Crystal-storing histiocytosis: An unusual relapsing inflammatory CNS disorder

Abstract

The differential diagnosis of acute leukoencephalopathy often focuses on central nervous system idiopathic inflammatory demyelinating diseases (IIDDs) such as multiple sclerosis (MS). However, a spectrum of conditions mimic IIDDs, therefore it is critical to consider whether symptoms, signs, imaging and/or response to therapies are compatible with the diagnosis. We describe a 32-year-old previously healthy woman presenting with a 2 year history of steroid-responsive relapsing episodes lasting 2–10 days characterized by transient visual blurring, right-hemiparesis, and spells of aphasia. MRI demonstrated multifocal, relapsing, predominantly white matter enhancing brain lesions, a longitudinally extensive cord lesion, and abnormal visual evoked potentials. Notably, some lesions persistently enhanced whereas others demonstrated progressive T2W hypointensity. Brain biopsy revealed an atypical plasma cell infiltrate and crystal-storing histiocytosis, which by mass spectrometry confirmed the presence of macrophages containing intracellular kappa-light chain restricted crystals. Bone marrow was negative. The patient did well for several years on pulse dexamethasone, however subsequent scans demonstrated increasing enhancement. Repeat biopsy demonstrated a clonal plasma cell proliferation. She was treated with melphalan, and has remained stable. Although this patient initially met McDonald criteria, atypical imaging prompted further workup, and advanced proteomic technology helped secured an accurate diagnosis. Crystal-storing histiocytosis should be considered in the differential diagnosis of inflammatory CNS disorders.

Localized crystal‐storing histiocytosis of the posterior fossa

“…2,3 These mechanisms may have been associated with isolated CNS-CSH without hematological disease. 5,7,13,14,16,17 However, there is no known association between CHS and hyperuricemia, which was present in our patient.…”

“…5,7,13–17 These cases, and the case reported here, presented as mass lesions (Table 1), but this is the first case localized to posterior fossa structures, including the caudal portion of the brainstem and cerebellum. Interestingly, all reported CNS-CSH cases, including our patient, share an isolated restriction to the CNS, suggesting that CNS-CSH occurs independently from systemic multiorgan involvement, which primarily affects the bone marrow, lymphoreticular system and kidneys.…”

“…1 Given the limited clinical experience with CSH in the CNS, the optimal treatment and prognosis remain unclear, and in most of the cases, the treatment was dependent on the associated underlying condition. Only in one previous case with isolated CNS-CSH 5 and in our patient, a course of steroids was given. The case reported by Constanzi at el 5 met criteria for diagnosis of multiple sclerosis that was initially steroid responsive, but due to the atypical clinical features, rapid progression and persistent white matter enhancement, a brain biopsy was performed, which revealed a clonal plasma cell proliferation in association with CSH.…”

“…In our case, the patient was given steroids secondary to an allergic reaction to antibiotics with resolution of his symptoms and enhancing lesion in brain through MRI assessment. In three other CNS-CSH cases 5,15,17 patients received treatment with positive response and stabilization of the disease. Interestingly, only our patient and a 38-year-old female patient 17 had documented resolution of their lesions after treatment.…”

“…1,12 CSH involvement of the central nervous system (CNS-CSH) is rare. 5,7,13–17 Here, we describe the first case of CNS-CSH involving the caudal brain stem and cerebellum. We also review the CNS-CSH literature to highlight the significance of this rare but important entity.…”