Carol J. Holman

IgG4‐related disease and idiopathic multicentric Castleman disease are rare conditions that can present with overlapping features, complicating diagnosis and delaying proper treatment.

Although Rosai-Dorfman disease has nonspecific imaging features, imaging remains essential for delineating disease extent, predicting prognosis, and assessing treatment response once the diagnosis is established through integrated clinical, imaging, and histopathologic evaluation.

Objectives: Hypereosinophilia (HE), defined as an absolute eosinophil count (AEC) ≥1.5 × 109/L, poses diagnostic challenges when distinguishing clonal myeloid neoplasms from idiopathic HE/hypereosinophilic syndrome, particularly under WHO-HAEM5 criteria. We characterized patients with HE of persistent/unknown cause (HEPU) undergoing bone marrow (BM) evaluation to refine diagnostic classification. Methods: We identified 307 BM biopsy specimens (2015-2023) mentioning “eosinophilia.” Patients with defined reactive or clonal etiologies were classified as group 2 (known etiology, n = 269). The remaining patients constituted group 1 (HEPU, n = 38). We reviewed clinical data, morphology, cytogenetics/fluorescence in situ hybridization (FISH), and myeloid next-generation sequencing (NGS), assigning final diagnoses via the fifth edition of the World Health Organization Classification of Haematolymphoid Tumours (WHO-HAEM5) criteria and the 2022 International Consensus Classification (ICC). Results: Compared to group 2, patients with HEPU were younger (median 48 vs 62 years; P = .004) and exhibited higher initial AECs (2.8 vs 0.6 × 109/L; P < .001). Comprehensive workup reclassified the HEPU cohort (n = 38) into the idiopathic spectrum (36.8%), reactive eosinophilia (28.9%), clonal disorders including myeloid and lymphoid neoplasms (28.9%), and mixed reactive vs idiopathic (5.3%) categories. While cytogenetics/FISH were largely noncontributory (detecting FIP1L1::PDGFRA in 2 cases), myeloid NGS detected mutations in 47% (7/15) of tested patients with HEPU, involving genes such as TP53, BCOR, SF3B1, and TET2. Conclusions: Integrated clinicopathologic and molecular assessment reclassified most HEPU cases as reactive or clonal, with only 39% remaining idiopathic. Myeloid NGS frequently identifies clonal variants critical for refining HE classification, although results require cautious interpretation within the WHO-HAEM5 and ICC 2022 context.

Objectives: We evaluated and compared the peripheral blood findings in patients with acute COVID-19 vs other viral respiratory infections. Methods: We retrospectively reviewed peripheral blood counts and smear morphology in patients with a positive viral respiratory panel (VRP) or SARS-CoV-2 test. Results: A total of 97 peripheral blood samples (COVID-19 infection, 53; VRP positive, 44) from 50 patients (mean [SD] age, 45.8 [20.8] years; females 52%) were reviewed. There were no statistically significant differences in the demographic characteristics between the 2 groups. The most common peripheral blood abnormalities were anemia, thrombocytopenia, absolute lymphopenia, and reactive lymphocytes. The following peripheral blood findings were significantly associated with other viral respiratory infections compared with COVID-19 infection: low red blood cell count, low hematocrit, high mean corpuscular volume, thrombocytopenia, low mean platelet volume, high red cell distribution width, band neutrophilia, and toxic granulation in neutrophils. Conclusions: Our study showed that there are several peripheral blood count and morphologic abnormalities seen in patients with COVID-19, but most of these findings lack specificity as they are also seen in the other viral respiratory infections.

Acute myeloid leukemia (AML) is maintained by self-renewing leukemic stem cells (LSCs). A fundamental problem in treating AML is that conventional therapy fails to eliminate LSCs, which can reinitiate leukemia. Heat shock transcription factor 1 (HSF1), a central regulator of the stress response, has emerged as an important target in cancer therapy. Using genetic Hsf1 deletion and a direct HSF1 small molecule inhibitor, we show that HSF1 is specifically required for the maintenance of AML, while sparing steady-state and stressed hematopoiesis. Mechanistically, deletion of Hsf1 dysregulates multifaceted genes involved in LSC stemness and suppresses mitochondrial oxidative phosphorylation through downregulation of succinate dehydrogenase C (SDHC), a direct HSF1 target. Forced expression of SDHC largely restores the Hsf1 ablation-induced AML developmental defect. Importantly, the growth and engraftment of human AML cells are suppressed by HSF1 inhibition. Our data provide a rationale for developing efficacious small molecules to specifically target HSF1 in AML.

