Mixed glioma
| Classification according to ICD-10 | |
|---|---|
| D33 | Benign neoplasm of the brain and central nervous system |
| D33.0 | Brain, supratentorial |
| D33.1 | Brain, infratentorial |
| D33.2 | Brain, unspecified |
| D33.3 | Cranial nerves |
| D33.4 | Spinal cord |
| D33.7 | Other parts of the central nervous system |
| D33.9 | Central nervous system, unspecified |
| D43 | New formation of unsafe or unknown behavior in the brain and central nervous system |
| D43.0 | Brain, supratentorial |
| D43.1 | Brain, infratentorial |
| D43.2 | Brain, unspecified |
| D43.3 | Cranial nerves |
| D43.4 | Spinal cord |
| D43.7 | Other parts of the central nervous system |
| D43.9 | Central nervous system, unspecified |
| C71 | Malignant neoplasm of the brain |
| C71.0 | Cerebrum, excluding lobes and ventricles |
| C71.1 | Frontal lobes |
| C71.2 | Temporal lobe |
| C71.3 | Parietal lobes |
| C71.4 | Occipital lobe |
| C71.5 | Cerebral ventricle |
| C71.6 | cerebellum |
| C71.7 | Brain stem |
| C71.8 | Brain, overlapping several areas |
| C71.9 | Brain, unspecified |
| C72 | Malignant neoplasm of the spinal cord, cranial nerves, and other parts of the central nervous system |
| C72.0 | Spinal cord |
| C72.1 | Cauda equina |
| C72.2 | Nn. olfactorii (I. cranial nerve) |
| C72.3 | N. opticus (2nd cranial nerve) |
| C72.4 | Vestibulocochlear nerve (VIII. Cranial nerve) |
| C72.5 | Other and unspecified cranial nerves |
| C72.8 | Brain and other parts of the central nervous system, overlapping several areas |
| C72.9 | Central nervous system, unspecified |
| ICD-10 online (WHO version 2019) | |
Mixed gliomas or oligoastrocytomas are diffuse gliomas in middle adulthood that have parts of an oligodendroglioma and an astrocytoma . According to the WHO classification of tumors of the central nervous system, they are divided into oligoastrocytomas WHO grade II and anaplastic oligoastrocytomas WHO grade III. Oligoastrocytomas are classified as oligodendroglial tumors.
causes
The cause of oligoastrocytomas is unknown. There are individual case reports of oligodendroglial tumors which occurred in the context of scars after CNS radiation or brain injuries. Individual oligodendroglial tumors have also been observed in patients with multiple sclerosis . Oligodendroglial tumors occurred more frequently in singular families.
Clinical symptoms
As with all gliomas, patients experience general signs of intracranial pressure such as headache, persistent nausea, and vomiting . Many patients first become conspicuous through an epileptic seizure . There are also focal symptoms, depending on the location of the tumor in the brain.
Imaging
Preoperative magnetic resonance imaging (MRI) with and without contrast agent administration has meanwhile become the primary imaging method. In some cases, magnetic resonance imaging is also recommended postoperatively. Contrast enhancement in the tumor is interpreted as a sign of anaplasia. The computed tomography (CT) also is used.
histology
For the histological properties and the grading of the oligodendroglial component see → Oligodendroglioma and for the astrocytic component see → Astrocytoma .
Oligoastrocytomas are neuropathologically ungrateful tumors because there are no sharply defined boundaries between the proportion of the oligodendroglial and the astrocytic component. Although a large number of limits have been suggested, such a definition is practically impossible: A histological section is always only a two-dimensional section of a spatial process. The pathologist assesses this section assuming that it is representative of the remaining tissue. But a quantitative assessment inevitably fails with such a concept.
Another aggravating problem in histopathological diagnostics is the reactive astrocytes in a glial tumor. These cells are a response of the non-tumorous glia of the CNS to the damage caused by the tumor. Reactive astrocytes are e.g. Sometimes difficult to differentiate from astrocytic tumor cells.
