96. Jahrestagung der Deutschen Gesellschaft für Pathologie e. V ...

liver did not correlate with the mutation status. However, the number
of CD34, MPO, GlycophorinA and CD61 positive hematopoietic cells
varied considerably from case to case and the number of mutated cases
was rather small. No mutation could be found in the lung specimens of
each autopsy.
Conclusions. GATA1 exon 2 mutations are acquired mutations and may
occur already in fetal hematopoiesis as early as 13th week of gestation. We
could not demonstrate a phenotypic correlation with quantitative fetal
liver hematopoiesis.
SO-040
Fetal acute myeloid leukemia in Down syndrome causing intrauterine
fetal death
H . Löser1 , M . Engels1 , S . Huss1 , R . Büttner1 , A . Müller2 , J . Fries1 1 2 University of Cologne, Institute of Pathology, Köln, University of Bonn,
Institute for Pathology
Aims. Down syndrome (DS) is associated with a 10- to 20-fold higher
risk for developing acute leukemia compared to non-DS children. About
10% of DS newborns are diagnosed with a “transient myeloproliferative
disorder” (TMD) and up to 30% of these children sustain a progression
to an acute myeloid leukemia (AML) within the following 3 years.
Methods. We report of a fetal, intrauterine AML in trisomy 21. While
no further fetal malformation was recognised in the pervious prenatal
screening of the 42-years old woman the fetus died in utero in the 24th
week of gestation without any detectable clinical cause. After informed
consent was obtained by the mother an autopsy was performed at the
Institute of Pathology, University of Cologne.
Results. We saw a phenotypically female fetus with an almost gestational
age-appropriate development without any apparent anomalies. The
internal organs regular, the membranous part of the ventricular septum
already closed. Histologically we found extensive tissue and vascular infiltrations
with megakaryoblasts in all organs including thymus gland,
heart, lungs, liver, pancreas, spleen, adrenal glands, kidneys, intestine,
and organs of the lesser pelvis. Immunohistologically positive for CD61,
this finding was consistent with an AML FAB-subtype M7. The placenta
showed pronounced infiltrations of leukemic cells in the villous vessels,
the larger villi and in the umbilical vein. The literature describes mutations
of the exon 2 and 3 of the GATA1 gene, an erythroid transcription
factor particularly in children with AML and DS.
Conclusions. Until now, no data has been published about prenatal GA-
TA1-mutations, although this is there most likely point in time of occurrence
when AML develops in early childhood. In the present case, we are
in the process of analysing whether GATA-1 mutations can be detected
in the fetal tissue by sequencing. Considering that the heart was also affected
by the massive intra- and extravascular dissemination of AML, it
is very likely that this is the crucial reason for the intrauterine fetal demise.
In accordance with published literature this is the first report of fetal
AML in DS. It extends the spectrum of possible differential diagnosis of
intrauterine fetal death in DS.
SO-041
On the correlation of coronal clefts and chromosomal aberrations
E . Doberenz1 , U . Gembruch2 , R . Schumacher3 , A .M . Müller4 1 2 University Bonn Medical Center, Institute of Pathology, Bonn, University
Bonn Medical Center, Dept . of Prenatal Medicine and Obstetrics, Bonn, 3Uni versity Clinic Freiburg, Department of Pediatrics, Freiburg, 4University Bonn,
Department of Pediatric Pathology, Bonn
Aims. Coronal vertebral clefts, radiologically defined as vertical radiolucent
bands in the middle of the vertebral body, are to our observation
associated with chromosomal aberrations. Published studies concerning
this are missing.
Methods. Hence 443 aborted fetuses were studied radiologically concerning
the incidence of coronal clefts and their association with proven
chromosomal aberrations. Furthermore they were studies histologically
concerning remnants of the notochord which are still discussed as cause
of coronal clefts.
Results. In 44 cases coronal clefts were visualized radiologically. In 93.2%
of these fetuses chromosomal aberrations were proven. On the other
hand, of all fetuses with trisomy only 30% showed this diagnostic finding.
Histologically coronal clefts displayed a missing ossification at the
center of the vertebral body. Remnants of the notochord could be excluded.
Conclusions. Summing up, coronal clefts represent a retarded ossification
of vertebral bodies in fetal development, nearly solely found in fetus
with chromosomal aberrations and malformations. On the other hand,
the genetic diagnosis of chromosomal malformation, especially trisomy,
does not automatically implicate coronal clefts.
SO-042
Molecular-genetic classification of glomerulocystic kidney
disease
J .K . Lennerz1 , H . Liapis2 1 2 University Ulm, Institute of Pathology, Ulm, Washington University,
Department of Pathology and Immunology, St . Louis, United States
Aims. Glomerular cysts (GCs) are defined as Bowman space dilatation
>2–3× normal that occupy >5% of glomeruli. GCs occur in pediatric and
adult kidneys. GCs are associated with a plethora of genetic- and nongenetic
diseases and present significant diagnostic challenges. We aim to
develop a molecular-genetic classification scheme to facilitate diagnosis.
Methods. We reviewed our biopsy and nephrectomy material and the
medical literature of >100 years (20+230 cases). Additionally, we performed
in silico experiments mapping gene-protein networks (Ingenuity-
Systems; MetaCoreV4.5).
Results. We identified 5 categories: Type I represents GCK in polycystic
kidney disease (PKD). Type II represents molecularly-recognized
(UMOD/TCF2) and inherited subtypes of GCK (other than PKD).
Type III represents syndromic-GCK, associated with malformations/
syndromes. Type IV includes obstructive-GCK (±dysplasia). Type V encompasses
sporadic-GCK, including ischemic- and drug-induced types,
which lack an inheritance pattern, syndromic features or obstruction/
dysplasia. In this scheme, types I/II can be regarded primary-GCK whereas
III–V represent secondary-GCK and emerge (not necessarily from
constitutional mutations but) from a loss-of-function of ‘maintenance
kidney genes’ involved in injury repair.
Conclusions. The clinical relevance of the various associations forms the
basis for this molecular-genetic classification scheme that provides a
framework for a structured differential diagnosis, suggests screening for
probable mutations, and opens new avenues in understanding common
kidney injuries.
SO-043
RSV- and hMPV-infections in BALB/c mice
M . Neumann1 , J . Lüsebrink2 , V . Ditt2 , O . Schildgen2 , A .M . Müller3 1 2 University Bonn Medical Center, Institute of Pathology, Bonn, University
Bonn Medical Center, Institute of Virology, Bonn, 3University Bonn, Department
of Pediatric Pathology, Bonn
Aims. hRSV (human respiratory syncytial virus) and hMPV (human
metapneumovirus) cause respiratory infections, leading to death in
approximately 200,000 toddlers and old patients each year. Numerous
aspects of the pathomechanisms and resulting pathomorphologic changes
of infection are sparsely studied. Murine models differ concerning
methodical parameters as well as inoculation methods resulting in a
limited comparability of published studies. By using a mild inoculati-
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