Pleomorphic anaplastic neuroblastoma (PAN) is a striking aspect of

neuroblastoma Neuroblastoma (NB) is a type of cancer that forms in certain types of nerve tissue. It most frequently starts from one of the adrenal glands but can also develop in the head, neck, chest, abdomen, or Vertebral column, spine. Symptoms may include ...

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 Cytogenetics is essentially a branch of genetics, but is also a part of cell biology/cytology (a subdivision of human anatomy), that is concerned with how the chromosomes relate to cell behaviour, particularly to their behaviour during mitosis an ...

and immunohistological analysis in a 28-year-old man. The case described by Navarro, et al. showed MYCN amplification (more than 10 copies) and a 1p36 deletion as measured with

FISH A fish (: fish or fishes) is an aquatic animal, aquatic, Anamniotes, anamniotic, gill-bearing vertebrate animal with swimming fish fin, fins and craniate, a hard skull, but lacking limb (anatomy), limbs with digit (anatomy), digits. Fish can ...

in 13% of cells. Additionally there was a main cell population with a DNA index of 2 indicating a

tetraploid Polyploidy is a condition in which the cells of an organism have more than two paired sets of ( homologous) chromosomes. Most species whose cells have nuclei (eukaryotes) are diploid, meaning they have two complete sets of chromosomes, one fro ...

DNA content and a high expression of MIBI (Ki-67), bel 2,

p53 p53, also known as tumor protein p53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory transcription factor protein that is often mutated in human cancers. The p53 proteins (originally thou ...

, and

P-glycoprotein P-glycoprotein 1 (permeability glycoprotein, abbreviated as P-gp or Pgp) also known as multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1 (ABCB1) or cluster of differentiation 243 (CD243) is an important protein ...

, either correlated with rapid progression of disease. __TOC__

Histopathology

Appearance of focal or diffuse presence of pleomorphic and

anaplastic Anaplasia () is a condition of cells with poor cellular differentiation, losing the morphological characteristics of mature cells and their orientation with respect to each other and to endothelial cells. The term also refers to a group of mor ...

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 Pathognomonic (synonym ''pathognomic'') is a term, often used in medicine, that means "characteristic for a particular disease". A pathognomonic sign is a particular sign whose presence means that a particular disease is present beyond any doubt. ...

, 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

{{Reflist, colwidth=25em * 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. Brain tumor