Contributed by Daniel Kirschenbaum,MD1, Christoph Woernle, MD2, Eugenia Haralambieva MD3, Ewerton Marques Maggio MD3, RenÚ Bernays, MD2, Ulrike Camenisch PhD3, Elisabeth J. Rushing, MD1
1Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland
2Neurosurgical Clinic Hirslanden, Zurich, Switzerland
3Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland
CLINICAL HISTORY AND IMAGING
A 72-year-old woman presented with a 4-year clinical history of increasing confusion, memory loss, depression, and dizziness. Neuroimaging studies including CT and MRI showed bifrontal dural masses (Figure 1a) and a right-sided tentorial mass in the cerebello-pontine angle (Figure 1b). The supratentorial masses were considered suspicious for multiple meningiomas or CNS lymphoma, whereas schwannoma was favored for the cerebello-pontine angle mass. Microsurgical resection was performed of the both frontal lesions and right cerebello-pontine mass. After the pathological diagnosis was rendered, systemic lesions were detected by PET in the humerus and femur, piriform sinus, ilium, clavicles and mandible (Figure 1c). The patient underwent a course of vemurafenib treatment, a BRAF-inhibitor, which improved the neurological status.
H&E-stained sections (Figure 1d) revealed a moderately cellular infiltrate arranged in sheets and nests partially and compartmentalized by connective tissue bands. Numerous foamy macrophages, some of which were multinucleated (Touton-like) (Figure 1e), were admixed with lymphocytes, plasma cells and granulocytes, and often concentrated around blood vessels. Scattered histiocytes contained engulfed inflammatory cells, reminiscent of emperipolesis (Figure 1f, arrow). Immunohistochemically, the foamy macrophages stained with CD68 (Figure 1g) and CD163; variable numbers of cells were S100 positive (Figure 1h). Rare cells stained for CD207, but CD21 and CD23 were negative. IgG and IgG4 had a normal ratio; immunohistochemical stains for kappa and lambda light chains revealed a mixed population, consistent with polyclonal plasma cells. The cells suggestive for emperipolesis were CD68 positive. Factor VIIIa, a marker for dendritic cells and histiocytes was focally positive. The Ki-67 index ranged between 10 and 20%. BRAFV600E immunostaining was positive (Figure 1i). PCR analysis confirmed a BRAFV600E mutation. (Scale bars Figures 1 d, e, f - 10 Ám; Figures 1g, h, i - 100 Ám.). What is your diagnosis?