Anthropometric traits and risk of multiple myeloma: differences by race, sex and diagnostic clinical features.

BACKGROUND: Obesity is an established modifiable risk factor for multiple myeloma (MM). However, associations of obesity and MM risk in Black populations, for whom obesity and MM are more common, is less clear. METHODS: Using participants enrolled in the Integrative Molecular And Genetic Epidemiology study, we evaluated the association of anthropometric traits with MM risk overall, stratified by race and sex. Among cases, we assessed the association of BMI with the presence of myeloma-defining events. RESULTS: We observed an 18% increase in MM risk for every 5 kg/m2 increase in usual adult BMI. Participants with severe obesity (BMI ≥ 40 kg/m2) had the highest risk compared to those with a normal usual adult BMI (18.5-24.9 kg/m2; OR = 1.87, 95% CI 1.25-2.80), particularly among Black men (OR = 3.94, 95% CI 0.90-17.36). Furthermore, MM cases with overweight/obesity (BMI ≥ 25 kg/m2) were more likely to present at diagnosis with low renal function (OR = 1.62, 95% CI 1.09-2.40), deletion 13q (OR = 1.73, 95% CI 1.08-2.76) and lytic lesions or compression fractures (OR = 2.39, 95% CI 0.82-7.01) and less likely to present with severe diffuse osteopenia (OR = 0.51, 95% CI 0.31-0.81). CONCLUSIONS: Findings underscore the importance of obesity as a modifiable risk factor for MM, particularly in high-risk populations, and for the clinical presentation of disease.

SMARCA4-deficient central nervous system metastases: A case series and systematic review.

SMARCA4 alterations can be encountered in a variety of human neoplasms, and metastases to the central nervous system (CNS) are rare, offering a challenge to neuropathologists despite not representing a distinct diagnostic entity. To better understand the clinical and histologic presentation of such neoplasms, we report an observational case series and systematic review of 178 unique articles that yielded 15 published cases and 7 cases from institutional files. In the systematic review, the median age was 58 years, the male-to-female ratio was 2:1, and the most common diagnosis was lung adenocarcinoma; all CNS metastases were discovered within 1 year of presentation. In the case series, the median age was 58 years, the male-to-female ratio was 6:1, and all known metastases originated from the lung. Most patients had a smoking history and died of disease. GATA-3 positivity was seen in most case series examples. Concurrent TP53 mutations (83.3%) and a high tumor mutation rate (60%) were common. To our knowledge, this is the only case series and systematic review in the English literature aimed at assessing SMARCA4-altered metastases in the CNS and vertebral column. We highlight the challenges of neuropathologic evaluation of such tumors and provide observational evidence of early metastases, histologic appearances, and immunohistochemical findings, including previously unreported GATA-3 positivity.

Brain Autopsy Findings in a Patient Who Received Lipid Emulsion Therapy for Suspected Drug Intoxication.

ABSTRACT: Lipid emulsion therapy (LET) is the intravenous administration of lipid solution for parenteral alimentation, especially in preterm infants and adults with debilitating illnesses. It has also been used in attempts of detoxification in suspected cases of drug overdose. Whether this interferes with circulation and/or perfusion is debatable, and it is suggested that it may interfere with coagulation process. The emulsifying agent has been identified microscopically mainly in the lungs of these patients, with rare reports in adults and even more rare ones in the brain; however, although it is rarely reported in other organs, to our knowledge, no reports of gross autopsy findings in the brain are available in the English literature, nor are there reports of pathologic findings after lipid emulsion therapy administration for drug toxicity. Although it is also debated in the literature whether this material forms as an artifact or represents the actual agent, here we report the gross and microscopic autopsy findings in the brain of a patient who received LET for suspected beta-blocker intoxication. It will be beneficial for pathologists who perform autopsies in the forensic or medical settings to be aware of these findings, along with the uses and potential complications of LET.

Distinct phenotype of neutrophil, monocyte, and eosinophil populations indicates altered myelopoiesis in a subset of patients with multiple myeloma.

Hematologic malignancies, including multiple myeloma (MM), promote systemic immune dysregulation resulting in an alteration and increased plasticity of myeloid cell subsets. To determine the heterogeneity of the myeloid cell compartment in the peripheral blood of patients with MM, we performed a detailed investigation of the phenotype and function of myeloid subpopulations. We report that a subset of MM patients exhibits a specific myeloid cell phenotype indicative of altered myelopoiesis characterized by significant changes in the properties of circulating granulocytic, monocytic, and eosinophilic populations. The subset, referred to as MM2, is defined by a markedly elevated level of CD64 (FcγRI) on the surface of circulating neutrophils. Compared to healthy controls or MM1 patients displaying intermediate levels of CD64, neutrophils from MM2 patients exhibit a less differentiated phenotype, low levels of CD10 and CXC chemokine receptor 2 (CXCR2), increased capacity for the production of mitochondrial reactive oxygen species, and an expansion of CD16neg immature neutrophil subset. Classical and patrolling monocytes from MM2 patients express elevated levels of CD64 and activation markers. MM2 eosinophils display lower levels of C-C Chemokine receptor 3 (CCR3), Toll-like receptor 4 (TLR4, CD284), and tissue factor (TF, CD142). The MM2 (CD64high) phenotype is independent of age, race, sex, and treatment type. Characteristic features of the MM2 (CD64high) phenotype are associated with myeloma-defining events including elevated involved/uninvolved immunoglobulin free light chain (FLC) ratio at diagnosis. Detailed characterization of the altered myeloid phenotype in multiple myeloma will likely facilitate the identification of patients with an increased risk of disease progression and open new avenues for the rational design of novel therapeutic approaches.

The #Path2Path Virtual Landscape During the COVID-19 Pandemic: Preparing for the 2020 Pathology Residency Recruitment Season.

On May 11, 2020, the Association of American Medical Colleges released recommendations discouraging in-person activities for away rotations and mandating virtual-only residency recruitment interviews. This paper focuses on how residency programs have attempted to adjust to this vastly different application cycle by using social media to reach their applicants. A total of 138 programs were identified through the Electronic Residency Application Services. The presence of Departmental/Residency program Twitter, Instagram, and Facebook as well as web pages offering virtual opportunities was recorded for each program on October 30, 2020. A total of 132 social media accounts were found; the majority of which were on Twitter, while fewer were on Instagram and Facebook. All 138 pathology residency programs had websites. Sixteen (11.5%) of those advertised virtual open houses and 2 (1.4%) advertised virtual subinternships; social media were more often used for advertisement of these virtual experiences. A total of 58 open house opportunities were advertised on Twitter, 21 on Instagram, and 20 on Facebook. Innovative virtual subinternships ranging from 2 to 4 weeks were developed, but only represented 6% of the usual 126 away rotations available. Pathology programs across the country utilized websites and social media as a method of communication to interact with applicants as part of the #Path2Path in 2020 and to provide virtual opportunities in preparation for a drastically different recruitment cycle.