Cholangiocarcinoma Associated With Biliary Cirrhosis Due to Congenital Biliary Atresia Prakash B. Kulkarni, MB BS, DCH,
Eugene C. Beatty, Jr,
\s=b\ An 11-year-old girl developed cholangiocellular carcinoma in association with biliary cirrhosis due to congenital biliary atresia. An exploratory laparotomy and an operative cholangiogram at 3 months of age had confirmed the diagnosis of extra\x=req-\ hepatic biliary atresia. A liver biopsy spec-
imen taken at 6 months of age showed cirrhosis. The subsequent clinical course was characterized by persistent moderate jaundice, anemia, malnutrition, rickets, pathologic fractures, and recurrent gastrointestinal bleeding. The presence of cholangiocellular carcinoma of the liver with advanced biliary cirrhosis was established at an exploratory laparotomy a week before her death. We discuss here the pathogenesis of biliary cirrhosis and carcinoma of the liver; there may be a relation between the two in the childhood
biliary
population. (Am J Dis Child 131:442-444, 1977) of two relatively diseases within a single organ is unique and may represent either an unusual coincidence or a causal relationship. This article re¬ ports such a case in a child and reviews the literature to consider possible pathogenetic mechanisms that may operate to produce either or both of these pathologic changes.
The
occurrence
rare
REPORT OF A CASE The
patient,
a
black
20, 1962, following pregnancy and
a
girl,
was
born
July
full-term, normal
delivery. Family history
unremarkable. Jaundice was noticed in the first week of life. As the jaundice increased, she was also noted to have darkcolored urine and acholic stools. At the age of 3 months, an exploratory laparotomy was
Departments of Pediatrics (Dr Pathology (Dr Beatty), Children's Mercy Hospital, Kansas City, Mo. Reprint requests to Department of Pediatrics, Children's Mercy Hospital, 24th and Gillham Rd, Kansas City, MO 64108 (Dr Kulkarni). From the Kulkarni) and
MD
done. A gallbladder cholangiogram showed that the common bile duct was normal, but there was absence of both hepatic ducts. A liver biopsy specimen was interpreted as showing neonatal hepatitis by one pathologist and biliary cirrhosis by another. At the age of 6 months she was admitted to the Children's Mercy Hospital with persistent jaundice, acholic stools, and rick¬ ets. A rose bengal study showed consid¬ erable loss of liver function and obstruc¬ tion. At a second exploration, the gall¬ bladder cholangiogram revealed the same picture as before. The liver biopsy spec¬ imen this time showed a striking increase in the degree of fibrosis and bile stasis (Fig was
1). The subsequent clinical course was char¬ acterized by persistent moderate jaundice with dark-colored urine and acholic stools,
anemia, malnutrition, rickets, pathologic fractures, and recurrent gastrointestinal bleeding. In January 1974, the patient was admitted
because of gastrointestinal time she did not have
bleeding. At this hepatomegaly.
In March 1974, at the age of 11 years and 10 months, the patient was readmitted because of persistent high temperature. Physical examination revealed an under¬ nourished child with deformities of the lower extremities secondary to rickets and old healed fractures. Moderate icterus was present. The liver was palpable 7 to 8 cm before the right costal margin. The spleen was palpable 2 cm below the left costal margin. Laboratory investigations showed a hemoglobin level of 7.4 gm/100 ml and a hematocrit value of 26%. The leukocyte count was 10,300/cu mm, with 81% polymorphonuclear leukocytes, 11% lympho¬ cytes, and 8% monocytes. The reticulocyte count was 2.4%; the platelet count was 465,000/cu mm. The prothrombin and partial thromboplastin times were normal. The plasma fibrinogen level was 310 mg/ 100 ml. The total serum bilirubin con¬ centration was 11.5 mg/100 ml; indirect, 4.9 mg/100 ml. The serum glutamic oxaloacetic transaminase level was 59 ImU/ml and
Downloaded From: http://archpedi.jamanetwork.com/ by a New York University User on 06/10/2015
