Primary Central Nervous System Lymphoma With Light Chain Deposition Disease (Aggregoma)

Clinical Correspondence Primary Central Nervous System Lymphoma With Light Chain Deposition Disease (Aggregoma) Tyler D. Boulter, BS, Ama Sadaka, MD, Mohammad Obadah Nakawah, MD, Stacy V. Smith, MD, Nail Alouch, MD, Shauna E. Berry, DO, Andrew T. Whyte, OD, Gregory N. Fuller, MD, PhD, Andrew G. Lee, MD A 64-year-old man with a medical history of wellcontrolled hypertension described a recent history of bilateral blurry vision and new onset headache. He reported weight loss of 8 pounds over 4 months, denied fever, seizures, chills, sensory loss, weakness, or dysarthria and was a former smoker of cigarettes. Brain computed tomography and MRI showed multifocal, irregular intracranial mass lesions in the right occipital and parietal lobes (Fig. 1). The patient subsequently underwent a craniotomy for biopsy of the right occipital lobe lesion. Histologic examination of the specimen showed perivascular small cell infiltrates with the brain parenchyma. The cellular infiltrate exhibited mixed lymphocytic and plasmacytic features. The vessel walls appeared thickened with deposition of amorphous eosinophilic material (Fig. 2A). Immunophenotyping and special stains were performed to characterize the lineage of the infiltrate and the nature of the amorphous material in the vascular walls (Table 1). Having morphologic features of lymphocytes and plasma cells, the lymphoplasmacytic infiltrates were strongly and diffusely positive for B-lymphocytic markers (CD20) (Fig. 2B) and plasma cells markers, including CD38 (Fig. 2C), CD138, and epithelial membrane antigen. The thickened vascular walls showed strong reactivity for kappa light chain (Fig. 2D) and no reactivity for lambda light chain (Fig. 2E). Beta-amyloid Department of Ophthalmology (TDB), Texas A&M Health Science Center, Bryan, Texas; Department of Ophthalmology (AS, SVS, SB, AGL), The Blanton Eye Institute, Houston Methodist Hospital, Houston, Texas; Department of Neurology (MON), Houston Methodist Hospital, Houston, Texas; Department of Pathology (NA, GNF), University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Ophthalmology (ATW, AGL), University of Texas MD Anderson, Houston, Texas; Departments of Ophthalmology (AGL), Weill Cornell Medicine, New York, New York; Department of Ophthalmology (AGL), UTMB, Galveston, Texas; and Department of Ophthalmology (AGL), Baylor College of Medicine, Houston, Texas; and Department of Ophthalmology (AGL), University of Iowa Hospitals and Clinics, Iowa City, Iowa. The authors report no conflicts of interest. Address correspondence to Andrew G. Lee, MD, Department of Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital, 6560 Fannin Street, Scurlock 450, Houston, TX 77030; E-mail: aglee@ houstonmethodist.org Boulter et al: J Neuro-Ophthalmol 2018; 38: 195-197 immunostaining and a Congo red special stain showed very focal, faint positivity. Liquid chromatography-mass spectrometry of the amorphous eosinophilic material identified the presence of alpha immunoglobulin heavy chains, kappa immunoglobulin light chains, and immunoglobulin J chain without evidence of amyloid deposition. The K-67 antigen proliferation index was low at 1.7%. The findings of a kappa-restricted cell population with B-lymphocytic and plasmacytic immunophenotype established the diagnosis of primary central nervous system (CNS) B-cell lymphoma with monoclonal kappa light chain deposition disease (LCDD) (aggregoma). Cerebrospinal fluid analysis was acellular, with a negative lymphoma panel and without beta macroglobulin. Protein electrophoresis of the urine and serum was normal. Evaluation for multiple myeloma, including full-body positron emission tomography, bone scan, and bone marrow biopsy, was negative. Postoperatively, the patient's visual acuity was 20/20 in each eye, and automated perimetry showed a left homonymous hemianopia. The remainder of the examination was normal. Empiric treatment with low-dose radiation was initiated (total dose: 4 Gy in 2 fractions). MRI showed decrease in the right occipital lobe lesion size with a small amount of postoperative and radiation changes. Follow-up at 38 months revealed a stable ophthalmic examination and no clinical or imaging signs of active disease in the brain or elsewhere. LCDD is characterized by clonal expansion of lymphoplasmacytic cells, overproduction of monoclonal immunoglobulin light chains, and subsequent deposition of these light chains in various tissues (1). The deposits can be