Histomorphometry of tumour cell nuclei in astrocytomas using shape analysis, densitometry and topometric analysis

Although tumour cell nuclei are important histological structures for grading of astrocytomas according to the WHO-classification of brain tumours, there is no reported morphometric study of astrocytomas which describes quantitatively the four main morphologic criteria of tumour cell nuclei: size, shape, texture (densitometric characteristics) and spatial relationships between the nuclei (topometric analysis). Using a set of morphometric parameters describing these criteria as well as the Ki67-proliferation index, 74 astrocytomas from 74 patients were studied by means of a digital image analysis system. The objective of the study was to test, if these morphometric parameters were sufficient for statistical discrimination between pilocytic astrocytomas WHO-grade I, astrocytomas grade II and anaplastic astrocytomas grade III. Our results showed a correct reclassification of 97.3% (72/74) of the cases with respect to the tumour grade by means of cross-validated discriminant analysis. Morphometric parameters characterizing nuclear shape (shape factors, Fourier-amplitudes) showed the most prominent differences between the three groups of cases, followed by topometric parameters (number of neighbours per nucleus, distances between the nuclei). Less pronounced differences between the tumour grades were found for parameters characterizing nuclear size, nuclear texture and the Ki67-proliferation index. In conclusion, the present morphometric procedure provided good discrimination between the tumour grades, supporting the view that histomorphometry of tumour cell nuclei could be a valuable tool for grading of astrocytomas.     

Clinical significance of quantitative studies of cell nucleus in lymphocytes of the cerebrospinal fluid in leukemia]

The nuclear content, area and perimeter of the nucleus of lymphocytes in the C.S.F. were determined quantitatively by means of image analysis technique. 26 cases of central nervous system lymphocytic leukemia (CNLL), and 8 suspected cases were studied, other 56 cases who did not have leukemic and neoplastic diseases and had normal C.S.F. lymphocytes were taken as a control. Our data showed that all the mean nuclear content (MNC), mean nuclear area (MNA), mean nuclear perimeter (MNP), and the maximum and minimum nuclear contents of the 2 groups of former patients were obviously higher than those of the contral (P less than 0.01). These results presented suggestion that the image analysis technique can be used for differentiating the leukemic lymphocyte from normal one especially in suspected cases, and thus the diagnosis of CNLL might be improved.     

Computerized classification of gliomas by automated microscope picture analysis (AMPA)

Summary A karyometric analysis of 346 Feulgenstained biopsy preparations (4 m) of gliomas (glioblastomas; fibrillar, protoplasmic and gemistocytic astrocytomas; pilocytic astrocytomas; oligodendrogliomas) using the automated microscope picture analysis (AMPA) was carried out in continuation of a previous paper (Martin and Voss 1982). Fifteen morphometrical, densitometrical and mitotic preparation features were evaluated:Parameters of the spatial density of nuclei — KRNZ, AREA; Parameters of nuclear size — KOFL, KFRL, P 250; Parameters of nuclear shape — FOFK, FOFR, P 150; Parameters of chromatin density — EXTU, EXTS, EXSR, EXTM, EXMR; Mitotic parameters — MITZ, VHMK.On the basis of these and some additional data (TIM 1, AGE, SEX, LOC) an automatic classifier has been elaborated which differentiates in an optimum manner the four tumour classes under study from one another. This classifier was elaborated on 172 slide preparations that had, on four occasions, been consistently classified and graded by three pathologists (classified sample). Subsequently, the classifier was used for the automatic classification of the whole material (346 slide preparations). From among the classified sample (n=172) the computer classified 159 tumours (92.4%) correctly and rejected 13 (7.6%); no tumour was classified wrongly. From among the whole material 295 tumours (85.3%) were classified correctly, 26 (7.5%) were rejected and 25 (7.2%) were classified wrongly.The following were the most important parameters for the discrimination and hence the automatic classification of the tumour classes: FOFK (form factor), FOFR (relative variation of form factors), KRNZ (number of nuclei), KFRL (relative variation of nuclear areas) and EXTS (mean extinction sum of tumour cell nuclei).Consequently, karyometrical data permit a reliable classification of glioblastomas and other gliomas. With the help of AMPA the necessary karyometrical data can be obtained in an easily objectifyable and reproducible manner requiring just about 10 min for each slide preparation.     

