Category Archives: carcinoma

carcinoma, malignant, pancreas, primary cancer

Pancreas Carcinoma

Introduction

Pancreatic carcinoma is an aggressive malignant disease with a very poor prognosis. It is one of the more common malignancies that affect the American population, and accounts for about 30,000 deaths in America per year. It has an increased incidence in industrialized and Western cultures and is more common in men, usually occurring over the age of 60 (80%) It appears that chronic pancreatitis, diabetes and smoking are predisposing factors. 90% of the carcinomas arise from the epithelial cells of the exocrine pancreas. The disease is characterized by desmoplastic behavior so that it invades and encases neighboring vital structures early.

In most instances by the time the patient becomes symptomatic the disease is inoperable, and the patients usually succumb to the disease within a year of diagnosis.

Approach in the asymptomatic patient

If we are going to play any role in making a difference in this disease, early diagnosis, before involvement of other organs, is a key challenge. Unfortunately finding a small curable carcinoma is a rare occurrence and most the time we are left with a disease that has advanced too far for effective cure. Nevertheless our focus when reviewing the pancreas in any abdominal CT should be on the head and uncinate process because about 70% of pancreatic carcinomas arise from this part of the pancreas. Since the carcinoma is characteristically hypovascular, we should therefore be looking for a small hypodense rascal in the head of the pancreas. This is not to say of course suggesting that you should not look elsewhere but a focus using probability of finding disease is recommended. You will only find what you look for and so an active mind with a preconceived notion will sometimes yield remarkable results. Our search unfortunately is made more difficult and confounding by a few normal structures that reside in the region, including prominent ducts of the uncinate, and the bile duct itself.

In the following case the subtle nature of pancreatic cancer is noted.

This is a 61 year old male who presented with painless obstructive jaundice and required a stent to relieve the obstruction. On review of the CT scan a subtle hypodense hypovascular mass was noted. Can you see the mass? It is lateral to stent and is just over 1 cms. in diameter. At this stage we are probably too late in our diagnosis for cure. 29970 Courtesy Ashley Davidoff MD

This is a 61 year old male who presented with painless obstructive jaundice and required a stent to relieve the obstruction. On review of the CT scan a subtle hypodense hypovascular mass was noted. In this image the mass is overlaid in maroon. 29970b Courtesy Ashley Davidoff MD

The following case deserves showing to expand on the importance of the analyzing the component parts of the head of the pancreas and the importance of following the pancreatic duct and the bile duct individually to their confluence. Any extra hypodensities must be explained, and heightened sensitivity must be maintained even for the most subtle of changes.

In this CTscan of the abdomen we identify a rounding out of the head and uncinate process with two hypodense components. Associated finding include a dilated gallbladder and a suggestion of intrahepatic bile duct dilatation. Our suspicion on this single image is of pancreatic carcinoma, but how do we interpret the findings in the head? We know that we should have at least two normal hypodensities in this region (bile duct and pancreatic duct), and we also know there is a hypodense mass lurking. The need to review all the images is wanting. 40839 Courtesy Ashley Davidoff MD

The

References

The

MCQ

The

Introduction

In most instances by the time the patient becomes symptomatic the disease is inoperable, and the patients usually succumb to the disease within a year of diagnosis.

Approach in the asymptomatic patient

If we are going to play any role in making a difference in this disease, early diagnosis, before involvement of other organs, is a key challenge. Unfortunately finding a small curable carcinoma is a rare occurrence and most the time we are left with a disease that has advanced too far for effective cure. Nevertheless our focus when reviewing the pancreas in anyabdominal CT should be on the head and uncinate process because about 70% of pancreatic carcinomas arise from this part of the pancreas. Since the carcinoma is characteristically hypovascular, we should therefore be looking for a small hypodense rascal in the head of the pancreas. This is not to say of course suggesting that you should not look elsewhere but a focus using probability of finding disease is recommended. You will only find what you look for and so an active mind with a preconceived notion will sometimes yield remarkable results. Our search unfortunately is made more difficult and confounding by a few normal structures that reside in the region, including prominent ducts of the uncinate, and the bile duct itself.

In the following case the subtle nature of pancreatic cancer is noted.

This is a 61 year old male who presented with painless obstructive jaundice and required a stent to relieve the obstruction. On review of the CT scan a subtle hypodense hypovascular mass was noted. In this image the mass is overlaid in maroon. 29970b Courtesy Ashley Davidoff MD

This CT scan series is of a patient with obstructive jaundice and shows a double duct sign suspicious for carcinoma off the head of the pancreas. A dilated pancreatic duct and a dilated CBD (“double duct” sign) is shown (a,b) and then 3 hypodensities and a rotund appearance of the head suggests an extra and unwanted component in the head of the pancreas. Can you identify the unwanted component from these images?. The findings nevertheless are consistent with a primary adenocarcinoma of the pancreas. 40840c01 Courtesy Ashley Davidoff MD

As we review the case with overlays the component parts in the head become clearer. This type of analysis is required in the head with suspicious findings. It is very important to identify pancreatic duct position, bile duct position. Any extra hypodense structures, no matter how small, warrants explanation and or suspicion.

This CT scan series through the pancreas shows the findings of carcinoma of the head of the pancreas in overlay. In a and e the bile duct (green) and pancreatic duct (pink) are both dilated. In “b” and “f” the dilated ducts are approaching each other, and the first hint of a hypodensity (maroon in f) is suggested. In c and g, the bile duct is smaller and the pancreatic duct seems to be pushed to the side by the enlarging mass. The mass, which appears with a matrix of hypodensity and a rim of isodensity starts to enlarge and continues to push and encircle the ducts. (d,h). 40840c02 Courtesy Ashley Davidoff MD

The plea is for careful analysis particularly of the head of the pancreas even on routine abdominal CTscans.

Approach in the symptomatic patient

Approximately 75% of all pancreatic carcinomas occur within the head or neck of the pancreas, 15-20% arises from the body of the pancreas, and 5-10% arises from the tail.

The pancreas has a very central location in the body and has significant and intimate contact or is closely apposed to many organs. The organs are tightly packed in the region of head where the stomach, duodenum, colon, liver, gallbladder, bile duct, right kidney, IVC, SMV, portal vein and SMA lie. The body of the pancreas is related to the stomach which lies anteriorly and the retroperitoneum with nerves aorta and IVC lie posteriorly. The splenic vein lies posteriorly and the splenic artery lies superiorly. The tail nestles in the hilum of the spleen but lies in close contact to the stomach, splenic artery and splenic vein as well.

