The fourth edition of the World Health Organization (WHO) classification of tumours of the central nervous system, published in 2007, lists several new entities, including angiocentric glioma, papillary glioneuronal tumour, rosette-forming glioneuronal tumour of the fourth ventricle, papillary tumour of the pineal region, pituicytoma and spindle cell oncocytoma of the adenohypophysis. Histological variants were added if there was evidence of a different age distribution, location, genetic profile or clinical behaviour; these included pilomyxoid astrocytoma, anaplastic medulloblastoma and medulloblastoma with extensive nodularity. The WHO grading scheme and the sections on genetic profiles were updated and the rhabdoid tumour predisposition syndrome was added to the list of familial tumour syndromes typically involving the nervous system. As in the previous, 2000 edition of the WHO ‘Blue Book’, the classification is accompanied by a concise commentary on clinico-pathological characteristics of each tumour type. The 2007 WHO classification is based on the consensus of an international Working Group of 25 pathologists and geneticists, as well as contributions from more than 70 international experts overall, and is presented as the standard for the definition of brain tumours to the clinical oncology and cancer research communities world-wide.

https://link.springer.com/content/pdf/10.1007%2Fs00401-007-0243-4.pdf

The 2007 WHO Classification of Tumours of the Central Nervous System

The 2016 World Health Organization Classification of Tumors of the Central Nervous System is both a conceptual and practical advance over its 2007 predecessor. For the first time, the WHO classification of CNS tumors uses molecular parameters in addition to histology to define many tumor entities, thus formulating a concept for how CNS tumor diagnoses should be structured in the molecular era. As such, the 2016 CNS WHO presents major restructuring of the diffuse gliomas, medulloblastomas and other embryonal tumors, and incorporates new entities that are defined by both histology and molecular features, including glioblastoma, IDH-wildtype and glioblastoma, IDH-mutant; diffuse midline glioma, H3 K27M-mutant; RELA fusion-positive ependymoma; medulloblastoma, WNT-activated and medulloblastoma, SHH-activated; and embryonal tumour with multilayered rosettes, C19MC-altered. The 2016 edition has added newly recognized neoplasms, and has deleted some entities, variants and patterns that no longer have diagnostic and/or biological relevance. Other notable changes include the addition of brain invasion as a criterion for atypical meningioma and the introduction of a soft tissue-type grading system for the now combined entity of solitary fibrous tumor / hemangiopericytoma-a departure from the manner by which other CNS tumors are graded. Overall, it is hoped that the 2016 CNS WHO will facilitate clinical, experimental and epidemiological studies that will lead to improvements in the lives of patients with brain tumors.

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The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary.

The Central Brain Tumor Registry of the United States (CBTRUS), in collaboration with the Centers for Disease Control (CDC) and National Cancer Institute (NCI), is the largest population-based registry focused exclusively on primary brain and other central nervous system (CNS) tumors in the United States (US) and represents the entire US population. This report contains the most up-to-date population-based data on primary brain tumors (malignant and non-malignant) and supersedes all previous CBTRUS reports in terms of completeness and accuracy. All rates (incidence and mortality) are age-adjusted using the 2000 US standard population and presented per 100,000 population. The average annual age-adjusted incidence rate (AAAIR) of all malignant and non-malignant brain and other CNS tumors was 23.79 (Malignant AAAIR=7.08, non-Malignant AAAIR=16.71). This rate was higher in females compared to males (26.31 versus 21.09), Blacks compared to Whites (23.88 versus 23.83), and non-Hispanics compared to Hispanics (24.23 versus 21.48). The most commonly occurring malignant brain and other CNS tumor was glioblastoma (14.5% of all tumors), and the most common non-malignant tumor was meningioma (38.3% of all tumors). Glioblastoma was more common in males, and meningioma was more common in females. In children and adolescents (age 0-19 years), the incidence rate of all primary brain and other CNS tumors was 6.14. An estimated 83,830 new cases of malignant and non-malignant brain and other CNS tumors are expected to be diagnosed in the US in 2020 (24,970 malignant and 58,860 non-malignant). There were 81,246 deaths attributed to malignant brain and other CNS tumors between 2013 and 2017. This represents an average annual mortality rate of 4.42. The 5-year relative survival rate following diagnosis of a malignant brain and other CNS tumor was 23.5% and for a non-malignant brain and other CNS tumor was 82.4%.

CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2007-2011.

Pathology and genetics of tumors of soft tissue and bone

Astrocytes are specialized glial cells that outnumber neurons by over fivefold. They contiguously tile the entire central nervous system (CNS) and exert many essential complex functions in the healthy CNS. Astrocytes respond to all forms of CNS insults through a process referred to as reactive astrogliosis, which has become a pathological hallmark of CNS structural lesions. Substantial progress has been made recently in determining functions and mechanisms of reactive astrogliosis and in identifying roles of astrocytes in CNS disorders and pathologies. A vast molecular arsenal at the disposal of reactive astrocytes is being defined. Transgenic mouse models are dissecting specific aspects of reactive astrocytosis and glial scar formation in vivo. Astrocyte involvement in specific clinicopathological entities is being defined. It is now clear that reactive astrogliosis is not a simple all-or-none phenomenon but is a finely gradated continuum of changes that occur in context-dependent manners regulated by specific signaling events. These changes range from reversible alterations in gene expression and cell hypertrophy with preservation of cellular domains and tissue structure, to long-lasting scar formation with rearrangement of tissue structure. Increasing evidence points towards the potential of reactive astrogliosis to play either primary or contributing roles in CNS disorders via loss of normal astrocyte functions or gain of abnormal effects. This article reviews (1) astrocyte functions in healthy CNS, (2) mechanisms and functions of reactive astrogliosis and glial scar formation, and (3) ways in which reactive astrocytes may cause or contribute to specific CNS disorders and lesions.

