Extracranial glioblastoma with synchronous metastases in the lung, pulmonary lymph nodes, vertebrae, cervical muscles and epidural space in a young patient - case report and review of literature

Abstract

Background: Extraneural and extracranial metastases of glioblastoma (GB) are very rarely reported in the literature. They occur in only 0.2% of all GB patients.

Case presentation: We present a 40 year old caucasian male with secondary GB and first diagnosis of an astrocytoma world health organisation (WHO) grade II through stereotactic biopsy in 2006. He presented a new hemiparesis and a progress of the known mass lesion in 2008. Subtotal tumor resection was performed and the histological examination verified a GB. After combined radio- and chemotherapy the adjuvant temozolomide therapy was not started because of non-compliance. In 2011 a second local relapse was resected and 4 month later the patient presented a fast progressing tetraparesis. Cervical CT and MRI scan showed a mass lesion infiltrating the fifth and sixth vertebra with infiltration of the spinal canal and large paravertebral tumor masses. Emergency surgery was performed. By additional screening further metastases were detected in the thoracal and lumbal spine and surprisingly also in the lung and pulmonary lymphnodes. Palliative radio- and chemotherapy of the pulmonal lesions was completed, further antitumor therapy was rejected. The patient died 10 months after diagnosis of the extraneural metastases.

Conclusion: Especially young "long-term-survivors" seem to have a higher risk of extraneural metastasis from a GB and appropriate staging should be performed in these cases.

Figure 1

MRI of the brain at four timepoints. Each row resembles one examination with coronal acquisition of Flair (or T2, d), coronal contrast enhanced T1 and axial T2 (or Flair,l). After the first MRI in 2006 (a,e,i), showing a non-enhancing tumor, the patient underwent surgery and Astrocytoma WHO II° was diagnosed. In 2008, recurrent tumor (b,f,j) with striking contrast enhancement (f), correlating with histologically proven malignisation to Glioblastoma WHO IV°, was proven by MRI. Again tumor recurrence with rim enhancing tumor (c, g, k), was documented in 04/2011 and surgery was performed. In 08/2011 (d,h,l) MRI of the brain showed that the local contrast enhancing tumor was under control and not responsible for the deteriorating neurological status.

Figure 2

Cervical MRI and CT. In the first and second row sagittal and parasagittal images of the cervical spine in T2 (a), T1 (b) and T1 with contrast enhancement (c) are shown. There is a vertebral tumor infiltration of the fifth and sixth vertebra with a small invasion into the spinal canal (arrow). Larger tumor masses are found in the right lateral paravertebral space (second row). The tumor is hyperintens in T2 (a, arrowheads), hypointens in T1 and is partially contrast enhancing (arrowhead) with central non-enhancing parts (arrow in c). Remarkably the tumor grows through the intervertebral foramina in an hour glass pattern (last row, a) like a schwannoma even with enlargement of the osseous canal (arrow in b, axial CT). The infiltrated vertebrae are only slightly hyperdens compared to the normal vertebrae (arrowheads in c).

Figure 3

Intraoperative view 1. First step of decompression through laminectomie of C5. Arrows show the spinal cord. Arrowhead 1 shows extraspinal tumormass infiltrating paravertebral muscles. Arrowhead 2 shows intraspinal/extradural tumormass.

Figure 4

Intraoperative view 2. Segment C5 after bony decompression. Arrows point on spinal cord. Arrowheads show the intraspinal tumormass with GB typical necrosis and compression of the myelon.

Figure 5

Staging with CT of the thorax and spinal MRI. Contrast enhanced CT of the thorax (a-d) revealed rapidly growing (a in 05/2011, b-d in 08/2011) hilar (white arrow in a and b) and infracarinal (black arrow in a,b,d) lymph node metastases with infiltration of the right pulmonary artery. Additionally thromboembolic material was found in branches of both pulmonary arteries (arrow in c). MRI of the thoracic (e) and lumbar (f) spine showed multifocal osseous metastases (arrows).

Figure 6

Neuropathological results. In the astrocytoma WHO grade II (A II°, left row) density and pleomorphy of the tumor cells are low to moderately pronounced. Tumor cells express GFAP, MAP2c, WT1 and mutated IDH1 (R132H). A subpopulation of ca. 1-2% shows a nuclear accumulation of p53. The glioblastoma multiforme WHO grade IV (GB IV°) has a markedly increased density and pleomorphy, combined with an increased mitotic and proliferative activity, necrotic areas and microvascular proliferations. Compared to the primary astrocytoma, GFAP expression is present only in a subpopulation of tumor cells (ca. 65%) whereas nuclear accumulation of p53 occurs in more tumor cells (5-10%). In the relapsed glioblastoma (rGB IV°) the percentage of tumor cells expressing GFAP (ca. 30%) and WT1 (ca. 10%) decreases. Both, the epidural (emetGB IV°) as well as the pulmonal (pmetGB IV°) metastasis demonstrate expression of GFAP in 10-20% and of WT1 only in small groups and single tumor cells (<10%). Bars = 50 μm, corresponding to a magnification ×200.