August Case 2021 Cedars-Sinai Skip to content Close Select your preferred language English عربى 简体中文 繁體中文 فارسي עִברִית 日本語 한국어 Русский Español Tagalog English English عربى 简体中文 繁體中文 فارسي עִברִית 日本語 한국어 Русский Español Tagalog Translation is unavailable for Internet Explorer Cedars-Sinai Home 1-800-CEDARS-1 1-800-CEDARS-1 Close Find a Doctor Locations Programs & Services Health Library Patient & Visitors Community My CS-Link Education clear Go Close Academics Academics Faculty Development Community Engagement Calendar Research Research Areas Research Labs Departments & Institutes Find Clinical Trials Research Cores Research Administration Basic Science Research Clinical & Translational Research Center (CTRC) Technology & Innovations News & Breakthroughs Education Graduate Medical Education Continuing Medical Education Graduate School of Biomedical Sciences Professional Training Programs Medical Students Campus Life Office of the Dean Simulation Center Medical Library Program in the History of Medicine About Us All Education Programs Departments & Institutes Faculty Directory Anatomic and Clinical Pathology Residency Back to Anatomic and Clinical Pathology Residency Application Information Explore the Residency Training Curriculum Autopsy Pathology Rotation Bone and Soft Tissue Head and Neck Pathology Rotation Breast Pathology Rotation Cardiovascular Pathology Rotation Clinical Chemistry Rotation Coagulation Rotation Cytopathology Rotation Dermatopathology Rotation Forensic Pathology Rotation Frozen Section Rotation Gastrointestinal and Liver Pathology Genitourinary Pathology Rotation Genomic Pathology Rotation Gynecologic Pathology Rotation Hematopathology Rotation Laboratory Management Rotation Microbiology Rotation Neuropathology Rotation Pulmonary and Mediastinal Pathology Rotation Renal Pathology Rotation Transfusion Medicine Rotation Surgical Pathology Pathology Physician Scientist Training Program Residents Graduates Case of the Month Archive Publications Leadership Frequently Asked Questions August Case 2021 Authors Xiaomo Alex Li (Resident), Jethro Hu, Serguei. I. Bannykh (Faculty) Neuropathology Clinical history A male patient in his 50s with a remote medical history of Guillain-Barre, left parietal infarct and seizure disorder, renal cell carcinoma, presented in the ED with altered mental status with associated confusion and somnolence in June 2015. MRI found a 2.5cm rim enhancing right parietal solitary mass with associated edema and possible central necrosis (Figure 1A). Patient underwent craniotomy for tumor resection. Pathology was of a glioblastoma. In house immunostains (IHC) showed negativity of Isocitrate dehydrogenase 1 (IDH1) mutations and high percent of MGMT staining. FISH showed no EGFR amplification. A. T1-post contrast MRI showing a right parietal, rim-enhancing lesion. B. H&E of the tumor showing endothelial proliferation with palisading necrosis C. ALK positively in ~5% of tumor cells. Clinical course Patient underwent a standard therapy with field radiation and temozolomide therapy which followed by adjuvant cycles of temozolomide chemotherapy. Subsequent studies by Foundation One detected point mutations in NF1 and ESR1, loss of CDKN2A/B and TERT promoter mutation. IHC analysis by Caris identified positivity for ALK, no evidence of IDH-1 and IDH-2 mutations by NGS and lack of promoter methylation on MGMT. We repeated ALK IHC in house and observed that only about 5% of tumor cells were positive (Figure 1C). The patient was started on ALK inhibitor Crizotinib in September 2015. He also underwent a total of 12 cycles of Temodar treatment (July 2015 to August 2016), and continued Crizotinib therapy till July 2020. Patient remained relatively stable until June 2021, but eventually progressed and expired shortly thereafter with evidence of white matter hemorrhage in a field of irradiation. Discussion Glioblastoma is the most frequent malignant brain tumor in adults, accounting for approximately 40-50% of all primary malignant tumors in the brain. The tumor most often centered in the subcortical white matter and deeper grey matter of the cerebral hemispheres. On imaging study, glioblastomas are irregularly shaped and have a ring-shaped zone of contrast enhancement around central area of necrosis. Typical pathologic features include prominent microvascular proliferation and palisading necrosis. Glioblastoma is a highly aggressive cancer with a median overall survival of 14 months. In contrast to a typical pattern of molecular alterations with overexpression/amplification and mutations in EGFR/PDGF/FGF pathway this patient's tumor showed the expression of ALK. Curiously, an addition of ALK inhibitor to his treatment regime showed a possible clinical benefit by apparently slowing down tumor progression and prolonged patient's life. 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