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Astrocytes: biology and pathology

Normal pituitaries, pituitaries showing CHC and selected adenomas were assessed for their possible content of intermediate filaments (IF), using immunohistochemical techniques. Normal pituitaries were stained for each of the five known IF (Cytokeratins (CK), glial fibrillary acidic protein (GFAP), desmin, vimentin, and neurofilaments (NF)). Desmin could not be demonstrated, and NF staining was limited to processes in the posterior gland. In serial sections, CK was demonstrated in some corticotrophs, somatotrophs, and lactotrophs. Vimentin was limited to processes in the posterior gland. Folliculo-stellate cells (FSC), demonstrated by staining for SlOO protein, exhibited a small subpopulation staining for CK, and another subpopulation staining for GFAP. GFAP was also demonstrated in glial processes in the posterior gland. Cells showing Crooke's hyaline change stained intensely for CK. Null cell adenomas did not stain for CK. Corticotroph adenomas, somatotroph adenomas, with or without fibrous bodies, and lactotroph adenomas contain CK-immunoreactive cells. We conclude that CK is the major IF present in the anterior pituitary gland, within some normal corticotrophs, somatotrophs and lactotrophs, and also in adenomas derived from these cells.

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Intermediate filaments in the human pituitary gland: an immunohistochemical study.

For a long time, it has been speculated that pregnancy stimulates the growth of acoustic schwannomas. To test this hypothesis, immunohistochemical stains for estrogen receptor, progesterone receptor, and proliferating cell nuclear antigen (PCNA) were performed. Flow cytometric studies for DNA ploidy and S-phase fraction determinations were also performed. The study subjects included 6 female patients with unilateral acoustic tumors; at the time of tumor removal, 1 woman was pregnant and the other 5 women were 2 to 10 months postpartum. The age-sex-matched control group consisted of 6 men and 12 nonpregnant women, all with acoustic schwannomas similar in size to those of the study group. The study found no statistically significant association between the presence or quantity of estrogen or progesterone receptors and pregnancy, DNA ploidy, proliferation indices, or clinical data. Based on PCNA indices, large tumors tended to be less "biologically active" than small lesions (P < .01). The authors concluded that pregnancy does not significantly stimulate the cellular growth of acoustic schwannomas.

Acoustic schwannoma and pregnancy: A DNA flow cytometric, steroid hormone receptor, and proliferation marker study

Oligodendroglia, so designated by del Rio Hortega1 on the basis of their cytology, particularly their scant processes, were subsequently postulated by Bailey and Cushing2 to be the progenitors of oligodendrogliomas. The latter authors encountered 9 such tumors in their series of gliomas. Accordingly, they formulated the following description, “Oligodendroglioma is a cellular tumor of peculiar type in which fibrillar astrocytes occasionally appear and the neoplastic cells have spherical nuclei with a heavy chromatin network, and are surrounded by a ring of cytoplasm which stains very feebly by ordinary staining methods. Between the cells is an indefinite material which stains neither for neu-rofibrillae, neuroglia, nor for connective tissue. This material may give the growth somewhat the appearance of the cross-section of a plant. No mitotic figures can be seen. These tumors are prone to become calcified.”

Oligodendroglioma: the ultrastructural spectrum.

Two cases of inflammatory pseudotumor are described The first patient, a 35-year-old white man, developed a progressive sensorimotor deficit in the right leg associated with a fusiform sciatic nerve mass in the posterior thigh The lesion, compressive in nature and situated entirely within the epineurium, was totally resected Histology revealed lymphocytic and plasmacellular inflammation as well as extensive fibrosis and collagen deposition The patchy infiltrate consisted equally of CD2, CD3, CD5, and CD7 positive T-lymphocytes as well as CD20-and CD22-positive B-lymphocytes expressing both kappa and lambda immunoglobulin light chains A selective biopsy of the encompassed and compressed nerve fascicles demonstrated both myelin loss and axonal injury The second case was that of an 18-year-old woman with focal enlargement of a radial nerve by an epineurial infiltrate of multinucleate histiocytes and T as well as occasional B lymphocytes No etiology was apparent in either case The differential diagnosis includes non-neoplastic processes (amyloidoma and tuberculoid leprosy) as well as tumors (benign and malignant peripheral nerve sheath tumors, lymphoma) Although rare, inflammatory pseudotumors must be included in the differential diagnosis of tumor-like lesions of peripheral nerve

Bernd W. Scheithauer

Papers

Intermediate filaments in the human pituitary gland: an immunohistochemical study.

Acoustic schwannoma and pregnancy: A DNA flow cytometric, steroid hormone receptor, and proliferation marker study

Oligodendroglioma: the ultrastructural spectrum.

Inflammatory pseudotumor of nerve.

Alpha-subunit immunoreactivity in plurihormonal pituitary adenomas of patients with acromegaly.