PMC8077488_01
Biopsy histology demonstrates sheets of round to spindled neoplastic cells with a high nuclear to cytoplasmic ratio and minimal cytoplasm. There is nuclear pleomorphism with variably sized nuclei and occasional prominent nucleoli, with scattered more prominently enlarged bizarre nuclei. There are frequent mitoses and apoptoses. H&E. Original magnification, x400.
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F1
Histopathologic examination of a biopsy specimen revealed neuroblastoma, undifferentiated subtype, with a high mitotic-karyorrhectic index (Fig. 1).
Isolated amplification of the 5'ALK region. Top panel: schematic view of ALK gene. Spectrum orange probe: chromosome 2: 28889680-29375856; spectrum green probe: chromosome 2: 29602379-30022356. All the coordinates are based on GRCh37/hg19. Lower panel: Comparison of FISH patterns. ALK, Anaplastic Lymphoma Kinase (ALK) Receptor Tyrosine Kinase; FISH, fluorescence in situhybridization.
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F2
Tarrytown, NY, USA). FISH revealed the presence of >20 copies of the 5' region of the ALK gene (spectrum green probe) in 26% of cells examined, suggestive of partial amplification of the ALK gene, with less than four copies of the 3' region of the ALK gene (spectrum orange) (Fig. 2).
Copy number assessment of the ALK gene. Top panel: Affymetrix OncoScan panel of chromosome 2. Lower panel: zoomed panel of the ALK region. ALK, Anaplastic Lymphoma Kinase (ALK) Receptor Tyrosine Kinase.
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F3
Of particular interest was a small region of low-level copy number gain with an average of 2.5 copies per cell, including exons 2-5 of the ALK gene on chromosome 2, comprising the 5' segment of the ALK coding region (Fig. 3).
Copy number assessment of chromosome 12. CN, copy number.
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F4
Copy number gain of several contiguous regions within 12q was also identified, including chr12:69,017,408-70,446,300 (average of 30 copies per cell) and a region extending to chr12:71,211,437 (average of 5 copies per cell) (Fig. 4).