Explore the vast range of titles available.

Abstract Objectives Ionized calcium binding adaptor molecule 1 (IBA1), a marker of microglia/macrophages, has not been investigated in human hematopathologic contexts. We evaluated its expression in mature and immature neoplasms of monocytic/histiocytic and dendritic cell (DC) origin. Methods Immunohistochemistry for IBA1, CD14, CD68, and CD163 was performed on a total of 114 cases, including a spectrum of monocytic/histiocytic and DC neoplasms (20 tissue based and 59 bone marrow based) and several nonhistiocytic/monocytic/DC neoplasms as control groups (15 tissue based and 20 bone marrow based). Results IBA1 expression was observed in all types of mature tissue-based histiocytic/DC neoplasms (20/20) but not in the corresponding control group (0/15). In bone marrow–based cases, IBA1 was expressed in most acute myeloid leukemias (AMLs) with monocytic differentiation (48/53), both blastic plasmacytoid dendritic cell neoplasms (2/2), and all chronic myelomonocytic leukemias (4/4), while it was positive in only one nonmonocytic AML (1/15) and none of the acute lymphoblastic leukemias (0/5). Collectively, IBA1 showed much higher sensitivity and specificity (93.7%, 97.1%) compared with CD14 (65.4%, 88.2%), CD68 (74.4%, 74.2%), and CD163 (52.6%, 90.6%). Conclusions IBA1 is a novel, highly sensitive, and specific marker for diagnosing neoplasms of monocytic/histiocytic and DC origin.

A 54-year-old man with an apparently unremarkable previous medical history presented from an outside hospital with abdominal pain and unintentional weight loss. Hematoxylin and eosin-stained histological images of this biopsy demonstrated distortion of architecture by interfollicular vaguely nodular expanses (evident on low power, indicated by white circles) of small to medium-sized cytologically monotonous cells with moderately dispersed chromatin (high-power inset) (Figure 1). The pDC nodules were the prominent morphological feature in the LN in this case, which was performed before bone marrow studies (and prior to knowledge of the FBC) and prompted consideration of CMML on the LN biopsy.

Natural killer (NK) cells are lymphocytes of the native immune system that play a pivotal role in host defense and immune surveillance. While the conceptual view of NK-neoplasms is evolving, little is known about the rare NK lymphoblastic leukemia (NK-LL), which remains as a provisional entity in the 2016 WHO Classification. The goal of this study is to characterize NK-LL cases and compare with other CD56 co-expressing acute leukemias. We identified 105 cases, diagnosed as NK-LL (6), CD56+ acute undifferentiated leukemia (AUL) (6), CD56+ T-lymphoblastic leukemia (T-LL) (51), and CD56+ acute myeloid leukemia (AML) (42). Compared to AUL patients, NK-LL patients were significantly younger (p = 0.021) and presented with higher white blood cell (WBC) (p = 0.037) and platelet counts (p = 0.041). Flow cytometry showed more frequent expression of cytoplasmic CD3 (cCD3, p = 0.064) and CD33, (p = 0.065), while HLA-DR was significantly absent from NK-LL (p = 0.035) compared to AUL. Compared to T-ALL, NK-LL cases showed less frequent cCD3 (p = 0.002), CD4 (p = 0.051), and CD10 expression (p = 0.06). The frequency of abnormal karyotypes was similar between NK-LL, AUL, and T-ALL. The mutational profile differed in four leukemia groups, with a significance enrichment of NOTCH1 (p = 0.002), ETV6 (p = 0.002) and JAK3 (p = 0.02) mutations in NK-LL as compared to AML. As compared to T-ALL, NK-LL cases showed a higher number of total mutations (p = 0.04) and significantly more frequent ETV6 mutations (p = 0.004). Clinical outcome data showed differences in overall survival between all four groups (p = 0.0175), but no difference in event free survival (p = 0.246). In this largest study to date, we find that that NK-LL shows clinical presentation, immunophenotypic and molecular characteristics distinct from AUL, T-ALL, and AML. Our findings suggest NK-LL is a distinct acute leukemia entity and should be considered in the clinical diagnosis of acute leukemias of ambiguous lineage.