A reasonable approach to imaging pancreatic carcinoma is to divide the disease into the three parts of the pancreas that it affects, head body and tail, and review the manifestations of the disease in each of these parts.

Nature of the disease.

Pancreatic carcinoma has a scirrhous and scurrilous nature.

This histopathologic specimen of pancreatic carcinoma shows a heterogeneous pattern to the cells, prominent nuclear to cytoplasmic ratio, and hyperchromatic nuclii. The cells do not obey the rules of the body and are rebels in the community without regard to the body at large. They invade the territory of neighboring structures. 15311 Courtesy Barbara Banner MD

The cells of adenocarcinoma of the pancreas are well appreciated in this cytological specimen from a biopsy. Noted is the heterogeneous pattern to the cells, prominent nuclear to cytoplasmic ratio, and hyperchromatic nuclii. 15310 Courtesy Barbara Banner MD

Thus the aggressive nature of malignant cells of the pancreas is characteristic of all malignant tissue. In addition to their aggressive nature they are characterized by desmoplastic behavior. As a result they encircle, constrict and strangle their neighbors.

The grosspathology specimen shows a white mass in the middle of the image. It was extremely hard to the touch because of the fibrosis shown at histopathology. The desmoplastic or fibrous nature of the tumor leads to encasement and narrowing of contiguous structures. This fibroblastic nature of the disease is characteristic of adenocarcinoma of the pancreas. 15307 Courtesy Barbara Banner MD

Aggression and desmoplasia are thus the pathological hallmarks of adenocarcinoma of the pancreas. Hypovacsularity is the radiologic hallmark

Head.

Ducts

The desmoplastic nature of the disease affects in characteristic location being near or within a few centimeters of the ampulla.

The following images come from a percutaneous transhepatic cholangiogram 9PTCA) and show a concentric stricture around the distal common bile duct with rat tailing of the stricture and secondary upstream dilatation. The location is characteristic, but not necessarily pathognomonic for carcinoma of the head of the pancreas. 04835c03 Courtesy Ashley Davidoff MD

The head of the pancreas houses the common bile duct which delivers 600-700ccs of bile to the duodenum per day. The pancreatic duct and bile duct fuse in the ampulla just prior to their common entrance into the duodenum. The bile duct is one of the closest allies if not the closest buddy of the pancreatic duct. In fact they are bosom buddies even from the time of organogenesis. On the other hand although they were born together and function together in health, in the presence of pancreatic carcinoma in the head they will commonly get sick together as well (“ ‘til death do us part”). The double duct sign implies the enlargement of both the bile duct and pancreatic duct and is almost pathgnomonic of carcinoma of the head of the pancreas. The association is taken one step further when as a result of the obstruction the gallbladder gets affected. This is part of the Courvoisier’s law that states ‘if in the presence of jaundice the gallbladder is palpable, then the jaundice is unlikely to be due to a stone.’ As an extension of this law, if in addition the jaundice is painless then carcinoma of the head of the pancreas is likely.

The case below demonstrates a classical double duct sign.

A 57 year old female presents with jaundice. Her ERCP shows dilatation of the bile duct and pancreatic duct – the “double duct” sign characteristic of adenocarcinoma of the head of the pancreas. In this case the stricture appears quite distal. Chronic pancreatitis can also rarely cause the “double duct” sign. In this case an ampullary carcinoma was the cause explaining the distal position of the strictures. 04655c03 Courtesy Ashley Davidoff MD

The combination of images below reflects the changes of the above case using a multimodality approach with pathological proof.

This is a series of images from the case history of a 57 year old female who presented with jaundice. The US image (a) shows a dilated bile duct and dilated pancreatic duct with no large mass between them. The CT shows a les impressive, but prominent pancreatic duct. The ERCP suggests a “double duct” sign. The pathology confirmed an ampullary carcinoma. 04655c05 Courtesy Ashley Davidoff MD

This ERCP shows a double duct sign with a dilated CBD and pancreatic duct. These findings are consistent with a primary adenocarcinoma of the pancreas. Chronic pancreatitis is a remote possibility. 31062c01 Courtesy Ashley Davidoff MD

Double duct sign is also used in other modalities and has the same implications.

This CT scan through the pancreas shows a dilated pancreatic duct and a dilated CBD (“double duct” sign). These findings are consistent with a primary adenocarcinoma of the pancreas. Chronic pancreatitis is a remote possibility. These findings are consistent with a diagnosis of a primary carcinoma of the pancreas. 40837 Courtesy Ashley Davidoff MD

The image from an MRCP shows the MRI version of the double duct. The separation of the two ducts suggests a large size of the mass. This patient had pancreatic carcinoma. 41371 Courtesy of Ashley Davidoff MD

The combination of images below reflects the changes of the above case at different levels. Cranially the liver is seen and caudally the pancreas is seen.

The image from an MRCP shows the MRI version of the “double duct” sign. The separation of the two ducts suggests a large size of the mass (a). Image b shows intrahepatic biliary dilatation, while image c shows CBD dilatation. Image d shows a mass in the head of the pancreas on the contrast enhanced sequence. This patient had pancreatic carcinoma. 41371c Courtesy of Ashley Davidoff MD

There are instances where the double duct sign represents other diseases.

This is an ERCP showing a “double duct” sign. With the heavy intraductal calcification chronic alcoholic pancreatitis is definite. It is conceivable that the patient has a superimposed malignancy. In this case the double duct was caused by the strictures of the ducts caused by chronic pancreatitis. 41245c06 Courtesy Ashley Davidoff MD

At first glance this image from an ERCP looks like a double duct sign. In fact it does show that both ducts are dilated, but for different reasons other than cancer. The main pancreatic duct drains into the accessory duct of Santorini, while the CBD drains in usual fashion into the ampulla. This is a case of pancreas divisum. No pancreatic cancer was found on further workup. The etiology of the mild dilation is probably due to benign narrowing of both ducts at their insertion sites. 40615 Courtesy Ashley Davidoff MD

Arteries and Veins in the head

The gastroduodenal artery is closely linked to the head of the pancreas, and the branches of the pancreaticoduodenal arcade lie within the head of the pancreas. In years prior to the exquisite detail provided by CT and MRI, an angiogram was part of the workup of patients with suspected carcinoma of the pancreas for both confirmation of the diagnosis but also for operability. The presence of encasement of the vessel supported the diagnosis, and the presence of portal vein encasement specifically suggested inoperability. The following cases exemplify the discussion.