the serum glutamic pyruvic transaminase level was 17 ImU/ml. The total serum protein level was 8.2 gm/100 ml; albumin, 2.6 gm/100 ml. Electrolyte values and the blood urea nitrogen level were normal. The possibility of hepatic abscess was consid¬ ered and an exploratory laparotomy was performed. Multiple firm nodules, 0.5 to 3.5 cm wide, were noted in the liver. Repeated attempts to aspirate purulent material were unsuccessful. A biopsy specimen of these nodules showed carcinoma of the liver of the mixed hepatocellular and bile duct type (Fig 2). The patient died eight days after the laparotomy. At autopsy, the liver weighed 1,480 gm (normal for age, 936 gm). The lobular pattern was distorted by a fine nodular cirrhotic pattern. Numerous neoplastic nodules were scattered throughout the liver (Fig 3). The common bile duct was patent, but hepatic ducts were not demon¬ strable. The portal vein was markedly distended and filled with a yellowish, friable neoplastic tissue. Microscopic examination of the liver showed two distinct pathologic processes. The first consisted of increased fibrous connective tissue in portal triads with extension into the interlobular septa. Many portal triads lacked bile ducts and contained chronic inflammatory cells. The second process consisted of diffuse infiltrative nodules of malignant neoplastic tissue, some representing bile ductal components and others hepatocellular components. The ductal components appeared to be invasive and filled much of the portal venous system. Necrosis of the larger neoplastic nodules was prominent. There were no metastatic lesions. The spleen weighed 160 gm and was congested. Other autopsy
findings
were
noncontributory. COMMENT
Extrahepatic biliary atresia is an entity; the absolute inci¬ dence is reported to be about 1:8,000 to 1:10,000 live births.1 Until recently, it was thought that in spite of medical uncommon
Fig 1.—Biliary cirrhosis secondary (hematoxylin-eosin, 160).
to
Fig 2.—Cholangiocellular (left)
extrahepatic biliary
and
surgical
was
atresia with biliary cirrhosis described by Craig et al,·" 39 died within the first year of life. These authors stated that although all their patients showed some degree of obstructive cirrhosis pathologically, the disease process had not continued long enough to cause many of the clinical sequelae of cirrhosis. The reported incidence of cirrhosis in chil¬ dren was 0.02% (16 patients in 80,000 children) at Harriet Lane Home in Baltimore.7 The reported incidence of primary carcinoma of the liver in the United
hepatic biliary
Fig
3.—Gross
specimen showing
multinodular
hepatic
carci¬
noma.
treatment the prognosis very poor in 95% of these chil¬ dren.- With the introduction of the Kasai operation'·4 there appears to be a chance for a favorable longterm survival. Liver transplantation has been performed in some cases with fair results. Without surgery, most of these patients die in the first decade of life. Of the 49 patients with extra¬
and
atresia
hepatocellular (right) components of hepatic
carcinoma
States is said to have an autopsy rate in children of 0.875% (13 times in 1,538 cases),'· which seems relatively high. Of the 126,000 admissions over a period of 14 years at Denver Chil¬ dren's Hospital, only nine had hepatic
carcinoma,
an
incidence
rate
of
0.0008%.u
of liver cirrhosis of all types, 49 with hepatoma and nine with cholangioma. Seventy-one of these cirrhotic cases were of the biliary type; one patient had hepatoma and seven had cholan¬ gioma. It is stated that cirrhosis was probably the result of biliary obstruc¬ tion instituted by the neoplasm itself, rather than the primary disease. In 1962, Cameron and Hou" stated that there were no cases of hepatoma re¬ ported in children with biliary cirrho¬ sis. In 1966, Mori111 reviewed 3,232 autopsies, disclosing 59 cases of primary hepatic cancer and 127 cases of liver cirrhosis. Of these 3,232 autopIn 1960, Gall·" reviewed 682
cases
Downloaded From: http://archpedi.jamanetwork.com/ by a New York University User on 06/10/2015
(hematoxylin-eosin,
200).
