An institutional experience with DICER1 mutated thyroid nodules-evaluating the cytomorphology and molecular phenotype.

INTRODUCTION: DICER1 mutated thyroid nodules are commonly seen in pediatric populations often, as part of DICER1 syndrome. We seek to evaluate DICER1 mutated thyroid nodules in adult populations to assess whether there exists distinctive clinical, cytologic, histologic, and molecular characteristics that underline our institutional cohort. MATERIALS AND METHODS: Retrospective analysis was performed on all fine-needle aspiration (FNA) specimens with a corresponding ThyroSeq panel, to select a cohort of cases with DICER1 mutations. Clinical, radiologic, and cytology materials were reviewed, and histology was reviewed for corresponding resection cases were available. ThyroSeq panel was further scrutinized for additional molecular alterations and variant allele frequency. RESULTS: DICER1 mutated thyroid nodules (n = 8), more commonly occurred in younger adults (P = 0.01) with larger (P = 0.01) nodules and only in female patients in our cohort. FNA commonly demonstrates cellular specimens with banal cytomorphologic cues including regular nuclei, inconspicuous nucleoli, smooth nuclear membranes, and abundant colloid. On retrospective review by 2 cytopathologists, the lesions were frequently diagnosed as Bethesda II (5 of 8) by both reviewers. Histology, when available, showed that all nodules were categorized as follicular adenomas (5 of 5), often demonstrating macrofollicles with papillary excrescences demonstrating bland nuclei (4 of 5). DICER1 mutational profile revealed a variant allele frequency of >40% in 25% of cases (2 of 8) and >30% in an additional 4 cases, highlighting a possible germline association. CONCLUSIONS: DICER1 mutated nodules may be under-reported due to banal cytomorphologic features and may be associated with an underlying germline alteration.

SARS-CoV-2 Infection-Associated Hemophagocytic Lymphohistiocytosis.

OBJECTIVES: A subset of coronavirus disease 2019 (COVID-19) patients exhibit clinical features of cytokine storm. However, clinicopathologic features diagnostic of hemophagocytic lymphohistiocytosis (HLH) have not been reported. We studied the reticuloendothelial organs of 4 consecutive patients who died of COVID-19 and correlated with clinical and laboratory parameters to detect HLH. METHODS: Autopsies were performed on 4 patients who died of COVID-19. Routine H&E staining and immunohistochemical staining for CD163 were performed to detect hemophagocytosis. Clinical and laboratory results from premortem blood samples were used to calculate H-scores. RESULTS: All 4 cases demonstrated diffuse alveolar damage within the lungs. Three of the 4 cases had histologic evidence of hemophagocytosis within pulmonary lymph nodes. One case showed hemophagocytosis in the spleen but none showed hemophagocytosis in liver or bone marrow. Lymphophagocytosis was the predominant form of hemophagocytosis observed. One patient showed diagnostic features of HLH with an H-score of 217, while a second patient likely had HLH with a partial H-score of 145 due to a missing triglyceride level. The remaining 2 patients had H-scores of 131 and 96. CONCLUSIONS: This is the first report of severe acute respiratory syndrome coronavirus 2-associated HLH. Identification of HLH in a subset of patients with severe COVID-19 will inform clinical trials of therapeutic strategies.