This series of percutaneous transhepatic cholangiography, PTCA (a), and arteriography (b) magnified in c, reveal an obstructed and dilated intrahepatic biliary system and encasement of some of the branches of the pancreaticoduodenal arcade.40328c Courtesy Ashley Davidoff MD

The following images are from the same case and the portal venous phase is demonstrated.

This series of arteriography of the common hepatic artery (a,c), with portal venous phase from an SMA injection(b,d) reveals the encasement of the pancreaticoduodenal arteries (c, yellow) magnified and portal vein (d yellow) The location and characteristic encasement point to pancreatic adenocarcinoma of the head of the pancreas. The portal vein involvement suggests inoperability. Courtesy Ashley Davidoff MD

The advent of MDCT has brought better resolution of soft tissue changes. The finding of a necklace of tumor around the SMA, and the degree to which it surrounds the SMA is being used as a predictor of operability.

This CT scan through the pancreas shows a small mass in the uncinate process of the pancreas associated with total encasement of the celiac axis. The CBD is dilated. These findings are consistent with a diagnosis of a primary carcinoma of the pancreas. Based on the desmoplastic nature of the process the tumor is most likely an adenocarcinoma. 20599 Courtesy Ashley Davidoff MD

This CT scan through the pancreas is a series with overlay from the above case, and shows a small mass in the uncinate process of the pancreas associated with encasement of the celiac axis and SMA, with a dilated CBD. These findings are consistent with a diagnosis of a primary carcinoma of the pancreas. Based on the desmoplastic nature of the process, the tumor is most likely an adenocarcinoma. The artery is in red the tumor orange and the normal pancreas is pink. 20607c06 Courtesy Ashley Davidoff MD

Stomach

40851c Courtesy Ashley Davidoff MD code abdomen stomach distended code stomach fx bezoar code pancreas pancreatic lateral uncinate process fx mass code dx carcinoma of the uncinate pancreas complicated by gastric outlet obstruction imaging radiology plain film KUB CT scan code neoplasm malignant primary tumor cancer mechanical code medical students 5 star

Duodenum

The head of the pancreas is housed in the c sweep of the duodenum and encasement at any point in the “c “ can be affected.

This CT scan through the pancreas shows a small mass in the uncinate process of the pancreas associated with a dilated and obstructed duodenum. These findings are consistent with a diagnosis of a primary carcinoma of the pancreas. Based on the desmoplastic nature of the process the tumor is most likely an adenocarcinoma. 20601 Courtesy Ashley Davidoff MD

This CT scan through the pancreas shows a hypodense mass in the pancreatic head, associated with a central dystrophic calcification and a dilated pancreatic duct. These findings are consistent with a cystadenoma, and a malignant transformation of a mucinous neoplasm has to be considered in view of the dilated duct. The calcifications in the spleen are granulomatous in origin. 19394c01 Courtesy Ashley Davidoff MD

The CT scan, MRI, US and ERCP of the pancreas shows a dilated pancreatic duct and a dilated CBD (“double duct” sign). These findings are consistent with a primary adenocarcinoma of the pancreas. 41293a16c Courtesy Ashley Davidoff MD

Body

The central part of the pancreas is closest to the vessels nerves lymphatics of the abdomen. Pancreatic adenocarcinoma shows an affinity for nerves and the involvement of the nerve results in significant back pain in patients with pancreatic carcinoma. This is more common with body and tail carcinomas.

The body and tail of the pancreas are close to the lymphatics and nerves. In this histological section the rounded nerve seen to the right in the image is surrounded by advancing malignant pancreatic carcinoma seen as cluster of blue nuclii.

Courtesy Barbara Banner MD

The CT scan of the abdomen of a 71 year old male shows a hypovascular mass in the body of the pancreas with widespread metastatic disease in the liver. Some of the lesions in the liver are larger than the primary tumor. 40343c Courtesy Ashley Davidoff MD

Duct in the body

In patients with obstructed ducts there is usually secondary

This CT scan through the pancreas shows a mass in the neck and body of the pancreas associated with pancreatic duct dilatation and secondary atrophy in the pancreatic tail. These findings are consistent with a diagnosis of a primary carcinoma of the pancreas. Based on the desmoplastic nature of the process the tumor is most likely an adenocarcinoma. 30101a05 Courtesy Ashley Davidoff MD

Arteries and Veins

This CT scan through the pancreas shows a mass in the body of the pancreas associated with encasement of the portal vein and splenic artery (subtotal occlusion) with an almost complete encirclement of the celiac axis by a necklace of aggressive tissue. These findings are consistent with a diagnosis of a primary carcinoma of the pancreas. Based on the desmoplastic nature of the process the tumor is most likely an adenocarcinoma. Courtesy Ashley Davidoff MD18103

The CT scan of the abdomen of a 85 year old female shows a hypovascular mass in the body and tail of the pancreas (a) which has resulted in splenic vein compromise and the development a large venous collateral seen coursing over the greater curvature of the stomach. The mass is hypoechoic (c) and hypovascular d) on the US. 24942c Courtesy Ashley Davidoff MD

Unusual masses

This CT scan through the pancreas shows a mass in the body of the pancreas associated with metastatic liver disease. The patient presented with Cushingoid features which was associated with ectopic ACTH biochemistry. An adrenal nodule is noted reflective of hyperplasia from the effect of ACTH. The mass at autopsy was consistent with a malignant gastrinoma associated with ectopic ACTH production. Courtesy Ashley Davidoff MD 19859

This is a series of images from a middle aged female with a hypervascular mass in the body of the pancreas. Since adenocarcinoma of the pancreas tends to be hypovascular it is unlikely that the histological type is the common form. In this case the diagnosis was a micronodular carcinoma 40640c02 Courtesy Ashley Davidoff MD ..

