Contributed by M.B.B. Nieuwenhuis MD1,2, S.M.A. van der Salm MD3, J.J.C. Verhoeff MD PhD4
A.J. van der Kooi MD PhD3, I. Slavujecvic-Letic MD5, S.T. Pals MD PhD5 J.M.I. Vos MD1,6
1Department of Hematology, 2Department of Anesthesiology, 3Department of neurology, 4Department of radiation Oncology, 5Department of Pathology
Academic Medical Centre, the Netherlands, 6Department of Hematology St. Antoniusziekenhuis, Nieuwegein, the Netherlands
A 43-year-old woman presented with a six month history of progressive nocturnal nausea and vomiting, resulting in 30 kilograms of weight loss. Subsequently, she developed gradual cognitive decline and a cerebellar syndrome with gait ataxia and nystagmus. MRI showed multifocal lesions localized periventricularly, parenchymal and in the pons on contrast-enhanced T1-weighted images (Figure 1). Examination of cerebrospinal fluid (CSF), whole body positron emission tomography computerized tomography (PET-CT) scan and bone marrow biopsy did not show extra cranial involvement. The differential diagnosis consisted of metastatic melanoma, lymphoma, multiple sclerosis, meningoencephalitis or a granulomatous infection. Stereotactic biopsy of the lesions was performed.
Morphologically, the tumor was composed of large atypical cells with wide eosinophilic, partially vacuolated and granular cytoplasm containing eccentrically placed enlarged polymorphic nuclei with prominent nucleoli. Multi nucleated giant cells were also observed as well as mitoses and atypical mitosis. (Figures 2 and 3) The percentage of Ki67-positive proliferating cells was approximately 20%. Immunohistochemical staining showed that neoplastic cells were positive for hemapoietic lineage, CD45 (Figure 4) and histiocytic markers (CD163 (Figure 5), CD68, and CD4). There was no expression of Langerhans cell (CD1a), myeloid (MPO, CD15, CD34), B cell (CD20, CD79a, PAX5), T cell (CD3, CD2, CD5, CD30, ALK-1), or melanocytic (MelanA) markers. Also markers for mesenchymal malignancies and sarcomas (rhabdomyosarcoma, synovial sarcoma) were negative. Molecular studies demonstrated that the T and B cell receptor genes were in germ-line configuration. What is your diagnosis?