Severe Hepatopathy in National Wilms Tumor Studies 3-5: Prevalence, Clinical Features, and Outcomes After Reintroduction of Chemotherapy.

Purpose: The safety of reintroducing chemotherapy in the pediatric renal tumor setting after severe hepatopathy (SH), including sinusoidal obstruction syndrome (SOS), is uncertain. We describe the incidence, severity, outcomes, and impact on subsequent treatment for patients with SH from National Wilms Tumor Study (NWTS) protocols 3-5.

Patients And Methods: Archived charts for patients enrolled on NWTS 3-5 who met study inclusion criteria for SH by using established hepatopathy grading scales and clinical criteria were reviewed for demographics, tumor characteristics, radio- and chemotherapy details, SH-related dose modifications, and oncologic outcomes.

Position paper: Rationale for the treatment of children with CCSK in the UMBRELLA SIOP-RTSG 2016 protocol.

The International Society of Paediatric Oncology-Renal Tumour Study Group (SIOP-RTSG) has developed a new protocol for the diagnosis, treatment, and follow-up monitoring of childhood renal tumours - the UMBRELLA SIOP-RTSG 2016 protocol (the UMBRELLA protocol). This protocol has been designed to continue international collaboration in the treatment of childhood renal tumours and will be implemented in over 50 different countries. Clear cell sarcoma of the kidney, which is a rare paediatric renal tumour that most commonly occurs in children between 2 and 4 years of age, is specifically addressed in the UMBRELLA protocol.

TCF21 hypermethylation regulates renal tumor cell clonogenic proliferation and migration.

We recently identified hypermethylation at the gene promoter of transcription factor 21 (TCF21) in clear cell sarcoma of the kidney (CCSK), a rare pediatric renal tumor. TCF21 is a transcription factor involved in tubular epithelial development of the kidney and is a candidate tumor suppressor. As there are no in vitro models of CCSK, we employed a well-established clear cell renal cell carcinoma (ccRCC) cell line, 786-O, which also manifests high methylation at the TCF21 promoter, with consequent low TCF21 expression.

Biology and treatment of renal tumours in childhood.

In Europe, almost 1000 children are diagnosed with a malignant renal tumour each year. The vast majority of cases are nephroblastoma, also known as Wilms' tumour (WT). Most children are treated according to Société Internationale d'Oncologie Pédiatrique Renal Tumour Study Group (SIOP-RTSG) protocols with pre-operative chemotherapy, surgery, and post-operative treatment dependent on stage and histology.

Mutually exclusive BCOR internal tandem duplications and YWHAE-NUTM2 fusions in clear cell sarcoma of kidney: not the full story.

Internal tandem duplication within the BCOR gene sequence that encodes the PUFD domain, important in the formation of the non-canonical or variant polycomb repressor complex 1 (v-PRC1), was very recently described in 100% of 20 clear cell sarcomas of kidney (CCSKs). None of those 20 cases bore the YWHAE-NUTM2 transcript, previously described by us in CCSK, and which constitutes the only other recurrent genetic aberration observed in CCSK, prompting consideration that these mutations might be mutually exclusive in CCSK. We analysed a cohort of 159 CCSKs and can now not only confirm that there is indeed mutual exclusivity of these BCOR and YWHAE mutations, but also show that a substantial proportion (in this series 11.

The clinical phenotype of YWHAE-NUTM2B/E positive pediatric clear cell sarcoma of the kidney.

Clear cell sarcoma of the kidney (CCSK) although uncommon, is the second most frequent renal malignancy of childhood. Until now, the sole recurrent genetic aberration identified in CCSKs is t(10;17)(q22;p13), which gives rise to a fusion transcript of YWHAE and NUTM2B/E. So far, the clinical relevance of this fusion transcript is unknown.

TCF21 hypermethylation in genetically quiescent clear cell sarcoma of the kidney.

Clear Cell Sarcoma of the Kidney (CCSK) is a rare childhood tumor whose molecular pathogenesis remains poorly understood. We analyzed a discovery set of 13 CCSKs for changes in chromosome copy number, mutations, rearrangements, global gene expression and global DNA methylation. No recurrent segmental chromosomal copy number changes or somatic variants (single nucleotide or small insertion/deletion) were identified.

Somatic thrombopoietin (THPO) gene mutations in childhood myeloid leukemias.

We report, for the first time, a non-syndromic infant with a reversible myeloproliferative disease that harbors a germline hereditary thrombopoietin (THPO) gene mutation, a condition that is known to induce familial thrombocytosis at increasing age. In order to investigate whether somatic THPO gene mutations play a role in sporadic pediatric myeloproliferative diseases, we performed a mutation screening of a large representative cohort of pediatric acute myeloid leukemia, myeloid leukemia of Down syndrome, and juvenile myelomonocytic leukemia samples and show that gain-of-function THPO mutations are extremely rare in sporadic pediatric myeloproliferative diseases.

Ultrasound-guided fine needle aspiration cytology as an addendum to sentinel lymph node biopsy can perfect the staging strategy in melanoma patients.

Background: Ultrasound guided fine needle aspiration cytology (US-guided FNAC) can identify microscopic involvement of lymph nodes as in breast cancer and avoid surgical sentinel node (SN). Its utility in melanoma patients is controversial and subject of this study.

Methods: Between 2001 and 2010 over 1000 stage I/II consecutive melanoma patients prospectively underwent US-FNAC prior to SN biopsy.

Peripheral stem cell harvest using regular chemotherapy schedules in childhood cancer.

Prediction of the best moment for the harvest of PBSCs after standard chemotherapy followed by filgrastim in children with cancer is difficult. We retrospectively analyzed the moment of harvesting of 152 procedures in 94 patients. The start of apheresis was guided by WBC count and CD34+ cell measurement in peripheral blood.

Imatinib mesylate for children with dermatofibrosarcoma protuberans (DFSP).

Dermatofibrosarcoma protuberans (DFSP) is a rare malignant soft tissue tumor in children. DFSP is characterized by a specific fusion of the platelet-derived growth factor beta (PDGFbeta) with the collagen type 1alpha1 (COL1alpha1) gene which renders these tumors responsive to targeted therapy with tyrosine kinase inhibitors, such as imatinib mesylate, as is reported in adults. In the current report, we describe the first small pediatric DFSP series, in which response to imatinib mesylate contributed to successful treatment outcome.