial but may include chemotherapy alone or combined-modality chemotherapy and radiation therapy. For patients with locally advanced disease either chemoradiotherapy or chemotherapy alone should be considered. Patients with metastatic disease should be considered for chemotherapy; however, the benefits for most patients remain limited.



FIGURE 7.32


CYSTADENOMA-CYSTADENOCARCINOMA. Cystadenomas and cystadenocarcinomas are often quite large at the time of clinical detection. (A) As their names imply, both tumors contain cystic elements and both frequently show internal calcification, often in a stellate pattern ( arrowheads ). (B, C) The tumor is typically hypervascular; angiography demonstrates hypertrophied pancreatic branches ( arrowheads ) of the splenic artery feeding the lesion in the tail of the pancreas.



FIGURE 7.33


CYSTADENOCARCINOMA. CT scan of a 33-year-old woman who presented with metastatic disease shows one of several large pancreatic cysts and many liver metastases.



FIGURE 7.34


PANCREATIC CARCINOMA. Endoscopic view shows a tumor invading the duodenal wall just above the papilla of the pancreatic duct. The folds are irregular and nodular.



Aug 13, 2019 | Posted by in ONCOLOGY | Comments Off on Cancer of the Gastrointestinal Tract and Neuroendocrine Tumors
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