Saudi Journal of Gastroenterology
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CASE REPORT Table of Contents   
Year : 2003  |  Volume : 9  |  Issue : 3  |  Page : 142-144
Hepatocellular carcinoma and gall bladder adenocarcinoma: Two primaries with no significant risk factors

Department of Pathology, College of Medicine, King Khalid University Hospital, Riyadh, Saudi Arabia

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Date of Submission09-Mar-2003
Date of Acceptance19-May-2003

How to cite this article:
Al-Shedoukhy AA, Al-Garni AA. Hepatocellular carcinoma and gall bladder adenocarcinoma: Two primaries with no significant risk factors. Saudi J Gastroenterol 2003;9:142-4

How to cite this URL:
Al-Shedoukhy AA, Al-Garni AA. Hepatocellular carcinoma and gall bladder adenocarcinoma: Two primaries with no significant risk factors. Saudi J Gastroenterol [serial online] 2003 [cited 2022 Jan 18];9:142-4. Available from:

Hepatocellular carcinoma is a common malignant neoplasm, it has (4:1) male predominance. Its highest incidence is in Central, South and West Africa, Southeast Asia and China while the lowest incidence is in Europe, North America and Australia. Its predisposing factors include viral hepatitis (HBV, HCV), some congenital and metabolic disorders, natural and synthetic carcinogens (e.g. Aflatoxin, Organophosphates), chronic alcoholism and smoking [1] . Gall bladder carcinoma is a less common malignancy with highest incidence being among females in Chile and Mexico. It has 2:1 female predominance. The probable associated factors include gallstones, anomalous pancreatic biliary-union, obesity and parity [2] . Currently, we present a 66-year-old Saudi male who had these two tumors synchronously coexist with no known risk factors other than diabetes.

   Case report Top

A 66-year-old Saudi male presented to King Khalid University Hospital with an incidentally discovered epigastric mass on June 2001 in a private clinic. The patient denied any history of weight loss, change in appetite, jaundice, fever or night sweat. The patient is known diabetic on insulin, and hypertensive on thiazides. He is a non-smoker.

The clinical examination was unremarkable apart from an abdominal epigastric mass that was non­tender, round and with smooth outline. No bruits or ascites were found. Hematological and biochemical investigation showed normocytic, normochronic, anemia, low albumin (25mg/dl), elevated liver ezymes namely (ALP=265iu/L, AST=46iu/L, GGT=275iufL). PT, PTT and bilirubin levels were within normal limits.

Viral hepatitis (HBV, HCV) profiles were negative. Alphafoetoprotein was not available. Radiological studies (ultrasound and CT scan) showed a single round solid tumor mass located in left hepatic lobe and measured about 10.2cm. in greatest dimension. No gallbladder mass detected. FNA diagnosis was hepatocellular carcinoma. Based on this, left hepatic lobectomy and cholecystectomy were done. The two specimens were received and sent for histopathological examination.

Grossly, the left hepatic lobe weighed 721 grams, measured 18.0x13.0x6.Ocm. and had an intact but stretched capsule showing nodular expansion. On serial sections, a large rounded tumor measuring 11.0x11.0x7.5cm. and occupying more than 2/3 of the left lobe was seen. Focal tumor necrosis was present. The uninvolved hepatic tissue measured 7.Ocms. in greatest dimension and was grossly unremarkable. The opened gallbladder measured 6.5x2.0xl.0cm. and showed a bulging hard to firm tumor mass in the fundus measuring 2.0xl.5x1.0cm., with solid whitish cut surface. No stones or other gross pathology was noticed.

Microscopic examination of the left hepatic lobe showed a tumor consisting predominantly of moderately differentiated malignant hepatocytes arranged in confluent cords and nests. Areas of clear cell changes, tumor giant cells, acinar (pseudoglandular) formations and tumor necrosis were noted. [Figure - 1]. No vascular or capsular invasion was seen. Surgical resection margins were free of tumor. The non-neoplastic hepatic tissue showed moderate inflammation with no cirrhosis or dysplasia.

The sections from the gallbladder and from the fundic tumor showed infiltrating moderately differentiated adenocarcinoma with overlying tubulovillous hyperplastic mucosa with focal severe dysplasia and carcinoma insitu [Figure - 2],[Figure - 3]. Focally, the tumor showed papillary architecture. The malignant cells extended in small groups and singly into the subserosal level, i.e. into extramuscular fibroadipose layer but not beyond the serosa. The remaining gallbladder tissue showed moderate inflammation and focal intestinal metaplasia.

The diagnosis of two primary malignant tumors was established; hepatocellular carcinoma, moderately differentiated and gallbladder adenocarcinoma, papillary type, moderately differentiated. Patient had uneventful post operative course and attended regular follow up visits to the outpatient surgical clinic with no complaint. His follow up investigations and U/S of liver were negative for residual or recurrent disease 18 months after surgery.

