A 53‐Year‐Old Woman with Progressive Headaches

Abstract

A 53-year-old woman presented with a 1-month history of severe headache and intractable vomiting. Physical examination revealed left facial palsy and generalized weakness of the extremities (grade IV/V all extremities) without other localizing signs. She had no known underlying disease and there was no significant family history. MRI of the brain disclosed multiple ill-defined high signal lesions in T2W at left lower pons, left thalamus, subcortical regions of temporal, parietal, and frontal lobes bilaterally, and periventricular white matter. Nodular enhancement was noted in the left frontal lobe lesion (Figure 1a), left thalamus (not shown) and left pons ( Figure 1b). Irregular leptomeningeal enhancement was also noted diffusely. The largest mass present at the left frontal lobe was 2 cm in largest dimension and showed marked peritumoral vasogenic edema (Figure 1a). High resolution chest CT revealed an ill-defined mass at the posterior basal segment of the right lower lobe, 3.2 cm in greatest dimension (not shown). There were also multiple small nodules involving both lungs, ranging from 0.4 to 0.5 cm. Stereotactic biopsy of the left frontal lobe lesion was performed. MICROSCOPIC PATHOLOGYSections showed papillary/perivascular structures present in variably necrotic and hypercellular backgrounds (Figure 1c). The former contained hyalinized vascular cores lined by single layers of rectangular to cuboidal cells. Some of these cells had intracytoplasmic vacuoles. These cells contained moderately pleomorphic hyperchromatic to vesicular nuclei with occasionally prominent nucleoli and frequent mitoses. The hypercellular parenchymal component contained moderately pleomorphic hyperchromatic nuclei with indistinct eosinophilic cytoplasm embedded within a fibrillar background (Figure 1d). Mitotic figure were exceptionally rare in this area. The intracytoplasmic vacuoles in the papillary structures were positive for mucicarmine (Figure 1e). Immunohistochemically, these cells strongly expressed CK7 (Figure 1f) and TTF-1 (Figure 1g), but were CK 20 negative (not shown). The interspersed parenchymal cells were positive for GFAP (not shown), p53 protein (not shown), and the R132H mutant form of IDH-1 protein (Figure 1h). The MIB-1 labeling index in this area was <1%. FISH studies for chromosome 1p and 19q status were non-informative despite multiple attempts. What is your diagnosis?