Distribution of nuclear size and internuclear distance are important criteria for grading astrocytomas

AIM: The differentiation between low-grade astrocytomas and anaplastic astrocytomas is susceptible to considerable inter-observer variability. In order to contribute to a better standardization of astrocytoma-grading based on quantitative data, the present study focuses on two important aspects not being considered in previous morphometric studies: elaboration of a decision flow chart for tumor grading based on morphometric parameters and appropriate cut-off-values, easily performed using low-cost equipment such as measuring oculars; investigation of the distribution (histograms) of parameters describing nuclear size and internuclear distance, which had been represented in previous studies by their mean and standard deviation only. MATERIAL AND METHODS: At least 300 tumor cell nuclei per case were investigated in paraffin sections from surgical specimen of 75 patients with astrocytomas WHO grade II (n = 23) and anaplastic astrocytomas WHO grade III (n = 52) by means of a digital image analysis system. RESULTS: The morphometric data showed significant differences between both groups of tumors. According to multivariate analysis, the best contribution to tumor grading was achieved by means of parameters concerning the distribution of values for nuclear diameters and internuclear distances. A decision tree was constructed using a knowledge based algorithm, which provided astrocytoma grading based on the distribution of values for nuclear diameter, as well as the numerical nuclear density and proliferation index. Measurements using a measuring ocular took an acceptable amount of time (1.5 hour per case) and showed good reproducibility when compared with measurement by means of digital image analysis. CONCLUSION: The study demonstrates that a morphometric examination of tumor cell nuclei in paraffin sections supports the clinically important differential diagnosis between low-grade and high-grade astrocytomas. The method for classification and the data published in the present study constitute a good basis for a standardized and reproducible grading procedure for astrocytomas, which can be performed in any histologic laboratory even without a digital image analysis system.     

A clinicopathological study of 323 patients with oligodendrogliomas

All patients with oligodendrogliomas (554) from the repository of the Armed Forces Institute of Pathology were retrospectively analyzed. The pathological diagnosis was confirmed in 323 patients and each case was graded according to a previously established grading system. The clinical features of these 323 verified cases of oligodendroglioma are presented, analyzed, and compared with findings in previous studies. There is a significant age skew according to tumor grade, with 68% of patients with grade A tumors under 40 years and 83% of patients with grade D tumors over 40 years of age. Headache was the most common symptom, followed by seizure, visual loss, papilledema, paralysis, and dementia. No symptoms showed a statistically significant correlation with tumor grade. However, tumor grading allowed significant prognostic statements to be made. Attention is drawn to several often neglected symptoms of oligodendrogliomas: ataxia, hemorrhage, stroke, and cerebrospinal fluid spread. This is, to our knowledge, the largest clinicopathological study of oligodendrogliomas to date.     

Automated image analysis of gliomas an objective and reproducible method for tumor grading

Summary A system of automated microscopic picture analysis was used in an examination of 272 gliomas (70 glioblastomas, 91 astrocytomas, 56 pilocytic astrocytomas or spongioblastomas, and 55 oligodendrogliomas). The specimens were prepared as Feulgen sections, 4m in thickness. Thirteen morphometricdensitometric parameters of tumor cell nuclei were tested together with two mitotic parameters. Objective and reproducible data on numerical nuclear density (KRNZ, AREA), nuclear size (KOFL, KFRL, P250), nuclear shape (FOFK, FOFR, P150), optical density (EXTU, EXTS, EXSR, EXTM, EXMR), and mitotic activity (MITZ, VHMK) of the gliomas were obtained from the morphometric-densitometric parameters. All gliomas but glioblastomas were subdivided by four tumor grades. The morphometric-densitometric and mitotic data recorded were statistically checked, depending on tumor grade (Student'st-test, Wilcoxon's test, =0.05). Numerical nuclear density, deformation of nuclei, and mitotic activity were found to grow with significance along with increasing tumor grade up to glioblastoma. The relative standard deviation (SD) of nuclear size (KFRL), relative SD of shape factors (FOFR), and relative SD of extinction sums (EXSR) are high-accuracy parameters for the pathologist to describe variability of sizes, polymorphism, and polychromasia of nuclei. These parameters show a significant increase of values in parallel with rising tumor grades, with maximum values being recordable from cases of glioblastomas. In cases of astrocytomas, optical values of nuclei decrease along with rising tumor grade. The data thus obtained were used as reference values for objective, reproducibel automatic glioma grading. The classifier method, described in an earlier publication, proved to be more effective than the regression method.     

