A 14-month-old boy with a large abdominal mass was admitted to our hospital. Serum neuron-specific enolase (NSE) was markedly elevated (1,000 ng/mL), while urinary homovanillic and vanillylmandelic acid were within the normal range. Magnetic resonance imaging (MRI) and computerized tomography revealed a left adrenal tumor with calcification and metastases to cranial bones, cranial base, bilateral orbits, left pleura, thoracic paravertebral soft tissue, para-aortic lymph nodes, soft tissue in the sacral canal, and bilateral kidneys (Figures 1(a), 1(c), and 1(e)). However, blood and urine tests indicated no impairment of renal function. Uptake of iodine-123-metaiodobenzylguanidine (123I-MIBG) was heterogeneous, being highly increased in cranial bones, cranial base, and bilateral orbits but only slightly increased in the primary lesion and bilateral kidneys and weak in other sites. Biopsy of the adrenal tumor was performed, and a diagnosis of poorly differentiated neuroblastoma with low mitosis-karyorrhexis index was confirmed. NSE immunohistochemistry was partially positive. Overall, histology was favorable based on International Neuroblastoma Pathology Classification; however, fluorescence in situ hybridization showed that tumor cells with and without amplification of the MYCN oncogene coexisted in the biopsied specimen. Bone marrow examination showed tumor cells with a highly amplified MYCN oncogene. The patient was diagnosed as high-risk according to the International Neuroblastoma Risk Group Classification System.
The patient received five cycles of induction chemotherapy, high-dose chemotherapy (HDC) with autologous peripheral blood stem cell transplantation (auto-PBSCT), followed by surgical resection of the primary tumor together with renal biopsy, and finally cranial irradiation (Table 1). Although all of the lesions shrank and serum NSE decreased to within the normal range, there were still residual masses in the primary site, left orbit, sacral canal, and bilateral kidneys after five courses of induction chemotherapy (Figures 1(b), 1(d), and 1(f)). The sizes of residual masses in the primary lesion, sacral canal, and bilateral kidneys were slightly reduced by HDC. Histological examination of the resected primary tumor and a biopsy specimen obtained from the left kidney were positive for synaptophysin, chromogranin A, and cluster of differentiation (CD) 56 but not NSE, confirming the presence of tumor cells (Figures 2(a)-2(h)). These findings supposed that some tumor cells also remained in the opposite renal metastatic nodules, which were depicted in the same manner on MRI. We chose the graft-versus-tumor (GVT) approach with allogeneic hematopoietic stem cell transplantation (allo-HSCT) as a potentially curative treatment to avoid bilateral nephrectomy or local radiotherapy to both kidneys. The patient underwent unrelated cord blood stem cell transplantation (CBT) from a human leukocyte antigen- (HLA-) C and DRB1 mismatched donor at four months after auto-PBSCT (Table 1). In addition, the HLA-C mismatch between the donor and the recipient induced killer cell immunoglobulin-like receptor- (KIR-) ligand incompatibility in the graft-versus-host direction to generate natural killer (NK) cell alloreactivity against neuroblastoma cells. The conditioning regimen consisted of fludarabine, melphalan, and total body irradiation (TBI), and tacrolimus with short-term methotrexate was administrated for graft-versus-host disease (GVHD) prophylaxis (Table 1). Radiotherapy to the primary tumor bed and sacrum was planned. However, the residual mass in the sacral canal was enlarged and a new metastatic lesion appeared in the pancreatic tail at three months after CBT. Tumor progression could not be controlled by additional chemotherapy and local radiotherapy, and the patient succumbed at 26 months after diagnosis and 12 months after relapse. There was no recurrence in cranial bones where 19.8 Gy of local radiotherapy was delivered between HDC and CBT. Furthermore, the metastatic nodules in bilateral kidneys did not increase in size before his death and there was no evidence of GVHD. We could not examine the histopathological status of the renal involvements because autopsy was not performed.