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EARLY CARCINOMA of the AMPULLA of VATER Primary EARLY CARCINOMA OF THE AMPULLA OF VATER JULIUS FOLDES, M.D., AND FREDERICK W. HEYER, M.D., F.A.C.S. Nanticoke, Pennsylvania Primary carcinoma of the ampulla of Vater is an extremely rare condition. According to Lieber,' only one proved case of this condition has been reported, for while many cases are described in the literature, careful scrutiny of the reports reveals that a possible origin from other nearby and closely related structures has not been excluded. There are four possible sources of origin of a tumor in this region: (1) the duodenal mucous membrane covering the papilla of Vater, (2) the terminal common bile-duct, (3) the proximal main pancreatic duct, and (4) the ampulla of Vater. The lesion is seldom con- sidered in arriving at a clinical diagnosis, and by the time the patient comes to autopsy the tumor has attained such a size as to involve two or more of the structures alluded to above. A decision as to its exact source is then obviously impossible. The case here reported is of particular interest since the patient was seen early, and the primary lesion observed at autopsy was small and self-limited so that a definite opinion could be formed as to its origin. A. P., a white man aged fifty-six years, was admitted to the Nanticoke State Hospital on Jan. 10, 1938, complaining of jaundice, epigastric pain, gaseous eructations, light stools, and dark brown urine. He had been in apparently good health until a week before admis- sion to the hospital, when jaundice appeared insidiously and increased progressively. Two days later he experienced gradually increasing pain in the epigastric region, associated with gaseous eructations but without nausea or vomiting. His appetite was good, but, in spite of this, there had been a loss of weight of ten pounds in the last six weeks. Chills and fever were absent, and constipation was not a feature. On physical examination, the skin and mucous membranes were jaundiced. The liver and spleen were not palpable. A circumscribed, tender mass, suspected to be the gallbladder, was palpated in the right upper quadrant of the abdomen, extending 3.5 cm. below the costal margin. The gallbladder was not demonstrable in cholecystographic studies. Roent- gen examination of the gastro-intestinal tract following a barium meal showed a normal stomach with hypertrophic rugae suggestive of a gastritis. There were no filling defects in the stomach or duodenum, and the intestinal pattern was normal. The urine was dark brown with a specific gravity of 1022 and contained bile, a faint trace of albumin, a few hyaline casts, numerous leukocytes and mucus. The hemoglobin content of the blood was 94 per cent, the red cell count was 4,620,000, and the white cell count 6,800 with 58 per cent polymorphonuclear neutrophils and 39 per cent lymphocytes. The Wassermann and Kahn reactions on the blood serum were negative. The sedimentation rate of the red blood cells was normal. The icterus index was 12.5. Chemical examination of the blood was negative. The stools were light yellow and showed no occult blood. The clinical diagnosis was carcinoma of the duodenum with obstruction of the bile-ducts or carcinoma of the head of the pancreas. Laparotomy was performed on Jan. 21, 1938. The abdomen contained a large amount of bile-stained fluid. The liver was enlarged and smooth, and the gallbladder was distended. The stomach and duodenum appeared normal. The head of the pancreas showed some thickening, but no new-growth was found. There was no evidence of calculi in the biliary Our heartiest appreciation is extended to Dr. M. M. Lieber, Pathologist of the Jefferson Medical College, for allowing us to review his article on a similar subject, unpublished when this report was submitted for publication, but since appearing in Ann. Surg. 109: 219, 383, 1939. 574 EARLY CARCINOMA OF AMPULLA OF VATER 575 tract. The cystic duct was bound down by old connective-tissue adhesions. Since careful search failed to reveal a tumor, a surgical diagnosis was made of hydrops of the gallbladder due to cholecystitis, and cholecystectomy and duct drainage were performed. Following operation, there was considerable drainage of bloody fluid from the operative site; there was increasing distention of the upper abdomen, and jaundice continued unabated. Death occurred on Jan. 31, 1938. Autopsy was performed seven hours after death. The combined gross and microscopic diagnoses were: primary adenocarcinoma of the ampulla of Vater; obstruction of the com- mon bile duct ; hydrohepatosis with marked jaundice; biliary nephrosis with adenoma of the right kidney; generalized arteriosclerosis ; acute generalized fibrinous peritonitis. There was a moderate amount of free and clotted blood in the right upper quadrant of the abdomen due to leakage of a small vessel in the omentum. The abdominal viscera were covered by a heavy, greenish-yellow fibrinous exudate, causing easily separable