Oligodendrogliomas with neurocytic differentiation. A report of 4 cases with diagnostic and histogenetic implications

Oligodendroglioma represents a distinct type of diffuse glioma with a relatively favorable prognosis. Although an O2A-like glial progenitor cell of origin has been suggested, a neuronal-oligodendroglial progenitor cell is also of interest, particularly because variable degrees of neuronal marker expression have been reported in typical oligodendrogliomas. We present 2 female and 2 male patients (ages 34-54) with frontal lobe oligodendrogliomas containing a) morphologically distinct collections of small round cells with hyperchromatic nuclei, b) well-formed Homer Wright-like and perivascular rosettes, and c) demonstrable neuronal differentiation by immunohistochemistry and/or electron microscopy in the rosette-associated regions. Unlike extraventricular neurocytomas, these cases featured an infiltrative growth pattern and a classic oligodendroglioma immunophenotype in non-rosette bearing portions of each tumor. FISH analysis demonstrated chromosome 1p and 19q codeletions in 3 (75%) cases, both in regions with and without rosettes. Recurrences were common, although all patients are currently alive 4 months to 13 yr from initial diagnosis. Based on clinicopathologic and genetic features, we diagnosed these tumors as oligodendrogliomas with neurocytic differentiation. However, it is unclear whether they represent a) gliomas with divergent neuronal differentiation, b) a distinctive form of glioneuronal neoplasm, or c) a reflection of glioneuronal histogenesis in oligodendrogliomas in general. In any case, their occurrence suggests a histogenetic overlap between oligodendroglioma and extraventricular neurocytoma not previously recognized.     

Morphology of proliferating and non‐proliferating tumor cell nuclei in glioblastomas correlates with preoperative data from proton‐MR‐spectroscopy

In contrast to the growing interest in proton‐MR‐spectroscopy (¹HMRS) for preoperative examination of patients with brain tumors, there is nearly no knowledge about a correlation between data from ¹HMRS and histomorphology as confirmed by quantitative morphological methods. Whether a correlation can be confirmed between data from ¹HMRS and quantitative histomorphology of glioblastomas representing the most frequent type of brain tumors was investigated in the present study. Furthermore, it was of interest, whether correlations between spectroscopic data and histomorphology can be confirmed for proliferating and non‐proliferating tumor cell nuclei independently. Using stringent inclusion criteria for this study, 24 patients were investigated by means of preoperative ¹HMRS and by means of digital image analysis of paraffin sections from the surgical specimen. Proliferating and non‐proliferating tumor cell nuclei were investigated separately in the region with the highest proliferative activity in each tumor using immunohistological staining for the proliferation marker Ki67. Main results showed highly significant correlations between total creatine and variables of nuclear size, as well as correlations between choline and variables of nuclear shape. These results were confirmed for both proliferating and non‐proliferating tumor cell nuclei. A significant correlation between N‐acetyl‐aspartate level and topometric variables (number of neighbors per nucleus, variables describing distances between tumor cell nuclei) was confirmed for proliferating tumor cell nuclei. Discriminant analysis provided a good separation of cases with high and with low values for these spectroscopic variables based on histomorphometric data. In conclusion, the results confirm a direct correlation between data from preoperative ¹HMRS and histomorphological characteristics of glioblastomas supporting the biological relevance of spectroscopic data for the examination of brain tumor patients.     