parsed into amyloid and nonamyloid types. Imaging techniques cannot differentiate between the 2; their histological picture distinguishes them (2). When restricted to 1 organ, amyloid light chain deposition is far more common than nonamyloid deposition and is referred to as amyloidomas (3). Nonamyloid light chain deposition is referred to as aggregoma. Light chain 195 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 1. Brain MRI. A. Axial precontrast T1 image shows hypointense area involving the right parieto-occipital region. B. Axial postcontrast T1 image reveals enhancing lesions in the right and left parieto-occipital region. C. Axial fluid-attenuated inversion recovery scan also demonstrates areas of increased signal in the frontal lobes bilaterally. deposits may be composed of either kappa or lambda light chains. In a literature review of all reported cases of LCDD, Singh et al (2) found that the deposits were derived from kappa immunoglobulin light chain in 80% of patients. Mean age of onset of LCDD is 56 years with a 2:1 male predominance (1). The kidney is the organ most often affected, but deposits can also occur in the heart, liver, lungs, cornea, and CNS (2,4). The rarity of CNS involvement has been attributed to the selectivity of the blood- brain barrier (2). Although most cases are associated with multiple myeloma, some are not, including our patient. There is also an association with monoclonal gammopathy of undetermined significance (1) and reports linking LCDD to other B-cell neoplasms (5). In our patient, the cellular infiltrate demonstrated the histologic and immunophenotypic features of plasma cell differentiation, adding plasma cell dyscrasias (multiple myeloma and plasmacytoma) to the differential diagnosis. However, the expression of B-lymphocyte markers such as CD20, which typically are lost during B lymphocyte to plasma cell conversion, militates against a diagnosis of plasma cell dyscrasia, and strongly favors lymphoma. The mean survival of patients with LCDD is 4 years (6). The poor prognosis may, in part, be related to a lack of standardized treatment protocols for this rare disease. The goal of therapy is to reduce the production and deposition of immunoglobulin light chains. Low-dose radiation was the treatment modality selected for our patient, and his disease and symptoms remain stable at this time. There are reports of benefit from local resection when treating intracerebral and pulmonary deposits (2,4), but this can be difficult in patients with multifocal cerebral lesions as in our patient. Chemotherapy is another option that has been shown to offer some benefit (7,8), with melphalan and bortezomib being most TABLE 1. Summary of histologic immunohistochemical and specials stains Stain CD20 CD38 CD138 Kappa light chain Lambda light chain Beta-amyloid Congo red Ki-67 196 Purpose Result B-lymphocytic marker Plasma cell marker Plasma cell marker Diffusely positive Positive Positive Diffusely positive Negative Very focal/weak (nonspecific) Very focal/weak (nonspecific) 1.7% (low) Stains amyloid Proliferation index Boulter et al: J Neuro-Ophthalmol 2018; 38: 195-197 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 2. Brain biopsy. A. Brain parenchyma shows small cell infiltrates with perivascular cuffing. There is also amorphous eosinophilic material in the vessel walls (hematoxylin & eosin, ·40). B. CD20 immunostain highlights perivascular lymphocytes (·100). C. CD38 immunostain reveals plasmacytoid cells (·100). Immunostain for kappa light chain in vessel walls is positive (D) but is negative for lambda light chain (E) (D, ·40 and E, ·40). frequently used. In addition, there are reports of treatment with stem cell transplantation (9). STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: T. D. Boulter, A. Sadaka, S. V. Smith, N. Alouch, S. Berry, M. O. Nakawah, A. T. Whyte, G. N Fuller, and A. G. Lee; b. Acquisition of data: T. D. Boulter, A. Sadaka, S. V. Smith, N. Alouch, M. O. Nakawah, A. T. Whyte, and A. G. Lee; c. Analysis and interpretation of data: T. D. Boulter, A. Sadaka, S. V. Smith, N. Alouch, M. O. Nakawah, A. T. Whyte, and A. G. Lee. Category 2: a. Drafting the manuscript: T. D. Boulter, A. Sadaka, S. V. Smith, N. Alouch, M. O. Nakawah, A. T. Whyte, and A. G. Lee; b. Revising it for intellectual content: T. D. Boulter, A. Sadaka, S. V. Smith, N. Alouch, M. O. Nakawah, A. T. Whyte, and A. G. Lee. Category 3: a. Final approval of the completed manuscript: T. D. Boulter, A. 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