sies, there were 25 cases of biliary cirrhosis, 17 secondary to biliary atre¬ sia. None of these patients with biliary cirrhosis had hepatic malig¬ nancy. He concluded that
specific liver and cirrhosis, biliary cardiac, seem to have no relation to the occurrence of any primary hepatic cancer. In 1961, Alcalde et al" reviewed 139 cases of primary carcinoma of the liver in children recorded in the litera¬ ture. Only eight (5.7%) had a concomi¬ tant diagnosis of cirrhosis. However,
there is no mention of the type of cirrhosis or whether it was secondary to the malignancy itself. There are eight reported cases,"' including our case, of primary liver cancer with biliary cirrhosis of the liver associated with biliary atresia (Table). The youngest child reported to have hepatoma with biliary cirrho¬ sis resulting from bile duct atresia was 5 months old, whereas the other patients were more than 2 years of "
'"
Reported Cases Source
Okayama,"
of
Extrahepatic Biliary Atresia
Age, yr/
Histological Type
Sex/Race 3/M Liver cell
1965 Absolon et al,'5 1965 Fish & McCary,' 1966
With Liver Cancer
Métastases
Lungs
Right
with
Involvement & Comments lobe of liver
¡ntrahepatic
metastasis Liver (seen on autopsy)
5 mo/F
Liver cell
2/M/W
Liver cell
Lungs
Death at 26 mo; carcinoma found at
Deoras & Dicus,' 1968
6/F/B
Liver cell
Lungs
Carcinoma found at
Fraumeni et al," 1968
3/M
autopsy
autopsy Autopsy showed biliary cirrhosis and histiocytic proliferation in many
Cholangiocellular
organs; mixed liver cell and bile duct carcinoma
Van Wyks et al,5 1972
12/F
Liver cell
Lungs after
·
transplant 4/F
Liver cell
No
Choledochogastrostomy
shortly after birth; liver transplant for tumor In right lobe; died 10 wk after transplant Liver transplant; doing well 18
mo
after
transplant; hepatoma found Present report, 1977
11/F/B
Cholangio-
No
after surgery 1 wk before
Laparotomy
death; showed presence of carcinoma, confirmed
cellular
at
age. Six of these had hepatocellular carcinoma. The case presented here is the second case of cholangiocellular carcinoma of the liver. Occurrence of primary liver cell carcinoma in pa¬ tients with giant cell hepatitis has also been reported.19·20 In an attempt to correlate the occurrence of these two rather rare pathological conditions occurring in the same individual, we present the following considerations. It has been recently postulated that biliary atre¬ sia, choledochal cyst, and neonatal hepatitis are different manifestations of the same or similar etiologies.21 In an excellent epidemiologie study of 76 cases of primary liver carcinoma in childhood, Fraumeni et al18 mentioned a case of mixed liver cell and bile duct carcinoma in a patient with biliary atresia. They found that five patients had antecedent liver disease, which is more than normally expected. They stated that the occurrence of liver carcinoma and congenital biliary atre¬ sia may signify a common embryologic defect, but since neoplasia is associated with various forms of cir¬ rhosis, it seems more likely that the relationship in biliary atresia is the secondary biliary cirrhosis. Primary carcinoma of the liver has been reported in patients with gly¬ cogen storage disease,22-2:i galactos¬ emia,24 tyrosinemia, and aminoacidu-
autopsy
ria.2'1 The common denominator in most of these conditions is chronic liver involvement with the potential for developing cirrhosis of the liver. Underlying liver injury, necrosis, and regeneration with possible cyto¬ logie aberration has been postulated to be the trigger mechanism for the production of hepatic carcinoma in patients having cirrhosis of the liver/ The association of hepatic malignancy with cirrhosis in adults has been well established,26·27 whereas this associa¬ tion was thought to be extremely rare in children.2"2S Rarity of reports of hepatic malignancy in patients with biliary atresia may be related to the early mortality in this group.1" With the longer survival of children with the chronic liver disease, particularly cirrhosis, more cases have been reported in the last decade. These data suggest that there may be more than a coincidental associa¬ tion of cirrhosis with primary hepatic carcinoma in the childhood popula¬ tion. Ruth Burke assisted in the article.
preparation of this
References 1. Silverman A: Pediatric Clinical GastroenSt Louis, CV Mosby Co, 1971, p 293. 2. Thaler M, Gellis S: Studies in neonatal hepatitis and biliary atresia in diagnosis. Am J Dis
terology.
Child 116:257-261,1968. 3. Koop CE: Biliary atresia and Kasai opera-
Downloaded From: http://archpedi.jamanetwork.com/ by a New York University User on 06/10/2015
tion: 4.
