International Society of Neuropathology‐Haarlem Consensus Guidelines for Nervous System Tumor Classification and Grading

Abstract

Major discoveries in the biology of nervous system tumors have raised the question of how non-histological data such as molecular information can be incorporated into the next World Health Organization (WHO) classification of central nervous system tumors. To address this question, a meeting of neuropathologists with expertise in molecular diagnosis was held in Haarlem, the Netherlands, under the sponsorship of the International Society of Neuropathology (ISN). Prior to the meeting, participants solicited input from clinical colleagues in diverse neuro-oncological specialties. The present "white paper" catalogs the recommendations of the meeting, at which a consensus was reached that incorporation of molecular information into the next WHO classification should follow a set of provided "ISN-Haarlem" guidelines. Salient recommendations include that (i) diagnostic entities should be defined as narrowly as possible to optimize interobserver reproducibility, clinicopathological predictions and therapeutic planning; (ii) diagnoses should be "layered" with histologic classification, WHO grade and molecular information listed below an "integrated diagnosis"; (iii) determinations should be made for each tumor entity as to whether molecular information is required, suggested or not needed for its definition; (iv) some pediatric entities should be separated from their adult counterparts; (v) input for guiding decisions regarding tumor classification should be solicited from experts in complementary disciplines of neuro-oncology; and (iv) entity-specific molecular testing and reporting formats should be followed in diagnostic reports. It is hoped that these guidelines will facilitate the forthcoming update of the fourth edition of the WHO classification of central nervous system tumors.

Molecular classification of diffuse cerebral WHO grade II/III gliomas using genome- and transcriptome-wide profiling improves stratification of prognostically distinct patient groups

“…In conclusion, our large-scale molecular profiling of WHO grade II and III cerebral gliomas provides important results for improving future classification of these tumors into clinically useful categories based on the integration of histological findings and defined molecular markers as recently proposed by the Haarlem Consensus Meeting [23]. Specifically, our findings support that patients with IDH1/2 mutant gliomas can be molecularly stratified into two prognostically distinct groups corresponding either to patients with 1p/19q co-deleted oligodendrogliomas or patient with 1p/19q intact astrocytomas.…”

Canadian brain cancer survival rates by tumour type and region: 1992–2008

“…Going forward, surveillance data may need to incorporate the new molecular classification systems emerging for this type of information, which is expected to be increasingly clinically relevant. 18 As the most populated provinces -Ontario and Quebec -tended to have the better survival rates, one might speculate that providing patient care for a rare disease is more effective when the number of patients is larger; but the better survival rates for the mixed tumours with oligo features outside of Ontario suggests that other health system factors may also be at play. Provinces with populations over large geographic regions may have urban/rural or socio-economic level factors that indirectly influence disease outcomes that have not been addressed in our analyses.…”

The Challenge of Cancer Genomics in Rare Nervous System Neoplasms

“…14 As a result, the International Society of Neuropathology-Haarlem Working Group, which is developing the upcoming version of the Diagnostic Manual for Tumours of the Central Nervous System, has proposed a diagnostic approach that integrates pathologic and molecular findings to better predict patient outcomes. 15 It is also now evident that there are several molecular subtypes of glioblastomas, 16 ependymomas, 5e8 diffuse intrinsic pontine gliomas, 11,17e19 and medulloblastomas, 20e22 each of which depends on distinct signaling cascades and thus potentially sensitive to different therapeutic agents. As a result, many academic centers are now performing oncogenomic testing to predict which drugs are potentially effective against a patient's tumor.…”