PMC4199188_01
Magnetic resonance imaging (MRI) findings. Brain MRI demonstrates two irregularities. The primary lesion was centered in the posterior-inferior parietal lobe (A, B, C) and a second contiguous lesion was identified in the posterior-central parietal lobe (D). The lesions were T1-hypointense (A) and T2-hyperintense (B) with peripheral irregular enhancement on T1 imaging following administration of gadolinium (C, D). Abnormal T2/FLAIR hyperintense signal surrounded both lesions.
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Figure1
T2-hyperintense lesion centered in the right parietal lobe (Figure 1). The lesion showed irregular areas of peripheral enhancement on T1 imaging with gadolinium (Figure 1C and Figure 1D). There was a second area of T2 hyperintensity with diffuse patchy enhancement superior to the main lesion (Figure 1D).
Pathology and immunophenotypic findings of CNS crystal-storing histiocytosis. A well circumscribed aggregate (top) was sharply demarcated from brain (bottom) (A). On higher magnification the infiltrate was composed of a mixed inflammatory infiltrate (B). A moderate number of plasma cells clustered around small blood vessels (C). Refractile, intracytoplasmic crystalline material was the hallmark feature of the lesion (D). Histiocytes expressed CD68 (E), while plasma cells expressed CD138 (F) and IgA by immunohistochemistry (G). In-situ hybridization studies for mRNA encoding immunoglobulin light chains showed kappa-restriction (H).
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Figure2
On histologic examination, the lesion consisted of a hypercellular infiltrate effacing the normal brain parenchyma (Figure 2A). At low magnification the lesion was characterized by an intense chronic inflammatory infiltrate in a perivascular distribution (Figure 2B). On higher power the chronic inflammatory infiltrate was composed primarily of plasma cells (Figure 2C). Within the histiocytes were needle-shaped eosinophilic cytoplasmic inclusions (Figure 2D).  Lesional histiocytes were strongly immunoreactive for CD68 (Figure 2E). Immunohistochemical study for CD138 confirmed the plasma cell predominance in the perivascular infiltrates (Figure 2F). Further immunophenotyping of the plasma cell infiltrate revealed immunopositivity for IgA (Figure 2G). Using chromogenic in situ hybridization, the plasma cells were found to be Ig-k-restricted (Figure 2H).
Mass spectrometry analysis with searches using previously published algorithms and probability score assignment revealed the abnormal infiltrates to be enriched by kappa-light chains and IgA heavy chains (stars). Other peptides identified likely represent brain parenchyma components.
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Figure3
IgA constant region (Figure 3). Interestingly, there was especially high signal for the somatically mutated variable domain fragment of the immunoglobulin kappa-light chain.