Pathology of peripheral neuroblastic tumors

Abstract

Neuroblastoma is the most prevalent extracranial solid tumor in pediatric age populations worldwide and the most common neoplastic disease diagnosed in the first year of life. The term neuroblastoma often encompasses all peripheral neuroblastic tumors (pNTs including neuroblastoma, ganglioneuroblastoma, and ganglioneuroma) of neural crest origin. Since pNTs demonstrate a wide range of clinical behaviors, including spontaneous regression, tumor differentiation/maturation, and aggressive progression refractory to even intensive treatment modalities, these tumors are believed to be distinguished into different biological/molecular groups. For the practical purpose, risk classification systems have been developed based on combinations of so-called prognostic factors.In this review of pNTs, we describe a history of pathology, summarize epidemiology and clinical features, and outline International Neuroblastoma Pathology Classification (INPC). Then we discuss advantages and limitations of core needle biopsy and conventional biopsy of neuroblastoma. Besides the INPC, we also describe other prognostic factors, such as age at diagnosis, clinical stage, and molecular/genetic factors, since they are included in widely used Risk Classification Systems. Additionally, we discuss further molecular abnormalities closely associated with highly aggressive neruoblastomas. Towards the end, we touch on rapidly advancing technologies for establishing an artificial intelligence-assisted INPC system.

Keywords: Alternative lengthening of telomeres; Artificial intelligence; Ganglioneuroblastoma; Ganglioneuroma; International neuroblastoma pathology classification; MYC; Neuroblastoma; Paired-like homeobox 2B; Percutaneous core needle biopsy; Telomerase reverse transcription.

Fig. 1

Neuroblastoma. A Gross appearance of adrenal neuroblastoma with soft consistency and extensive hemorrhage; (B) Undifferentiated subtype composed of small round blue cells without clearly recognizable neurite production. (Note: This tumor demonstrates markedly increased mitotic and karyorrhectic activities and has MYCN oncogene amplification) (400x); (C) Poorly differentiated subtype composed of tumor cells with neurite production demonstrating multiple rosette formations (400x); (D) Differentiating subtype predominantly composed of differentiating neuroblasts with active neurite production (400x)

Fig. 2

Ganglioneuroblastoma and Ganglioneuroma. A Gross appearance of adrenal Ganglioneuroblastoma, intermixed with a solid and elastic cut surface; (B) Ganglioneuroblastoma, intermixed demonstrating randomly distributed microscopic nests of neuroblastic cells with their naked neurites in a background of Schwannian stroma containing ganglion cells (400x); (C) Ganglioneuroma showing mature and maturing ganglion cells in Schwannian stroma. (Note: Completely mature ganglion cells are covered with satellite cells. No naked neurites are detected around the ganglion cells, since they are incorporated in the cytoplasm of Schwannian stromal cells.) (400x); (D) Gross appearance of Ganglioneuroblastoma, nodular, characterized by the presence of well-defined nodular mass within solid elastic background; (E) Ganglioneuroblastoma, nodular composed of two distinct histologies; neuroblastomatous nodule (left) and Ganglioneuroblastoma, intermixed (right) (40x). [Gross image of Ganglioneuroblastoma, nodular (Fig. 2D) was contributed by Dr. Nick Shillingford, Children’s Hospital Los Angeles]

Fig. 3

PHOX2B immunohistochemistry in poorly differentiated neuroblastoma tissue specimen

Fig. 4

The MYCN gene amplification in neuroblastoma detected by fluorescence in hybridization (FISH) examination. Green: MYCN signals, Red: Control (Chromosome 2) signals