Pleomorphic anaplastic neuroblastoma (PAN) is a striking aspect of neuroblastoma first described by Cozzutto and Carbone in 1988.Cozzutto C, Carbone A (1988). Pleomorphic (Anaplastic) neuroblastoma. Arch Pathol Lab Med 112:621-625. Another case was thereafter reported by Cowan, et al. with cytogenetic and immunohistological analysis in a 28-year-old man.Cowan J, Dayal Y, Schaitzberg S, Tischler AS (1997). Cytogenetic and immunohistological analysis of an adult anaplastic neuroblastoma. Am J Surg Pathol 21(8):957-963. 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.Navarro S, Noguera R, Pellin A, Mejia C, Ruiz A, Llombart-Bosch A (2000). Pleomorphic anaplastic neuroblastoma. Med Pediat Oncol 35:449-502. 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.
__TOC__ Histopathology
Appearance of focal or diffuse presence of pleomorphic and anaplastic cells is the hallmark of this neuroblastoma variant.Fletcher CDM (2007). Diagnostic Histopatholoy of tumors. Churchill Livingstone, p. 1774. Rosai (2004).Rosai and Ackerman's Surgical Pathology. Philadelphia, Mosby, p.1128. 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. Undifferentiated neuroblasts may show enlarged and vesicular nuclei with thick nuclear membranes and prominent nucleoli, often a clue to forthcoming anaplastic change.
Controversy
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.Chatten J (1989). Anaplastic neuroblastomas. Letter to the editor. Arch Pathol Lab Med 113:9-10. 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.Abramowsky CR, Katzenstein HM, Alvarado CS, Shehata BM (2009). Anaplastic large cell neuroblastoma. Pediat Devel Pathol 12(1):1-5. Joshi, et al. did not find any meaningful difference in clinical outcome between cases with or without anaplasia.Joshi VV, Cantor AB, Altshuler G, Larkin EW et al. (1992). Age-linked prognostic categorization based on a new histologic grading system of neuroblastomas. A clinicopathologic study of 211 cases from the pediatric oncology group. Cancer 69:2197-2211. Dehner pointed out the importance of recognizing this variant for differential diagnostic purposes.Dehner LP (1989). Anaplasia in solid malignant tumors of childhood. Arch Pathol Lab Med 113:11-12. Expressions of pleomorphism-anaplasia have been fully acknowledged among the multifarious features of neuroblastoma in the classification by the International Neuroblastoma Pathology Committee.Shimada H, Ambros IM, Dehner LP, Joshi VV, Roald B (1999). Terminology and morphologic criteria of neuroblastic tumors. Recommendations by the International Neuroblastoma Pathology Committee. Cancer 86(2):349-363. 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.Tornòczky T, Kàlmàn E, Kajtàr PG, Nyàri T, Pearson AD, Tweddle DA, Board J, Shimada H (2004) Large cell neuroblastoma. A distinctive phenotype of neuroblastoma with aggressive clinical behavior. Cancer 100(2):390-397.
References
Shimada H, Ambros IM, Dehner LP, Hata J, Joshi VV, Roald B (1999). Terminology and morphologic criteria of neuroblastic tumors. Recommendations by the International Neuroblastoma Pathology Committee. Cancer 86(2) 349–363.