Low grade diffuse gliomas: Shared cellular composition and morphometric differences

Low grade diffuse gliomas arising in the brain are challenging to treat because of their ability to infiltrate adjacent tissue. We attempted to clarify the cellular composition and histopathological features of low grade gliomas by utilizing morphometric and immunohistochemical analyses. Seventy‐eight cases of low grade gliomas were examined including 21 diffuse astrocytomas (DA), 36 oligodendrogliomas (OL), and 21 oligoastrocytomas (OA), based on the WHO classification system. Moreover, OL were subdivided into three types based on the morphological characteristics advocated by Daumas‐Duport et al.: OL type I, OL type II, and OL type III. The cellularity, nuclear form factor, and conditional entropy corresponding to the nuclear pleomorphism were measured in each sample by the image analysis software “Gunmetry.” Twenty‐two cases were immunohistochemically analyzed for the expression of several antigens. Morphometric data indicated that the cellularity of OL type II was significantly higher than that of DA, and that the conditional entropy of OL type III was significantly lower than that of DA. Although the results of the immunohistochemical studies were almost consistent with previous reports, there were significant differences in the expression of GFAP, nestin and p53 between DA and OL. Double immunostaining revealed that expression of Olig2 and GFAP, and Olig2 and nestin was mutually exclusive in most glioma cells. Moreover, the coexpression of nestin and GFAP occurred in DA and OA, but not in OL. We conclude that each glioma include cells expressing GFAP, cells expressing nestin, and cells expressing Olig2 in a characteristic proportion for each tumor type. We suggest that diffuse gliomas share cellular compositions in different ratios and that they can be distinguished by morphometrical analysis.     

Karyometry and cytophotometry of oligodendroglial DNA in the corpus callosum of rats treated with vicristine during the second part of foetal life

The effect of transplacentally administered vincristinee on postnatal developmental events occurring in the oligodendroglial cell nuclei of the corpus callosum were studied by means of an automatic analyzer of microscopic pictures "Morphoquant" (VEB Carl Zeiss Jena, GDR). Karyometric and cytophotometrically determined developmental changes of the DNA content were studied in both, the vincristine treated and control rats aged 3, 7, 14, 21 and 28 days. vincristine was administered to pregnant rats four times during the second term of gestation, the single dose containing 0.01 mg of Vincristin per kg of body weight. In the Vincristin treated animals we have found an advanced developmental increase of the perimeter, the surface and convexion areas of oligodendroglial cell nuclei as well as statistically significant differences of parameters characterizing the nuclear shape. In comparison with control animals, the intoxicated ones demonstrated a higher DNA content in oligodendroglial cell nuclei both during the premyelinating (7 days postnatal) and during the early stage of myelination (14 and 21 days postnatal).     

Flow-through fluorocytophotometry of different brain tumours

Summary The flow-through cytophotometric method was used to investigate the single-cell DNA content in 60 tumours of the CNS and allied structures (9 meningiomas, 5 ependymomas, 15 astrocytomas, 11 anaplastic astrocytomas, 8 glioblastomas, 7 medulloblastomas, 2 oligodendrogliomas, 1 anaplastic oligodendroglioma, and 2 neurinomas). The cytophotometric parameters were correlated with morphological and clinical data of the tumours. The results are summarised in Tables 1–7. With regard to the DNA content of their cell nuclei, the gliomas present a behaviour similar to tumours in other organs, but in the present study the cytophotometric signs of malignancy in gliomas are not so evident as in carcinomas or sarcomas. The information obtained by flow cytophotometric methods may be helpful in diagnosing the degree of malignancy in brain tumours.     

