Pediatric growing teratoma syndrome of the ovary A case report and review of the literature

Rationale: Growing teratoma syndrome is defined as an increase in tumor size during or after systemic chemotherapy for germ cell tumors. These cases involve normal tumor maker levels and histological features of only mature teratoma. We report a rare case of an ovarian immature teratoma in a Japanese child that was diagnosed as growing teratoma syndrome. Patient concerns: A 12-year-old girl presented a painful abdominal mass. She underwent left salpingo-oophorectomy for grade 1 immature teratoma in the left ovary. She did not undergo additional chemotherapy or radiotherapy. Four months later, she presented with grade 3 immature teratoma disseminated into the abdomen and pelvis. Chemotherapy resulted in the tumor maker levels returning to their normal ranges, although the tumors had grown slightly. Diagnosis: The specimens resected by laparotomy after the chemotherapy consisted of mature tissue predominantly, although primitive neuroepithelium was observed in a small part of the specimen. The pathological diagnosis was grade 1 immature teratoma, notwithstanding the clinical diagnosis was growing teratoma syndrome based on the clinical features and pathogenesis. Interventions: Laparotomy was performed at 7 months after the first operation, with resection of various tumors as well as the rectum, sigmoid colon, residual left fallopian duct, and a small part of the ileum and omentum. Some small tumors at the parietal peritoneum were ablated, although many tiny tumors around the uterus were left untreated. Outcomes: The patient has been free from recurrence for 5 years. Lessons: Growing teratoma syndrome can develop in children, and their tumor size is comparable to that in adolescents and adults. Furthermore, development of growing teratoma syndrome from a primary germ cell tumor is presumably faster in children than in adolescents and adults. Complete resection of all growing teratoma tissue is recommended, although fertility-sparing surgery should be considered when possible

A Case of Refractory Langerhans Cell Histiocytosis Complicated with Hemophagocytic Lymphohistiocytosis Rescued by Cord Blood Transplantation with Reduced-intensity Conditioning

　We diagnosed a female infant with Langerhans cell histiocytosis (LCH) who was refractory to conventional chemotherapy. She showed refractory inflammation that was complicated with hemophagocytic lymphohistiocytosis (HLH) during LCH chemotherapy; therefore, we changed the protocol to HLH2004 (dexamethasone, cyclosporine A and VP16). However, there were no signs of hematological recovery. We therefore performed cord blood transplantation with reduced-intensity conditioning, and she achieved complete remission for over 2 years. As salvage therapy for refractory LCH, hematopoietic stem cell transplantation may be a good therapeutic choice, especially when LCH is complicated with HLH

Remission of Congenital Multi-system Type Langerhans Cell Histiocytosis with Chemotherapy

Patients with multi-system (MS)-type langerhans cell histiocytosis (LCH) show poor outcomes, especially congenital MS LCH cases were shown in high mortality rate. We experienced a congenital case of MS LCH with high risk organs, who needed intensive respiratory support after birth. Even though intensive chemotherapy was discontinued, this patient’s lung LCH lesions gradually became reduced and his respiratory condition recovered; therefore, we restarted and completed maintenance chemotherapy. The patient maintained complete remission for more than 4 years after the end of chemotherapy. Our case suggests that congenital MS LCH even with severe organ involvement can be treated successfully with chemotherapy

Neonatal hemochromatosis with epsilon gamma delta beta-thalassemia: a case report and analysis of serum iron regulators

Background Neonatal hemochromatosis causes acute liver failure during the neonatal period, mostly due to gestational alloimmune liver disease (GALD). Thalassemia causes hemolytic anemia and ineffective erythropoiesis due to mutations in the globin gene. Although neonatal hemochromatosis and thalassemia have completely different causes, the coexistence of these diseases can synergistically exacerbate iron overload. We report that a newborn with epsilon gamma delta beta-thalassemia developed neonatal hemochromatosis, which did not respond to iron chelators and rapidly worsened, requiring living-donor liver transplantation. Case presentation A 1-day-old Japanese boy with hemolytic anemia and targeted red blood cells was diagnosed with epsilon gamma delta beta-thalassemia by genetic testing, and required frequent red blood cell transfusions. At 2 months after birth, exacerbation of jaundice, grayish-white stool, and high serum ferritin levels were observed, and liver biopsy showed iron deposition in hepatocytes and Kupffer cells. Magnetic resonance imaging scans showed findings suggestive of iron deposits in the liver, spleen, pancreas, and bone marrow. The total amount of red blood cell transfusions administered did not meet the criteria for post-transfusion iron overload. Administration of an iron-chelating agent was initiated, but iron overload rapidly progressed to liver failure without improvement in jaundice and liver damage. He underwent living-donor liver transplantation from his mother, after which iron overload disappeared, and no recurrence of iron overload was observed. Immunohistochemical staining for C5b-9 in the liver was positive. Serum hepcidin levels were low and serum growth differentiation factor-15 levels were high prior to living-donor liver transplantation. Conclusions We reported that an infant with epsilon gamma delta beta-thalassemia developed NH due to GALD, and that coexistence of ineffective erythropoiesis in addition to erythrocyte transfusions may have exacerbated iron overload. Low serum hepcidin levels, in this case, might have been caused by decreased hepcidin production arising from fetal liver damage due to neonatal hemochromatosis and increased hepcidin-inhibiting hematopoietic mediators due to the ineffective hematopoiesis observed in thalassemia