Commentary. Pediatrics 55:9-11, 1975. Lilly JR: The Japanese operation for biliary
atresia. Pediatrics 55:12-19, 1975. 5. Van Wyks J, Halgrimson CG, Giles G, et al: Liver transplantation in biliary atresia with concomitant hepatoma. S Afr Med J 46:885-889, 1972. 6. Craig JM, Gellis SS, Hsia DY: Cirrhosis of liver in infants and children. Am J Dis Child 90:229-322, 1955. 7. Gall EA: Tumors of the liver, in Diseases of the Liver, ed 2. Philadelphia, JB Lippincott Co, 1963, p 702. 8. Mitchell AG, Nelson WE: Textbook of Pediatrics. Philadelphia, WB Saunders Co, 1946, p 678. 9. Packard GB, Palmer HD: Primary neoplasm of the liver in infants and children. Ann Surg 142:214-227, 1955. 10. Gall EA: Primary and metastatic carcinoma of the liver: Relationship to hepatic cirrhosis. Arch Pathol 70:226-232, 1960. 11. Cameron R, Hou PC: Biliary Cirrhosis. Pathologic monograph 1, Springfield, Ill, Charles C Thomas Publisher, 1962, p 121. 12. Mori W: Cirrhosis and primary cancer of the liver. Cancer 20:627-631, 1967. 13. Alcalde VM, Truisman HS, Baffes T: Primary carcinoma of the liver in infancy and childhood. Am J Dis Child 104:245-251, 1962. 14. Okayama K: Primary liver cell carcinoma associated with biliary cirrhosis due to congenital bile duct atresia. Pediatrics 67:89-93, 1965. 15. Absolon KB, Rikkers H, Aust JB: Thoracic duct lymph drainage in congenital biliary atresia. Surg Gynecol Obstet 120:123-127, 1965. 16. Fish JC, McCary RG: Primary cancer of the liver in childhood. Arch Surg 93:355-359, 1966. 17. Deores MP, Dicus W: Hepatocarcinoma associated with biliary cirrhosis: A case due to congenital bile duct atresia. Arch Pathol 86:338\x=req-\ 341, 1968. 18. Fraumeni JF, Miller RW, Hill JA: Primary carcinoma of the liver in childhood: An epidemiologic study. J Natl Cancer Inst 40:1087-1099, 1968. 19. Roth D, Duncan A: Primary carcinoma of the liver after giant cell hepatitis of infancy. Cancer 8:986-991, 1955. 20. Fajers CM, Falkmers FE, Pehrson M: Primary carcinoma of the liver and giant cell hepatitis in infancy. Acta Paediatr 49:96-110, 1960. 21. Landing BH: Consideration of the pathogenesis of neonatal hepatitis, biliary atresia and choledochal cysts: The concept of infantile obstructive cholangiopathy. Prog Pediatr Surg 6:113-139, 1974. 22. Mason HH, Anderson DH: Glycogen disease of the liver (von Gierke's disease) with hepatoma: Case report with metabolic studies. Pediatrics 16:785-799, 1955. 23. Zengeneh F, Limbeck GA, Kelley VC: Type I glycogen storage (GSD) and malignant hepatoma. Read before the annual meeting of the American Pediatric Society, Atlantic City, NJ, April 26-29, 1952. 24. Edmonds AM, Henninger GR, Crooks R: Galactosemia: Report of a case with autopsy. Pediatrics 10:40-47, 1952. 25. Ein SH, Stephens CA: Malignant liver tumors in children. J Pediatr Surg 9:491-494, 1974. 26. Brires A: Primary tumors of the liver. Am J Clin Pathol 3:221-235, 1933. 27. Hoyne RM, Kernohun JN: Primary carcinoma of the liver: A study of 31 cases. Arch Intern Med 79:532-551, 1947. 28. Steiner M: Primary carcinoma of the liver in childhood. Am J Dis Child 55:807-827, 1938. 29. Bigelow N, Wright A: Primary carcinoma of liver in infancy and childhood. Cancer 6:170\x=req-\ 178, 1953. 30. Jones E: Primary carcinoma of the liver with associated cirrhosis in infants and children. Arch Pathol 70:5-11, 1960.