Idiopathic acquired aplastic anemia (AA) is a rare lymphocyte-mediated bone marrow aplasia. No specific mechanisms or triggers of AA have been identified. We recently observed several patients who developed AA after Hodgkin lymphoma (HL). We hypothesized that the co-occurrence of HL and AA is not random and may be etiologically significant. To test this hypothesis, we determined the incidence of AA in HL patients at our institution. We identified four patients with co-occurring HL and AA, with the incidence of AA in HL patients >20-fold higher compared to the general population. We identified 12 additional patients with AA and HL through a systematic literature review. Of the 16 total patients,15 (93.8%) developed AA after or concurrent with a HL diagnosis. None of the patients had marrow involvement by HL. Five of 15 patients were in complete remission from HL at the time of AA diagnosis, and six had a concurrent presentation with no prior cytotoxic therapy, with diagnostic timeframe information unavailable for four patients. The median interval between HL diagnosis and AA onset was 16 months, ranging from concurrent to 14 years after a HL diagnosis. The median survival after AA diagnosis was 14 months (range: 1 month to 20 years). Our results show that patients with HL have a higher incidence of AA compared to the general population and suggest that HL-related immune dysregulation may be a risk factor for AA. Better recognition and management of AA in HL patients is needed to improve outcomes in this population.

Polymerase chain reaction (PCR) followed by next-generation sequencing (NGS) studies revealed both a monoclonal TRG (graphical representation of dominant clones, bottom left), while a monoclonal IGH rearrangement (capillary electrophoresis, bottom right) was detected by PCR using Biomed-2 FR2 and FR3 primers. CONFLICT OF INTEREST STATEMENT The authors have no conflicts of interest to disclose. DATA AVAILABILITY STATEMENT Data sharing is not applicable to this article as no new data were created or analyzed in this study.

Background Acute myeloid leukemia (AML) with RAM immunophenotype is a newly recognized high‐risk AML immunophenotypic subcategory characterized by blasts with bright expression of CD56 and weak to absent expression of CD45, HLA‐DR, and CD38, as first described by the Children's Oncology Group (COG). The relationship between AML‐RAM and other CD56‐positive acute leukemias is unclear. The goal of this study is to characterize the clinicopathological characteristics of AML with RAM phenotype and compare them with other CD56 co‐expressing acute leukemias. Methods From a multi‐institutional search, we identified a total of 160 CD56+ acute leukemia cases, including AML‐RAM (n = 28), CD56+ acute undifferentiated leukemia (AUL) (n = 11), CD56+ T‐lymphoblastic leukemia (n = 39), and CD56+ AML (n = 81). We compared the clinical and pathologic findings of these groups. Results AML‐RAM patients were significantly younger and presented with significantly higher platelet and white blood cell counts and bone marrow (BM) blast percentages when compared to AUL (p > 0.05) and had higher median BM blast percentages than T‐ALL and CD56+ AML groups (both p < 0.05). Flow cytometry showed significantly brighter expression of CD56 on blasts as compared to other CD56+ AML cases, partial CD34 expression compared to AUL, and AML, weak‐to‐absent CD38 expression compared to all groups, and absent HLA‐DR and terminal deoxynucleotidyl transferase as compared to AUL and T‐ALL (all p < 0.05). The frequency of abnormal karyotypes was significantly higher among RAM when compared to all groups (p < 0.05). Next‐generation sequencing profiles differed among the leukemia groups, with significant enrichment of CBFA2T3::GLIS2 fusions (p < 0.05) and TP53 mutations (p < 0.05) in RAM cases compared to other AML control groups, and U2AF1 (p < 0.05), serine and arginine‐rich splicing factor 2 (p < 0.05), and BCL6 co‐repressor (p < 0.05) mutations compared to AUL. Clinical outcome analysis demonstrated significantly lower 3‐year overall survival of the RAM subgroup (36 months) compared to control groups (p = 0.002). Conclusion We find that AML with RAM phenotype occurs primarily in younger ages, with distinct clinicopathological, immunophenotypic, and mutational presentations, and worse prognosis. This diagnosis should be considered in the clinical differential diagnosis of CD56‐positive acute leukemias.

