Pleomorphic anaplastic neuroblastoma (PAN) is a striking aspect of neuroblastoma first described by Cozzutto and Carbone in 1988.[1] Another case was thereafter reported by Cowan, et al. with cytogenetic and immunohistological analysis in a 28-year-old man.[2] The case described by Navarro, et al. showed MYCN amplification (more than 10 copies) and a 1p36 deletion as measured with FISH in 13% of cells.[3] Additionally there was a main cell population with a DNA index of 2 indicating a tetraploid DNA content and a high expression of MIBI (Ki-67), bel 2, p53, and P-glycoprotein, either correlated with rapid progression of disease.
Appearance of focal or diffuse presence of pleomorphic and anaplastic cells is the hallmark of this neuroblastoma variant.[1][4][5] Hyperchromatic and bizarre nuclei in neuroblasts and ganglion cells in undifferentiated or poorly differentiated foci are far too pathognomonic, although anaplastic expressions can be found in differentiating foci alike.[1][4][5] Undifferentiated neuroblasts may show enlarged and vesicular nuclei with thick nuclear membranes and prominent nucleoli, often a clue to forthcoming anaplastic change.[citation needed]
Whether pleomorphism-anaplasia warrants a worse prognosis has not been fully assessed so far. Chatten argued that increasing anaplasia in stage IV in comparison with stage III found in her cases suggested a trend toward higher stage (and worse prognosis) with anaplasia.[6] However, within-stage differences were not significant, although cases without anaplasia fared better in each stage than those with. Abramowsky's et al. series of 7 children with anaplastic large cell neuroblastoma showed a better survival than previously reported cases.[7] Joshi, et al. did not find any meaningful difference in clinical outcome between cases with or without anaplasia.[8] Dehner pointed out the importance of recognizing this variant for differential diagnostic purposes.[9] Expressions of pleomorphism-anaplasia have been fully acknowledged among the multifarious features of neuroblastoma in the classification by the International Neuroblastoma Pathology Committee.[10] Recently Tornòczky et al. described 7 cases of large cell neuroblastoma characterized by larger nuclei with thick nuclear membranes and prominent nucleoli suggesting they might represent a distinct phenotype of neuroblastoma with aggressive clinical behavior.[11]