gms | German Medical Science

Objective: Cerebral glioblastoma patient therapy has improved over the past decade, whereas the prognosis of gliosarcoma patients often treated similarly tends to remain poor. The therapeutic options in the cases of secondary spinal glioblastoma or gliosarcoma are of salvage nature and the disease tends to be fatal. Targeted therapy may improve the prognosis. This in turn requires a specific diagnostic tool. The microarray-based comparative genomic hybridization (array-CGH) may allow tumor profiling and accurate distinction.

Method: We report of a female patient 66 years at the diagnosis of a frontal glioblastoma WHO Grade IV. The standard concomitant radiochemotherapy had to be disrupted for 2 months due to wound infection. After repeated wound surgery, at a PFS of 6 months under Temozolomide chemotherapy the local recurrent tumor was surgically removed. The histological evidence of a biphasic tissue pattern with alternating areas of glial and mesenchymal differentiation allowed the diagnoses of a gliosarcoma. Within further 9 months spinal manifestation occurred at the thoracic spine level. Histological analysis hereof, showed almost complete loss of the glial tumor component. Under spinal radiation we saw rapid spinal tumor progressive disease whereas the cerebral tumor was stable. Assuming sarcoma, salvage therapy with Doxorubicin was implemented. Unfortunately, there was further tumor progress at both the spinal and cerebral tumor location. At this stage of the disease, no further active cancer therapy was performed. This ambiguous tumor characteristic and therapy resistance caused us to perform an array-CGH analysis on the extirpated fresh-frozen tumor specimens of the cerebral and spinal tumors. Using the microarray-based comparative genomic hybridization technology the copy number alterations of the cDNA was profiled.

Results: Genomic alterations consisting of gains and losses of the chromosomal regions were detected. In all the analyzed tumors, recurrent regions of DNA copy number alteration were identifiable and consistent. Both cerebral and spinal tumors showed losses of chromosomes 10, and losses of large portions of chromosomes 13 and 22. This matches described patterns particular to glioblastomas.

Conclusions: This case depicts that in difficult and rare diagnostic situations, the genotypic profiling using an array-CGH may help in setting an accurate tumor diagnosis, which in turn influence the therapy decision.