BackgroundRhabdomyosarcoma (RMS) is a malignant tumor of mesenchymal origin and comprises the largest category of soft-tissue sarcomas both in children and adolescents. From a pediatric oncology point of view, RMS has traditionally been classified into alveolar (ARMS) and embryonal (ERMS) subtypes. The anatomical localization of the tumor may vary, but commonly involve the head/neck regions, male and female urogenital tract or the trunk and extremities.Case presentationHere, we report two challenging cases involving 17- and 9-years-olds males where diffuse and multiplex bone lesions suggested either a hematological disease or a primary bone tumor (mesenchymal chondrosarcoma). Biopsies, proved a massive infiltration of the bone marrow cavity with rhabdomyosarcoma. In both cases, the ARMS subtype was confirmed using FOXO1 break-apart probes (FISH). Radiological examination could not identify primary soft tissue component in any localization at the time of diagnosis in either cases.ConclusionsPrimary alveolar rhabdomyosarcoma of the bone as a subtype of ARMS, seems to be a distinct clinico-pathological entity with challenging diagnostic difficulties and different, yet better, biological behavior in comparison to soft tissue ARMS. However, it is difficult to be characterized or predict its prognosis and long-term survival as only sporadic cases (four) were reported so far.

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Erdheim–Chester disease (ECD) is a rare histiocytic disorder, characterized by the xanthomatous infiltration of tissues by CD68-positive and CD1a-/CD100-negative foamy histiocytes. In childhood, ECD is exceptionally rare, and only a dozen cases have been published so far. The cooccurence of Langerhans cell histiocytosis (LCH) and ECD is even rarer. Here, we report a 2-year-old boy, the youngest patient in the literature so far, who was diagnosed with concomitant BRAF mutation-positive LCH and ECD. In his case, conventional LCH treatment proved to be ineffective, but he is the youngest patient who was successfully treated with the BRAF inhibitor vemurafenib.

Soft tissue sarcomas (STS) and neuroblastomas (NBL), are childhood malignancies still associated with poor prognoses despite the overall improvement in childhood tumor survival of the past decades. Anaplastic lymphoma kinase (ALK) inhibition is promising new strategy to improve the outcome of these pediatric tumors. Eighteen histologic samples of pediatric STS and 19 NBL patients were analyzed for ALK abnormalities using fluorescent in situ hybridization (FISH) with break-apart probes and immunohistochemistry (IHC). ALK alterations were presented in 20 of the 37 sections. The presence of ALK alteration in NBL samples were detected using IHC in 84,2% of all cases compared to 21,1% FISH positivity. In STS cases the results were less different (IHC 16,7% vs FISH 22,2%). The difference can be explained by the different type of molecular alterations. FISH method detected translocation and amplification, but not the point mutation of ALK gene. IHC confirmed the diagnosis by detecting the expression of ALK protein.After ALK positivity was proven, the effectiveness and safety of the crizotinib therapy was examined in 4 patients (1 alveolar rhabdomyosarcoma (RMA), 1 embryonal rhabdomyosarcoma (RME), 1 inflammatory myofibroblastic tumor (IMT), 1 NBL). We observed continuous remission of the IMT patient, all other cases the inhibitor treatment was not curative.Our findings underline the importance of screening the ALK status parallel with both IHC and FISH. Crizotinib treatment had a long-term effect in ALK positive IMT patients, however itwas only temporary efficient in relapsed, progressive STS and NBL.

Background Wilms’ tumor is a common renal malignancy of early childhood with a generally favorable prognosis depending upon histological subtype. It is becoming increasingly clear that differences in miRNA (microRNA) expression signature represent important clues helping us predict a tumor’s response to chemotherapy. In our study, we aimed to reveal miRNAs deregulated in regressive Wilms’ tumors from FFPE (formalin-fixed, paraffin-embedded) samples, also showing whether such samples are reliable miRNA sources in Wilms’ tumor. Material/Methods Samples from 8 Hungarian patients (3 males, 5 females, aged 1 to 7 years) were analyzed by qRT-PCR (quantitative real-time PCR). A PCR array was used in a pilot experiment, and selected miRNAs (miR-128-3p, miR-184, miR-194-5p, miR-203a) were studied in the rest of the samples using individual primers. Results miR-194-5p was underexpressed in all tumor samples. miR-184 and miR-203a were underexpressed in 7 cases, the exception being a case with a high ratio of necrotic blastemal tissue. Results obtained with miR-128-3p are difficult to interpret due to varying directions of expression changes. Conclusions We conclude that a downregulation of miR-184, miR-194-5p, and miR-203a expression is observed in both regressive and blastemal tumors, but larger-scale studies are needed to confirm whether the degree of their underexpression correlates with the number of blastemal elements in a sample. In most of our FFPE samples aged up to 9 years, RNA extraction provided miRNA with quantity and quality sufficient for qRT-PCR-based analysis, emphasizing the relevance of pathological archives as miRNA sources in future studies.

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