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Hepatic cholangiodysplastic pseudocirrhosis with multiple disseminated intrahepatic nodules of pancreatic tissue
Study Group: PediatricPathology/ Pathology- Research and Practice 200 (2004) 359-363
Aims: The understanding of the development of the biliary system is a crucial step to interpret categories of neonatal and infantile cholangiopathies. Quantification of primitive biliary structures (ductal plate, remodeling ductal plate) and their maturity (remodeled bile ducts) may be useful in the evaluation of the maturation of the intrahepatic biliary tree. Aim was to study the remodeling of the intrahepatic biliary tree using a computer-based image-analysis. Methods: Liver specimens of the right lobe from 57 human foetuses and infants of gestational age of 15 through 40 weeks were obtained from the files of the Institute of Pathology, University of Heidelberg, following ethical approval. Anti-Bile duct cytokeratin epithelial markers (7 and 19) were used to detect the development of the intrahepatic biliary tree by immunohistochemistry.We used a computer image analysis technique to quantify the remodelling of the ductal plate to the formation of an interlobularbile duct. Results: We found that the surface and the perimeter of the portal tracts, the longest axis of the structures belonging to the ductal plate, and the maturation of bile ducts follow a process continuous and active up to term. However, a slow down was identified between the 20th and the 32"dweek of gestation. Conclusions: Although continuity is an important pace maker during embryogenesis, slow-downs do not seem to be uncommon. The Desmet's original idea of a vulnerable period for some neonatal cholangiopathies might be supported from our studies.
95 Hepatic Cholangiodysplastic Pseudocirrhosis with Multiple Disseminated Intrahepatic nodules of Pancreatic Tissue A. QUAAS, M. BURDELSKP, H. SCHAFER Institut for Pathologie, Universit~it Hamburg aKlinik ftir Kinder- und Jugendmedizin, Universit~t Hamburg
Aims: A very unusual case with multinodular formation of exocrine pancreatic tissue in the liver is described in a 12 years old boy who underwent combined liver and kidney transplantation after diagnosis of recessive multicystic kidney disease (RMCKD) and liver fibrosis. Methods: Explanted liver was investigated by standard histology and immunohistochemical stainings of HepParl and D 11 antigens, cytokeratin 7 (CK7), pancreatic amylase (PA), lipase, synaptophysin, chromogranin, insulin, glucagon and the MIB 1 proliferation marker. Results: Histology of the liver explant revealed typical findings of cholangiodysplastic pseudocirrhosis with ramified multicystic dilatation of augmented bile ducts. Some bile duct epithelial cells showed increased proliferative activity, others the expected negativity of HepPar 1, but expression of the hepatocellular D 11 antigen. Surprising was the finding of several disseminated intrahepatic nodules of different sizes consisting of ductal and acinar pancreatic tissue. Sometimes budding of pancreatic tissue from bile ducts was visible. Detected pancreatic tissue was exclusively exocrine with immunhistochemical positivity of pancreatic amylase and lipase and negativity of synaptophysin, chromogranin, insulin and glucagon. In normal control liver tissue immunohistochemicalpancreatic markers were completely negative; even single positive cells were lacking. Conclusions: To our knowledge only 6 cases with intrahepatic pancreatic tissue have been reported in the literature. From these cases disseminated micronodular occurrence was reported in only one case, an adult with hepatitis B-related liver cirrhosis, underlining rarity of our observation. It remains open whether intxahepatic formation of pancreatic tissue is a primary malformation possibly promoted by the genetic abnormality of RMCKD or a secondary phenomenon of possibly stem cell- derived mis-directed regeneration.
363
396 Agnathia-Otocephaly Complex: Presentation of Four Cases C. SCHIFFER, G. TARIVERDIAN, M. SCHIESSER2, C. SERGP Gen. Polikl., Inst. Humangenetik, Univ. Heidelberg, Germany 2Dept. of Obstetrics and Gynaecology, Univ. Heidelberg, Germany 3Dept. of Paed. Pathology, St. Michael's Univ. Hosp., Bristol, UK
Aims: Agnathia-Otocephaly Complex (AOC) is a lethal malformation complex characterized by absence of the mandible, microstomia, aglossia, and positioning of the ears toward the midline. We report four sporadic cases of AOC with different associated features of embryonic maldevelopment. Methods: Ultrasound and morphological data were examined in detail. In one case the maxillo-facial structures were cut serially and studied collectivelly and individuallyin a multiplanar fashion. Results: The study of these cases supports the concept that an altered embryologic development might have taken place at Carnegie stages l0 (embryonic days 22 or 23) and 11 (embryonic days 23-26). Conclusions: The differentiation of somites into sclero-, myo-, and dermatomes is under the influence of inductive signals from surrounding tissues. The association of agnathia and otocephaly may likely be interpreted as the result of different causal events acting simultaneously on a coordinated temporal and spatial embryologic unit, including the prosencephalon and first branchial arch. Twisted gastrulation mice show a striking similarity to the human phenotype (Petryk et al. in press).
