Which types of this tumor are malignant? How can I recognize a benign one from a malignant one? What differences are there between all types of astrocytomas?
Please note, I am NOT a certified neuropathologist. To my understanding, there are many pathologists in clinical settings in many countries, but much less neuropathologists specialized in diagnosing the different types of more or less rare brain tumors (compared to the more frequent other cancers). Usually, the neuropathologist should be close to a neurosurgery department where the brain tumors can be removed or at least stereotaxically biopsied for a diagnosis. I am not sure how much the WHO (world health organisation) classification of brain tumors is the only or leading standard by now, or, how much it overlaps with the standards used in the US. To my understanding, Pilocytic Astrocytoma are WHO grade I, but biologically totally different from the other ones: low-grade astrocytoma/also referred as WHO grade II), anaplastic astrocytoma (WHO grade II), glioblastoma multiforme (WHO grade IV). Although it may be relatively easy to diagnose most of these tumors with no doubt, there may be slight differences in some rare cases depending on the classification used. I once checked about 10 of each of those tumors for p53 mutations in the known hotspot exons and found no mutations in WHO grade I (Eibl, unpubl.), and about 50% already in WHO grade II, as well as in III and GBM IV (these data were then reproduced with my trainee from Harvard and published: von Deimling, Eibl, et al.). I never published the lack of p53 mutations in WHO I pilocytic astrocytomas.
It is needless to say how important a correct diagnosis is for the clinicians to decide for the later treatment of the patient.
Article p53 mutations are associated with 17p allelic loss in Grade ...
Although atrocytomas normally do not spread aoutside the CNS, they should be referred to as malignant depending on the grading. The most aggressive form, the glioblastoma multiforme, belongs to the tumors with the poorest prognosis.
The grading is made upon mitosis rate, growth speed, invasiveness of adjacent CNS structures, etc.
Not all astrocytomas are malignant tumors! They are devided in low grade (grade I and II) and high grade (grade III and IV). Only the high grade astrocytomas (anaplastic astrocytoma and glioblastoma) are malignant tumors. The histomorphological criteria which differentiate the various types of astrocytomas are best described in the "WHO Classification of Tumours of the Central Nervous System", edited by David N. Louis, Hiroko Ohgaki, Otmar Wiestler and Webster Cavenee. Published by International Agency for Research on Cancer. Lyon 2007. I hope to have helped you with your questions. Sincerely, Dimitrios N. Kanakis
All correct but I add that pilocytic astrocytomas are not infiltrative, grade I and have better prognosis, surgically curative depending on location (best in cerebellum). They have no mitotic activity but vascular proliferation may be seen.
The diffuse astrocytomas are infiltrative, not possible to resect them completely. The low grade astrocytomas (grade II) have no mitotic activity, microvacular proliferation or necrosis. They may remain stable for years but eventually they transform to high grade anaplastic astrocytoma (grade III) or secondary glioblastoma (grade IV). High grade astrocytomas have mitotic acitivity (grade III), and microvascular proliferation and necrosis also present in glioblastoma. There are though further subtypes. The WHO book is good, but you may want to consult with a neuropathologist.
A There is a spectrum of astrocytic tumours ranging from WHO grade 1 varieties, which may be surgically cured, depending on antomical location, to Glioblastoma WHO grade 4, which may not metastasise outside of the brain but has a survival time of 12-18 months at best. WHO grade 2 astrocytomas usually become more malignant and end up as Glioblastomas.
It depends on how you define malignant, but astrocytomas of WHO grade 2 or higher are generally fatal within a few years, which most people would consider malignant
Grade 3 and 4 would be universally considered malignant. I avoid the term "benign" for any glioma as a rule in favor of "low grade" since most if not all grade 2s eventually return as hgher grades making the concept of "benign" misleading. Low grade essentially implies "benign for now"... not cure. Even grade 1s can act up although less commonly.
Is astrocytoma a malignant cancer?
