Focal Leptomeningeal Disease with Perivascular Invasion in EGFR-Mutant Non-Small-Cell Lung Cancer

Histopathology. A, Hematoxylin-eosin image shows cohesive epithelioid neoplastic cells closely associated with parenchymal blood vessels (black arrows). Immunohistochemical staining (brown coloration) for CK7 (B) and TTF1 (C) supports a lung origin and highlights the involvement of the perivascular spaces. D, Growth of tumor within the Virchow-Robins spaces (marked brown again with CK7 immunostaining) creates an impression of scattered tumor foci within the unstained brain tissue rather than the typical solitary metastatic mass. E and F, Evidence of leptomeningeal involvement with adenocarcinoma closely associated with and encircling larger thick meningeal-type vessels (black arrows). F, A high-power view of the red box seen in E highlights that most of the increased cellularity is tumor cells.

Brain MR imaging for patient 2, a 62-year-old man with EGFRm NSCLC. Sagital (A) and axial (B) projections demonstrate an enhancing lesion spreading along the cerebellar folia after several months of treatment with gefitinib.

Brain MR imaging for patient 3, a 49-year-old man with EGFRm NSCLC with an enhancing lesion in the left parietal lobe 14 months following WBRT.

Brain MR imaging for patient 4, a 77-year-old woman with EGFRm NSCLC. Axial projection demonstrates a right frontal lobe lesion following 18 months of gefitinib treatment.

Brain MR imaging for patient 5, a 46-year-old woman with EGFRm NSCLC. Sagital (A) and axial (B) projections demonstrate an enhancing right cerebellar lesion with spread along the cerebellar folia, 1 year following stereotactic radiosurgery and several years of gefitinib treatment.