METASTATIC CANCER OF THE EXTRAHEPATIC BILE DUCTS PRODUCING JAUNDICE*

Transcription

1 METASTATIC CANCER OF THE EXTRAHEPATIC BILE DUCTS PRODUCING JAUNDICE* PETER A. HERBUT, M.D. AND JOHN S. WATSON, M.D. From the Clinical Laboratories, Jefferson Medical College Hospital, Philadelphia, Pa. Recent medical literature contains no report of jaundice resulting from compression of the extrahepatic bile ducts by metastatic cancer. Most text books and papers dealng with the subject of obstructive jaundice list the offending agents as being within the lumen, within the wall, or pressing upon the ducts from without, and while secondary cancer is didactically mentioned in each of these locations, specific references are made to articles in ancient literature only, or are not to be found at all. Thus Rolleston and McNee 3 cite 2 cases, one a primary carcinoma of the liver reported in 1895 and another in a primary carcinoma of the gallbladder reported in 1901, in each of which neoplastic tissue extended into the lumen of the common bile duct and produced obstruction. They give no references to secondary growths within the walls of the bile ducts, and although they state that malignant infiltration of the nodes is the most frequent cause of compression from without, they quote reports of but a few cases of primary carcinoma of the stomach producing such metastases. Weiss 4 only mentions secondary tumors producing jaundice and gives no references to any reports, while Lichtman 2 in speaking of lymphadenopathies producing obstruction quotes a paper by Brauneck in 1888 in which is described leucemia, infectious mononucleosis, lymphosarcoma and Hodgkin's disease. Because a thorough search of the literature since 1924 disclosed no report of jaundice caused by obstruction of the extrahepatic bile ducts by metastatic cancer we believe the following 3 cases merit recording. The first is that of a primary carcinoma of the splenic flexure of the colon producing multiple papillary metastases to the lumen of the extrahepatic bile ducts. The second is that of a lymphosarcoma uniformly infiltrating the walls of all the extrahepatic bile ducts, and the third is that of a carcinoma of the descending colon metastasizing to the lymph nodes of the hilum of the liver where it both compressed and invaded the common hepatic duct. REPORT OF CASES Case 1. A white man 60 years of age was admitted to the hospital with a history of attacks of indigestion, belching, vomiting, low abdominal pain and a full feeling in the rectum of 2 years' duration. His most recent attack was 5 weeks prior to admittance and consisted of weakness, pain in the right lower quadrant, belching, dizziness and jaundice. The pain, severe enough to require a hypodermic injection for its relief, persisted throughout the 5 week period and the jaundice increased in intensity. Stools were yellow to dark in color and he suffered from diarrhea, tenesmus and gas. Physical examination disclosed jaundice, a markedly distended abdomen, ascites, enlarged liver, and a mass the size of a "grapefruit," in the region of the gallbladder. Rectal * Received for publication, March 24,

2 366 P. A. HEBBUT AND J. S. WATSON examination was normal. Except for moderate anemia and a positive direct van den Bergh, laboratory tests were within normal limits. A barium enema disclosed an annular carcinoma just distal to the splenic flexure of the colon. -Operation revealed a primary carcinoma of the colon with metastases to the pancreas and liver. In an attempt to relieve the jaundice and the intestinal obstruction there were performed an anastomosis between the gallbladder and jejunum and a colostomy. In spite of this the patient's condition rapidly deteriorated and he died one week after operation. At necropsy a primary carcinoma that measured 8 cm. in diameter was found in the splenic flexure of the colon. It completely encircled the bowel, penetrated the entire wall, and obstructed the lumen. There were numerous metastatic nodules in the mesentery, one in the liver and one in a lymph node in the hilum of the liver. The latter measured 5 cm. in FIG. 1. (Case 1). Photograph of the liver showing 5 polypoid masses in the common bile and hepatic ducts. diameter. It was well encapsulated and on section disclosed a peripheral rim of neoplastic tissue and a center filled with necrotic semi-fluid material. At one point this mass was closely adherent to the common bile duct from which it was separated with difficulty. The lumen of the latter and of the common hepatic duct contained 6 polypoid masses some of which were discrete while others were conglomerate, measured as much as 4 x 1.5 x 0.8 cm. (fig. 1), and were firmly attached to the wall by relatively broad pedicles. Their apices were smooth, globular, deep reddish brown, and quite soft but not friable. The lowest nodule was situated 1.5 cm. proximal to the ampulla of Vater. Above this point the entire biliary tree was dilated to as much as 2 cm. in diameter. The extrahepatic bile ducts contained fluid bile but the intrahepatic ones were filled with inspissated material. The liver was yellow to green and extremely firm. Externally it was finely pebbled and cut surfaces revealed accentuated liver lobules surrounded by depressed bands of grey tissue. The

