Thyroid cytology during the COVID-19 pandemic: a single centre experience

Background: In our study, thyroid fine-needle aspiration biopsy (FNAB) data in the same calendar period of 1 year before and after the COVID-19 pandemic were compared.Methods: Thyroid FNAB data for the same calendar period of 1 year before and after the COVID-19 pandemic were included in the study. The patients were grouped according to age, gender and thyroid FNABs according to the Bethesda system for reporting thyroid cytopathology, and the data of both groups were compared considering the diagnoses of the patients who underwent thyroid surgery afterwards.Results: In the post-pandemic period, the number of thyroid FNABs and the number of patients over the age of 40 decreased (all p<0.001). In the post-pandemic period, the rates of atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS), follicular neoplasm or suspicious for a follicular neoplasm (FN/SFN), suspicious for malignancy, and malignant cytology increased despite the decrease in the number of patients (p=0.001). Furthermore, the malignant tumour rate was 1.4% before the pandemic in patients who underwent surgical thyroidectomy and/or lobectomy; this rate was 3.5% in the post-pandemic period (p=0.045).Conclusions: We found an increase in the percentage of AUS/FLUS, FN/SFN, suspicious for malignancy, and malignant cases during the period when there were restrictions, such as pandemics, and the sampling was reduced. This finding is valuable in terms of detecting an increased malignancy rate by performing less thyroid FNAB by carefully determining the indications for thyroid aspiration biopsy regarding the latest guidelines.

Monoclonal gammopathy of undetermined significance and COVID-19: a population-based cohort study

Multiple myeloma (MM) patients have increased risk of severe coronavirus disease 2019 (COVID-19) when infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Monoclonal gammopathy of undetermined significance (MGUS), the precursor of MM has been associated with immune dysfunction which may lead to severe COVID-19. No systematic data have been published on COVID-19 in individuals with MGUS. We conducted a large population-based cohort study evaluating the risk of SARS-CoV-2 infection and severe COVID-19 among individuals with MGUS. We included 75,422 Icelanders born before 1976, who had been screened for MGUS in the Iceland Screens Treats or Prevents Multiple Myeloma study (iStopMM). Data on SARS-CoV-2 testing and COVID-19 severity were acquired from the Icelandic COVID-19 Study Group. Using a test-negative study design, we included 32,047 iStopMM participants who had been tested for SARS-CoV-2, of whom 1754 had MGUS. Among these participants, 1100 participants, tested positive, 65 of whom had MGUS. Severe COVID-19 developed in 230 participants, including 16 with MGUS. MGUS was not associated with SARS-CoV-2 infection (Odds ratio (OR): 1.05; 95% confidence interval (CI): 0.81–1.36; p = 0.72) or severe COVID-19 (OR: 0.99; 95%CI: 0.52–1.91; p = 0.99). These findings indicate that MGUS does not affect the susceptibility to SARS-CoV-2 or the severity of COVID-19.

A Rare Cause of Acquired Factor X Deficiency in an 87-Year-Old Female

Factor X deficiency is a rare coagulopathy that can be inherited or acquired. Acquired factor X deficiency has been associated with plasma cell dyscrasias, amyloids, and use of vitamin K antagonists. Of plasma cell dyscrasias, most cases in the literature have been associated with multiple myeloma with or without concomitant AL amyloidosis. Here, we present a rare case of acquired isolated factor X deficiency in an elderly patient with immunoglobulin A (Ig A) monoclonal gammopathy of undetermined significance (MGUS). Herein, we highlight a rare cause of acquired factor X deficiency, and we hope to contribute to the growing literature of plasma cell dyscrasias associated with factor X deficiency.

Non-Invasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features Is Not a Cytological Diagnosis, but It Influences Cytological Diagnosis Outcomes: A Systematic Review and Meta-Analysis

Background: A low-risk thyroid tumour, non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was introduced in 2016. NIFTP criteria require a thorough histological examination to rule out capsular and lymphovascular invasion, which denies the possibility of preoperative cytological diagnosis. Nevertheless, since the adoption of the new entity, the cytology of NIFTP has been a subject of interest. Objectives: The present systematic review and meta-analysis investigate the cytological diagnosis of NIFTP. Method: An online PubMed literature search was conducted between March 1, 2020, and June 30, 2020, for all original articles considering the cytology of histologically proven NIFTP. The studies including data on fine needle aspiration specimens classified by The Bethesda System for Reporting Thyroid Cytology (TBSRTC) categories, risk of malignancy (ROMs) in the TBSRTC categories, and cytomorphological features of NIFTP were included in the meta-analysis. Non-English studies and case reports were excluded. The data were tabulated and statistical analysis was performed with Open Meta-Analyst program. Results: Fifty-eight studies with a total of 2,553 NIFTP cases were included in the study. The pooled prevalence of NIFTP cases was calculated among 25,892 surgically resected cases from 20 studies and the results show that NIFTP consisted 4.4% (95% confidence interval [CI]: 3.5–5.4%) of all cases. Most of the NIFTP cases (79.0%) belonged to the intermediate categories of TBSRTC. The pooled distribution of NIFTP cases in each TBSRTC category was 1.3% (95% CI: 0.8–1.7%) in non-diagnostic (ND), 8.9% (95% CI: 6.9–10.8%) in benign, 29.2% (95% CI: 25.0–33.4%) in atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS), 24.2% (95% CI: 19.6–28.9%) in follicular neoplasm (FN), 19.5% (95% CI: 16.1–22.9%) in suspicious for malignancy (SM), and 6.9% (95% CI: 5.2–8.7%) in malignant. Compared to pre-NIFTP era, the pooled risk differences of ROM were reduced by 2.4% in ND, 2.7% in benign, 8.2% in AUS/FLUS, 8.2% in FN, 7.3% in SM, and 1.1% in the malignant category. The cytomorphological features of NIFTP were similar to follicular variant of papillary thyroid carcinoma (FVPTC) but lesser to papillary thyroid carcinoma (PTC). Conclusions: Based on our results, NIFTP remains a histological diagnosis. Although cytomorphological features cannot be used in differentiating NIFTP from FVPTC, they may guide in separating NIFTP from PTC. Features such as papillae, microfollicles, giant cells, psammoma bodies, and the amount of papillary-like nuclear features should be taken into account when suspicious of NIFTP. NIFTP should not have papillae or psammoma bodies, and giant cells were rarely observed.