It is z. A distinction was made between biphasic oligoastrocytomas with a clear oligodendroglial and an astrocytic component and between diffuse oligoastrocytomas. In these tumors, individual astrocytic tumor cells are found between oligodendroglial tumor cells. However, it has not yet been possible to show that these individual astrocytic tumor cells are actually tumor cells and non-reactive astrocytes (see above). Because of this non-sharp demarcation between oligodendrogliomas and oligoastrocytomas, the incidence of oligoastrocytoma varies considerably; some neuropathologies try to avoid the diagnosis to a large extent, others make it more frequently than that of oligodendroglioma.
Another problem of oligoastrocytomas is the graduation: according to the WHO definition of astrocytic tumors, the detection of more than one mitosis is an important reason to graduate the tumor as WHO grade III anaplastic astrocytoma. In the case of oligodendrogliomas, however, several mitoses are allowed for a WHO grade II. It can therefore happen that the same tumor is assessed as WHO grade II oligodendroglioma by one neuropathology and as WHO grade III anaplastic oligoastrocytoma by the other. However, this requires different therapeutic concepts (see below).
Immunohistochemistry
The most important immunohistochemical markers are GFAP-specific antibodies, which mark astrocytic but not oligodendroglial tumor cells. Furthermore, the rate of proliferation should be determined using Mib1-specific antibodies.
Molecular pathology
Oligoastrocytomas usually have either an oligodendroglial ( allele loss 1p / 19q) or an astrocytic genotype (TP53 mutations). These two pathogenetic changes are exclusive. Furthermore, it could be shown that both histological components of the oligoastrocytoma have an identical genotype, i. H. the oligoastrocytoma is of monoclonal origin. In the course of the transition to anaplasia , homozygous deletions on the chromosomal arm 9p with the tumor suppressor genes CDKN2A and CDKN2B are seen. Allele losses also occur on chromosome 10 .
Cell of origin
The cell of origin of the oligoastrocytoma is not known. It is questionable whether these are tumors that arise from the glia , as the name of the glial tumors suggests. Rather, glial tumors are malignant transformed glial progenitor cells or even degenerate stem cells . The current scientific literature offers some reference for this. An interesting observation is the evidence of monoclonality of oligoastrocytomas. From the observation that both histological components show the same genetic changes, it can be concluded that the postulated degenerate precursor cell has the potential to adopt either an astrocytic or an oligodendroglial phenotype . Thus, the hypothesis can be formulated that the glial phenotype is less a consequence of a specific pathogenetic genotype, but is more determined by unknown tissue environmental factors. In the exaggerated form, oligoastrocytomas can possibly be used as a model to show that the morphological classification of glial tumors is further removed from the actual tumor than the genetic classification.
therapy
The therapy of oligoastrocytomas is the same as that of oligodendrogliomas and astrocytomas . The focus is on the surgical resection of the tumor. Due to the infiltrative growth character of gliomas, a cure through surgery is hardly possible. However, resection reduces the tumor volume so that, among other things, the intracranial pressure problem is alleviated and there is less cell mass that can further dedifferentiate. In the case of anaplastic oligoastrocytomas WHO grade III, radiation therapy of 50 to 60 Gy is also recommended. BCNU chemotherapy is an alternative. Obviously, the oligoastrocytomas with an oligodendroglial genotype (allele loss 1p / 19q) are significantly more vulnerable to radiation and chemotherapy than such tumors without losses. A determination of allele losses on 1p and 19q should be aimed for.
forecast
Due to the diagnostic uncertainty of oligoastrocytic tumors, it is difficult to compare different studies. The detection of allele losses on 1p and 19q may be more important for the prognosis than the histology. Overall, the prognosis of oligoastrocytomas is similar to that of oligodendrogliomas and astrocytomas .
literature
- P. Kleihues, WK Cavenee: Pathology and genetics of tumors of the nervous system. 2nd edition. IARC Press, Lyon 2000
- G. Reifenberger, DN Louis: Oligodendroglioma: toward molecular definitions in diagnostic neuro-oncology. In: J Neuropathol Exp Neurol . (2003); 62, pp. 111-126. Review.