Eugene C. Beatty, Jr,
\s=b\ An 11-year-old girl developed cholangiocellular carcinoma in association with biliary cirrhosis due to congenital biliary atresia. An exploratory laparotomy and an operative cholangiogram at 3 months of age had confirmed the diagnosis of extra\x=req-\ hepatic biliary atresia. A liver biopsy spec-
imen taken at 6 months of age showed cirrhosis. The subsequent clinical course was characterized by persistent moderate jaundice, anemia, malnutrition, rickets, pathologic fractures, and recurrent gastrointestinal bleeding. The presence of cholangiocellular carcinoma of the liver with advanced biliary cirrhosis was established at an exploratory laparotomy a week before her death. We discuss here the pathogenesis of biliary cirrhosis and carcinoma of the liver; there may be a relation between the two in the childhood
biliary
population. (Am J Dis Child 131:442-444, 1977) of two relatively diseases within a single organ is unique and may represent either an unusual coincidence or a causal relationship. This article re¬ ports such a case in a child and reviews the literature to consider possible pathogenetic mechanisms that may operate to produce either or both of these pathologic changes.
The
occurrence
rare
REPORT OF A CASE The
patient,
a
black
20, 1962, following pregnancy and
a
girl,
was
born
July
full-term, normal
delivery. Family history
unremarkable. Jaundice was noticed in the first week of life. As the jaundice increased, she was also noted to have darkcolored urine and acholic stools. At the age of 3 months, an exploratory laparotomy was
Departments of Pediatrics (Dr Pathology (Dr Beatty), Children's Mercy Hospital, Kansas City, Mo. Reprint requests to Department of Pediatrics, Children's Mercy Hospital, 24th and Gillham Rd, Kansas City, MO 64108 (Dr Kulkarni). From the Kulkarni) and
MD
done. A gallbladder cholangiogram showed that the common bile duct was normal, but there was absence of both hepatic ducts. A liver biopsy specimen was interpreted as showing neonatal hepatitis by one pathologist and biliary cirrhosis by another. At the age of 6 months she was admitted to the Children's Mercy Hospital with persistent jaundice, acholic stools, and rick¬ ets. A rose bengal study showed consid¬ erable loss of liver function and obstruc¬ tion. At a second exploration, the gall¬ bladder cholangiogram revealed the same picture as before. The liver biopsy spec¬ imen this time showed a striking increase in the degree of fibrosis and bile stasis (Fig was
1). The subsequent clinical course was char¬ acterized by persistent moderate jaundice with dark-colored urine and acholic stools,
anemia, malnutrition, rickets, pathologic fractures, and recurrent gastrointestinal bleeding. In January 1974, the patient was admitted
because of gastrointestinal time she did not have
bleeding. At this hepatomegaly.
In March 1974, at the age of 11 years and 10 months, the patient was readmitted because of persistent high temperature. Physical examination revealed an under¬ nourished child with deformities of the lower extremities secondary to rickets and old healed fractures. Moderate icterus was present. The liver was palpable 7 to 8 cm before the right costal margin. The spleen was palpable 2 cm below the left costal margin. Laboratory investigations showed a hemoglobin level of 7.4 gm/100 ml and a hematocrit value of 26%. The leukocyte count was 10,300/cu mm, with 81% polymorphonuclear leukocytes, 11% lympho¬ cytes, and 8% monocytes. The reticulocyte count was 2.4%; the platelet count was 465,000/cu mm. The prothrombin and partial thromboplastin times were normal. The plasma fibrinogen level was 310 mg/ 100 ml. The total serum bilirubin con¬ centration was 11.5 mg/100 ml; indirect, 4.9 mg/100 ml. The serum glutamic oxaloacetic transaminase level was 59 ImU/ml and
Downloaded From: http://archpedi.jamanetwork.com/ by a New York University User on 06/10/2015
