Benedikt Bernbeck

Germ cell tumors of the head and neck: Report from the MAKEI Study Group

Germ cell tumors (GCTs) of the head and neck region are rare but may pose significant problems for perinatal management as well as surgical and adjuvant therapy.

Malignant ectomesenchymoma in children and adolescents: Report from the Cooperative Weichteilsarkom Studiengruppe (CWS)

Malignant ectomesenchymoma (MEM) is a soft tissue tumor with heterologous rhabdomyoblastic components believed to arise from pluripotent migratory neural crest cells. To date merely 50 cases have been published and the knowledge about the course of disease and optimal treatment is limited.

Brain metastases during follow-up of children and adolescents with extracranial malignant germ cell tumors: risk adapted management decision tree analysis based on data of the MAHO/MAKEI-registry.

The overall risk for brain metastases among children and adolescents with extracranial malignant germ cell tumors (mGCT) is low but may vary between subgroups. Early identification of subgroups with an increased risk for brain metastasis is therefore important.

Long time survival after reduced chemotherapy in a 15-year-old patient with AML and Candida krusei sepsis and eye involvement.

A 15-year-old boy with AML develops a fulminant candida krusei sepsis complicated by acute blindness due to enophthalmitis and subsequent bleeding during prolonged pancytopenia after induction therapy. Despite a low dose prophylaxis with oral nystatine and i. v. amphotericin B (ampho B) three times a week (0.8 mg/kg). Under an early intensified therapy with ampho B (1.5 mg/kg/d) combined with 5-flucytosin (160 mg/kg/d)the sepsis could be controlled and visual acuity slowly improved. A vitrectomy is due to the bleeding unavoidable. Despite a therapy delay of 4 weeks and omission of two cycles of the intensification treatment the patient is in continuous complete remission for longer than 10 years after diagnosis. If it is within the treatment protocols manageable to detect patients with increased sensitivity against cytostatic drugs and correspondingly highly sensitive leukemic cells, such complications could be avoided due to primary treatment adaptation.

Childhood supratentorial ependymomas with YAP1-MAMLD1 fusion: an entity with characteristic clinical, radiological, cytogenetic and histopathological features

Ependymoma with YAP1‐MAMLD1 fusion is a rare, recently described supratentorial neoplasm of childhood, with few cases published so far. We report on 15 pediatric patients with ependymomas carrying YAP1‐MAMLD1 fusions, with their characteristic histopathology, immunophenotype and molecular/cytogenetic, radiological and clinical features. The YAP1‐MAMLD1 fusion was documented by RT‐PCR/Sanger sequencing, and tumor genomes were studied by molecular inversion probe (MIP) analysis. Significant copy number alterations were identified by GISTIC (Genomic Identification of Significant Targets in Cancer) analysis. All cases showed similar histopathological features including areas of high cellularity, presence of perivascular pseudo‐rosettes, small to medium‐sized nuclei with characteristic granular chromatin and strikingly abundant cells with dot‐like cytoplasmic expression of epithelial membrane antigen. Eleven cases presented features of anaplasia, corresponding to WHO grade III. MRI showed large supratentorial multinodular tumors with cystic components, heterogeneous contrast enhancement, located in the ventricular or periventricular region. One of two variants of YAP1‐MAMLD1 fusions was detected in all cases. The MIP genome profiles showed balanced profiles, with focal alterations of the YAP1 locus at 11q22.1–11q21.2 (7/14), MAMLD1 locus (Xp28) (10/14) and losses of chromosome arm 22q (5/14). Most patients were female (13/15) and younger than 3 years at diagnosis (12/15; median age, 8.2 months). Apart from one patient who died during surgery, all patients are alive without evidence of disease progression after receiving different treatment protocols, three without postoperative further treatment (median follow‐up, 4.84 years). In this to date, largest series of ependymomas with YAP1‐MAMLD1 fusions we show that they harbor characteristic histopathological, cytogenetic and imaging features, occur mostly in young girls under 3 years and are associated with good outcome. Therefore, this genetically defined neoplasm should be considered a distinct disease entity. The diagnosis should be confirmed by demonstration of the specific fusion. Further studies on large collaborative series are warranted to confirm our findings.