====== Diffuse astrocytoma ======

{{ ::diffuseastrocytoma.jpeg|}}

grade II [[astrocytic tumor]]

In the [[World Health Organization Classification of Tumors of the Central Nervous System 2016]] 
((Louis DN, Ohgaki H, Wiestler OD, et al. WHO classification of tumors of the central nervous system. Lyon, France 2016))
the term diffuse [[astrocytic tumor]]s (sometimes called [[diffuse astrocytoma]]s) refers to the class of infiltrating CNS tumors composed of [[astrocyte]]s (some- times called [[diffuse glioma]]s), whereas the term [[diffuse astrocytoma]] can refer to a lower grade ([[WHO grade II]]) subset of this class, with higher-grade lesions consisting of [[anaplastic astrocytoma]] ([[WHO grade III]]) and [[glioblastoma]] ([[WHO grade IV]]).

===== Classification =====

[[Diffuse astrocytoma classification]].
----
[[WHO grade]] determinations are still made on the basis of histologic criteria. Another reason why [[phenotype]] remains essential is that, there are individual [[tumor]]s that do not meet the more narrowly defined phenotype and [[genotype]] criteria, e.g., the rare phenotypically classical diffuse astrocytoma that lacks the [[signature]] genetic characteristics of [[IDH]] and [[ATRX]] mutations. Nevertheless, it remains possible that future WHO classifications of the diffuse gliomas, in the setting of deeper and broader [[genomic]] capabilities, will require less histological evaluation—perhaps only a diagnosis of “diffuse glioma.” For now, the [[World Health Organization Classification of Tumors of the Central Nervous System 2016]] is predicated on the basis of combined phenotypic and genotypic classification, and on the generation of “integrated” diagnoses.

Diffuse astrocytoma and [[oligodendroglioma]]s are in this classification now nosologically more similar than are diffuse astrocytoma and [[pilocytic astrocytoma]]; the family trees have been redrawn.

In the setting of a diffuse astrocytoma or anaplastic astrocytoma, if IDH testing is not available or cannot be fully performed (e.g., negative immunohistochemistry without available sequencing), the resulting diagnosis would be diffuse astroctyoma, NOS, or anaplastic astrocytoma, NOS, respectively.

Historically, the prognostic differences between [[WHO grade II]] diffuse astrocytomas and [[WHO grade III]] anaplastic astrocytomas were highly significant.

Some studies, however, have suggested that the prognostic differences between IDH-mutant WHO grade II diffuse astrocytomas and IDH-mutant WHO grade III [[anaplastic astrocytoma]]s are not as marked.

Nonetheless, this has not been noted in all studies. At this time, it is recommended that WHO grading is retained for both IDH-mutant and IDH-wildtype astrocytomas, although the prognosis of the IDH-mutant cases appears more favorable in both grades. Cautionary notes have been added to the 2016 classification in this regard.

Of note, two diffuse astrocytoma variants have been deleted from the WHO classification: [[protoplasmic astrocytoma]], a diagnosis that was previously defined in only vague terms and is almost never made any longer given that tumors with this histological appearance are typically characterized as other more narrowly defined lesions; and [[fibrillary astrocytoma]], since this diagnosis overlaps nearly entirely with the standard diffuse astrocytoma. As a result, only [[gemistocytic astrocytoma]] remains as a distinct variant of diffuse astrocytoma IDH-mutant.

===== Differential diagnosis =====

[[Diffuse astrocytoma differential diagnosis]].

===== Treatment =====
[[Diffuse astrocytoma treatment]].

===== Outcome =====
For the [[diffuse astrocytoma]]s, there have been many such studies over the past century and these have proven useful in estimating prognosis for patients. With the advent of [[molecular diagnostics]] and the recent World Health Organization (WHO) Classification of Tumors of the Central Nervous System it is necessary testing for [[isocitrate dehydrogenase]] (IDH) gene status in the classification of diffuse astrocytic gliomas. Novel approaches to diffuse astrocytic tumor grading are required in the era of IDH testing
((von Deimling A, Ono T, Shirahata M, Louis DN. Grading of Diffuse Astrocytic
Gliomas: A Review of Studies Before and After the Advent of IDH Testing. Semin
Neurol. 2018 Feb;38(1):19-23. doi: 10.1055/s-0038-1636430. Epub 2018 Mar 16.
PubMed PMID: 29548048.
)).
----
Alattar et al. determined the influence of [[age]] and tumor [[location]] on [[survival]] benefit from [[GTR]] in [[diffuse astrocytoma]] (DA).

They used [[The Surveillance, Epidemiology and End Results]] ([[SEER]]) [[database]] (1999-2010). They used [[Kaplan-Meier]] curves and [[Cox]] survival models to determine the survival benefit from GTR in populations stratified by age and tumor location. They determined the [[prevalence]] of the [[IDH mutation]] (mIDH) using The [[Cancer Genome Atlas]] (TCGA).

They identified 1980 patients with DA. For frontal DAs, GTR resulted in improved survival relative to subtotal resection in all ages (age ≤50 years hazard ratio [HR], 0.56; P = 0.002; age >50 years HR, 0.41; P < 0.001). For nonfrontal DAs, only patients ≤50 years experienced improved survival with GTR (age ≤50 years HR, 0.55; P = 0.002; age >50 years HR, 0.78; P = 0.114). For patients ≤50 years with frontal tumors, survival was comparable between DA and AA after GTR (75% survival DA: 80 months, AA: 89 months, P = 0.973). In TCGA, these tumors were nearly uniformly mIDH (DA: 98%; AA: 90%, P = 0.11). However, for patients ≤50 years with nonfrontal tumors, there was a survival difference after GTR (75% survival DA: 80 months, AA: 30 months, P = 0.001) despite comparable mIDH prevalence (DA: 82%, AA: 75%, P = 0.49).

Age and tumor location modify the survival benefit derived from GTR in DA. Survival patterns in SEER imperfectly correlated with mIDH prevalence in TCGA, suggesting that tumor grade and mIDH status convey [[nonredundant]] prognostic information in select clinical contexts
((Alattar AA, Carroll KT, Bryant AK, Hirshman B, Joshi R, Carter BS, Harismendy 
O, Chen CC. Prognostic Importance of Age, Tumor Location, and Tumor Grade in
Grade II Astrocytomas: An Integrated Analysis of the Cancer Genome Atlas and the 
Surveillance, Epidemiology, and End Results Database. World Neurosurg. 2019
Jan;121:e411-e418. doi: 10.1016/j.wneu.2018.09.124. Epub 2018 Sep 26. PubMed
PMID: 30266697.
)).

===== References =====