Tumor to normal single-cell mRNA comparisons reveal a pan-neuroblastoma cancer cell.

Neuroblastoma is a childhood cancer that resembles developmental stages of the neural crest. It is not established what developmental processes neuroblastoma cancer cells represent. Here, we sought to reveal the phenotype of neuroblastoma cancer cells by comparing cancer (n = 19,723) with normal fetal adrenal single-cell transcriptomes (n = 57,972). Our principal finding was that the neuroblastoma cancer cell resembled fetal sympathoblasts, but no other fetal adrenal cell type. The sympathoblastic state was a universal feature of neuroblastoma cells, transcending cell cluster diversity, individual patients, and clinical phenotypes. We substantiated our findings in 650 neuroblastoma bulk transcriptomes and by integrating canonical features of the neuroblastoma genome with transcriptional signals. Overall, our observations indicate that a pan-neuroblastoma cancer cell state exists, which may be attractive for novel immunotherapeutic and targeted avenues.

Paternal exposure to recreational drugs before conception and its effect on live-born offspring: A scoping review.

BACKGROUND: Men of reproductive age increasingly use recreational drugs. While many of these substances may reduce the quantity and quality of sperm, less is known about the effects of these exposures on their offspring. We performed a scoping review to summarize the available literature and identify areas for future research on the outcome of live-born offspring of fathers who were exposed to recreational drugs before conception. METHODS: A systematic search was conducted of the Medline, EMBASE, and Web of Science databases, which included keywords for the following substances: cannabis-related products, cocaine, heroin, hallucinogens, ecstasy and amphetamines. In total, 2,983 records were screened, and 129 publications were selected for full-text assessment. Publications were included if (a) the timing of exposure included the preconceptional period, and (b) if outcomes in live-born offspring were compared with an unexposed group. RESULTS: We included 30 publications, of which 15 animal studies and 15 human studies. Animal studies showed neurocognitive abnormalities, in particular in male offspring. Interestingly, these outcomes depend significantly on the method of exposure (i.e., fixed-dose administration vs. variable self-administration, which mimics addiction). Human studies were limited to specific congenital malformations and childhood cancers, which showed small increased odds ratios. CONCLUSIONS: While animal studies describe impaired neurocognitive outcomes following paternal exposure to recreational drugs, data in humans is currently lacking. Human studies require sound methodology in order to confirm findings on congenital malformations and childhood cancers. In addition, future neurocognitive studies require parental neurocognitive assessments to correct for confounding effects (i.e., role of genetics).

MYCN Amplified Relapse Following Resolution of MYCN Nonamplified 4S Neuroblastoma With Placental Involvement: A Case Report and Review of the Literature.

Congenital neuroblastoma with placental involvement is exceptionally rare, but mortality is high. Detailed examination of placenta including MYCN amplification and segmental chromosomal aberrations should be performed in all suspected cases, as it is noninvasive and readily available. Maternal dissemination has not been reported. In this manuscript, we describe an infant with placental diagnosis of MYCN nonamplified congenital neuroblastoma. This is the first report of a recurrence of congenital 4S neuroblastoma following resolution in which MYCN amplification is only detected in the recurrence. Germline sequencing using a large comprehensive cancer panel did not reveal variants in candidate cancer predisposition genes.

Chemotherapy-Colchicine Interaction in a Child with Familial Mediterranean Fever and Hodgkin Lymphoma.

Familial Mediterranean fever (FMF) has been associated with hematological malignancies but has not been reported in association with Hodgkin lymphoma (HL). We hereby describe the first pediatric patient with FMF and stage IIA nodular sclerosis HL. She was treated with prednisone, doxorubicin, vincristine and etoposide (OEPA) being on therapy with colchicine. However, she suffered more than expected treatment-related toxicity attributed either to chemotherapy (severe neutropenia) or colchicine (Abdominal pains and diarrhoea). Colchicine had to be discontinued. In the absence of colchicine, she tolerated very well the second cycle of chemotherapy. Currently, she is in remission at 17 months after her HL diagnosis, and her FMF is under control with colchicine without any signs of toxicity.

[A boy with a painful tumour of his skull]. / Een jongen met een pijnlijke zwelling op zijn hoofd.

A 12-year-old boy presented with an increasing painful swelling of the skull. Physical examination revealed in the left parieto-occipital region a skin-coloured solid mass of 2-3 cm in diameter. The X-ray of the skull was highly suspicious for Langerhans cell histiocytosis. Histopathology of a biopsy of the lesion confirmed the diagnosis.