ANOCEF's Atlas of Neuro-Oncology

Pr. Jean-Marie BRUCHER     Pr. Marcel CHATEL    
Dr. Françoise DARCEL     Dr. Ricardo THEAUX    

W.H.O. classification and grading

Despite the efforts of the W.H.O., the neuro-oncological concepts of numerous practitioners still appear to be too imprecise and variable as concerns terminology, definition of the main entities, and especially the significance of grading. Since publication of the first multilingual edition of the W.H.O. classification (K.J. Zülch, Histological typing of tumors of the central nervous system, World Health Organisation, Geneva, 1979) , the W.H.O. grading has often been confused with other "histological grading systems", such as that of Kernohan, that schematically designate the phases (or "stages") of dedifferentiation and increasing malignancy of a tumor. In contrast, W.H.O. grades must be considered a scale of malignancy reflecting the biological behavior and thus the "average" clinical prognosis of all tumor entities of the same grade. W.H.O. grades thus essentially have a prognostic value, and must be considered degrees of malignancy rather than stages of malignancy , even though certain grade III or IV tumors are the result of malignant transformation of a pre-existent tumor.

In the W.H.O. classification, slow-growing ( "low grade" ) tumors are classified either grade I or grade II, depending on whether they are circumscribed or not. Grade I tumors are circumscribed and thus have a better prognosis than grade II tumors, because the latter's poorly-defined margins or diffuse spread (erroneously referred to as "infiltrative") often preclude complete surgical resection. "High grade" tumors are characterized by rapid growth, either in anaplastic foci that develop in a low grade tumor, or in a large portion or the entire volume of the tumor mass. The appearance of anaplastic foci in a pre-existent grade I or II tumor results in classification as a grade III tumor. Marked signs of anaplasia in a large portion of the tumor or in the entire mass leads to classification as grade IV. Clinical experience has shown that grade III tumors progress less rapidly than grade IV tumors.

Particular attention must thus be paid to whether or not a tumor is circumscribed and to any signs of rapid growth (whether focal and moderate or generalized and intense). Histological signs of rapid growth include high cellularity, an elevated mitotic index, and anaplasia (loss of normal cellular differentiation). The last character precisely explains why grade III tumors are named "anaplastic". Necrosis and vascular proliferation are common in grade IV tumors, but they are inconstant and unreliable signs of rapid growth.

The following diagram summarizes the main features of tumors grouped together by grade. Grade I tumors are circumscribed (encapsulated or not) and exhibit moderate cellularity, reflecting slow growth. Grade II tumors also have moderate cellularity, but their margins are poorly-defined or diffuse. Grade III tumors contain one or more "anaplastic" foci that have developed within a pre-existent low grade tumor (I or II). Grade IV tumors are characterized by very marked anaplasia that may be generalized (up to the margins of the tumor mass) or focal (within a pre-existent tumor of lower grade).

BIOLOGICAL GRADING OF CNS TUMORS

WHO Grading Schema

In this atlas, the various tumor entities are also grouped together as a function of their grade, in keeping with increasingly common clinical practice. This original approach to neuro-oncological classification will undoubtedly be appreciated for its practical nature by neuropathologists and neuroradiologists alike, as well as by neurologists, neurosurgeons and even anatomopathologists, radiologists, oncologists, internists, and general practitioners. The terminology and the grading comply with the current recommendations of the World Health Organization (P. Kleihues, P.C. Burger, B.W. Scheithauer, Histological typing of tumors of the central nervous system, Springer, Berlin, 1993) .

As a reminder, grade I tumors are benign because they have a slow growth pattern and are circumscribed. The tumor entities indexed in this group are more numerous than in the other three groups, and were thus subdivided into four categories according to their main localization:

* benign intraparenchymal tumors (I.01 to I.08)
* benign ventricular tumors (I.09 to I.13)
* benign tumors of the nerve roots and the meninges (I.14 to I.24)
* benign tumors of the pineal gland and the pituitary region (I.25 to I.29)

Note that osseocartilaginous tumors are not included in this atlas.

Grade II tumors also have a slow growth pattern but, in contrast to grade I tumors, their margins are poorly demarcated. The more or less diffuse nature of these neoplasms adversely influences their prognosis owing to the difficulties encountered for complete surgical resection. The tumor entities in this group, less numerous than those of grade I, almost all have an intraparenchymal localization.

Low grade tumors (groups I and II) sometimes ulteriorly develop one or more anaplastic foci, characterized by increased cellularity, a higher mitotic index, and loss of cellular differentiation. The W.H.O. system classifies such "anaplastic" tumors as grade III because their growth pattern is more rapid than that of grade I or II tumors. However, as described hereafter, certain "highly anaplastic" foci exhibit histological signs of very rapid growth (very high mitotic index, marked anaplasia, necrosis), which results in classification as grade IV. Many low grade entities are susceptible to become anaplastic, but they are not all illustrated in this atlas (i.e. anaplastic gangliocytoma, anaplastic ganglioma, anaplastic epidermoid cyst, etc.). At neuroradiological examination, anaplastic foci show contrast uptake, provided they are sufficiently extensive. Accurate histologic diagnosis thus requires a search for the presence of one or more anaplastic foci within a grade I or II tumor. Stereotactic biopsies must include both components of these anaplastic tumors.

Malignant grade IV tumors exhibit histological signs of very rapid growth in all regions examined or in vast foci that have developed within a pre-existent tumor, which may have been diagnosed at previous surgery. In the case of an initial surgical procedure, the pre-existent, low grade tumor can be diagnosed if there are clinical signs of long duration, if calcifications are observed in the malignant tumor, or if quiescent and well differentiated areas of tumor are still visible next to the highly anaplastic foci.

This atlas presents the essential morphological features of each tumor entity, including the gross appearance when contributory. More detailed morphological data should be obtained from specialized works that can also provide useful information on histogenesis and genetics (cytogenetics and molecular genetics). Recent developments in these last fields help to explain the definition and the origin of several tumor entities (in particular, consult P. Kleihues & W.C. Cavenee (eds), Pathology & Genetics. Tumors of the Nervous System, International Agency for Research on Cancer, Lyon, 1997) .

The histological methods most commonly used for the illustrations in this atlas are hematoxylin-eosin (HE) stain and Masson trichrome stain (MT). Other techniques are illustrated in certain cases. For immunohistochemical techniques, the antigenic marker is designated by the abbreviation commonly used in the literature. The magnification indicated corresponds to the primary format (24 x 36 mm slide). Instructions for access to the various image formats and an explanation of the image numbering system can be found in the "Instructions for Use of the Atlas"


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