the serum glutamic pyruvic transaminase level was 17 ImU/ml. The total serum protein level was 8.2 gm/100 ml; albumin, 2.6 gm/100 ml. Electrolyte values and the blood urea nitrogen level were normal. The possibility of hepatic abscess was consid¬ ered and an exploratory laparotomy was performed. Multiple firm nodules, 0.5 to 3.5 cm wide, were noted in the liver. Repeated attempts to aspirate purulent material were unsuccessful. A biopsy specimen of these nodules showed carcinoma of the liver of the mixed hepatocellular and bile duct type (Fig 2). The patient died eight days after the laparotomy. At autopsy, the liver weighed 1,480 gm (normal for age, 936 gm). The lobular pattern was distorted by a fine nodular cirrhotic pattern. Numerous neoplastic nodules were scattered throughout the liver (Fig 3). The common bile duct was patent, but hepatic ducts were not demon¬ strable. The portal vein was markedly distended and filled with a yellowish, friable neoplastic tissue. Microscopic examination of the liver showed two distinct pathologic processes. The first consisted of increased fibrous connective tissue in portal triads with extension into the interlobular septa. Many portal triads lacked bile ducts and contained chronic inflammatory cells. The second process consisted of diffuse infiltrative nodules of malignant neoplastic tissue, some representing bile ductal components and others hepatocellular components. The ductal components appeared to be invasive and filled much of the portal venous system. Necrosis of the larger neoplastic nodules was prominent. There were no metastatic lesions. The spleen weighed 160 gm and was congested. Other autopsy
findings
were
noncontributory. COMMENT
Extrahepatic biliary atresia is an entity; the absolute inci¬ dence is reported to be about 1:8,000 to 1:10,000 live births.1 Until recently, it was thought that in spite of medical uncommon
Fig 1.—Biliary cirrhosis secondary (hematoxylin-eosin, 160).
to
Fig 2.—Cholangiocellular (left)
extrahepatic biliary
and
surgical
was
atresia with biliary cirrhosis described by Craig et al,·" 39 died within the first year of life. These authors stated that although all their patients showed some degree of obstructive cirrhosis pathologically, the disease process had not continued long enough to cause many of the clinical sequelae of cirrhosis. The reported incidence of cirrhosis in chil¬ dren was 0.02% (16 patients in 80,000 children) at Harriet Lane Home in Baltimore.7 The reported incidence of primary carcinoma of the liver in the United
hepatic biliary
Fig
3.—Gross
specimen showing
multinodular
hepatic
carci¬
noma.
treatment the prognosis very poor in 95% of these chil¬ dren.- With the introduction of the Kasai operation'·4 there appears to be a chance for a favorable longterm survival. Liver transplantation has been performed in some cases with fair results. Without surgery, most of these patients die in the first decade of life. Of the 49 patients with extra¬
and
atresia
hepatocellular (right) components of hepatic
carcinoma
States is said to have an autopsy rate in children of 0.875% (13 times in 1,538 cases),'· which seems relatively high. Of the 126,000 admissions over a period of 14 years at Denver Chil¬ dren's Hospital, only nine had hepatic
carcinoma,
an
incidence
rate
of
0.0008%.u
of liver cirrhosis of all types, 49 with hepatoma and nine with cholangioma. Seventy-one of these cirrhotic cases were of the biliary type; one patient had hepatoma and seven had cholan¬ gioma. It is stated that cirrhosis was probably the result of biliary obstruc¬ tion instituted by the neoplasm itself, rather than the primary disease. In 1962, Cameron and Hou" stated that there were no cases of hepatoma re¬ ported in children with biliary cirrho¬ sis. In 1966, Mori111 reviewed 3,232 autopsies, disclosing 59 cases of primary hepatic cancer and 127 cases of liver cirrhosis. Of these 3,232 autopIn 1960, Gall·" reviewed 682
cases
Downloaded From: http://archpedi.jamanetwork.com/ by a New York University User on 06/10/2015
(hematoxylin-eosin,
200).