397
Unusual Fibromuscular Dysplasia of Left Coronary Artery in Hypoplastic Left Heart Syndrome H. SCI-IAFER, U. REICHELT, CH. HAUN 1 Institut ftir Pathologic, Universit~it Hamburg 1Klinik ftir Kinder- und Jugendmedizin, Universitat Hamburg
Aims: We present the rare observation und pathogenetical interpretation of a particular type of coronary fibromuscular dysplasia combined with hypoplastic left heart syndrome, atresia of aortic valve and intrauterine pre-term closure of the atrial foramen ovale. Case History: A male newborn died in the age of 2 days presenting clinical signs of hypoplastic left heart syndrome. Results: Autopsy of the normally developed child revealed findings of severe hypoplasia of left ventricle and complete atresia of aortic valve. Foramen ovale was completely closed by a stable fibrous membrane indicating premature intrauterine closure. Cardiac connection of large arterial and venous vessels was normal, but preductal aortic arch was distinctly hypoplastic. Right heart and pulmonary trunk were hypertrophied and dilated. Ductus Botalli was widely open. Right coronary artery was normal. Remarkable, however, was a distinct prominence and curling of the proximal part of the left coronary artery particularly of the anterior interventricular branch. Histology of the markedly thickened coronary wall at this site presented typical signs of fibromuscular dysplasia without signs of inflammationor calcification. Adjacent left-ventricular myocardium showed a normal structure of the peripheral branches of the coronary system, but pronounced formation of deep ramified intramyocardial sinus of the ventricular lumen with a wall structure of the sinus resembling that of the dysplastic proximal coronary arteries. Both lungs presented distinct venous and lymphatic ectasia combined with terminal interstitial emphysema. Conclusions: The described type of coronary fibromuscular dysplasia may be secondary to transmyocardial ventriculo-sinu-coronary blood bypass induced by atresia of aortic valve and promoted by additionnal intrauterine pre-term closure of the foramen ovale.
Aims: The understanding of the development of the biliary system is a crucial step to interpret categories of neonatal and infantile cholangiopathies. Quantification of primitive biliary structures (ductal plate, remodeling ductal plate) and their maturity (remodeled bile ducts) may be useful in the evaluation of the maturation of the intrahepatic biliary tree. Aim was to study the remodeling of the intrahepatic biliary tree using a computer-based image-analysis. Methods: Liver specimens of the right lobe from 57 human foetuses and infants of gestational age of 15 through 40 weeks were obtained from the files of the Institute of Pathology, University of Heidelberg, following ethical approval. Anti-Bile duct cytokeratin epithelial markers (7 and 19) were used to detect the development of the intrahepatic biliary tree by immunohistochemistry.We used a computer image analysis technique to quantify the remodelling of the ductal plate to the formation of an interlobularbile duct. Results: We found that the surface and the perimeter of the portal tracts, the longest axis of the structures belonging to the ductal plate, and the maturation of bile ducts follow a process continuous and active up to term. However, a slow down was identified between the 20th and the 32"dweek of gestation. Conclusions: Although continuity is an important pace maker during embryogenesis, slow-downs do not seem to be uncommon. The Desmet's original idea of a vulnerable period for some neonatal cholangiopathies might be supported from our studies.
