Bing-Neel Syndrome: An Initial Manifestation of Waldenstrom Macroglobulinemia.

Waldenstrom macroglobulinemia (WM) is a low-grade B-cell lymphoma characterized by bone marrow infiltration by monoclonal lymphoplasmacytic cells plus an IgM monoclonal gammopathy. Bing-Neel syndrome (BNS) is a rare manifestation of WM where malignant lymphoplasmacytic cells infiltrate the central nervous system (CNS). Though only present in 0.8% of WM cases, it is likely underdiagnosed and may present before or during WM treatment. Here, we present a case of BNS as an initial sign of WM. A 75-year-old male presented with confusion, gait instability, and expressive aphasia. MRI demonstrated a 5.5-cm mass in the right frontal lobe, crossing midline. Brain biopsy showed CNS lymphoma and later tested positive for the MYD88L265P mutation suggesting WM (as is a mutation in 90-95% WM patients). Indeed, quantitative serum immunoglobulins showed elevated IgM. Initial treatment for WM was started with rituximab, methylprednisolone, carfilzomib, and ibrutinib. MRI two months after initiation showed good response, and the patient was transitioned to ibrutinib monotherapy. Surveillance MRI one year later showed patchy right frontal lobe enhancement indicating disease progression, and therefore the patient was placed back on his initial treatment regimen. However, ibrutinib later had to be held due to thrombocytopenia. Two months after re-starting chemotherapy, he presented with bizarre behavior, and MRI showed extensive disease progression. He was then transitioned to palliative chemotherapy with high-dose methotrexate and rituximab. He has responded well to this regimen, and MRI two years after diagnosis showed no recurrent disease. BNS is a rare but easily missed manifestation of WM. As per the recent National Comprehensive Cancer Network (NCCN) guidelines and the 8th International Workshop on WM (IWWM-8), no standardized diagnostic or management guidelines for BNS is available. Direct brain biopsy is the gold standard for diagnosis. Due to its low incidence, rarity, and limited prospective trial, there is a lack of a clear standard of care therapy. Specific treatment regimen depends on the patient factors and treatment tolerability. IWWM-8 suggests the use of a variety of cytotoxic chemotherapies or ibrutinib. A high-quality meta-analysis of existing reports is critical to characterize the diagnostic features and optimal treatment for BNS. The prognosis of BNS remains unclear, with an estimated three- and five-year survival rate at 59% and 71%, respectively. BNS is an infrequent complication of WM. Clinicians should suspect BNS with persistent, unexplained neurologic symptoms in WM.

Nation-Wide Trends in Incidence-Based Mortality of Patients with Ocular Melanoma in USA: 2000 to 2018.

BACKGROUND: Ocular and orbit melanoma is a rare subtype of melanoma for which outcomes have not been adequately reported. We have analyzed the incidence-based mortality trends of ocular and orbit melanoma over 15 years in USA. Most ocular melanomas originate from the uvea and, to a lesser extent, from the conjunctiva. Primary orbital melanoma is exceedingly rare. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was queried to find the incidence-based mortality for all patients diagnosed with ocular and orbit melanoma for the years 2000 to 2018. Results were grouped by gender and race (Caucasian/White, African American/Black, American Indian/Alaskan Native, and Asian/Pacific Islanders). A paired t-test was used to determine the statistically significant difference between various subgroups (p < 0.05). RESULTS: Incidence-based mortality has been the highest in Caucasian/White patients from 2000 to 2018, followed by African American/Black and Asian/Pacific Islander patients. American Indian/Alaskan native patients appear to have the least mortality. There was a statistically significant difference (p<0.05) in mortality between Caucasian/White patients from 2000 to 2018, and African American/Black and Asian/Pacific Islander patients. The sample size for African American/Black and American Indian/Alaskan native patients was too low to discern a meaningful trend in mortality. Overall, it appears that Caucasian males and females have a far higher and worsening incidence-based mortality compared to other races. CONCLUSION: Ocular melanoma and orbit melanoma are rare entities that are predominantly seen in Caucasian/White patients. This study shows that incidence-based mortality has been worsening for these patients in the past two decades. These entities have a poor prognosis and have not been studied extensively in immunotherapy trials. There is a need for new clinical trials to help improve mortality rates.

An overview of MCT1 and MCT4 in GBM: small molecule transporters with large implications.

Monocarboxylate transporters (MCTs) represent a diverse group of transmembrane proteins encoded by the SLC16 gene family found ubiquitously across mammalian species. Two members of this family, MCT1 and MCT4, have been linked to key roles in the metabolic activity of tissues through the proton-coupled transport of monocarboxylates, most notably L-lactate, ketone bodies, and pyruvate. This review aims to provide an overview of MCT1 and MCT4, followed by the implications of their expression in a multitude of cancers and in glioblastoma (GBM) specifically. Further, the possible mechanisms underlying these effects will be discussed. Given the relationships between MCT1 and MCT4 and cancer, they offer a unique opportunity for novel treatment strategies. We aim to explore current therapies focused on MCT1 and MCT4 and propose future studies to better understand their role in GBM to optimize future treatment regimens.