sies, there were 25 cases of biliary cirrhosis, 17 secondary to biliary atre¬ sia. None of these patients with biliary cirrhosis had hepatic malig¬ nancy. He concluded that
specific liver and cirrhosis, biliary cardiac, seem to have no relation to the occurrence of any primary hepatic cancer. In 1961, Alcalde et al" reviewed 139 cases of primary carcinoma of the liver in children recorded in the litera¬ ture. Only eight (5.7%) had a concomi¬ tant diagnosis of cirrhosis. However,
there is no mention of the type of cirrhosis or whether it was secondary to the malignancy itself. There are eight reported cases,"' including our case, of primary liver cancer with biliary cirrhosis of the liver associated with biliary atresia (Table). The youngest child reported to have hepatoma with biliary cirrho¬ sis resulting from bile duct atresia was 5 months old, whereas the other patients were more than 2 years of "
'"
Reported Cases Source
Okayama,"
of
Extrahepatic Biliary Atresia
Age, yr/
Histological Type
Sex/Race 3/M Liver cell
1965 Absolon et al,'5 1965 Fish & McCary,' 1966
With Liver Cancer
Métastases
Lungs
Right
with
Involvement & Comments lobe of liver
¡ntrahepatic
metastasis Liver (seen on autopsy)
5 mo/F
Liver cell
2/M/W
Liver cell
Lungs
Death at 26 mo; carcinoma found at
Deoras & Dicus,' 1968
6/F/B
Liver cell
Lungs
Carcinoma found at
Fraumeni et al," 1968
3/M
autopsy
autopsy Autopsy showed biliary cirrhosis and histiocytic proliferation in many
Cholangiocellular
organs; mixed liver cell and bile duct carcinoma
Van Wyks et al,5 1972
12/F
Liver cell
Lungs after
·
transplant 4/F
Liver cell
No
Choledochogastrostomy
shortly after birth; liver transplant for tumor In right lobe; died 10 wk after transplant Liver transplant; doing well 18
mo
after
transplant; hepatoma found Present report, 1977
11/F/B
Cholangio-
No
after surgery 1 wk before
Laparotomy
death; showed presence of carcinoma, confirmed
cellular
at
age. Six of these had hepatocellular carcinoma. The case presented here is the second case of cholangiocellular carcinoma of the liver. Occurrence of primary liver cell carcinoma in pa¬ tients with giant cell hepatitis has also been reported.19·20 In an attempt to correlate the occurrence of these two rather rare pathological conditions occurring in the same individual, we present the following considerations. It has been recently postulated that biliary atre¬ sia, choledochal cyst, and neonatal hepatitis are different manifestations of the same or similar etiologies.21 In an excellent epidemiologie study of 76 cases of primary liver carcinoma in childhood, Fraumeni et al18 mentioned a case of mixed liver cell and bile duct carcinoma in a patient with biliary atresia. They found that five patients had antecedent liver disease, which is more than normally expected. They stated that the occurrence of liver carcinoma and congenital biliary atre¬ sia may signify a common embryologic defect, but since neoplasia is associated with various forms of cir¬ rhosis, it seems more likely that the relationship in biliary atresia is the secondary biliary cirrhosis. Primary carcinoma of the liver has been reported in patients with gly¬ cogen storage disease,22-2:i galactos¬ emia,24 tyrosinemia, and aminoacidu-
autopsy
ria.2'1 The common denominator in most of these conditions is chronic liver involvement with the potential for developing cirrhosis of the liver. Underlying liver injury, necrosis, and regeneration with possible cyto¬ logie aberration has been postulated to be the trigger mechanism for the production of hepatic carcinoma in patients having cirrhosis of the liver/ The association of hepatic malignancy with cirrhosis in adults has been well established,26·27 whereas this associa¬ tion was thought to be extremely rare in children.2"2S Rarity of reports of hepatic malignancy in patients with biliary atresia may be related to the early mortality in this group.1" With the longer survival of children with the chronic liver disease, particularly cirrhosis, more cases have been reported in the last decade. These data suggest that there may be more than a coincidental associa¬ tion of cirrhosis with primary hepatic carcinoma in the childhood popula¬ tion. Ruth Burke assisted in the article.
preparation of this
References 1. Silverman A: Pediatric Clinical GastroenSt Louis, CV Mosby Co, 1971, p 293. 2. Thaler M, Gellis S: Studies in neonatal hepatitis and biliary atresia in diagnosis. Am J Dis
terology.
Child 116:257-261,1968. 3. Koop CE: Biliary atresia and Kasai opera-
Downloaded From: http://archpedi.jamanetwork.com/ by a New York University User on 06/10/2015
tion: 4.