3 CANCER OF BILK DUCTS 367 pancreas was firm but disclosed no tumors and the remaining organs except for being jaundiced revealed no other contributory changes. Histologic sections of the primary tumor in the colon showed carcinoma. There was a gradual transformation of the regular epithelial cells to malignant cells in adenomatous formation that penetrated all the coats of the bowel. The cells were tall columnar and disclosed a marked tendency to slough into the lumen. The cytoplasm was abundant, deep pink and only occasionally showed vacuoles. The nuclei were round or oval, evenly stained, and basilar in position. Usually there was one to a cell but sometimes there ap peared to be 2 or 3. The supporting stroma was scanty but dense and was diffusely in FIG. 2. (Case 1). Section through one of the masses in the common bile duct showing several collections of cancerous cells in adenomatous formation in the serosa of the duct and similar cells irregularly distributed in the inner portion of the duct opposite the base of the broad pedicle. In the upper half are shown papillae composed of thin cores of fibrous tissue some of which are covered with malignant columnar cells. The spaces between the villi are filled with desquamated neoplastic cells. Hematoxylin and eosin. X75. filtrated with plasma cells and lymphocytes. Sections of nodules in the mesentery and in the liver were essentially similar. Sections of the bile ducts at the attachment of the papillomatous masses disclosed scattered neoplastic tissue in glandular formation in the submucosa and between the muscle bundles. The bases of the papillomas were composed of broad bands of fibrous tissue which on one side were directly continuous with the submucosa of the ducts and on the other with numerous finger-like projections of cores of fibrous tissue protruding into the lumen (fig. 2). These were well vascularized, were infiltrated with plasma cells and lymphocytes, and although they were denuded of surface epithelium in many areas, in others they were still covered with malignant cells. The latter were tall columnar, had abundant pink nonvacuolated cytoplasm and round oval evenly stained basilar nuclei. Often masses of sloughed cells were lying freely in the lumen of the glands and so in all respects the epithe-