Management of patient with immune thrombocytopenia with antiphospholipid syndrome and monoclonal gammopathy of undetermined significance

Immune thrombocytopenia with antiphospholipid syndrome and monoclonal gammopathy of undetermined significance poses therapeutic dilemmas – whether we should modify the immune thrombocytopenia treatment in antiphospholipid syndrome, what is the influence of monoclonal gammopathy of undetermined significance on the course of immune thrombocytopenia and whether we should and how to prevent the progression of monoclonal gammopathy of undetermined significance to multiple myeloma.

Similar Survival and Genetic Features between Clonal Cytopenia of Undetermined Significance and Lower-Risk Myelodysplastic Syndrome

Background Idiopathic cytopenia of undetermined significance (ICUS) is characterized by a persistent and clinically significant cytopenias which does not meet the diagnostic criteria for myelodysplastic syndrome (MDS). In some patients with ICUS, disease evolution to MDS or acute myeloid leukemia after variable periods of time was observed in several studies. However, the incidence and predictive factors of progression as well as management guidelines for ICUS patients are not well established. We aimed to identify the clinical and genetic characteristics of ICUS in comparison with lower-risk MDS for understanding the pathophysiologic features and providing guidance for treating physicians. Methods We performed targeted deep sequencing including 61 myeloid neoplasm-related genes with a MiSeqDx sequencer (Illumina) using bone marrow (BM) samples obtained from the patients with ICUS (n=139) and MDS (n=226) between May 2009 and December 2019. The cut-off level of variant allele frequency (VAF) was set to 2.0% of mutant allele reads. Cloncal cytopenia of undetermined significance (CCUS) was defined as ICUS with ≥ 2% VAF of mutations and lower-risk MDS was defined as MDS with revised international prognostic scoring system ≤3.5. Results When we compared the overall survival (OS) of the patients according to the disease subtypes, OS of CCUS (77.0% at 5-year) was significantly better than that of higher-risk MDS (41.0%, P&lt;.001) and worse than non-clonal ICUS (94.1%, P=.050), but it was similar to the OS of lower-risk MDS (67.9%, P=.363). Next, we compared the clinical and mutational features between CCUS (n=78) and lower-risk MDS (n=99). As shown in Table, there was no significant difference of patient characteristics between two groups except for higher hemoglobin level (10.5 vs. 9.0 g/dL, P=.008) in CCUS than lower-risk MDS, and the rate of red blood cell transfusion dependency was not different (P=.738). The median number of mutated genes of CCUS and lower-risk MDS were 1 (range, 0-4) and 1 (range, 0-6) (P=.651), and the median mutation numbers were 1 (range, 0-5) in CCUS and 2 (range, 0-7) in lower-risk MDS, respectively (P=.711). The mutational profiles of 61 genes were also similar between CCUS and lower-risk MDS except for SF3B1 (2.6% in CCUS and 18.2% in lower-risk MDS; P=.001) and STAT3 (5.1% in CCUS and 0% in lower-risk MDS; P=.023). Overall, 11 of 78 CCUS and 24 of 99 MDS died, and the causes of death were not different between two groups (P=.861). Conclusion In our study, CCUS and lower-risk MDS showed similar OS which was significantly better than higher-risk MDS and worse than non-clonal ICUS. The clinical and mutational characteristics were also similar except for the degree of anemia and the SF3B1 and STAT3 mutation. Our findings suggest that the patients with CCUS may be regarded and treated as the lower-risk MDS despite a lack of significant dysplasia or MDS-associated definitive chromosomal abnormality. Disclosures Choi: Ingenium Therapeutics, Daejeon, Korea: Consultancy, Current holder of individual stocks in a privately-held company. Lee: Ingenium Therapeutics, Daejeon, Korea: Consultancy, Current holder of individual stocks in a privately-held company. Lee: Korean Society of Hematology: Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Other: Advisory board; Astellas Pharma, Inc.: Consultancy, Honoraria, Other: Advisory board.