Commentary. Pediatrics 55:9-11, 1975. Lilly JR: The Japanese operation for biliary
atresia. Pediatrics 55:12-19, 1975. 5. Van Wyks J, Halgrimson CG, Giles G, et al: Liver transplantation in biliary atresia with concomitant hepatoma. S Afr Med J 46:885-889, 1972. 6. Craig JM, Gellis SS, Hsia DY: Cirrhosis of liver in infants and children. Am J Dis Child 90:229-322, 1955. 7. Gall EA: Tumors of the liver, in Diseases of the Liver, ed 2. Philadelphia, JB Lippincott Co, 1963, p 702. 8. Mitchell AG, Nelson WE: Textbook of Pediatrics. Philadelphia, WB Saunders Co, 1946, p 678. 9. Packard GB, Palmer HD: Primary neoplasm of the liver in infants and children. Ann Surg 142:214-227, 1955. 10. Gall EA: Primary and metastatic carcinoma of the liver: Relationship to hepatic cirrhosis. Arch Pathol 70:226-232, 1960. 11. Cameron R, Hou PC: Biliary Cirrhosis. Pathologic monograph 1, Springfield, Ill, Charles C Thomas Publisher, 1962, p 121. 12. Mori W: Cirrhosis and primary cancer of the liver. Cancer 20:627-631, 1967. 13. Alcalde VM, Truisman HS, Baffes T: Primary carcinoma of the liver in infancy and childhood. Am J Dis Child 104:245-251, 1962. 14. Okayama K: Primary liver cell carcinoma associated with biliary cirrhosis due to congenital bile duct atresia. Pediatrics 67:89-93, 1965. 15. Absolon KB, Rikkers H, Aust JB: Thoracic duct lymph drainage in congenital biliary atresia. Surg Gynecol Obstet 120:123-127, 1965. 16. Fish JC, McCary RG: Primary cancer of the liver in childhood. Arch Surg 93:355-359, 1966. 17. Deores MP, Dicus W: Hepatocarcinoma associated with biliary cirrhosis: A case due to congenital bile duct atresia. Arch Pathol 86:338\x=req-\ 341, 1968. 18. Fraumeni JF, Miller RW, Hill JA: Primary carcinoma of the liver in childhood: An epidemiologic study. J Natl Cancer Inst 40:1087-1099, 1968. 19. Roth D, Duncan A: Primary carcinoma of the liver after giant cell hepatitis of infancy. Cancer 8:986-991, 1955. 20. Fajers CM, Falkmers FE, Pehrson M: Primary carcinoma of the liver and giant cell hepatitis in infancy. Acta Paediatr 49:96-110, 1960. 21. Landing BH: Consideration of the pathogenesis of neonatal hepatitis, biliary atresia and choledochal cysts: The concept of infantile obstructive cholangiopathy. Prog Pediatr Surg 6:113-139, 1974. 22. Mason HH, Anderson DH: Glycogen disease of the liver (von Gierke's disease) with hepatoma: Case report with metabolic studies. Pediatrics 16:785-799, 1955. 23. Zengeneh F, Limbeck GA, Kelley VC: Type I glycogen storage (GSD) and malignant hepatoma. Read before the annual meeting of the American Pediatric Society, Atlantic City, NJ, April 26-29, 1952. 24. Edmonds AM, Henninger GR, Crooks R: Galactosemia: Report of a case with autopsy. Pediatrics 10:40-47, 1952. 25. Ein SH, Stephens CA: Malignant liver tumors in children. J Pediatr Surg 9:491-494, 1974. 26. Brires A: Primary tumors of the liver. Am J Clin Pathol 3:221-235, 1933. 27. Hoyne RM, Kernohun JN: Primary carcinoma of the liver: A study of 31 cases. Arch Intern Med 79:532-551, 1947. 28. Steiner M: Primary carcinoma of the liver in childhood. Am J Dis Child 55:807-827, 1938. 29. Bigelow N, Wright A: Primary carcinoma of liver in infancy and childhood. Cancer 6:170\x=req-\ 178, 1953. 30. Jones E: Primary carcinoma of the liver with associated cirrhosis in infants and children. Arch Pathol 70:5-11, 1960.
