Case Report: Metastases from glioblastoma multiforme disguised as a new primary malignancy

Case Summary

The patient is a 65-year-old gentleman with a history of glioblastoma multiforme (GBM) of the right frontotemporal lobes treated with radiotherapy and concurrent/adjuvant temozolomide (TMZ).  He recurred three months after that standard  chemoradiotherapy and was subsequently treated with bevacizumab, lomustine, and Gamma Knife stereotactic radiosurgery (GKSRS).  Following GKSRS, he was treated with Novocure TTF.  He later developed back pain, right-sided ptosis, and sinus congestion-like symptoms.  Spinal CT imaging showed multi-level spinal disease and MR imaging showed lesions in T8-10. Imaging of the head suggested a new paranasal sinus primary, suspicious for the origin of his metastatic disease.  He underwent a T7-8 kyphoplasty, the pathology from which showed GFAP, EMA, and CD138 positivity, suggestive but not definitive for metastatic GBM.  He represented with worsening sinus congestion/ptosis and repeat imaging of the head was obtained (see below).  Body imaging showed pulmonary and hepatic lesions. He underwent a biopsy of his paranasal sinus disease and the result was consistent with metastatic GBM.

Imaging Findings

An MRI of the head showed destructive changes in the paranasal sinuses with destruction of the left maxillary sinus and extension into the left retroantral fat, pterygopalatine fossa, and hard palate.  The left lamina papyracea and left orbital roof were being invaded by a soft tissue mass in the left orbit measuring 2.6x0.9cm which engulfed the superior rectus, oblique, and medial rectus muscles (Figures 1 and 2).

Figure 1. An MRI of the brain and sinuses in T2/FLAIR sequence showing abnormal soft tissue within the superior/medial aspect of the left orbit which appears to be contiguous with abnormal soft tissue filling the left frontal and ethmoid sinuses (solid white arrow).  There is a small amount of mass effect on the left medial rectus muscle.

Figure 2. An MRI of the brain and sinuses in SPGR post-contrast sequence again showing the left-sided abnormal soft tissue within the left ethmoid sinus with some mass effect on the left medial rectus muscle. Also imaged is abnormal soft tissue extending into the inferior aspect of the right orbit (solid white arrow) as well as a focus of intra-cerebral disease (dashed arrow).

Diagnosis

The patient was diagnosed with widely metastatic glioblastoma multiforme.  The initial suspicion was that he had developed a metastatic paranasal sinus primary, which was disproved by his biopsy.

Discussion

Glioblastoma (GBM) is the most common histology of malignant primary brain tumors in adults (1).  Despite advances in surgical, medical, and radiation therapies, the mortalities of GBM remain high, with a median survival ranging between 40 and 70 weeks (2) though recent clinical trial data has shown promise for improving outcomes with the addition of Novocure Tumor Treating Fields (3). The majority of GBM recur locally, and distant metastasis is rare, estimated to occur in less than 2% of patients (4). In spite of infrequent clinical presentation of distant metastases, circulating GBM cells have been detected in up to 20.6% of patients (5), which may lead to metastases to lymphatics, lungs, bone, liver, and other organs (6).  

A diagnosis of glioblastoma multiforme is a grim diagnosis from the first.  When patients survive long enough to develop metastatic disease, however, the median time from detection of metastatic disease to death has been reported to be as short as 1.5 months (6).  Though data is limited, there is a suggestion that metastases to the liver have a lesser impact on survival than metastases to the lung (7).  The treatment of choice for asymptomatic patients is systemic therapy, though when quality of life is being impacted by disease burden, surgical intervention or focal radiotherapy can be entertained, as was the case with our patient.

References

1. Quinn T. Ostrom, Haley Gittleman, Peter Liao, Chaturia Rouse, Yanwen Chen, Jacqueline Dowling, Yingli Wolinsky, Carol Kruchko, and Jill Barnholtz-Sloan. CBTRUS Statistical Report: Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2007–2011. Neuro Oncol 2014; 16: iv1-iv63.

2. Jigisha P. Thakkar, Therese A. Dolecek, Craig Horbinski, Quinn T. Ostrom, Donita D. Lightner, Jill S. Barnholtz-Sloan, and John L. Villano. Epidemiologic and Molecular Prognostic Review of Glioblastoma. Cancer Epidemiol Biomarkers Prev October 2014; 23:1985-1996.

3. Stupp R, Taililbert S, Kanner A, et al. Tumor treating fields (TTFields): A novel treatment modality added to standard chemo- and radiotherapy in newly diagnosed glioblastoma-First report of the full dataset of the EF14 randomized phase III trial. J Clin Oncol 33, 2015 (suppl; abstr 2000).

4. Mohamed H. Khattab, Ariel E. Marciscano, Simon S. Lo, et al. Antiangiogenic Therapies and Extracranial Metastasis in Glioblastoma: A Case Report and Review of the Literature. Case Reports in Oncological Medicine 2015; 2015: 431819.

5.C. Muller, J. Holtschmidt, M. Auer et al. Hematogenous dissemination of glioblastoma multiforme. Science Translational Medicine 2014; 6 (247): 247ra101.

6. Melody Lun, Edwin Lok, Shiva Gautam, Erxi Wu, Eric T. Wong. The natural history of extracranial metastasis from glioblastoma multiforme. Journal of Neuro-Oncology 2011; 105 (2): 261-273.

7. Fonkem E., Lun M., Wong ET. Rare phenomenon of extracranial metastasis of glioblastoma. Journal of Clinical Oncology 2011; 29(34): 4594-5.

Joshua L. Rodriguez-Lopez, BS, is with Ponce Health Sciences University School of Medicine, Ponce, Puerto Rico. Zachary D Horne, MD, and John C Flickinger, MD,University of Pittsburgh Cancer Institute, Department of Radiation Oncology, Pittsburgh, PA.