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The spectrum of background, incidental, and experimentally induced lesions affecting NSG and NOG mice has been the subject of intense investigation. However, comprehensive studies focusing on the spontaneous neuropathological changes of these immunocompromised strains are lacking. This work describes the development of spontaneous early-onset neurodegeneration affecting both juvenile and adult NSG, NOG, and NXG mice. The study cohort consisted of 367 NSG mice of both sexes (including 33 NSG-SGM3), 61 NOG females (including 31 NOG-EXL), and 4 NXG females. These animals were primarily used for preclinical CAR T-cell testing, generation of humanized immune system chimeras, and/or tumor xenograft transplantation. Histopathology of brain and spinal cord and immunohistochemistry (IHC) for AIF-1, GFAP, CD34, and CD45 were performed. Neurodegenerative changes were observed in 57.6% of the examined mice (affected mice age range was 6-36 weeks). The lesions were characterized by foci of vacuolation with neuronal degeneration/death and gliosis distributed throughout the brainstem and spinal cord. IHC confirmed the development of gliosis, overexpression of CD34, and a neuroinflammatory component comprised of CD45-positive monocyte-derived macrophages. Lesions were significantly more frequent and severe in NOG mice. NSG males were considerably more affected than NSG females. Increased lesion frequency and severity in older animals were also identified. These findings suggest that NSG, NOG, and NXG mice are predisposed to the early development of identical neurodegenerative changes. While the cause of these lesions is currently unclear, potential associations with the genetic mutations shared by NSG, NOG, and NXG mice as well as unidentified viral infections are considered.

To characterize the clinical features, associated disorders, and treatment of necrobiotic xanthogranuloma (NXG), a rare non-Langerhans cell histiocytosis, we conducted a retrospective review of pathologically confirmed NXG at Mayo Clinic Arizona from 1987 to June 2017. Data on clinical findings, laboratory findings, associated disorders, therapy, and response to therapy were extracted. Nineteen patients were identified. Mean age was 54 years (range, 17-84) with equal gender distribution. Median follow-up was 5.5 years (range, 1-18). Most patients had a detectable monoclonal protein (84%), and IgG kappa constituted 58%. The most common cutaneous lesions involved the periorbital region (53%). The majority of patients had extracutaneous manifestations, most commonly affecting the liver (32%) and the sinuses (21%). Hematologic malignancies were diagnosed in 26% of patients and included Hodgkin lymphoma, chronic lymphocytic leukemia (CLL), smoldering myeloma, and multiple myeloma. The most common treatment was chlorambucil with or without systemic corticosteroids. Response was seen in most patients (95%), and most patients received 1-3 lines of therapy (74%). NXG is a reactive histiocytic disorder that commonly involves multiple organ systems and requires a high degree of clinical suspicion for accurate diagnosis. Treatment decisions should be based on coexisting conditions and pattern of disease involvement.

Necrobiotic xanthogranuloma (NXG) is a rare chronic granulomatous disorder of the skin associated with a monoclonal gammopathy.
The present report describes the findings from a single tertiary medical center retrospective study, including the clinical features of 35 patients with NXG and monoclonal gammopathy from 2000 to 2015 and their subsequent disease course and treatment response. The median age at diagnosis was 56 years (range, 26-88 years).
Most patients had a plasma cell dyscrasia consisting of monoclonal gammopathy of undetermined significance in 28 patients and smoldering multiple myeloma in 5 patients; the remaining 2 patients had chronic lymphocytic leukemia. An IgG isotype of monoclonal gammopathy was present in almost all the patients (97%). The most common site of cutaneous involvement of NXG was periorbital (66%). The treatments were heterogeneous and included excision, intralesional injection, radiotherapy, and systemic chemotherapy. The median follow-up period was 46 months (range, 4 to 234 months). The median overall survival had not been reached at the analysis, and 80% of the patients were still alive. Eight patients (23%) had disease progression to multiple myeloma at a median of 67 months (range, 21 to 107 months), demonstrating that although the clinical course is generally indolent, malignant transformation is not uncommon. At the last follow-up visit, 80% had signs of either clinical improvement or stable skin disease.
Cutaneous objective responses can be achieved with treatment of lymphoplasmacytic malignancies.