4 368 P. A. HERBTJT AND J. S. WATSON lium here was identical with that in the primary tumor in the colon. Sections of the liver disclosed advanced biliary cirrhosis and sections of other organs showed no contributory changes. Case 2. A white boy 13 years old developed anorexia, vomiting, and attacks of colicky abdominal pain one month before admission to the hospital. The latter was followed by a "tightening" feeling in the epigastrium. Three days before admittance his mother noticed that his scleras were yellow and that the veins over the chest and abdomen were prominent. He lost 15 lb. in weight in one month and during this illness took pills (presumably a sulfa compound) that were prescribed by his physician for what was thought to be rheumatic heart disease. Physical examination revealed jaundice, dilated veins over the chest and abdomen, ascites, tenderness over the right costal margin, a palpable liver, edema of the ankles and rales at the bases of the lungs. The significant laboratory tests disclosed hemoglobin 84 per cent, erythrocyte count 4,600,000, leukocyte count 12,400 with normal differential values, blood urea nitrogen 17.6 mg. per 100 cc, total blood proteins 4.7 Gm. (albumin 3.7 Gm. and globulin 1.0 Gm.), serum bilirubin 15 mg., and a positive direct van den Bergh test. Ascitic fluid removed at peritoneoscopy had a specific gravity of 1.014, and a smear of the sediment disclosed lymphocytic cells. The patient died one week after entering the hospital. Necropsy revealed intense jaundice, partially digested blood exuding from the mouth, and 2000 cc. of orange colored fluid in the peritoneal cavity. In the anterior mediastinum and extending to the diaphragm there was a yellowish grey, moderately firm tumor measuring 20 x 10 x 2 cm. The diaphragm was covered with nodules of similar tissue and there were scattered tumors in the heart, omentum, intestines, appendix, pancreas, gallbladder, and kidneys. All of the extrahepatic bile ducts were completely replaced with moderately firm grey neoplastic tissue. Because of this the walls were thickened to as much as 7 mm. in diameter and the entire lumen was reduced to a totally collapsed slit. This infiltration ended at the junction of the extra-hepatic ducts with the liver. Above this point the bile ducts were prominent and filled with stringy bile fluid. The liver weighed 1880 Gm. It was yellowish brown and firm but disclosed no tumors or grossly evident cirrhosis. Histologic sections of the common bile and hepatic ducts disclosed a diffuse infiltration of the entire wall with lymphoblastic cells (fig. 3). Except for a few strands of smooth muscle all normal tissue was completely crowded out. The lining epithelium was, however, still intact but the lumen of the ducts was completely collapsed. Sections of practically all other organs and tissues of the body showed slight or extensive infiltration with lymphoblastic cells. Sections of the liver disclosed severe fatty metamorphosis of the central portions of the lobules, brown pigment in the bile canaliculi, and varying degrees of dilatation of the bile ducts but no cirrhosis. Sections of the remaining organs showed no other contributory changes. Case 3. A white man 56 years old was well until 6 weeks before hospitalization when he gradually developed loss of appetite, weakness, loss of weight, pain in the right side of the abdomen, nausea and vomiting, some fever and more recently jaundice. Physical examination disclosed jaundice, enlargement of the liver and an intraperitoneal mass the size of a lemon situated just to the left of the umbilicus. Pertinent laboratory data consisted of failure to visualize the gallbladder by cholecystogram, slight anemia, positive direct van den Berth test, serum bilirubin 14.6 mg., blood urea nitrogen 106 mg., and bile pigment in the urine. At operation there was found a carcinoma of the descending colon with metastases to the extrahepatic bile ducts and liver. He died on the fifteenth post operative day. Gross examination of the specimen removed at operation disclosed a carcinoma of the large bowel. Necropsy revealed that the lymph nodes which drained the resected portion of the colon and those along the aorta and in the hilum of the liver were enlarged by tumor up to 3 cm. in diameter. One of these nodes was situated at the union of the left and right

5 CANCER O F B I L E DUCTS 369 F I G. 3. (Case 2). Semi-gross photograph of a histologic section through the common bile duct showing the entire wall diffusely infiltrated with lymphoblastic cells. R e m n a n t s of muscle bundles can be seen near the periphery. The lumen is reduced to a narrow slit. Hematoxylin and eosin. X15. F I G. 4. (Case 3). Photograph of the hilum of the liver showing tumor tissue infiltrating the liver and common hepatic duct. Tumor tissue posterior to the duct has been cut away and the duct, which a t autopsy was collapsed, has been distended with a black applicator.

6 370 P. A. HERBUT AND J. S. WATSON hepatic ducts at which point it compressed and invaded the common hepatic duct and also infiltrated the adjoining portion of the liver (fig. 4). The bile ducts above the point of obstruction were dilated up to 1 cm. in diameter. The liver was greenish yellow and contained several metastatic nodules. The lungs showed congestion and edema and each kidney weighed 355 Gm. There were no other pertinent findings. Histologic sections of the tumor in the colon and metastatic nodules were typical of primary carcinoma of the large intestine. Sections of the common hepatic duct at the level of the tumor disclosed massive infiltration of the periductal connective tissue with cancerous cells (fig. 5). In several areas these cells penetrated the wall of the duct and were found both between the muscle coats and in the submucosa. Sections of the liver disclosed both FIG. 5. (Case 3). Histologic section of the common hepatic duct showing cancerous tissue in adenomatous formation infiltrating the serosa (below) and the submucosa (above). Hematoxylin and eosin. X50. cancerous tissue and early biliary cirrhosis. The kidneys revealed degeneration or necrosis of the epithelium of the proximal convoluted tubules, casts in the lumen of the more distant nephrons, and edema and leukocytic infiltration of the interstitial connective tissue. There were no other relevant findings. COMMENT Although jaundice consequent to metastatic carcinoma usually results from massive destruction of the hepatic parenchyma by malignant tissue, it may also result from obstruction of the extrahepatic biliary system. In either case the prognosis is hopeless and these cases may, therefore, be considered more of aca-

