Pleomorphic anaplastic neuroblastoma

Histopathology

Appearance of focal or diffuse presence of pleomorphic and anaplastic cells is the hallmark of this neuroblastoma variant. 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. 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. Joshi, et al. did not find any meaningful difference in clinical outcome between cases with or without anaplasia. Dehner pointed out the importance of recognizing this variant for differential diagnostic purposes. Expressions of pleomorphism-anaplasia have been fully acknowledged among the multifarious features of neuroblastoma in the classification by the International Neuroblastoma Pathology Committee. 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.

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.

References

1. Cozzutto C, Carbone A (1988). Pleomorphic (Anaplastic) neuroblastoma. Arch Pathol Lab Med 112:621-625.
2. 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.
3. Navarro S, Noguera R, Pellin A, Mejia C, Ruiz A, Llombart-Bosch A (2000). Pleomorphic anaplastic neuroblastoma. Med Pediat Oncol 35:449-502.
4. Fletcher CDM (2007). Diagnostic Histopatholoy of tumors. Churchill Livingstone, p. 1774. Rosai (2004).
5. Rosai and Ackerman's Surgical Pathology. Philadelphia, Mosby, p.1128.
6. Chatten J (1989). Anaplastic neuroblastomas. Letter to the editor. Arch Pathol Lab Med 113:9-10.
7. Abramowsky CR, Katzenstein HM, Alvarado CS, Shehata BM (2009). Anaplastic large cell neuroblastoma. Pediat Devel Pathol 12(1):1-5.
8. 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.
9. Dehner LP (1989). Anaplasia in solid malignant tumors of childhood. Arch Pathol Lab Med 113:11-12.
10. 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.
11. 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.