Case Descriptions
Case 1
A 6-year-old boy with no prior history of note presented with a mass
under the right costal margin. Computed tomography (CT) demonstrated a
tumor with huge cysts and partial calcification between the right lobe
of the liver and kidney, arising from the right retroperitoneum (Figure
1A). No evidence of bone marrow infiltration or other metastases was
seen. Open biopsy demonstrated amplified MYCN gene and revealed
neuroblastoma of round cell type, poor prognosis group. The tumor was
classified as high-risk group with stage L2 disease based on the
International Neuroblastoma Risk Group Staging System (INRGSS)3). He received three courses of chemotherapy
including cyclophosphamide (CPM), vincristine (VCR), pirarubicin (THP),
cisplatin (CDDP), etoposide (VP-16), and ifosfamide. Then he underwent
right segmental liver resection, right nephrectomy, and partial
diaphragm resection due to direct tumor invasion, followed by two
courses of chemotherapy and irradiation with 15 Gy to the entire abdomen
and 30 Gy to the left supraclavicular fossa and posterior mediastinum
under the shielding of the liver and the kidneys. Allogeneic bone marrow
transplantation (BMT) from a sibling was then performed after
myeloablative conditioning with total body irradiation (TBI), VP-16 and
cyclophosphamide (CY). Methotrexate was used for graft-versus-host
disease (GVHD) prophylaxis. Grade I acute GVHD manifested as exanthema
but resolved spontaneously. After BMT, he received additional
chemotherapy with CPM, dacarbazine and VCR. Treatment was completed in 2
years when he was 8 years old. Ten years after that, the patient was
hospitalized due to massive gastrointestinal hemorrhage. Upper
gastrointestinal endoscopy revealed ruptured esophageal varices, and CT
demonstrated portal vein aneurysm with extensive collateral vein
formation (Figure 1B). He met the clinical criteria for hepatic
cirrhosis and portal hypertension, although liver enzymes remained
within normal limits. His severe condition settled and he was
discharged, but the patient committed suicide 1 year after this event at
19 years old, 11 years after BMT.
Case 2
A 24-year-old man with no prior history of note presented with pain in
the lower back and pancytopenia. Bone biopsy revealed neuroblastoma
cells, and CT showed an abdominal mass arising from the right adrenal
gland. Infiltrations into bone marrow and bone throughout the body were
identified. INRGSS high-risk MYCN -non-amplified stage M
neuroblastoma was diagnosed. He received 5 courses of chemotherapy with
VCR, CPM, THP and CDDP and underwent autologous peripheral blood SCT
(PBSCT) with myeloablative conditioning comprising busulfan (BU) and CY.
He then underwent tumor resection and irradiation to the whole spine and
right adrenal gland (19.8 Gy), and to the skull, pelvis and femur (5.4
Gy). Secondary aplastic anemia was developed, and oral administration of
cyclosporine (CsA) was initiated. Due to the frequent blood
transfusions, iron overload gradually progressed but rapidly improved by
administration of deferasirox. He was discharged 10 months after the
PBSCT. One and a half years after discharge, bone marrow and bone
recurrence occurred. He received 4 cycles of chemotherapy with
irinotecan, VP-16 and carboplatin, followed by allogeneic cord blood
transplantation (CBT) with myeloablative conditioning of BU, VP-16 and
CY. CsA and methylprednisolone were used for GVHD prophylaxis. Moderate
veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS) was
treated with danaparoid sodium and ursodeoxycholic achieving rapid
improvement. Grade II acute GVHD manifesting as diarrhea was controlled
with additional prednisolone. Cytomegalovirus (CMV) antigenemia was also
well controlled by administration of ganciclovir. From around 50 days
after transplantation, pleural effusion and ascites retention gradually
worsened along with deterioration of renal function. Relapse of
neuroblastoma was negative, but his condition had gradually worsened.
Ten months after CBT, CT showed liver atrophy and marked ascites
retention. Blood Mac-2-binding protein glycosylation isomer index and
the 15-min retention rate of indocyanine green was elevated, both
suggesting development of cirrhosis. Upper gastrointestinal endoscopy
showed no esophageal varices. His general condition continued to worsen,
and he died of liver failure 1 year after CBT, at 29 years old.
Histological examination of needle liver autopsy demonstrated
characteristics of bridging and pericellular fibrosis with architectural
distortion and spotty necrosis, consistent with cirrhotic changes, and
severe hepatocyte damage with slight infiltration of inflammatory cells
(Figure 2A, B). Fibrotic hyperplasia and mild infiltration of
inflammatory cells were also evident around the portal vein. No
histological evidence of GVHD or sinusoidal obstruction was seen. A
definitive histological diagnosis of cirrhosis was made.