This CT scan through the pancreas shows a complex cystic mass with central calcification in the tail of the pancreas associated with complex masses in the left kidney and surgically absent right kidney. These findings are consistent with a diagnosis of von Hippel-Lindau syndrome with a variety of cystic and solid, benign and malignant tumors of the pancreas and kidney. 40463c Courtesy Ashley Davidoff MD

Tail

Spleen

This CT scan through the pancreas shows a mass in the tail of the pancreas associated with splenic invasion ascites, a probably liver metastasis, and thickened omentum. These findings are consistent with a diagnosis of a primary carcinoma of the pancreas, with metastatic disease. 20796 Courtesy Ashley Davidoff MD

Peritoneum

Sometimes more than 2/3 of the circumference of the tail of the pancreas is covered by peritoneum making it a peritoneal structure. Thus more than any of the other parts of the pancreas malignancy in the tail may spread directly into the peritoneal cavity.

This CT scan through the pancreas shows a cystic mass in the pancreatic tail associated with thickened gastrolienal ligament and ascites. This case represents transperitoneal spread of a known pancreatic carcinoma. Metastatic nodules are also noted in the liver. 20114 Courtesy Ashley Davidoff MD

Cystadenocarcinoma

The cystic lesions of the pancreas are discussed as a separate entity in detail. However they are a variant of carcinoma but have a different biology and nature. Specifically they do not demonstrate the desmoplastic behavior of the more commonly occurring scirrhous adenocarcinoma.

This CTscan of an 83 year old female is through the body and tail of the pancreas shows a complex cystic mass in the tail with a more solid appearing tail that is in the body. (a,b). In c and d, the cystic component with a thickened wall is shown in yellow, and the solid component medially with a focal calcification is shown in brown. The pancreatic duct which is minimally prominent is shown in pink. These findings are consistent with a mucinous cystadenocarcinoma which was pathologically proven. 19911c01b03 Courtesy Ashley Davidoff MD

References

Courvoisier LJ. Casuistisch-statistische beitrage zur pathologie und chirurgie der gallenweger. Leipzig: Vogel; 1890.

Pancreatic Carcinoma from Radiologyassistant.nl web pressentation

carcinoma, gallbladder, malignant, neoplasm, primary cancer

Gallbladder Carcinoma

Carcinoma

Definition

Gallbladder carcinoma is a malignant disease usually originating in the epithelium lining. Its cause is unknown, but the high incidence of associated cholesterol gallstones (>75%) creates an etiological link between the two diseases.

Tumors of the biliary system are found mostly in the elderly in the seventh decade of life and are 3-4 times as common in women as in men. It is strongly associated with gallstones, but while nearly 80% of those with carcinoma have concomitant gallstones, less than 0.5% of all patients with gallstones will develop carcinoma. Porcelain gallbladder predisposes to the development of carcinoma.(25% incidence)

Structurally it can present with focal thickening of the wall, polypoid lesion, or a mass, and is most common in the fundus (60%) , followed by the body 30%, and then the neck (10%).

Functional impairment is limited and it is for this reason that presentation is late and prognosis is poor.

Complications include early spread to the regional nodes and direct invasion into the liver through the gallbladder fossa.

Clinically the patient usually presents late in the disease with symptoms similar to that of cholelithiasis. RUQ pain, jaundice, and nausea with vomiting. Occasionally this results in a palpable gallbladder before invasion into the adjacent structures. Still, it is rarely found at a time when surgical resection is possible, and thus has a 5-year survival rate of ~1%.

The diagnosis is rarely suspected given the above symptoms, and is often only found incidentally on resection of a gallbladader for symptomatic cholelithiasis.

From an imaging standpoint, ultrasonography will often reveal a thickened wall or polypoid masses, though these features may not specific for carcinoma. A polyp that is larger than 1cms is suspicious for carcinoma. CT may also identify a mass or thickening within the gallbladder, but the diagnosis is usually suggested when spread to the liver adjacent to the gallbladder fossa is identified or when regional adenopathy is present. Magnetic resonance cholangiopancreatogrphy may also help visualize the liver, biliary treee and neighboring lymph nodes but offers no clinical advantages over CT scan.

Surgical treatment is provides the only opportunity for cure but only a minority of patients are candidates. Patients who have a porcelain gall;bladdder should have elective cholecystectomy because of the high incidence of gallbladder cancer. The role of adjuvant chemotherapy following surgery is to control microscopic disease. Role of radiation therapy is unclear.

Carcinoma Thickening and Granular Appearance

This is a resected gallbladder cut longitudinally and opened like a book. You are looking into the lumen in the two halves created by the cut. The cystic duct is over the left side of the label, and the fundus of the gallbladder is over the right side. The tumor is in the fundus as tan-white tissue thickening the wall, and causing a granular appearance in the mucosa. There is a separate, 0.8 cm mucosal nodule nearby. The rest of the mucosal surface is normal appearing with small ridges, and a green-brown color. The wall is only about 1 – 2 mm thick. This carcinoma was found incidentally in this gallbladder, which was removed for gallstone. Unfortunately many gallbladder carcinomas are not diagnosed early. They are either found incidentally, like this one, or they are detected after they spread, when it is too late for effective therapy.

11951c01.8s gallbadder carcinoma grosspathology Courtesy Barbara Banner MD

Carcinoma – Mass

This gallbladder has been opened longitudinally and you are looking at the mucosal surface. Gallstones are present. Notice that the surface is pale tan, and irregular. The tumor produces only subtle changes in the mucosa; it is rare to have a large noticeable mass. Usually irregularity and granularity of the surface and thickening of the wall are the clues to the diagnosis.

11941.8s gallbladder carcinoma grosspathology Courtesy Barbara Banner MD

Carcinoma – Papillary Form

This photograph shows a gallbladder opened so that you are looking onto the lumenal surface. The gallbladder was enlarged to the size of a grapefruit, and only about half of it is visible in this picture. The warty excresences which cover the whole lumenal surface are papillary projections of a papillary carcinoma. This carcinoma grew over the mucosal surface and into the lumen, causing the gallbladder to be greatly distended. There was no invasion of the wall itself. A small part of the wall can be seen at one side of the picture. This is an uncommon form of adenocarcinoma of the gallbladder. It is by far more common for the carcinoma to invade through the gallbladder wall.

11947.81s gallbadder carcinoma grosspathology Courtesy Barbara Banner MD

Most exophytic carcinoma occurs in the fundus and the neck of the gallbladder.