Delayed Methotrexate Elimination after Administration of a Medium Dose of Methotrexate in a Patient with Genetic Variants Associated with Methotrexate Clearance

Polymorphisms in methotrexate transporter pathways have been associated with methotrexate toxicities and clearance. Recent genome-wide association studies have revealed that the SLCO1B1 T521C variant is associated with methotrexate elimination. We present a case of a pediatric patient with acute lymphoblastic leukemia who suffered from persistently high plasma methotrexate concentrations and acute kidney injuries after the admin-istration of a medium dose of methotrexate. Subsequent genetic analysis showed that he was a carrier of dys-functional genetic variants associated with methotrexate clearance. This case highlights that polymorphisms of methotrexate transporter pathways can adversely affect methotrexate elimination in a clinically significant manner

Long-term Remission of Hepatitis-associated Aplastic Anemia Possibly due to Immunosuppressive Therapy after Liver Transplantation

Hepatitis-associated aplastic anemia (HAAA) is an acquired bone marrow failure syndrome that develops after seronegative fulminant hepatitis. Abnormal cytotoxic T-cell activation with cytokine release is a possible pathophysiology. We present the case of a 16-month-old Japanese male who developed HAAA following living-donor liver transplantation for fulminant hepatitis. His aplastic anemia was successfully treated with immunosuppressive therapy. He had been administered tacrolimus for prophylaxis against hepatic allograft rejection. Ten years after the HAAA onset, the patient’s bone marrow was found to be slightly hypoplastic. Tacrolimus may be effective in controlling abnormal immune reactions that can cause recurrent impaired hematopoiesis

Utility of Comprehensive Genomic Profiling for Precise Diagnosis of Pediatric-Type Diffuse High-Grade Glioma

In the current World Health Organization classification of central nervous system tumors, comprehensive genetic and epigenetic analyses are considered essential for precise diagnosis. A 14-year-old male patient who presented with a cerebellar tumor was initially diagnosed with glioblastoma and treated with radiation and concomitant temozolomide chemotherapy after resection. During maintenance temozolomide therapy, a new contrast-enhanced lesion developed in the bottom of the cavity formed by the resection. A second surgery was performed, but the histological findings in specimens from the second surgery were different from those of the first surgery. Although genome-wide DNA methylation profiling was conducted using frozen tissue for a precise diagnosis, the proportion of tumor cells was insufficient and only normal cerebellum was observed. We then performed comprehensive genetic analysis using formalin-fixed paraffin-embedded sections, which revealed MYCN amplification without alteration of IDH1, IDH2, or Histone H3. Finally, the patient was diagnosed with pediatric-type diffuse high-grade glioma, H3-wildtype and IDH-wildtype. In conclusion, comprehensive genetic and epigenetic analysis should be considered in pediatric brain tumor cases

A Long-term Survivor after Congenital Acute Myeloid Leukemia with t(8 ; 16)(p11 ; p13)

The treatment of patients with congenital leukemia is difficult and often results in a poor prognosis. We present here the case of a female child with congenital acute myeloid leukemia (AML) with t(8 ; 16) (p11 ; p13) who received chemotherapy and survived for more than 10 years without relapse. A novel MOZ-CBP chimera was found in her diagnostic sample. Although adult AML patients with MOZ-CBP have mainly been reported as having therapy-related AML and showed poor prognoses, the present case supports the idea that AML with MOZ-CBP in the pediatric population might show better prognoses