Peripheral blood abnormalities like variant lymphocytes, Pelger-Huët anomaly, and granulocytic left shift have been reported in patients with active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the specificity of these findings for SARS-CoV-2 infection is unknown as there is a lack of comparative data between SARS-CoV-2 and other viral respiratory illnesses. In this study, we examined the peripheral blood findings in patients admitted with acute SARS-CoV-2 and other viral respiratory infections. We reviewed the complete blood differential counts and peripheral blood leukocyte morphology on peripheral smears received from patients admitted with a positive viral respiratory panel (VRP) or SARS-CoV-2 test from March 20^th – May 31^st, 2020. Cases where the specimen was collected 10 days after the symptom onset were excluded. During the study period, we reviewed 122 blood specimens from 59 patients (mean±SD age: 46.7±21.7 years, female: 49.2%). Of these, 53 (43.4%) specimens were from patients with SARS-CoV-2 infection and 69 (56.6%) specimens from patients with other viral respiratory infections. There were no significant differences in the demographic characteristics of the two groups. For the blood cell counts, absolute leukopenia (11.3% versus 40.6%, P), low red blood cell count (45.3% versus 78.3%, P), low hemoglobin (56.6% versus 76.8%, P0.018), low hematocrit (43.4% versus 78.3%, P), high mean corpuscular volume (3.8% versus 31.9%, P), high mean corpuscular hemoglobin concentration (1.9% versus 14.5%, P0.016), thrombocytopenia (11.3% versus 58.0%, P), low mean platelet volume (3.9% versus 15.0%, P0.048), and high red cell distribution width (13.2% versus 53.6%, P) were all less common in patients with SARS-CoV-2 infection as compared to those with other viral respiratory infections. There were no significant differences in the differential leukocyte counts between the two groups, except neutropenia was less common in SARS-CoV-2 infection (17.3% versus 44.1%, P0.002). Among the peripheral blood smear findings, toxic granulation in neutrophils (1.9% versus 42.01%, P) and the presence of myelocytes (13.2% versus 29.0%, P0.042) were less commonly seen in SARS-CoV-2 infection. Other findings like elevated band neutrophils (8.3% versus 27.5%, P0.081), presence of metamyelocytes (13.2% versus 27.5%, P0.060), presence of promyelocytes (5.7% versus 13.0%, P0.186), plasmacytoid lymphocytes (66.7% versus 91.7%, P0.177), and hypogranular neutrophils (7.6% versus 8.7%, P0.819) showed a trend towards being less common in patients with SARS-CoV-2 infection but the differences were not statistically significant. On the contrary, reactive lymphocytes (43.4% versus 33.3%, P0.257) and uni- or bi-lobate neutrophils showed a trend towards being more common in SARS-CoV-2 infection (18.9% versus 17.4%, P0.833), however, the differences were not statistically significant. Abnormalities in peripheral blood count and blood smear findings seem to be less frequent in hospitalized patients with SARS-CoV-2 infection as compared to those with other viral respiratory infections.

Objectives: Follicular helper T cell (TFH) markers are expressed in angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma of the TFH phenotype (PTCL-TFH). However, differential expression and coexpression of these markers in benign and other malignant lymphoid proliferations have not been well studied. Methods: We performed programmed death-1 (PD-1), C-X-C motif chemokine ligand 13 (CXCL13), inducible costimulator (ICOS), CD10, and B-cell lymphoma 6 protein (BCL-6) immunohistochemistry on AITL, PTCL not otherwise specified (PTCL-NOS), PTCL-TFH, T-cell or histiocyte-rich large B-cell lymphoma (THRLBCL), classic Hodgkin lymphoma (CHL), atypical paracortical hyperplasia (PCH), progressive transformation of germinal centers (PTGC), and reactive follicular hyperplasia (RFH). Results: CXCL13 and ICOS were more sensitive but less specific for AITL than PD-1, CD10, and BCL-6. Moreover, 74% of AITL (none of PTCL-NOS or PTCL-TFH) coexpressed more than 2 TFH markers. In background T cells of THRLBCL, 70% of cases coexpressed more than 1 marker. The background T cells of CHL expressed all TFH markers except CD10 in all cases. In addition, 13% of PCH cases coexpressed more than 1 marker. In RFH and PTGC, all markers were expressed mainly in germinal centers with rare extrafollicular staining. Conclusions: AITL, PTCL-NOS, and PTCL-TFH show differential expression of TFH markers. AITL frequently coexpresses more than 2 TFH markers. TFH markers can be expressed in PCH and in background T cells of THRLBCL and CHL. Consequently, caution should be used before a diagnosis of AITL is established, particularly with limited samples.

Objectives: We sought to investigate the clinical utility of flow cytometry (FC) and fluorescence in situ hybridization (FISH) in the workup of myeloma.Methods: We retrospectively reviewed the reports of bone marrow biopsies received for myeloma evaluation between October 2015 and January 2019.Results: A total of 1,708 biopsy specimens from 469 myeloma patients (mean age, 64.5 years [SD, 9.3]; female, 41.4%) were reviewed. Both FC and FISH had comparable detection rates at the time of initial diagnosis (97.6% vs 98.8%) and for follow-up cases (28.6% vs 28.2%). FC and FISH results were concordant in 98.8% of the initial diagnosis cases and 89.6% of the follow-up cases. The FISH-positive (FISH+)/FC-negative (FC−) discordance and FISH−/FC+ discordance occurred among 81 (5.0%) and 87 (5.4%) follow-up cases. In comparison with all concordant cases, FISH+/FC− discordant cases were more likely to have received treatment with daratumumab (P < .05).Conclusions: Plasma cell–enriched FISH and FC have comparable abnormal plasma cell detection rates, and approximately 10% of the follow-up cases have discordant FISH and FC results in which residual disease is detected by only one of these modalities. FISH testing should be considered for cases with negative FC, especially in patients who have received treatment with daratumumab or in cases in which there is concern about specimen adequacy.

As a result of an author oversight in the original article [1], the legend of Figure 5A and C is inaccurate and one panel in Figure 5C (FOXM1N H929 cells shown in the top row, left) is wrong.