Xanthogranulomatous Cholecystitis – Acute on Chronic

This gallbladder was opended longitudinally to show the lumenal surface. Four gallstones are present. The mucosal surface looks hemorrhagic, indicative of active inflammation. The most striking aspect of this gallbladder is the marked thickening and yellow color of its walls. This is due to extrusion of bile into the wall during inflammation when the integrity of the mucosa is interrupted. Once in the tissues of the wall, the bile triggers an intense inflammatory reaction, and a response by histiocytes, which phagocytose the bile and attempt to break it down. The marked accumulation of lipids and their break-down products imparts the yellow color. The significance of this variant of chronic cholecystitis is that it mimicks carcinoma by the way it thickens the wall. The radiologist, the surgeon, and even the pathologist may think this is carcinoma until the microscopic sections are examined.

11937b01.8s gallbladder dx cholelithiasis grosspathology Courtesy Barbara Banner MD

Morphology of gallbladder carcinoma may be infitrating or exophytic. The infiltrating pattern is more common, and is characterized by deep ulcerations of the wall. These may occasionally lead to fistulous tracts forming with adjacent visceral structures, most often the liver.

82755c01.8s

Porcelain Gallbladder – Variant of Chronic Inflammation

This is a specimen xray of a resected gallbladder. The walls were thin, fibrotic and heavily calcified, accounting for the radiodense (white) areas on the radiograph. This variant of chronic cholecystitis is a risk factor for development of carcinoma.

11939.8s gallbladder porcelain gallbladder X-ray Courtesy Barbara Banner MD

Porcelain Gallbladder

The plain film of the right upper quadrant shows faint calcification (white lines in b)) of the wall of the body and of the entire neck. This finding is subtle since it is intermingled with calcification of the costal cartilage, but it is important and poentially life saving since the patient has to undergo elective cholecystectomy because of the high association with carcinoma. (up to 25% incidence)

Porcelain Gallbladder

The gallbladder in this instance is contracted, and has porcelain like calcification. This suggests chronic cholecytitis though no stones are identified. The patient requires to undergo elective cholecystectomy.

47683c01 gallbladder fx calcification in wall calcified wall dx porcelain gallbladder CTscan Davidoff MD

Porcelain Gallbladder with Calcified Stone

In this CTscan calcification of the wall of the gallbladder (green) is associated with a large calcified stone (yellow) that appears to be impacted in the neck. Cholesterol stones are usually isodense with the bile but in this case it has calcified. The large size of the stone suggests its cholesterol nature in this case.

76225c01 gallbladder wall calcification calcified porcelain gallbladder premalignant CTscan Courtesy Ashley Davidoff MD

Carcinoma in Situ

This high power photomicrograph shows the mucosal epithelium and lamina propria, and part of the muscle layer of a gallbladder containing a carcinoma. In this picture, the epithelium is a normal simple, columnar epithelium at one side, (right) and it undergoes a change to a dense, disorganized, malignant epithelium (carcinoma-in-situ) as you follow it across to the other side of the picture. (left)

11946.8s gallbladder carcinoma histopathology Courtesy Barbara Banner MD

Carcinoma Pleomorphic Nuclii

This medium power photomicrograph shows the epithelium in a case of gallbladder carcinoma. The cells retain a columnar structure, but their nuclei are pleomorphic, and there is variable staining quality of their cytoplasm from cell to cell. Some of the cells look like Paneth cells, with their large, eosinophilic cytoplasmic granules. Variability in size, shape, and staining quality of cells is one of the hallmarks of malignancy.

11943.8s gallbladder carcinoma histopathology Courtesy Barbara Banner MD

Carcinoma – Back to Back Gland Arrangement

11944.8s gallbladder carcinoma histopathology Courtesy Barbara Banner MD

Carcinoma – Back to Back Gland Arrangement and Irregular Nuclii

This medium power photomicrograph shows an infiltrating adenocarcinoma of the gallbladder. Note the “back-to-back” gland arrangement, and the irregular distribution of cell nuclei within the glands. The histologic features of this adenocarcinoma are common to adenocarcinomas from many sites, such as the GI tract, pancreas, lung, endometrium etc. but they are also quite typical of gallbladder carcinomas. In this picture the nest of malignant glands is growing across bundles of muscle in the gallbladder wall. The muscle bundles are the deeply eosinophilic structures on either side of the tumor.

gallbladder carcinoma histopathology Courtesy Barbara Banner MD 11948s

Carcinoma – Papillary Form

This is a whole-mount section through the wall of a gallbladder with a non-invasive papillary carcinoma. Note how the tumor grows as complex papillary projections, which in the complete specimen projected into and filled up the lumen of the gallbladder. Although this carcinoma is also capable of invading into the wall, this one grew over the interior surface of the gallbladder without invading into the wall. In this picture, the wall is the dense eosinophilic part beneath the papillary projections of the tumor.

11945.8s gallbladder carcinoma histopathology Courtesy Barbara Banner MD

In the exophytic patterin illustrated above, the neoplasm remains within the wall, taking on a characteristic cauliflower like appearance. The luminal portion can be necrotic, hemmorrhagic and ulcerated.

Carcinoma – Lymph Nodes

This picture illustrates the major routes of spread of carcinoma (T) of the gallbladder, (GB) which are direct invasion into the liver, (L) and metastasis to regional lymph nodes. (LN) This is a slice taken through the gallbladder and porta hepatis, including small portions of the liver, stomach, and pancreas, from the autopsy of a patient who died of metastatic carcinoma of the gallbladder. The gallbladder wall is thickened by pale tan-white tumor. (T) The same tan-white tumor is present in lymph nodes (LN – black) of the porta hepatis (cystic node) situated along the common bile duct. These lymph nodes can cause extrahepatic biliary obstruction by compressing the common bile duct as they enlarge. The portions of Ampulla of Vater, (amp) stomach (ST) and pancreas seen in this picture are negative for tumor. Not shown is the fact that this tumor invaded directly through the gallbladder wall and directly into the liver.

11949bs gallbadder carcinoma grosspathology Courtesy Barbara Banner MD

Carcinoma – Restricted to the Gallbladder

Carcinoma of the Fundus CT and MRI

Mucosal and Submucosal Infiltration

In this patient the CTscan (a,b)shows a thick walled and contracted fundus of the gallbladder. The mucosa (pink) and the lamina propria muscular and serosal layer orange are thickened. The fundal lumen is small while the lumen of the body (green) of the gallbladder is normal. This non specific thickening was carcinoma of the gallbladder. The T1 weighted MRI reveals multiple small filling defects in the body of the gallbladder, that were obviously not calcified by CT. By these imaging techniques the carcinoma is confined to the gallbladder (at least macroscopically) and a chance of surgical cure is possible.

