INTRODUCTION: Extracranial metastases of high-grade gliomas are traditionally thought to be a rare event, with a reported frequency of 0.44%. Recently published case reports have demonstrated distant metastases primarily from Glioblastoma Multiforme (WHO Grade-IV glioma) to regional lymph nodes, lungs, pleura, bone, liver; and rarely to skin, parotid and pancreas.(1,2) We describe a case of Anaplastic Oligoastrocytoma (WHO Grade-III Glioma) with rapidly progressive pulmonary metastasis after debulking of glial tumor.
CASE PRESENTATION: 51 years old previously healthy male admitted with heterogeneous enhancing right frontal lesion and midline shift on MRI brain. Patient underwent resection of tumor and placement of gliadel wafers followed by chemoradiation for cerebral mass. Histopathology confirmed a mixed anaplastic oligoastrocytoma, WHO grade-III Glioma. Four months later patient was admitted with increased symptoms, radiological progression of disease on MRI brain and a new onset cough. CXR showed a 2.5 X 2.2 cms nodule in the left lung. Resection and debulking of glioma was re-attempted. Multiple large blood vessels within the tumor bed were coagulated. Histopathology was similar to previous cerebral tumor (anaplastic oligoastrocytoma).Lung nodule was followed by serial CT scans of chest that demonstrated rapid progression and extensive spread. Thoracotomy and wedge resection of the lung mass was performed. Histopathology confirmed malignant neoplasm with abundant eosinophilic to pale cytoplasm, nuclear variability, prominent nucleoli, abundant misitoses and central necrosis typical of anaplastic tumors. Immunohistochemical stains ruled out Primary lung cancer and were positive for S-100, Vimentin, epithelial membrane antigen (EMA), thyroid transcription factor-1(TTF-1, cytoplasmic positivity only) and Glial fibrillary acidic protein (GFAP). Tumor cells did not stain for Synaptophysin, cytokeratin (CK), HMB45 and melan-A (A103) ruling out other lung secondaries. Patient received 4 cycles of Avastin with Irinotecan followed by PCV (vincristine, lomustine, procarbazine) regimen and radiation to chest. Despite aggressive chemo-radiation patient continued clinical and radiological progression of metastatic disease and died in 16 months.
DISCUSSIONS: Lower incidence of metastizing high-grade gliomas is attributed to absence of cerebral lymphatics, dense dural covering of cranial sinuses, immunological response of host organ to neuroglial tumor cells and short survival of patients. Previous literature suggests debulking surgery as a common characteristic feature in all cases except few. (1) We speculate that surgery and institution of chemotherapy in this patient may have provoked the metastatic cascade leading to vascular invasion, immunosupression and egress of anaplastic cells into the systemic circulation. An interesting feature of our patient is immunohistochemical expression of TFT 1 in pulmonary deposits, which is also expressed in structures of diencephalic origin. We are not sure if common embryonic origin of TTF-1 expression in lung anlage and neuroblast cells have a role in cell determination and metastatic spread complimenting “Seed and Soil Hypothesis” of metastatic spread. Our patient had mixed anaplastic oligoastrocytoma, WHO grade-III Glioma along with possible surgical contagion and TFT 1 signature on anaplastic cells suggesting a possibility of prevention and or early detection .
CONCLUSION: High-grade gliomas are rapidly progressive and can metastise extensively to lung parenchyma with out major respiratory symptoms. A high degree of clinical suspicion and radiological surveillance may provide early diagnosis. Further research on genomic signatures of pulmonary metastases may have an impact on early diagnosis and survival.