VEXAS syndrome: A review of bone marrow aspirate and biopsies reporting myeloid and erythroid precursor vacuolation.

Myeloid and erythroid precursor vacuolation is a common dysplastic finding associated with myeloid malignancies, toxins, drug, and nutritional deficiencies. It has been described as a core morphologic feature in VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. We sought to determine the number of cases attributable to VEXAS syndrome in bone marrow biopsies and aspirates (BAMB) reporting myeloid precursor vacuolation. We reviewed 1318 individual BAMB reports from January 2020 to July 2021 where "vacuole(s)," "vacuolation," or "vacuolated" was reported. Bone marrow biopsies with vacuolation confined to blasts or those completed as routine workup prior to stem cell transplant or post induction chemotherapy for AML (acute myeloid leukemia) were excluded. Myeloid and erythroid precursor vacuolation was noted in 219 reports representing 210 patients. The most common etiology was myelodysplastic syndrome (MDS) (38.6%), AML (16.7%), lymphoproliferative disorders and multiple myeloma (7.6%), drug or toxin exposure (5.2%) myeloproliferative neoplasm (MPN) or MPN/MDS overlap syndrome (4.3%). VEXAS syndrome was determined to be the etiology in 2.9% of patients. Two additional cases of VEXAS syndrome with bone marrow biopsies reported in the specified time frame did not explicitly report myeloid or erythroid precursor vacuolation but were identified based on clinical suspicion and repeat BAMB review. Myeloid and erythroid precursor vacuolation is a dysplastic feature attributable to VEXAS syndrome in at least 2.9% of cases. Standardized reporting of vacuolization, triaging of molecular sequencing and optimal treatment of this disorder are critical issues facing those seeing patients with suspected VEXAS syndrome.

Adaptations of transfusion systems to the COVID-19 pandemic in British Columbia, Canada: Early experiences of a large tertiary care center and survey of provincial activities.

BACKGROUND: In March 2020, a state of emergency was declared to facilitate organized responses to the coronavirus disease 2019 (COVID-19) pandemic in British Columbia, Canada. Emergency blood management committees (EBMCs) were formed regionally and provincially to coordinate transfusion service activities and responses to possible national blood shortages. STUDY DESIGN AND METHODS: We describe the responses of transfusion services to COVID-19 in regional health authorities in British Columbia through a collaborative survey, contingency planning meeting minutes, and policy documents, including early trends observed in blood product usage. RESULTS: Early strategic response policies were developed locally in collaboration with members of the provincial EBMC and focused on three key areas: utilization management strategies, stakeholder engagement (collaboration with frequent users of the transfusion service, advance notification of potential inventory shortage plans, and development of blood triage guidance documents), and laboratory staffing and infection control procedures. Reductions in transfusion volumes were observed beginning in mid-March 2020 for red blood cells and platelets relative to the prepandemic baseline (27% and 26% from the preceding year, respectively). There was a slow gradual return toward baseline beginning one month later; no product shortage issues were experienced. CONCLUSION: Provincial collaborative efforts facilitated the development of initiatives focused on minimizing potential COVID-19-related disruptions in transfusion services in British Columbia. While there have been no supply issues to date, the framework developed early in the pandemic should facilitate timely responses to possible disruptions in future waves of infection.

IgG4 plasma cell myeloma without clinical evidence of IgG4-related disease: a report of two cases.

Background: Serum IgG4 is typically measured to investigate for Immunoglobulin G4-related Disease (IgG4-RD), a fibroinflammatory condition associated with polyclonal increase in serum IgG4. However, increased IgG4 can also be monoclonal, and little is known about IgG4 myeloma. Methods: We describe two cases of IgG4 myeloma without clinical, radiologic, or laboratory features of IgG4-related disease. Results: An 84 year old man presented with anemia and compression fractures and a 77 year old man presented with anemia, hypercalcemia and renal failure. Both had markedly elevated monoclonal serum IgG4, 34 g/L and 48 g/L in the beta region, and increased IgG positive bone marrow plasma cells, 50% and 80%, respectively. Neither had clinical or radiological manifestations of IgG4-related disease (IgG4-RD) such as salivary or lacrimal gland swelling, autoimmune pancreatitis , or retroperitoneal fibrosis. Both cases responded well to standard myeloma therapy. The IgG4 paraprotein caused spuriously elevated beta-2 microglobulin of 45.2 mg/L in case two due to interference with the assay. Conclusion: These cases illustrate the importance of performing serum protein electrophoresis in tandem with IgG subclasses to distinguish between polyclonal and monoclonal increases in serum IgG4. The lack of typical IgG4-RD features in these two patients suggests that monoclonal elevation in serum IgG4 alone is insufficient to cause the organ damage characteristic of IgG4-RD. Larger studies of IgG myeloma subtypes are warranted to explore whether IgG1, IgG2, IgG3 and IgG4 myeloma differ in natural history and whether the interference with beta-2 microglobulin is specific to IgG4 monoclonal proteins.

Calculator for ovarian carcinoma subtype prediction.

With the emerging evidence that the five major ovarian carcinoma subtypes (high-grade serous, clear cell, endometrioid, mucinous, and low-grade serous) are distinct disease entities, management of ovarian carcinoma will become subtype specific in the future. In an effort to improve diagnostic accuracy, we set out to determine if an immunohistochemical panel of molecular markers could reproduce consensus subtype assignment. Immunohistochemical expression of 22 biomarkers were examined on tissue microarrays constructed from 322 archival ovarian carcinoma samples from the British Columbia Cancer Agency archives, for the period between 1984 and 2000, and an independent set of 242 cases of ovarian carcinoma from the Gynaecologic Tissue Bank at Vancouver General Hospital from 2001 to 2008. Nominal logistic regression was used to produce a subtype prediction model for each of these sets of cases. These models were then cross-validated against the other cohort, and then both models were further validated in an independent cohort of 81 ovarian carcinoma samples from five different centers. Starting with data for 22 markers, full model fit, backwards, nominal logistic regression identified the same nine markers (CDKN2A, DKK1, HNF1B, MDM2, PGR, TFF3, TP53, VIM, WT1) as being most predictive of ovarian carcinoma subtype in both the archival and tumor bank cohorts. These models were able to predict subtype in the respective cohort in which they were developed with a high degree of sensitivity and specificity (κ statistics of 0.88±0.02 and 0.86±0.04, respectively). When the models were cross-validated (ie using the model developed in one case series to predict subtype in the other series), the prediction equation's performances were reduced (κ statistics of 0.70±0.04 and 0.61±0.04, respectively) due to differences in frequency of expression of some biomarkers in the two case series. Both models were then validated on the independent series of 81 cases, with very good to excellent ability to predict subtype (κ=0.85±0.06 and 0.78±0.07, respectively). A nine-marker immunohistochemical maker panel can be used to objectively support classification into one of the five major subtypes of ovarian carcinoma.