Carcinoma – Extending into the Liver via the Gallbladder Fossa

Direct Invasion into the Liver and Bile Duct Obstruction

The CTscan of this patient shows a normal sized gallbladder (green) associated with a 4-5cms mass (orange) adjacent to the gallbladder, and extending from the gallbladder fossa. There is asssociated biliary obstruction (dark green tubes) This case represents invasive gallbladder carcinoma with bile duct obstruction. Images c and d show the almost universal association of gallstones in patients with carcinoma. In this case the stones (white) are in the centre of the gallbladder. (green)

16254c03.8s gallbladder anterior wall liver invasion space occupatopn obstruction bile ducts aggressive gallbladder carcinoma complicated by direct invasion metastasis liver windows narroe windws tumor settings gallbladder fossa GBF CTscan Courtesy Ashley Davidoff copyright 2008

Dystrophic Calcification – Carcinoma of the Gallbladder Extending into the Gallbladder Fossa

The non-contrast CT of the 75year old female patient, shows dystrophic calcification in a mass that seems to be part of the wall of the gallbladder. The mass extends into the liver. These findings are consistent with an inoperable gallbladder mucinous adenocarcinoma, metastatic to the liver by direct extension. Calcification of adenocarcinomas is usually found in the mucinous variant of the disease.

24404c.8s 75 female gallbladder calcification adjacent mass in the liver local invasion into the gallbladder fossa dystrophic calcification probably mucinous adenocarcinoma of the gallbladder carcinoma stones cholelithiasis hydronephrosis

Carcinoma – Extending into the Liver via the Gallbladder Fossa and Additional Metastases

Local Invasion and Separate Liver Mestastasis

The CTscan in this patient shows two calcified gallstones in the gallbladder (green), with a mass like malignant abnormality extending into the liver on either side (yellow) and a remote metastasis (orange) which is deforming the liver edge.

Disease Extension Beyond the Liver

Cholangiocarcinoma with Involvement of the Gallbladder and Bile Duct

The multiple imaging modalities of this patient who is elderly female who presents with obstructive jaundice. Deformity of the gallbladder by CT is noted, with extension of a mass into the surrounding liver (a,b,c) In addition to a mass in the gallbladder (d), the ultrasound shows a shadowing stone (e). An ERCP (f), shows a circumferential stricture of the bile duct. The stricture is in the region of the cystic duct – bile duct junction, with non visualization of the cystic duct suggesting extension of the gallbladder cancer into the cystic duct and bile duct. Lymph node involvement with bile duct obstruction is a less likely possibility due to the circumferential nature of the stricture.

40018c02b.8s elderly female cholelithiasis obstructive jaundice common bile duct stricture dilated intrahepatic ducts irregular enhancing thickening of the gallbladder wall stent gallbladder carcinoma with extension into the CBD or CBD carcinoma with extension into the wall of the gallbladder CTscan USscan ultrasound ERCP Courtesy Ashley DAvidoff MD copyright 2008

Luminal Invasion

The CT scan through the gallbladder shows a central low density mass (gray) with a surrounding irregular wall (yellow). The ultrasound (c,d), shows complex echoes in the lumen (orange in d) probaly representing a combination of solid mass and tumefactive bile. A single shadowing stone can be seen in c (arrow) with shadowing confirming its presence. (arrow in d)

16254c05 gallbladder space occupation gallbladder carcinoma by CT it appears as a low density centrally and enhancing soft tissue peripherally by USscan looks like the whole lumen is filled with soft tissue tumor question of delayed tumor enhancement vs necrosis CTscan USscan ultrasound Courtesy Ashley Davidoff copyright 2008

Gallbladder Carcinoma with Perforation and Abscess Formation

This is the same case noted above, but it exemplifies extension of the tumor into the surrounding organs, and in this case probably colon with secondary abscess formation (small black airbubbles in c and d ) fluid collection (yellow) in c, and edematous changes in the surrounding fat and peritoneum (pink in c and d). The tumor has central non enhancing matrix (gray) surrounded by more solid enhancing tumor (orange)

16254c01b02.8s gallbladder thickened irregular wall air anterior wall small fluid collection gallbladder carcinoma complicated by perforation and abscess formation CTscan Courtesy Ashley Davidoff copyright 2008

Conclusion

From the anatomical point of view it is interesting to note that gallbladder cancer occurs most commonly in the fundus, and from the pathophysiological point of view it is so frequently associated with gallstones. It is attractive to consider the fact that in the “day” position of the gallbladder, the most dependant, concentrated bile is in contact with the mucosa, and similalrly stones will be in contact with the fundal mucosa for the longest time. In the prone position (if the person sleeps in prone position) stones will be in contact with the anteriorly positioned fundus as well. hence chronoic contact, chronic irritation of the fundus and aberrant chemical environments such as excessive bile salts, or cholesterol make a fertile environment for the evolution of the mucosa to dysplasia and carcinoma.

Gallbladder Cancer and Stones

The greenpepper sectioned in long axis has a mass like base, and remnant seeds reminiscent of the combination of fundal carcinoma in the presence of cholelithiasis.

11528b.8 gallbladder food in the body green pepper cancer carcinoma gall stones cholelithiasis Davidoff art Davidoff photography copyright

References

Denshaw-Burke Mary Denshaw-Burke, MD, Gallbladder Cancer eMedicine 2008

Szarnecki Gregory M Szarnecki, MD, Gallbladder, Carcinoma e Medicine 2007

References provided by e Medicine

National Cancer Institute. Treatment statement for health professionals: gallbladder cancer. Updated 2/15/07. Med News. Available at http://www.meb.uni-bonn.de/cancer.gov/CDR0000062904.html. Accessed August 23, 2007.

Fong Y, Wagman L, Gonen M, et al. Evidence-based gallbladder cancer staging: changing cancer staging by analysis of data from the National Cancer Database. Ann Surg. Jun 2006;243(6):767-71; discussion 771-4. [Medline]. [Full Text].

Levy AD, Murakata LA, Rohrmann CA Jr. Gallbladder carcinoma: radiologic-pathologic correlation. Radiographics. Mar-Apr 2001;21(2):295-314; questionnaire, 549-55. [Medline]. [Full Text].

Douglass HO Jr, Kim SY, Merpol NJ. Neoplasms of the gallbladder. In: Holland JF, Frei E III, Best RC Jr, eds. Cancer Medicine. Vol 2. 4th ed. Baltimore, Md: Williams & Wilkins; 1997:1955-63.

