WHO 2016 classification: changes and advancements in the diagnosis of miscellaneous primary CNS tumours

Abstract

This short review highlights significant changes and recent findings incorporated to varying extent in the WHO 2016 definition of a variety of tumours, including peripheral nerve sheath tumours, meningiomas, mesenchymal nonmeningothelial tumours, melanocytic tumours, lymphomas and histiocytic tumours, germ cell tumours and non-neuroendocrine pituitary tumours. Most notable classification changes include: adding 'hybrid nerve sheath tumours' to the spectrum of benign nerve sheath tumours; an updated definition of atypical meningioma (WHO grade II), including cases with brain invasion; recognizing dural solitary fibrous tumour (SFT) and haemangiopericytoma (HPC) as a single tumour entity characterized by NAB2 and STAT6 gene fusions for which the term SFT/HPC was chosen; recognizing that pituitary granular cell tumour, spindle cell oncocytoma, and pituicytoma all share nuclear expression of TTF-1, possibly representing a spectrum of a single nosological entity derived from posterior pituitary glial cells. The most significant diagnostic markers which have emerged include: inactivation of NF1, CDKN2A, and PRC2 components, SUZ12 and EED in MPNST, leading to neurofibromin and H3K27me3 expression loss; GNAQ and GNA11 mutations in CNS primary melanocytic tumours; BRAFV600E mutation in histiocytic tumours (Langerhans cell histiocytosis and Erdheim-Chester disease) and papillary craniopharyngioma, which provides both a diagnostic marker in the appropriate pathological setting and a therapeutic target. The WHO 2016 Classification has balanced cutting-edge knowledge on the molecular characteristics of the miscellaneous CNS tumours reviewed here with a practical approach for their daily diagnostic work-up. Much more progress can be expected in the classification of these neoplasms in the near future.

Primary central nervous system marginal zone B‐cell lymphoma arising from the dural meninges: A case report and review of literature

“…They express CD19, CD20, and CD79a antigens. The prognostic importance of other biomarkers such as B‐cell CLL/lymphoma 6 (BCL6) and 2 (BCL2), melanoma‐associated antigen (mutated) 1 (MUM1)/interferon regulatory factor 4 (IRF4) remains unclear, but they are reported to be positive in many cases …”

“…Immunological staining is generally positive for CD20, CD22, CD19 and CD79a and PAX‐5. Tumor cells are positive for BCL2, and half of the cases are CD43 positive …”

“…The prognostic importance of other biomarkers such as B-cell CLL/lymphoma 6 (BCL6) and 2 (BCL2), melanoma-associated antigen (mutated) 1 (MUM1)/interferon regulatory factor 4 (IRF4) remains unclear, but they are reported to be positive in many cases. 14 Treatment strategies for PCNSL continue to be explored. Newer studies have demonstrated that high-dose methotrexate (MTX)-based induction chemotherapy combined with other chemotherapeutic agents is highly effective, which has now become the standard of care in newly diagnosed PCNSL.…”

“…Tumor cells are positive for BCL2, and half of the cases are CD43 positive. 14 Primary dural lymphoma usually have a very favorable prognosis as compared to PCNSL with parenchymal involvement, or systemic lymphoma with CNS metastasis. PDL is very seldom the first identifying lesion that leads to the diagnosis of systemic lymphoma.…”

Primary Malignant Melanoma of Brainstem Medulla Mimicking as Cavernoma – Case Report

“…In addition to histology, the presence of positive S100 and HMB-45 are confirmatory features of malignant melanoma on immunohistochemical staining [11].…”