95 Hepatic Cholangiodysplastic Pseudocirrhosis with Multiple Disseminated Intrahepatic nodules of Pancreatic Tissue A. QUAAS, M. BURDELSKP, H. SCHAFER Institut for Pathologie, Universit~it Hamburg aKlinik ftir Kinder- und Jugendmedizin, Universit~t Hamburg
Aims: A very unusual case with multinodular formation of exocrine pancreatic tissue in the liver is described in a 12 years old boy who underwent combined liver and kidney transplantation after diagnosis of recessive multicystic kidney disease (RMCKD) and liver fibrosis. Methods: Explanted liver was investigated by standard histology and immunohistochemical stainings of HepParl and D 11 antigens, cytokeratin 7 (CK7), pancreatic amylase (PA), lipase, synaptophysin, chromogranin, insulin, glucagon and the MIB 1 proliferation marker. Results: Histology of the liver explant revealed typical findings of cholangiodysplastic pseudocirrhosis with ramified multicystic dilatation of augmented bile ducts. Some bile duct epithelial cells showed increased proliferative activity, others the expected negativity of HepPar 1, but expression of the hepatocellular D 11 antigen. Surprising was the finding of several disseminated intrahepatic nodules of different sizes consisting of ductal and acinar pancreatic tissue. Sometimes budding of pancreatic tissue from bile ducts was visible. Detected pancreatic tissue was exclusively exocrine with immunhistochemical positivity of pancreatic amylase and lipase and negativity of synaptophysin, chromogranin, insulin and glucagon. In normal control liver tissue immunohistochemicalpancreatic markers were completely negative; even single positive cells were lacking. Conclusions: To our knowledge only 6 cases with intrahepatic pancreatic tissue have been reported in the literature. From these cases disseminated micronodular occurrence was reported in only one case, an adult with hepatitis B-related liver cirrhosis, underlining rarity of our observation. It remains open whether intxahepatic formation of pancreatic tissue is a primary malformation possibly promoted by the genetic abnormality of RMCKD or a secondary phenomenon of possibly stem cell- derived mis-directed regeneration.
363
396 Agnathia-Otocephaly Complex: Presentation of Four Cases C. SCHIFFER, G. TARIVERDIAN, M. SCHIESSER2, C. SERGP Gen. Polikl., Inst. Humangenetik, Univ. Heidelberg, Germany 2Dept. of Obstetrics and Gynaecology, Univ. Heidelberg, Germany 3Dept. of Paed. Pathology, St. Michael's Univ. Hosp., Bristol, UK
Aims: Agnathia-Otocephaly Complex (AOC) is a lethal malformation complex characterized by absence of the mandible, microstomia, aglossia, and positioning of the ears toward the midline. We report four sporadic cases of AOC with different associated features of embryonic maldevelopment. Methods: Ultrasound and morphological data were examined in detail. In one case the maxillo-facial structures were cut serially and studied collectivelly and individuallyin a multiplanar fashion. Results: The study of these cases supports the concept that an altered embryologic development might have taken place at Carnegie stages l0 (embryonic days 22 or 23) and 11 (embryonic days 23-26). Conclusions: The differentiation of somites into sclero-, myo-, and dermatomes is under the influence of inductive signals from surrounding tissues. The association of agnathia and otocephaly may likely be interpreted as the result of different causal events acting simultaneously on a coordinated temporal and spatial embryologic unit, including the prosencephalon and first branchial arch. Twisted gastrulation mice show a striking similarity to the human phenotype (Petryk et al. in press).
397
Unusual Fibromuscular Dysplasia of Left Coronary Artery in Hypoplastic Left Heart Syndrome H. SCI-IAFER, U. REICHELT, CH. HAUN 1 Institut ftir Pathologic, Universit~it Hamburg 1Klinik ftir Kinder- und Jugendmedizin, Universitat Hamburg
Aims: We present the rare observation und pathogenetical interpretation of a particular type of coronary fibromuscular dysplasia combined with hypoplastic left heart syndrome, atresia of aortic valve and intrauterine pre-term closure of the atrial foramen ovale. Case History: A male newborn died in the age of 2 days presenting clinical signs of hypoplastic left heart syndrome. Results: Autopsy of the normally developed child revealed findings of severe hypoplasia of left ventricle and complete atresia of aortic valve. Foramen ovale was completely closed by a stable fibrous membrane indicating premature intrauterine closure. Cardiac connection of large arterial and venous vessels was normal, but preductal aortic arch was distinctly hypoplastic. Right heart and pulmonary trunk were hypertrophied and dilated. Ductus Botalli was widely open. Right coronary artery was normal. Remarkable, however, was a distinct prominence and curling of the proximal part of the left coronary artery particularly of the anterior interventricular branch. Histology of the markedly thickened coronary wall at this site presented typical signs of fibromuscular dysplasia without signs of inflammationor calcification. Adjacent left-ventricular myocardium showed a normal structure of the peripheral branches of the coronary system, but pronounced formation of deep ramified intramyocardial sinus of the ventricular lumen with a wall structure of the sinus resembling that of the dysplastic proximal coronary arteries. Both lungs presented distinct venous and lymphatic ectasia combined with terminal interstitial emphysema. Conclusions: The described type of coronary fibromuscular dysplasia may be secondary to transmyocardial ventriculo-sinu-coronary blood bypass induced by atresia of aortic valve and promoted by additionnal intrauterine pre-term closure of the foramen ovale.