Phenotype versus genotype correlation in oligodendrogliomas and low-grade diffuse astrocytomas

Oligodendrogliomas typically show loss of heterozygosity (LOH) on chromosomes 1p and 19q, which correlates with their response to chemotherapy, whereas low-grade astrocytomas are characterized by frequent TP53 mutations and lack of sensitivity to alkylating therapeutic agents. Unequivocal histological distinction of low-grade diffuse astrocytomas from oligodendrogliomas and oligoastrocytomas is often difficult. To elucidate the relationships between morphological phenotype and genetic profile, we screened 19 oligodendrogliomas (WHO grade II) and 23 low-grade diffuse astrocytomas (WHO grade II) for TP53 mutations and LOH on 1p and 19q. In oligodendrogliomas, LOH on chromosomes 1p and/or 19q was found in 15 cases (79%) and TP53 mutation was detected in 4 cases (21%). The presence of a typical perinuclear halo in >50% of tumour cells and a chicken-wire vascular pattern were significantly associated with LOH on 1p or 19q (93% of cases). This suggests that oligodendrogliomas with classical histologic features are likely to have a better prognosis. In low-grade diffuse astrocytomas, LOH on chromosomes 1p and/or 19q was found in three cases (13%) and TP53 mutation was detected in ten cases (43%). Histologically, five low-grade astrocytomas (22%) contained small areas with oligodendroglial differentiation, but this did not correlate with the presence of TP53 mutations or LOH on 1p and 19q. In both oligodendrogliomas and astrocytomas, LOH on chromosomes 1p or 19q and TP53 mutation were mutually exclusive. Methylation of the promoter of the gene for O (6)-methylguanine-DNA methyltransferase (MGMT), a DNA repair protein, which confers resistance to chemotherapy with alkylating agents, was detected in 47% of oligodendrogliomas and 48% of low-grade diffuse astrocytomas. There was no correlation with LOH on chromosomes 1p/19q, suggesting that MGMT may not be a prognostic marker for oligodendrogliomas.     

Histopathological-molecular genetic correlations in referral pathologist-diagnosed low-grade "oligodendroglioma"

Allelic loss of chromosome 1p predicts increased chemosensitivity and better survival in oligodendroglial tumors. Clinical testing for 1p loss in oligodendroglial tumors at our hospital has allowed us to postulate that certain histological appearances are associated with 1p allelic status. Forty-four cases received for genetic testing were diagnosed by referring pathologists as pure low-grade oligodendroglioma. Central neuropathological review divided the series equally into 22 cases with classical oligodendroglioma histology and 22 with more astrocytic features. Molecular genetic analyses demonstrated 1p loss in 19 of 22 classic oligodendrogliomas (86%) and maintenance of both 1p alleles in 16 of 22 gliomas with astrocytic features (73%). No glial fibrillary acidic protein-positive cell type (gliofibrillary oligodendrocyte, minigemistocyte, cellular processes) was associated with 1p allelic status. Fourteen of the 44 cases were treated with chemotherapy at tumor progression: 3 "astrocytic" gliomas with 1p loss responded to PCV chemotherapy and 2 classic oligodendrogliomas that maintained both 1p alleles included a responder and a non-responder. These results suggest that histological appearance correctly predicts genotype in approximately 80% of low-grade gliomas, but that tumor genotype more closely predicts chemosensitivity. As a result, such objective molecular genetic analyses should be incorporated into patient management and into clinical trials of low-grade diffuse gliomas.     

