Clinical features and prognosis of paediatric rhabdomyosarcoma with bone marrow metastasis: a single Centre experiences in China

Background The aim of this study was to summarize the clinical characteristics, therapeutic effects and prognosis of patients with rhabdomyosarcoma (RMS) and bone marrow metastasis, improve the understanding of this disease. Method This was a single-institution retrospective study involving the children with RMS, who presented with bone marrow metastasis at initial presentation to our hospital between 1st, Jan, 2006 and 31st, Dec,2019. Follow-up concluded on 31st, Dec, 2020 and the clinical data were collected and analysed. Result Between 1st Jan 2006 and 31st Dec 2019, 13 eligible patients presented to our hospital, including 10 males and 3 females, these eligible patients accounted for 4.5% of all RMS patients. The median age at onset was 5.6 years (range 1.7-14 years). The patients not only had unfavourable primary sites, but also had multiple metastases. The bone marrow aspirate samples of the patients comprised 8-95% blast-like cells. Nine of 13 patients were misdiagnosed with haematological malignancies or other solid tumours. With respect to histology, four of 13 children were classified as embryonal RMS and nine as alveolar RMS. Eleven patients underwent PAX-FOXO1 fusion testing; eight had the POX- FOXO1 fusion gene. Immunohistochemically(IHC) analysis revealed that the tumour cells were positive for Desmin, Vimentin, Myo-D1 and Myogenin. More importantly, the patients had extremely poor prognoses, the median EFS was 12.0 months (range 3-28.3 months) and the median OS was 27.0 months (range6-46.2 months). Conclusion This study demonstrates that children with RMS and bone marrow metastasis usually exhibit atypical primary sites and multiple metastases, with presentation mimicking haematological malignancies or other solid tumors at initial presentation. Pathology and IHC analysis combined with POX-FOXO1 fusion gene detections can effectively confirm the diagnosis. These patients are more likely to relapse or progress during early treatment and are prone to intracranial metastasis. While multidisciplinary therapy combined with Temozolomide may prevent it, further prospective research is required to evaluate the therapeutic effects.

Landscape of Bone Marrow Metastasis in Human Neuroblastoma Unraveled by Transcriptomics and Deep Multiplex Imaging

While the bone marrow attracts tumor cells in many solid cancers leading to poor outcome in affected patients, comprehensive analyses of bone marrow metastases have not been performed on a single-cell level. We here set out to capture tumor heterogeneity and unravel microenvironmental changes in neuroblastoma, a solid cancer with bone marrow involvement. To this end, we employed a multi-omics data mining approach to define a multiplex imaging panel and developed DeepFLEX, a pipeline for subsequent multiplex image analysis, whereby we constructed a single-cell atlas of over 35,000 disseminated tumor cells (DTCs) and cells of their microenvironment in the metastatic bone marrow niche. Further, we independently profiled the transcriptome of a cohort of 38 patients with and without bone marrow metastasis. Our results revealed vast diversity among DTCs and suggest that FAIM2 can act as a complementary marker to capture DTC heterogeneity. Importantly, we demonstrate that malignant bone marrow infiltration is associated with an inflammatory response and at the same time the presence of immuno-suppressive cell types, most prominently an immature neutrophil/granulocytic myeloid-derived suppressor-like cell type. The presented findings indicate that metastatic tumor cells shape the bone marrow microenvironment, warranting deeper investigations of spatio-temporal dynamics at the single-cell level and their clinical relevance.

Clinicopathological Evaluation of Metastatic Carcinomas of Bone Marrow Presenting as Cytopenia

Background – Metastatic carcinomas can involve bone marrow and may lead to subsequent marrow fibrosis and failure. The Bone marrow examination is important in patients diagnosed or patients on chemotherapy for cancer, who presented with peripheral cytopenia. The metastasis of bone marrow by these tumors is a sign of advanced stage of disease with poor prognosis. Methods – Our study is a retrospective study, in which we reviewed a total of 702 bone marrow procedures, out of which 118 bone marrow procedures done in patients with a diagnosis of cancer or patients on chemotherapy presented as cytopenia in Great Eastern Medical College and Hospital during a period of 10 years. Result – In our study of 118 patients 74 males and 44 females. Peripheral smear examination of these cases - 24 out of 32 (75%) presented with anemia, which was the commonest clinical presentation. Others were, thrombocytopenia in 18 (50%), bleeding manifestations in 10 (31.2%), Pancytopenia in 9 (28.1%), bi-cytopenia in 4 (12.5%). During this study period, among 118 malignancies reported in histopathology, 32 cases show bone marrow metastasis. 17.1% were carcinoma breast, 25% were carcinoma stomach 33.3% were carcinoma prostate and carcinoma urinary bladder, 23.5% were SCC carcinoma lung, 0% carcinoma Cervix, all cases of Ewing’s sarcoma, neuroblastoma and poorly differentiated carcinoma show bone marrow metastasis. Conclusion - Bone marrow examination is valuable tool in the diagnosis and staging of hematologic and nonhematological disease, as well as in the assessment of overall bone marrow cellularity, pattern of marrow involvement in metastatic carcinomas.

Chromosome 10 abnormality predicts prognosis of neuroblastoma patients with bone marrow metastasis

Background Neuroblastoma (NB) is the most common extracranial solid tumor in children. It is known for high heterogeneity and concealed onset. In recent years, the mechanism of its occurrence and development has been gradually revealed. The purpose of this study is to summarize the clinical characteristics of children with NB and abnormal chromosome 10, and to investigate the relationship between the number and structure of chromosome 10 abnormalities and NB prognosis. Methods Chromosome G-banding was used at the time of diagnosis to evaluate the genetics of chromosomes in patients with NB and track their clinical characteristics and prognosis. All participants were diagnosed with NB in the Medical Oncology Department of the Beijing Children’s Hospital from May 2015 to December 2018 and were followed up with for at least 1 year. Results Of all 150 patients with bone marrow metastases, 42 were clearly diagnosed with chromosomal abnormalities. Thirteen patients showed abnormalities in chromosome 10, and chromosome 10 was the most commonly missing chromosome. These 13 patients had higher LDH and lower OS and EFS than children with chromosomal abnormalities who did not have an abnormality in chromosome 10. Eight patients had both MYCN amplification and 1p36 deletion. Two patients had optic nerve damage and no vision, and one patient had left supraorbital metastases 5 months after treatment. Conclusions The results indicated that chromosome 10 might be a new prognostic marker for NB. MYCN amplification and 1p36 deletion may be related to chromosome 10 abnormalities in NB. Additionally, NB patients with abnormal chromosome 10 were prone to orbital metastases.