   Discussion Top

Synchronous coexistence of second primary malignancy with hepatocellular carcinoma is uncommon but is a well known phenomenon. The most common type of coexisting malignancies is cholangiocarcinoma (intrahepatic bile duct carcinoma) followed by colorectal cancers [3].

To the best of our knowledge, only one Japanese case had been reported to have a collision tumor of primary HCC and gallbladder carcinoma, but it was accompanied by anomalous pancreatobiliary duct union and congenital intrahepatic bile duct dilatation [4] . However, in our case, no accompanying risk factor is noted apart from diabetes [1] .

As prognosis is concerned, we should notice that in HCC, the 5-year survival rate is approximately 23% while in gallbladder adenocarcinoma, it falls to be 5-10% [5] . Factors influencing the prognosis in gallbladder carcinoma are differentiation of the adenocarcinoma, finding of unsuspected carcinoma in a cholecystectomy specimen, microscopic extension and microscopic invasion. Epithelial dysplasia is considered a premalignant lesion since the mucosa adjacent to the carcinomatous area shows this change at the rate of 66.7% to 33.8% [6] . In our present case, we found foci of epithelial hyperplasia and dysplasia. Survival analysis of patients with gallbladder carcinoma showing subserosal infiltrate, stage II, (the tumor has invaded the extramuscular fibroadipose layer of the gallbladder but with no invasion to adjacent organs), who underwent curative resection had a significantly better survival than those treated by simple cholecystectomy [7] . Curative resection involves regional lymph node resection and postoperative radiotherapy. Both papillary adenocarcinoma of the gallbladder and extrahepatic bile ducts are noted to be associated with the best outcome of all histologic type, this may explain the good outcome noted in this patient after 18 months of follow-up.

Since, the liver, gallbladder, bile ducts and pancreas have a common embryonic origin, it is not surprising to have multiple cancers arising at different sites at the same time, as they are expected to share similar spectrum of histologic types [2].

Early diagnosis of gallbladder carcinoma is the only way to improve the poor prognosis for these patient, by detecting the tumor at an early stage, when simple cholecystectomy is a curative procedure. The first step along this line is to become familiar with the early lesions of this tumor [8] . Having said that, early diagnosis might not be possible, since these tumors are usually silent and in our case, if it was not for the hepatic mass, the adjacent gallbladder carcinoma would have been missed to be discovered later on with advanced disease. We think that there must be other unknown risk factors that can predispose to hepatocellular carcinoma and/or gallbladder carcinoma other than the common and usual known ones.

Acknowledgement: The authora are grateful for Mr. Syed Muzfar Shah for his excellent secretarial support.

   References Top

1.LaVecilia C, Negri E, Decarli A, Franceshi S. Diabetes mellitus and the risk of primary liver cancer. Int J Cancer 1997; 73: 204-7.  Back to cited text no. 1    
2.Carriaga MT, Harson DE. Liver, gallbladder, extra hepatic bile ducts and pancreas. Cancer Supplement 1995, 75; 1: 171-90.  Back to cited text no. 2    
3.Lai CR, Liu HC. Hepatocellular carcinoma coexisted with a second malignancy: a study of 13 cases from a consecutive 440 autopsy cases of HCC. Chung-Hua­1-Hsueh-Tsa-Chih-Taipei, 1990; 46: 202-7.  Back to cited text no. 3    
4.Makino Y, Nakayama T, Hiyama Y, Tsukamoto S, Seki Y, Ohto M. A case of carcinoma collision tumor of hepatocellular carcinoma and gallbladder carcinoma accompanied by anomalous pancreatico biliary ductal union and congenital intrahepatic bile duct dilatation. Nippon-Shokakibyo-Gakkai-Zasshi, 1989; 86: 2816-21.  Back to cited text no. 4    
5.Yamaguchi K, Enjoji M, Munetomo Enjoji. Carcinoma of the gallbladder. A clinicopathology of 103 patients and a newly proposed staging. Cancer 1988, 62: 1425-32.  Back to cited text no. 5    
6.Albores-Saavedra J. The precursor lesions of invasive gallbladder carcinoma: hyperplasia, atypical hyperplasia and carcinoma in situ. Cancer 1980; 45: 919-27.  Back to cited text no. 6    
7.De Aretxabala XA, Roa IS, Burgos LA, Araya JC, Villaseca MA, Silva JA. Curative resection in potentially respectable tumors. The gallbladder. Eur J Surgery 1997; 163: 419-26.  Back to cited text no. 7    
8.Hart J, Moan B. Factors affecting survival of patients with gallbladder neoplasm. Arch Intern Med 1972; 129: 931-4.  Back to cited text no. 8    

Correspondence Address:
Ahlam Abdullah Al-Shedoukhy
Department of Pathology, College of Medicine, King Khalid University Hospital, P. 0 Box 2529, Riyadh 11461
Saudi Arabia
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Source of Support: None, Conflict of Interest: None

PMID: 19861819

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  [Figure - 1], [Figure - 2], [Figure - 3]


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