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.