Morphometric parameters of the superior colliculus of albino and pigmented rats

The superior colliculus (SC) or optic tectum of mammals consists of seven layers, numbered I-VII from superficial to deep, each of which has distinct connectivity patterns and electrophysiological response properties. The present study is devoted to a morphometrical analysis of neuronal diameters, densities, and numbers in different layers and regions of the SC of albino as well as pigmented rats in order to present a quantitative characterization of the collicular neuronal population involved in the different connectivities and functions of these compartments. The morphometric parameters were calculated from tracings of nuclei and cell bodies by means of Kontron-Videoplan equipment and a Micro PDP 11/23 computer. The mean soma diameter per superior colliculus appears to be 12.0 microns, the average neuronal density 70 cells per 0.001 mm3, and the total number of neurons about 600,000. The mean soma diameter gradually increases from superficial to deep layers (i.e., from 10.0 to 14.0 microns). Cellular density is highest in layer III, the retinal afferent layer (90 cells per 0.001 mm3), and decreases both in more superficial layers (to about 80 in layer I) and deeper layers (to about 44 in layer VII). About 25% of all collicular neurons are situated in layer II whereas layer I contains the lowest percentage of cells (4%). Rostrally within each collicular layer, cellular volumes are about 25% larger than caudally. On the other hand, neuronal densities are rostrally about 38% lower than caudally in all layers except for layers VI and VII. We conclude that collicular neurons, in contrast to collicular axons, are not arranged in distinct layers or clusters but basically establish a random network with only gradual transitions. In this respect, no statistically significant differences were observed between albino and pigmented rats.     

Morphophenotype of medulloblastoma in children and adults. The size of nuclei

OBJECTIVE: Uniform cells with round, regular nuclei characterize the typical histologic aspect of medulloblastoma. Enlargement of nuclei distinguishes the large-cell medulloblastoma variant and is associated with a poor prognosis in pediatric medulloblastomas. The aim of the present study was to compare the size of nuclei between pediatric and adult medulloblastomas by a morphometric analysis. MATERIAL AND METHODS: In 79 neurosurgical specimens of cerebellar medulloblastomas, the maximum nuclear diameter of the largest nuclei was measured. Measurements were performed with a digital-image analysis system. The measure of the maximum diameter was chosen in order to reduce the split cell error. RESULTS: The difference between the mean values in children and adults was statistically significant (p = 0,001). The distribution of maximum values measured in each case had two distinct peaks in the two age groups, in 3.5% of adult cases and in more than 30% of pediatric cases the maximum nuclear size was superior to 12 microm. CONCLUSIONS: The present results show that nuclei of tumor cells in pediatric medulloblastomas are larger than those in adult medulloblastomas and confirm that the phenotype of medulloblastoma is different in the two age groups. Distinct genetic events can, thus, underlie medulloblastoma in childhood and adult age, the prognostic role of genetic variables can differ by age.     

Descending projections from the superior olivary complex to the cochlear nucleus of the cat

Subdivisions of the cochlear nuclear complex give rise to a number of discrete projections to certain cell groups of the superior olivary complex and also received substantial descending projections from the periolivary nuclei. In the present study, we sought to determine by means of retrograde transport of horseradish peroxidase (HRP), and anterograde transport of radiolabeled protein, if the periolivary nuclei give rise to discrete projections to the various subdivisions of the cochlear nuclear complex. Following medium to large injections of HRP into the cochlear nucleus, irrespective of location, labeled cells were found in all periolivary nuclei bilaterally. In every case more than 40% of the labeled cells were found in the lateral nucleus of the trapezoid body on the same side and the ventral nucleus of the trapezoid body of both sides. Other periolivary nuclei contributing more than 5% of the total number of cells in individual cases were the contralateral lateral nucleus of the trapezoid body and the ipsilateral anterolateral and dorsal periolivary nuclei. Injections of tritiated leucine into periolivary nuclei gave rise to axonal labeling to the trapezoid body and the dorsal acoustic stria, usually bilaterally, and to terminal labeling that was widely distributed within the cochlear nuclear complex. In several cases with small injections, particularly in the lateral nucleus of the trapezoid body, the projections from the periolivary nuclei to the anteroventral and dorsal cochlear nuclei connected areas described as having similar best-frequency representation. The autoradiographic data corroborated the main results from the HRP experiments and provided additional information permitting these conclusions: the projections from the periolivary nuclei to the cochlear nuclear complex are organized tonotopically, at least in part; each periolivary nucleus (and perhaps individual cells), projects widely throughout the cochlear nuclear complex; the pattern of termination of projections from different periolivary nuclei to a given region of the cochlear nuclear complex are similar, as seen in autoradiograms, and the lateral and dorsal periolivary nuclei project mainly ipsilaterally, while the medial periolivary nuclei project bilaterally with a contralateral bias. The magnitude of these projections and their widespread distribution within the cochlear nuclear complex would suggest an important role for the descending projections in the normal functioning of the cochlear nucleus.     