Dudiak CM, Lawson TL. Carcinoma of the gallbladder. Diagnostic Ultrasound (Second Series) Test and Syllabus. St Louis, Mo: Mosby-Year Book; 1994:324-62.

Elsayes KM, Oliveira EP, Narra VR, El-Merhi FM, Brown JJ. Magnetic resonance imaging of the gallbladder: spectrum of abnormalities. Acta Radiol. Jun 2007;48(5):476-82. [Medline].

Grainger RG, Allison E. Grainger and Allison’s Diagnostic Radiology: a Textbook of Medical Imaging. Vol 2. 3rd ed. New York, NY: Churchill Livingstone; 1996:1224.

Greene FL, Page DL, Fleming ID, eds. Gallbladder. AJCC Cancer Staging Manual. 6th ed. New York, NY: Springer-Verlag; 2002:139-44.

Haubrich WS, Schaffner F, Berk JE, eds. Bockus Gastroenterology. Vol 3. 5th ed. Philadelphia, Pa: WB Saunders; 1995:2739-44.

Kai M, Chijiiwa K, Ohuchida J, et al. A curative resection improves the postoperative survival rate even in patients with advanced gallbladder carcinoma. J Gastrointest Surg. Aug 2007;11(8):1025-32. [Medline].

Kim MJ, Kim KW, Kim HC, et al. Unusual malignant tumors of the gallbladder. AJR Am J Roentgenol. Aug 2006;187(2):473-80. [Medline]. [Full Text].

Mekeel KL, Hemming AW. Surgical management of gallbladder carcinoma: a review. J Gastrointest Surg. Sep 2007;11(9):1188-93. [Medline].

Memel DS, Balfe DM, Semelka RC. The biliary tract. In: Lee JKT, Sagel SS, Stanley RJ, eds. Computed Body Tomography With MRI Correlation. Vol 2. 3rd ed. Philadelphia, Pa: Lippincott-Raven; 1997:810-3.

Miller G, Schwartz LH, D’Angelica M. The use of imaging in the diagnosis and staging of hepatobiliary malignancies. Surg Oncol Clin N Am. Apr 2007;16(2):343-68. [Medline].

Numata K, Oka H, Morimoto M, et al. Differential diagnosis of gallbladder diseases with contrast-enhanced harmonic gray scale ultrasonography. J Ultrasound Med. Jun 2007;26(6):763-74. [Medline].

Oe A, Kawabe J, Torii K, et al. Distinguishing benign from malignant gallbladder wall thickening using FDG-PET. Ann Nucl Med. Dec 2006;20(10):699-703. [Medline].

Shih SP, Schulick RD, Cameron JL, et al. Gallbladder cancer: the role of laparoscopy and radical resection. Ann Surg. Jun 2007;245(6):893-901. [Medline].

Srivastava AK, Singh B, Gupta SL. Prevalence of Toxoplasma antibodies in sheep and goats in India. Trop Anim Health Prod. Nov 1983;15(4):207-8. [Medline].

Vitetta L, Sali A, Little P, Mrazek L. Gallstones and gall bladder carcinoma. Aust N Z J Surg. Sep 2000;70(9):667-73. [Medline].

Yamada T, Alpers DH, Owyang C, Powell DW, Silverstein FE, eds. Textbook of Gastroenterology. Vol 2. 2nd ed. Baltimore, Md: Lippincott Williams & Wilkins; 1999:2335-40.

carcinoma, esophagus, malignant, primary cancer

Esophagus Carcinoma

Carcinoma

Definition

Esophageal cancer is a malignant growth disorder of esophageal mucosa. Historically squamous cell cancer was the predominant type; however, more recently, a surge in adenocarcinoma as the more common entity has evolved. Sqaumous cell carcinoma characteristically occurs in the thoracic esophagus while adenocarcinoma occurs at the GE junction.

Many different causative factors have been associated with this condition including GERD, Barrett’s esophagus, dietary factors, smoking and geographic location.

The disease results in an aggressive space occupying mass that progressively impinges on the lumen of the esophagus to cause dysphagia

It is most commonly diagnosed by endoscopy and biopsy, staged with CT and PET scan, and best treated with a combination of surgical and medical therapies.

The overall prognosis is quite poor, with 5 year survival estimated to be between 10-13% for advanced disease. With the increased diagnosis of Barrett’s esophagus, and the routine surveillance that follows, earlier detection of cancer allows for treatment and better survival rates. Survival rates are much improved with more superficial cancers that are found with increasing frequency during endoscopic surveillance.

Ulcerating Squamous Cell Carcinoma of the Esophagus

02425 02420 code esophagus + mass narrowing stricture ulceration heaped edges squamous cell carcinoma + grosspathology

Ulcerating Esophageal Carcinoma with Heaped Edges

01270c code esophagus + fx mass + dx carcinoma + barium swallow upper GI UGI imaging radiology contrast X-Ray mass neoplasm malignant primary carcinoma cancer tumor Courtesy Ashley Davidoff MD

Causes and Predisposing Factors

ie etiology and pathogenesis

Squamous cell carcinoma and adenocarcinoma each have their own predisposing conditions, and as such, will be described separately.

Causes Related to Squamous Cell Carcinoma:

Geographic location has been shown to be a risk factor for the development of squamous cell carcinoma of the esophagus. Asian countries have a higher incidence than that of the western part of the world.

Dietary risk factors also exist. Much like that of other gastrointestinal cancers, foods with n-nitroso compounds are thought to increase the risk. Within the Asian countries, the common practice of chewing of the Betel nut, has been associated with squamous cell carcinoma.

Other dietary risk factors include the consumption of alcohol. A correlation between the amount consumed and the risk of cancer exists.

Tobacco use has also been closely associated with squamous cell esophageal cancer.

Patients with underlying conditions that affect the esophagus are also at increased risk. A previous history of caustic ingestion, classically with lye, increases the risk.

Causes Related to Adenocarcinoma:

The most important risk factor for the development of adenocarcinoma of the esophagus is a history of Barrett’s esophagus. The progression of Barrett’s to carcinoma is well documented and reviewed at length in the section on Barrett’s.