7 CANCER OF BILE DUCTS 371 demic than of practical interest. Nevertheless, if such a possibility is kept in mind the patient may be spared unnecessary surgical manipulation. Case 1 is of particular interest for pathologically it offered a diagnostic problem both grossly and at first microscopically. Benign polypoid tumors of the extrahepatic bile ducts producing obstructive jaundice have been sporadically reported in the literature under the titles of adonoma and papilloma 1. When first seen the multiple mucosal growths in this case appeared similar to these benign lesions and so were very suggestive of primary bile duct tumors entirely independent of the carcinoma in the colon. Such a lesion could conceivably offer considerable difficulty at the operating table if the common bile duct were being explored because of obstructive jaundice. Even microscopically we were at first led to consider them as primary papillomas. On closer examination, however, the cells lining the villi were identical morphologically with those in the primary tumor in the colon. Furthermore, sections through the duct at the site of the attachment of the hilar lymph node disclosed similar neoplastic cells in the serosa, muscle layers and submucosa. The distribution of the malignant cells suggested that the duct was invaded directly from without and that the subsequent spread was either along the tissue planes of the wall or conceivably by way of the lymphatics. From such locations malignant cells grew into the lumen of the extrahepatic ducts at irregular levels and produced the papillary formations. Clinically, the second case presented a diagnostic problem. Because the jaundice was of such short duration and because it followed the administration of a drug which was thought to be sulfadiazine the first impression was that the patient was suffering from acute diffuse hepatic necrosis as a result of sulfonamide poisoning. The absence of enlared peripheral nodes and the presence of a normal differential blood count further strengthened this suspicion. Ascites and edema were thought to be the result of a failing rheumatic heart. Pathologically, the unusual feature of this case was not the widespread involvement of the many organs but the uniform infiltration of the entire extrahepatic bile ducts with complete obstruction of the lumen. The mechanism of involvement here as in the previous case was probably the permeation of lymphoblastic cells along the natural planes of the bile ducts. As already indicated, reports of cases similar to case 3, while very few, have appeared in the literature from time to time and this case, therefore, merits no further elucidation. SUMMARY A review of recent medical literature discloses no reports of metastatic cancer to the extrahepatic bile ducts producing obstructive jaundice. In this paper we have presented 3 such cases. The first two are unique in that similar cases have not apparently been previously recorded. Case 1 is that of a carcinoma of the colon producing multiple papillomatous metastases in the mucosa of the common bile and hepatic ducts. Case 2 is that of a lymphosarcoma producing a diffuse permeation of the entire wall of the extrahepatic bile ducts with a uniform reduc-

8 372 P. A. HEBBUT AND J. S. WATSON tion of the lumen to a non-functioning slit. Case 3 is that of a carcinoma of the colon producing obstruction of the common hepatic duct both by compression from without and by direct infiltration of the wall. REFERENCES 1. CHRISTOPHER, F.: Adenoma of the ampulla of Vater. Surg. Gynec. and Obst., 56: 202- < 204, LICHTMAN, S. S.: Diseases of the liver, gallbladder and bile ducts. Lea and Febiger,. Philadelphia, 1942, pp ; 3. ROLLESTON, H., AND MCNEE, J. W.: Diseases of the liver, gallbladder and bile ducts. ] Ed. 3. Macmillan& Co., Ltd., London, 1929, pp j 4. WEISS, S., GRANT, J. P., AND QITIMBY, A. J.: Diseases of the liver, gallbladder, ducts and i pancreas. Paul B. Hoeber, Inc., New York, 1935, p :