Skeletal spread of an anaplastic astrocytoma (WHO grade III) and preservation of histopathological properties within metastases.
BACKGROUND
The incidence of extraneural metastases of glioma is low. Metastases occur at different sites and, infrequently, as diffuse bone marrow infiltration. Direct contact of a glioma with extrameningeal tissues might be a reason for extraneural metastases. However, the role of haematogenous spread remains unclear.


METHODS
We report on a young patient who suffered from a left frontal anaplastic WHO grade III astrocytoma, which was treated with gross total resection and irradiation (60 Gy). No local relapse occurred during the following course, but a diffuse infiltration of the bone marrow was diagnosed 12 months after the initial diagnosis. The patient died 6 months later, as a result of hypercalcaemia and pancytopenia. The histopathological properties of the tumour and its bone metastases were analysed, as well as the mutations of the isocitrate dehydrogenase 1 gene (IDH1). To study the route of tumour dissemination, the peripheral blood of the patient was analysed for circulating tumour cells (CTCs).


RESULTS
This study describes a rare case of an extraneurally metastasised WHO grade III anaplastic astrocytoma. The occurrence of bone marrow infiltration coinciding with the finding of a stable intracranial tumour is a notably unusual situation. The properties of the primary tumour were maintained within the metastases in our patient. No CTCs were found in the peripheral blood at one random time point after the diagnosis of bone metastases.


CONCLUSIONS
Despite young patient age, a stable intracranial course with a single location and mutations in the IDH1 gene, the patient's overall survival was short at 18 months after diagnosis. This finding illustrates the therapeutic dilemma in patients with bone marrow involvement complicating the use of alkylating agents, such as temozolomide. Repeated and systematic blood sampling in a large cohort of patients is needed for the detection of CTCs in glioma patients with systemic tumour spread. Future studies investigating how intrinsic factors in glioma cell biology cause rare metastases in these tumours are needed.
Department of Neurological Surgery, University Medical Centre Hamburg-Eppendorf, Germany. t.martens@uke.uni-hamburg.de
T
T
Martens
J
J
Matschke
C
C
Müller
S
S
Riethdorf
S
S
Balabanov
M
M
Westphal
O
O
Heese
D000328:Adult; D001254:Astrocytoma / Q000473:pathology* / Q000601:surgery; D015415:Biomarkers; D001706:Biopsy; D019046:Bone Marrow Neoplasms / Q000473:pathology / Q000601:surgery; D001859:Bone Neoplasms / Q000473:pathology* / Q000556:secondary*; D001932:Brain Neoplasms / Q000473:pathology* / Q000601:surgery; D002097:C-Reactive Protein / Q000378:metabolism; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D017809:Fatal Outcome; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D006934:Hypercalcemia / Q000209:etiology; D007150:Immunohistochemistry; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D008279:Magnetic Resonance Imaging; D008297:Male; D009360:Neoplastic Cells, Circulating; D019635:Neurosurgical Procedures; D016133:Polymerase Chain Reaction; D014057:Tomography, X-Ray Computed; D025521:Tumor Suppressor Proteins / Q000235:genetics
D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D025521:Tumor Suppressor Proteins; D002097:C-Reactive Protein; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes