Sympathoblasts and their malignant progeny: the cellular mosaic of neuroblastoma

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Abstract

This review provides a comprehensive analysis of current knowledge on neuroblastoma in the context of embryonic development of the sympathoadrenal system. The evolution of scientific concepts regarding this tumor is traced from its first descriptions in the second half of the 19th century to the present day. The review outlines the conceptual framework of the modern understanding of neuroblastoma as a consequence of disrupted differentiation of neural crest cells. Particular attention is given to embryological aspects of sympathoadrenal system development, including neural crest cell migration, differentiation under the influence of external signals, and the formation of bipotential sympathoblasts capable of generating both neuronal and mesenchymal lineages. A substantial portion of the review focuses on the cellular heterogeneity of neuroblastoma, manifested by the coexistence of H-type (adrenergic) neuronal cells and C-type (mesenchymal) adhesive cells. The authors analyze findings from recent studies and highlight challenges in identifying tumor cell populations, emphasizing the need for validated species-specific markers. The review underscores the importance of integrating knowledge of key embryogenic stages with modern genomic technologies to develop more effective therapeutic strategies for this aggressive pediatric tumor.

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About the authors

Dmitry M. Konovalov

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology; Russian Medical Academy of Continuous Professional Education

Author for correspondence.
Email: dmk_nadf@mail.ru
ORCID iD: 0000-0001-7732-8184
SPIN-code: 4037-8636

MD, Cand. Sci. (Medicine), Assistant Professor

Russian Federation, Moscow; Moscow

Anastasia S. Sharlai

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology

Email: stasysharlay@yandex.ru
ORCID iD: 0000-0001-5354-7067
SPIN-code: 9720-5686
Russian Federation, Moscow

Pavel E. Trakhtman

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology

Email: pavel.trakhtman@dgoi.ru
ORCID iD: 0000-0002-0231-1617
SPIN-code: 8135-1761

MD, Dr. Sci. (Medicine), Assistant Professor

Russian Federation, Moscow

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2. Fig. 1. Histological diversity of neuroblastoma: a, poorly differentiated neuroblastoma with solid sheets of undifferentiated neuroblasts and areas of intercellular reticular matrix formation (neuropil); b, poorly differentiated neuroblastoma with undifferentiated neuroblasts forming rhythmic rosette-like structures; c, ganglioneuroblastoma with discrete foci of undifferentiated neuroblastoma within mature Schwannian stroma; d, ganglioneuroma with ganglion cells of varying degrees of maturation located within mature Schwannian stroma. Hematoxylin and eosin staining, ×200 magnification.

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3. Fig. 2. Immunohistochemical features of marker expression in neuroblastoma: a, absence of vimentin expression in neuroblasts; expression in neuroblasts and neuropil of (b) PGP9.5 protein, (c) synaptophysin, and (d) chromogranin A. ×200 magnification.

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