Morphometric differences in the normal and low-intensity laser-irradiated spinal neurons of the cat

Structural parameters of neurons of normal and low-intensity Ge-Ne laser irradiated cat spinal cords were investigated by the morphometrical technique. Observed statistical alterations of the soma volume and nuclear surface values as well as cellular nuclear space relations were associated with the evoked changes in the cell metabolism.     

Cholinergic staining of bronchus- associated lymphoid tissue

The cholinergic staining of human bronchus-associated lymphoid tissue (BALT) was studied in humans. Morsels of the human lung (containing BALT) were harvested, after having obtained the appropriate approvals, during autopsies in 24 human subjects. The samples were stained by means of the enzymatic technique of acetylcholinesterase (AChE) and/or the monoclonal immunohistochemical method of choline acetyltransferase (ChAT). A morphometrical analysis was performed by means of quantitative analysis of images and statistical analyses of the data. AChE and proteins were also measured by biochemical assay. Our results demonstrate that both AChE and ChAT are localized in the BALT of young and old humans. These enzymes undergo age-related changes. The biochemical values of AChE are as follows: 22.3 +/- 2.5 international units in young subjects and 78.5 +/- 1.9 international units in old ones. The morphometrical values of AChE confirm the biochemical ones. The morphometrical data for ChAT are 31.6 +/- 1.4 conventional units in young subjects and 71.2 +/- 1.5 conventional units in old ones. Further results are needed to draw definite conclusions concerning the location and the distribution of these two enzymatic activities in BALT. In our opinion, the presence of AChE and ChAT in BALT can be both 'non-neuronal', with a role in general metabolism, and/or 'neuronal' with a role in neuroimmunomodulation.     

Neural antigens in oligodendrogliomas and dysembryoplastic neuroepithelial tumors

Oligodendrogliomas and dysembryoplastic neuroepithelial tumors (DNT) are frequently associated with epilepsies and share the presence of oligodendroglia-like cells with small round nuclei and optically empty perinuclear halos. The two entities may be difficult to discriminate in small surgical specimens and the origin and differentiation of the oligodendroglia-like cells has been controversial. To better characterize and distinguish the two entities we examined 25 oligodendrogliomas and 16 DNT immunohistochemically for the presence of the proliferation–associated Ki-67 antigen and the following neural antigens: the α₁ subunit of the GABA_A receptor (GABAR), N-methyl-d-aspartate receptor subunit 1 (NR1), glutamate decarboxylase, neuronal nuclei antigen (NeuN), the embryonal form of the neural cell adhesion molecule (E-NCAM), synaptophysin, neurofilament protein (NFP), and glial fibrillary acidic protein (GFAP). Labeling indices for the Ki-67 antigens were generally less than 1% in both entities. In oligodendrogliomas, more than 50% of the tumors contained NR1- or E-NCAM-positive oligodendroglia-like cells, whereas NeuN-positive tumor cells were never observed. In DNT, NeuN- and NR1-positive tumor cells were present in 44% of the cases each; E-NCAM positivity was less frequent (19%). In both entities, immunoreactivity of oligodendroglia-like cells for GABAR and glutamate decarboxylase was rare and positivity for synaptophysin and neurofilament protein was absent. Some GFAP-positive tumor cells were present in approximately 70% of the cases in both entities. Except for the striking difference in NeuN positivity, the immunohistochemical profiles of oligodendroglia-like cells in DNT and oligodendrogliomas largely overlap and the differential diagnosis continues to rest mainly on conventional histopathological features. The NR1 positivity and the recently reported generation of action potentials in oligodendroglioma cells are consistent with neuronal differentiation and may contribute to the high epileptogenic potential of oligodendrogliomas. Received: 10 April 1997 / Accepted: 7 June 1997