Yes. When it is found as a grade II (that is slow growing) it should be called "pre-cancerous" tumor. In fact, the natural history of grade II gliomas, despite the cellular component, is to progress toward higher grade. Beside, this tumor can kill a patient either by increasing intracranial pressure or by infiltrating vital structures (basal ganglia, brain stem etc..).
Which types of this tumor are malignant?
Typically, grade III and grade IV are immediately considered malignant, but, as mentioned above, it's dangerous to consider a low-grade astrocytomas (grade II) as a "benign" tumor. Eventually, even a grade I can progress to higher grades.
How can I recognize a benign one from a malignant one?
The most precise method is the pathological examination. Microscopy and immunohistochemistry. These methods allow to define the cellular subtypes, state a grade (based on WHO criteria) and search for genetic and biological markers of rapid growth rate. These parameters are the most reliable to formulate a possible prognosis. Hence it is fundamental to obtain a specimen of the tumor (biopy or resection).
The most important from the practical point of view is to know precisely the histological grade..And for that we must have sufficient sample. Actually since even Grade 1 may be diffuse not be considered benign
As a neuropathologist, I am in line with Martyn Carey. Glial tumors of which astrocytomas are part of are graded according to WHO- criteria. The last update of WHO criteria dates from 2007. Grading of gliomas is driven by both histopathology (cell density, cellular polymorphis, mitotic activity, microvascular (endothelial) proliferation, necrosis) and clinical behaviour (progression free and overall surival). The grading system defines four grades from WHO grade I (the most benign) to WHO grade IV the most aggessive (glioblastoma).
As for your question, I would also agree with Martyn Carey, that astrocytomas WHO grade II, anaplastic astrocytomas WHO grade III and glioblastomas WHO- grade IV should be considered as "malignant".
However, tradionally, and as rightly pointed out by Christopher Mascott, WHO grade II gliomas are clinically often addressed as "low- grade" and anaplastic gliomas and glioblastomas as "high- grade gliomas" - suggesting a less malignant behavior of the WHO grade II tumors.
Again, low- grade WHO grade II gliomas will eventually recur and progress to more malignant gliomas (anaplastic WHO grade III and secondary glioblastomas WHO grade IV) - therefore I would also agree that these tumor should not be addressed as being "benign" tumors.
Sorry, but pilocytic astrocytoma, grade I is NOT a premalignant lesion. (They rarely recur but question about residual tumour after "complete" surgical resection remains). However, pilocytic astrocytoma might be a difficult neuropathological diagnosis and misdiagnosis is possible. On the other hand, if an astrocytoma has pilocytic features but infiltrative with mitotic activity, it is probably not a pilocytic astrocytoma but a diffuse glioma and definitely not to be graded I. As I stressed this could be difficult and misdiagnosis occurs. Nevertheless, there are transformed pilocytic astrocytomas on record, but many people doubt their existence. Neuroradiological features are unreliable to give a grade; e.g., pilocytic astrocytoma may appear as ring enhancing lesion similar to glioblastoma.
A grade I astrocytoma is usually encapsulated enough to allow for complete surgical resection however this depends on location. Obviously if located in the brainstem surgical resection can be difficult and a low grade tumour can be associated with a poor outcome depending on location. At time a patient may have a really good outcome from a grade II or above tumour, however again this depends on location. Whilst a grade II astrocytoma may be classed as benign by some they can transform to a higher grade tumour and I would caution against the term benign, the 5 year survival is still quite low.
Amongst low grade tumors, pilocytic astrocytomas (grade 1) can have aggressive behaviour even when maintaining benign histology. I have had a few pilocytics develop multifocality and one with widespread pial and subarachnoid involvement requiring chemotherapy. Some other rare gliomas (usually more developmental in nature ) can have a cure rate. I have follow up on a ganglioglioma with no recurrence 29 years after surgery and several DNETs several decades out.