adhesions of FIG. 1. OPENEDPAPILLA OF VATER,SHOWING THICKENING OF ITS WALL The inner surface exhibits many fine, granular excrescences. The common bile-duct above is markedly dilated. The tissues lateral to the opened papilla represent adjacent portions of normal duodenal mucosa. the intestinal loops. The stomach and proximal duodenum were normal. The papilla of Vater was enlarged and projected forward and downward into the lumen of the duodenum. It was firm and indurated, but the mucous membrane covering it appeared normal. A probe easily entered the lumen of the apex of the papilla but was arrested immediately beyond this. When incised, the wall of the papilla was firm and gray, measuring 3 mm. in thick- ness (Fig. 1). The inner surface, corresponding to the ampulla of Vater, exhibited many fine granular excrescences. The common bile-duct was dilated, measuring 4 cm. in circum- ference. The duct of Wirsung was normal and joined the common duct at a point about 2 mm. proximal to the primary neoplasm. The duct of Santorini was normal. ‘The liver weighed 1600 gm. and was covered by a fibrinous exudate. It cut with in- creased resistance, and the cut surface was greenish-yellow with dilated biliary ducts and indistinct lobular markings. The kidneys were slightly enlarged and were yellowish-green and red. On the posterior surface of the upper pole of the right kidney was a yellowish-white circumscribed nodule 1.5 cm. in diameter. 5 76 JULIUS FOLDES AND FREDERICK W. HEYER FIG. 2. CROSS-SECTIONOF THE ANTERIORTHIRD OF THE SPECIMENTHROUGH THE AMPULLAAND DUODENUM,SHOWING INVADING MALIGNANT ACINI BELOWTHE NORMAL DUODENALMUCOSA. X 80 FlG. 3. MALIGXANTCHANGES ON THE SURFACE OF THE AMPULLAOF VATER. x 80 The pancreas was covered by a fibrinous exudate, but cut sections were negative. Microscopically, a cross-section through the extreme apex of the papilla of Vater showed a number of small and large atypical acini (Fig. 2) lined by cylindrical cells lying within its lumen, and a few of these formed short finger-like processes which projected through the orifice into the duodenum. The duodenal mucous membrane covering the papilla was everywhere normal and stopped abruptly without change at the margins of the exit of the ampulla of Vater. Longitudinal sections through the opened papilla of Vater (Fig. 3), in- cluding the ampulla of Vater and dilated common bile-duct, showed a gradual malignant transformation occurring at a point in the ampulla 5 mm.from the apex of the papilla. This change was characterized by irregularity, hyperchromasia, and a proliferation of the cells lining the acini in the wall of the ampulla with a heaping up of these cells into eccentric multiple layers. The acini became elongated and extended to the surface with the forma- EARLY CARCINOMA OF AMPIJLLA OF VATER 577 tion of flat and rounded excrescences which were in turn followed by short, branching, papil- lary projections. The atypical acini in the depths of the tissue became particularly numerous towards the apex of the papilla, where infiltration of the muscularis of the duodenum was noted. Tumor acini extending for a short distance into the adjacent pancreatic tissue were also noted. The atypical epithelial cells were generally well differentiated and occurred as cylindri- cal or columnar elements with sharply defined outlines and with faintly acidophilic, homo- geneous or vacuolar cytoplasm. The nuclei were basally situated in the cells and were uniformly hyperchromatic. Mitotic figures were rarely observed. The stroma was gen- erally abundant but not very vascular. A few small focal collections of inflammatory cells, lymphocytes. and monocytes were present in the stroma. The liver showed the characteristic changes of biliary stasis with pigmentation of the inner two-thirds of the lobules, necrosis of the hepatic cells about the central veins, and a slight increase of connective tissue in the portal areas, which were infiltrated with small round cells. The kidney showed pigmentation of the tubular epithelium and necrosis of the cells, particularly in the proximal convoluted tubules. Rile casts and desquamated cells and tissue dCbris were noted in the collecting tubules. DISCUSSION This case is a proved instance of carcinoma primary in the ampulla of Vater. The terminal common bile duct, proximal pancreatic duct, and mucous membrane covering the papilla of Vater were entirely free of neoplastic growth. Since the primary tumor was small and self-limited, it was possible to make serial microscopic sections of it as well as of the neighboring structures. The clinical picture justified the diagnosis of carcinoma of the head of the pancreas or of the duodenum. At laparotomy, careful palpation of the pan- creas and duodenum failed to reveal a new growth, and a simple cholecystec- tomy was performed for hydrops of the gallbladder. It is possible that if a duodenotomy had been performed, the true nature of the condition would have been recognized.
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