Other risk factors for the development of adenocarcinoma of the esophagus include tobacco use, obesity, GERD, and other conditions that will increase acid exposure in the esophagus

Statistics

In the USA it is relatively uncommon with about 10,000 new cases per year or between 2 – 8 people per 100,000

There are certain areas in China with 100 new cases per 100,000

Race

Higher in the black population – could this show a genetic predisposition?

Sex

M:F range from
2:1 to 20:1.

Age

adult disease
usually over age 50

Other Statistics

1% of all cancers
10% of gastrointestinal malignancies

Result

Since the lymphatic network in the submucosa is so allows both circumferential and longitudinal spread and the disease is usually more extensive than the macrsosopic appearance and early lymphatic spread to areas remote from main mass is characteristic. As mentioned above, the 5 year survival rates for esophageal cancer are quite low. Early detection is important as if found prior to metastasis, the treatment options are more plentiful.

Gross Pathology

polypoid or fungating (common)
ulcerating form
infiltrating form
varicoid form

Ill Defined GE Junction Tumor – Adenocarcinoma

00567c03 distal esophagus GE junction gastroesophageal junction stomach GE junction tumor fx nodular appearance to the GE junction dx adenocarcinoma of the GE junction grosspathology malignant cancer Courtesy Ashley Davidoff MD

Histopath

squamous cell carcinoma (95%) Squamous cell carcinomas are moderately to well differentiatedsquamous cell carcinoma (common)
adenocarcinoma (4%)
Barrett 70%
GE junction 30%

other
adenoid cystic carcinoma
carcinosarcoma

Squamous cell carcinomas are moderately to well differentiatedsquamous cell carcinoma (common)

They pesent as;

well differentiated (common)
mderately differentiated (common)
poorly differentiated

Complications

The mass may cause local obstruction. Local extension into mediastinal structures is early and common. Tracheoesophageal fistula can occur in 5 -10%. Other complications include ulceration, bleeding airway compression, and invasion into the aorta. Systemic complications are characterized by metatastasis to nodes, lung, liver, adrenal gland.

Classification based on Staging

TNM system:

T, tumor <5 cm in length without circumferential involvement

T2 tumor >5 cm in length / circumferential or obstructive lesion

T3 extraesophageal spread

classification based on radiologic appearance

Diagnosis

Clinical

Clinically, patients present with a myriad of complaints, the most common of which is dysphagia. As the lumen narrows for the growth of the lesion, food is unable to pass smoothly thru the esophagus. Patients can present with upper gastrointestinal bleeding, weight loss, halitosis, in addition to many non-specific complaints.

The onset of the dysphagia is insidious. The esophagus is a pliable and mobile organ and is therefore forgiving and can accomodate the advancing mass. Thus clinical presentation and the onset of dysphagia is late.The delay in time to clinical presentation implies advanced disease at presentation and this affects outcome.

Imaging

With clinical suspicion, most patients undergo an upper endoscopy to evaluate the symptoms. This modality allows for direct visualization of the lesion and for biopsy for tissue diagnosis.

Carcinoma of the Esophagus

73940.400 73941.400 esophagus distal mass ulcerating bleeding carcinoma of the esophagus endoscopy endoscopic view Courtesy Joshua Namias MD

Carcinoma of the Esophagus

73941.400 73941.400 esophagus distal mass ulcerating bleeding carcinoma of the esophagus endoscopy endoscopic view Courtesy Joshua Namias MD

Irregular Distal Esophagus with Stricture – Adenocarcinoma of the GE junction

75711c01 dysphagia esophagus distal irregular stricture dx adenocarcinoma of the esophagus barium swallow Courtesy Ashley Davidoff MD

Long Relatively Smooth Malignant Stricture

Courtesy Ashley Davidoff MD 01240 esophagus + fx irregular stricture + dx carcinoma + barium swallow upper GI UGI imaging radiology contrast X-Ray mass neoplasm malignant primary carcinoma cancer tumor

Long Mid Esophagus Malignant Stricture

Courtesy Ashley Davidoff MD 01246 code esophagus + fx irregular + fx long fx narrowed + dx squamous cell carcinoma + barium swallow upper GI UGI imaging radiology contrast X-Ray mass neoplasm malignant primary carcinoma cancer tumor

Depending on the initial complaint, a barium study may also be performed.

Findigs may include a polypoid or fungating form, ulcerating form, or infiltrating form. If ulcerated a filling defect would be apparent, anf if it involves the esophagus ircumferentially an apple core lesion or a focal narrowing will be present. Once the diameter of the lumen becomes less than 13mm partial obstruction occrs, the lumen becomes functionally compromised the proximal esophagus dilates and dysphagia ensues.Any mucosal irregularity that raises uspicion should be evaluated an biopsied as dwcided by the endoscopist at the tine.

CT shows wall thickening anf the relationship to
mediastinal structures. Ominous signs iclude 1oss of fat planes invasion into trachea, aorta, pericardium, and distant metastases

Once a lesion is found, further diagnostic studies are often performed. Endoscopic ultrasound allows for great definition of the extent of the disease. This modality allows for visualization of the layers of the esophagus, such that the level of invasion can be identified. Biopsies of involved tissue and nodes can be performed.

CT scan allows for evaluation for metastatic disease as well.

Staging by Non Invasive Method

29885c03 esophagus lymph nodes primary esophageal carcinoma probably squamous carcinoma metastases to lymph nodes mediastinal lymphadenopathy mediastinum irregular lumen long segment single contrast bariu swallow CTscan PET scan NM Courtesy Ashley Davidoff MD

Treatment

Treatment of esophageal cancer greatly depends on the staging of the disease.

If the tumor is localized to the esophagus, without evidence of direct or metastatic spread, surgery provides a cure. Typically an esophagectomy with gastric pull up is the treatment of choice. Mucosal resections, photodynamic therapies, and ablative techniques can be entertained.

If the disease is not resectable at the time of diagnosis, chemotherapy, often in combination with radiation therapy is undertaken.

Stent in the Distal Esophagus

18203c esophagus carcinoma stricture tube stent dilatation treatment Courtesy Ashley Davidoff MD

Gastric Pull Through

76384 esophagus carcinoma cancer gastric pull through surgery treatment differential diagnosis dd dilated esophagus barium swallow Courtesy Ashley Davidoff MD 76386c01

Prognosis

3 – 75% 5-year survival rate

For superficial superficial esophageal carcinoma 5-year survival rate is 75% and for advanced lesions 5-25% 5-year survival rate. The presence of involved Iymph node metastases at the time of resection reduces the 5 year survival.