Pediatric renal cell carcinomas (RCC) differ from their adult counterparts not only in histologic subtypes but also in clinical characteristics and outcome. However, the underlying biology is still ...largely unclear. For this reason, we performed whole-exome and transcriptome sequencing analyses on a cohort of 25 pediatric RCC patients with various histologic subtypes, including 10 MiT family translocation (MiT) and 10 papillary RCCs. In this cohort of pediatric RCC, we find only limited genomic overlap with adult RCC, even within the same histologic subtype. Recurrent somatic mutations in genes not previously reported in RCC were detected, such as in CCDC168, PLEKHA1, VWF, and MAP3K9. Our papillary pediatric RCCs, which represent the largest cohort to date with comprehensive molecular profiling in this age group, appeared as a distinct genomic subtype differing in terms of gene mutations and gene expression patterns not only from MiT-RCC but also from their adult counterparts.
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•WES and RNA-seq of 25 pediatric RCCs with various histologic subtypes•Detected only limited genomic overlap with adult RCC•Revealed recurrent somatic mutations in genes not previously reported in RCC•Discovery of a CRK-PITPNA fusion gene in a pediatric papillary RCC
Genomics; Cancer
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Peripheral neuroblastic tumors represent the fourth-largest group of malignant tumors in childhood. The majority of these tumors are neuroblastomas, which can be classified into undifferentiated, ...poorly differentiated, and differentiating subtypes. In addition, peripheral neuroblastic tumors include ganglioneuroblastoma, a composite tumor composed of Schwannian cell stroma and neuroblasts as well as benign ganglioneuroma. In this overview, histopathological diagnostic criteria and grading systems, as well as common molecular alterations that are of prognostic and therapeutic significance, are discussed.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Paediatric adrenocortical carcinomas (ACC) are highly aggressive malignancies with a dismal prognosis in advanced and metastatic diseases. Little is known about outcome of patients with refractory ...and relapsed (r/r) disease.
National retrospective multicentre study including r/r ACC diagnosed in patients aged< 18 years registered in the MET studies between January 1997 and December 2021
A total of 16 patients (5 male; median age 12.9 years) with refractory disease were included. Median time to progression was 0.6 years 0.0–1.3. Site of progression was locoregional (n = 1), distant (n = 3), and combined (n = 12). 3-year overall (OS) and progression-free (PFS) survival were both 0%. Thirty patients with relapse (11 male; median age 7.3 years) were identified. Median time to relapse was 0.7 years 0.1–3.2. Site of relapse was locoregional (n = 8), distant (n = 15), and combined (n = 7). At last follow-up, 20 patients had died of disease or complications or were alive with disease, 10 patients were in second complete remission (median follow-up: 6.8 years 0–10.5). 3-year OS and PFS following relapse were 39.1% and 31.9%. Survival was superior in patients with distant relapse (59.6%) compared to locoregional (28.6%) and combined (14.3%) (p = 0.028) and in patients with complete surgical resection of all sites of recurrence (70.0%) compared to incomplete (21.4%) and no surgery (0%) (p = 0.003).
For patients nonresponsive to first-line therapy or who experience relapse, prognosis is dismal and options are scarce. Site of relapse and resectability define prognosis. Novel therapeutic concepts are needed to improve the outcome of paediatric patients with r/r ACC.
•Refractory ACC has a dismal prognosis with a 3-year OS and PFS of 0%.•Outcome of relapsed ACC depends on site of relapse and resectability.•OS after event is 28.6% in local, 59.6% in distant and 14.3% in combined relapse.•Only 4 of 17 relapsed patients with initial stage II were rescued.•Novel diagnostic and therapeutic concepts are urgently needed to improve outcomes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Central nervous system (CNS) involvement remains a challenge in the diagnosis and treatment of acute lymphoblastic leukemia (ALL). In this study, we identify CD79a (also known as Igα), a signaling ...component of the preB cell receptor (preBCR), to be associated with CNS-infiltration and -relapse in B-cell precursor (BCP)-ALL patients. Furthermore, we show that downregulation of CD79a hampers the engraftment of leukemia cells in different murine xenograft models, particularly in the CNS.
Pediatric spindle cell tumors are rare and often difficult to diagnose due to a similar morphology and a non-specific immunohistochemical profile. Genetic characterization of these lesions has been ...constantly improving, which has led to the identification of new subgroups that were partly included in the WHO classification. Receptor tyrosine kinase fusions play a special role in these tumors and their verification has diagnostic relevance and can be an option for target-oriented therapies. In the case of pediatric spindle cell tumors, genetic fusions form especially with NTRK1‑3, ALK, RET, and ROS1. Overall, pediatric tumors with receptor tyrosine kinase fusions are predominantly low-grade tumors, which are often subdivided into the group of intermediate-malign tumors.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
Pediatric germ cell tumors (GCT) are rare and very heterogeneous neoplasms that show a high diversity in tumor biology and histology. The clinical behavior cannot be predicted based on ...morphology or immunohistochemistry. The aim of this study was to investigate a large number of pediatric GCT regarding chromosomal gains of 12p and 1q.
Methods
One hundred and eighty pediatric nonseminomatous GCT, that is, mature teratomas, immature teratomas, yolk sac tumors, and mixed germ cell tumors, from three age groups were evaluated for 1q and 12p gains by fluorescence in situ hybridization in tissue micro arrays. The results were correlated with tumor biology and clinical data.
Results
Eleven out of 143 GCT showed gains of 1q. In 29/157 GCT a gain of 12p was found. Prepubertal patients (≤6 years of age) more often displayed gains of 1q compared to pubertal/adolescent patients (11‐17 years of age), whereas pubertal/adolescent patients showed gains of 12p most frequently. Twenty‐one out of 155 patients suffered from relapse or metachronous disease. Patients with and without gains of 1q or 12p did not differ in frequency of these events. However, the likelihood of occurrence of these clinical events varied depending on the histological type of the tumor.
Conclusion
The biological behavior of pediatric GCT depends more on the histological type of the tumor than on the genetic aberrations examined in this study. Gains of 1q and 12p are not suitable to predict the clinical outcome of GCT in childhood. Nevertheless, both genetic alterations might be used as biomarkers to distinguish different histological types of GCT and therefore could be of diagnostic value, especially in borderline cases.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Rhabdomyosarcomas (RMS) are rare and often lethal diseases. It is assumed that the tumor microenvironment (TME) of RMS exerts an immunosuppressive function, but there is currently no systematic ...analysis of the immune cells infiltrating sarcoma tissue. Focusing on two common types of RMS (alveolar RMA and embryonal RME), we performed a comprehensive immunohistochemical analysis of tumor-infiltrating immune cells in the TME. We performed a qualitative estimation of infiltrating immune cells in the tumor microenvironment by an experienced pathologist as well as a quantitative digital pathology analysis. We found that (1) manual and automatic quantification of tumor-infiltrating immune cells were consistent; (2) RME tumors showed a higher degree of immune cell infiltration than RMA tumors but (3) the number of tumor infiltrating lymphocytes was low compared to other solid tumor types; (4) microvascular density correlated with immune cell infiltration and (5) CD163 positive macrophages as well as CD54 positive microvessels were more often detected in RME than in RMA and correlated with patient overall and event free survival. Our systematic analysis provides a comprehensive view of the immune landscape of RMS which needs to be taken into account for developing immunotherapies for this rare type of cancer.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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