- C. Hartmann, W. Mueller, A. von Deimling: Pathology and molecular genetics of oligodendroglial tumors. In: J Mol Med . 2004 Oct; 82 (10), pp. 638-655. Review.
- CI Huang, WH Chiou, DM Ho: Oligodendroglioma occurring after radiation therapy for pituitary adenoma. In: J Neurol Neurosurg Psychiatry . (1987); 50, pp. 1619-1624.
- C. Perez-Diaz, A. Cabello, RD Lobato, JJ Rivas, A. Cabrera: Oligodendrogliomas arising in the scar of a brain contusion. Report of two surgically verified cases. In: Surgical Neurology . (1985); 24, pp. 581-586.
- MT Giordana, A. Mauro, R. Soffietti, M. Leone: Association between multiple sclerosis and oligodendroglioma. Case report. In: Ital J Neurol Sci. (1981); 2, pp. 403-409.
- JM Kros, ST Lie, SZ Stefanko: Familial occurrence of polymorphous oligodendroglioma. In: Neurosurgery . (1994); 34, pp. 732-736.
- JA Kraus, J. Koopmann, P. Kaskel, D. Maintz, S. Brandner, J. Schramm, DN Louis, OD Wiestler, A. von Deimling: Shared allelic losses on chromosomes 1p and 19q suggest a common origin of oligodendroglioma and oligoastrocytoma . In: J Neuropathol Exp Neurol. (1995); 54, pp. 91-95.
- W. Mueller, C. Hartmann, A. Hoffmann, W. Lanksch, J. Kiwit, J. Tonn, J. Veelken, J. Schramm, M. Weller, OD Wiestler, DN Louis, A. von Deimling: Genetic signature of oligoastrocytomas correlates with tumor location and denotes distinct molecular subsets. In: Am J Pathol . (2002); 161, pp. 313-319.
- MN Hart, CK Petito, KM Earle: Mixed gliomas. In: Cancer . (1974); 33, pp. 134-140.
- JS Smith, A. Perry, TJ Borell, HK Lee, J. O'Fallon, SM Hosek, D. Kimmel, A. Yates, PC Burger, BW Scheithauer, RB Jenkins: Alterations of chromosome arms 1p and 19q as predictors of survival in oligodendrogliomas, astrocytomas, and mixed oligoastrocytomas. In: J Clin Oncol . (2000); 18, pp. 636-645.
- JC Buckner, D. Gesme, Jr., JR O'Fallon, JE Hammack, S. Stafford, PD Brown, R. Hawkins, BW Scheithauer, BJ Erickson, R. Levitt, EG Shaw, R. Jenkins: Phase II trial of procarbazine, lomustine, and vincristine as initial therapy for patients with low-grade oligodendroglioma or oligoastrocytoma: efficacy and associations with chromosomal abnormalities. In: J Clin Oncol. (2003); 21, pp. 251-255.
- C. Dai, JC Celestino, Y. Okada, DN Louis, GN Fuller, EC Holland: PDGF autocrine stimulation dedifferentiates cultured astrocytes and induces oligodendrogliomas and oligoastrocytomas from neural progenitors and astrocytes in vivo. In: Genes Dev. (2001); 15, pp. 1913-1925.
- D. Maintz, K. Fiedler, J. Koopmann, B. Rollbrocker, S. Nechev, D. Lenartz, AP Stangl, DN Louis, J. Schramm, OD Wiestler, A. von Deimling: Molecular genetic evidence for subtypes of oligoastrocytomas. In: J Neuropathol Exp Neurol. (1997); 56, pp. 1098-1104.