I would like to thank everybody for the precious contribution. I'm going to read all yours opinions and I hope to get a clearer idea about astrocytoma. Thanks
astrocytomas are classified in 4 grades according to WHO. Grade I and II may appear as non aggressive lesions but do recurr, generally as malignant. Grades II and IV are frnakly aggressive and malignant. Those with oligodendroglial components are less aggressive. Other parameters should at preseny be considered: Metilation state, some genetic features. The definition of grade II is nowadays not enaugh precise to define that tumor. Its behaviour may be quite different from one individual to another.
Please note, I am NOT a certified neuropathologist. To my understanding, there are many pathologists in clinical settings in many countries, but much less neuropathologists specialized in diagnosing the different types of more or less rare brain tumors (compared to the more frequent other cancers). Usually, the neuropathologist should be close to a neurosurgery department where the brain tumors can be removed or at least stereotaxically biopsied for a diagnosis. I am not sure how much the WHO (world health organisation) classification of brain tumors is the only or leading standard by now, or, how much it overlaps with the standards used in the US. To my understanding, Pilocytic Astrocytoma are WHO grade I, but biologically totally different from the other ones: low-grade astrocytoma/also referred as WHO grade II), anaplastic astrocytoma (WHO grade II), glioblastoma multiforme (WHO grade IV). Although it may be relatively easy to diagnose most of these tumors with no doubt, there may be slight differences in some rare cases depending on the classification used. I once checked about 10 of each of those tumors for p53 mutations in the known hotspot exons and found no mutations in WHO grade I (Eibl, unpubl.), and about 50% already in WHO grade II, as well as in III and GBM IV (these data were then reproduced with my trainee from Harvard and published: von Deimling, Eibl, et al.). I never published the lack of p53 mutations in WHO I pilocytic astrocytomas.
It is needless to say how important a correct diagnosis is for the clinicians to decide for the later treatment of the patient.
Article p53 mutations are associated with 17p allelic loss in Grade ...
I will agree that there may be slight differences in some rare cases depending on the classification used, but I think most of the Neuropathologists (including me) have as a gold standard for our diagnosis the book of WHO that I previously introduced. The improvements concerning the classification of CNS tumors is a continuous process that could be best understood by following the various changes (in classification) that have been undertaken from the first publication of WHO book. Since you have published with some of the world known Neuropathologists (as I can see in the attached publication) it is worthless to add anything more about the importance of the WHO book in the diagnosis of CNS tumors.
After a particular review of more than 200 LGG, I have in mind the Xantochromic Astrocytoma and the Anaplastic Astrocytoma (not LGG for definition) as good examples of Astrocytomas with potential malignant transformation, also some Fibrillary can do it. Further to the WHO 2007 Classification, I like a new one proposal that suggest this kind of tumours must to be sub-classified as diffuse or non-diffusedepending of their infiltrative behaviour; this behaviour could explain their "potential malignant transformation", and can be present is some rare Pilocytic Astrocytomas worsening the prognosis specially in those located in areas where GTR is impossible to achieve (e.g. BsT or OPW).
I guess a good source for info about Astrocytomas and other Brain Cancer is.
'WHO Classification of Tumors of the Central Nervous System', edited by David N. Louis, Hiroko Ohgaki, Otmar D. Wiestler, Webster K. Cavence., WHO 2007, I don't know if there's a more recent edition,
it can be bought in:
www.who.int/bookorders ,
the section about Astrocityc tumors contains the following entities:
*Pilocytic Astrocytoma (WHO grade I)
*Subependimal giant cell astrocytoma (WHO grade I)
*Pleomorphic xanthoastrocytoma (WHO grade II)
*Diffuse astrocytoma (WHO grade II)
*Anaplastic astrocytoma (WHO grade III)
*Glioblastoma (WHO grade IV)
+Gliomatosis cerebri
Some Astrocytomas may be more malignant than others, but I won't like catching anyone of it. By the way, GBM seems having some link to CMV infection or sero-postivity, and a letter by Cecilia Soderberg-Naucler in NEJM, oct 9 2013, is about:
'Survival in patients with Glioblastoma receiving Valgancylovir', some previous work existed about the subject, for example: PMID 21632859, by Sampson JH in Clin Cancer Res, Jul 2011.
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