Although cytogenetics-based prognostication systems are well described in acute myeloid leukemia (AML), overall survival (OS) remains highly variable within risk groups. An integrated genetic prognostic (IGP) model using cytogenetics plus mutations in nine genes was recently proposed for patients ≤60 years to improve classification. This model has not been validated in clinical practice. We retrospectively studied 197 patients with newly diagnosed de novo AML. We compared OS curves among the mutational profiles defined by the IGP model. The IGP model assigned patients with intermediate cytogenetics as having favorable, intermediate or unfavorable mutational profiles. The IGP model reassigned 50 of 137 patients with intermediate cytogenetics to favorable or unfavorable mutational profiles. Median OS was 2.8 years among 14 patients with intermediate cytogenetics and favorable mutational profiles (mutant NPM1 and mutant IDH1 or IDH2) and 1.3 years among patients with intermediate mutational profiles. Among patients with intermediate cytogenetics labeled as having unfavorable mutational profiles, median OS was 0.8 years among 24 patients with FLT3-ITD positive AML and high-risk genetic changes (trisomy 8, TET2 and/or DNMT3A) and 1.7 years among 12 patients with FLT3-ITD negative AML and high-risk mutations (TET2, ASXL1 and/or PHF6). OS for patients with intermediate cytogenetics and favorable mutational profiles was similar to OS for patients with favorable cytogenetics (p = 0.697) and different from patients with intermediate cytogenetics and intermediate mutational profiles (p = 0.028). OS among patients with FLT3-ITD positive AML and high-risk genetic changes was similar to patients with unfavorable cytogenetics (p = 0.793) and different from patients with intermediate IGP profile (p = 0.022). Patients with FLT3-ITD negative AML and high-risk mutations, defined as 'unfavorable' in the IGP model, had OS similar to patients with intermediate IGP profile (p = 0.919). The IGP model was not completely validated in our cohort. However, mutations in six out of the nine genes can be used to characterize survival (NPMI, IDH1, IDH2, FLT3-ITD, TET2, DNMT3A) and allow for more robust prognostication in the patients who are re-categorized by the IGP model. These mutations should be incorporated into clinical testing for younger patients outside of clinical trials, in order to guide therapy.

A patient with refractory CLL had delayed development of the rapid tumor lysis syndrome and remission after an infusion of T cells engineered to express an antigen receptor capable of recognizing B cells (CD19) coupled to two signaling molecules. With the use of gene-transfer techniques, T cells can be genetically modified to stably express antibodies on their surface, conferring new antigen specificity. Chimeric antigen receptors combine an antigen-recognition domain of a specific antibody with an intracellular domain of the CD3-zeta chain or FcγRI protein into a single chimeric protein. 1 , 2 Although chimeric antigen receptors can trigger T-cell activation in a manner similar to that of endogenous T-cell receptors, a major impediment to the clinical application of this technique to date has been limited in vivo expansion of chimeric antigen receptor T cells and disappointing clinical activity. 3 , 4 Chimeric antigen . . .

The etiology of anemia in adults is often multifactorial. This case highlights an uncommon combination of causes of anemia and the importance of a diagnostic workup guided by a patient's unique history, risk factors, and laboratory findings. The etiology of anemia in adults is often multifactorial. This case highlights an uncommon combination of causes of anemia and the importance of a diagnostic workup guided by a patient's unique history, risk factors, and laboratory findings.

Antitumor effects were noted in a heavily pretreated patient with CD19-negative myeloma who received CD19-specific chimeric antigen receptor T cells. The mechanism of the antitumor effects is unclear. Transduction of autologous T cells to express CD19-specific chimeric antigen receptors is a promising immunotherapeutic approach for the treatment of B-cell cancers. 1 We previously reported sustained regression of refractory chronic lymphocytic leukemia and B-cell acute lymphoblastic leukemia 2 – 5 after infusion of CTL019 cells, which consist of autologous T cells expressing a CD3-zeta/CD137–based anti-CD19 chimeric antigen receptor from a lentiviral vector. Multiple myeloma is a B-lineage cancer that is reported to express CD19 infrequently 6 ; hence, CD19 is not generally considered a valid immunotherapeutic target in multiple myeloma. Several reports, however, have suggested that a minor component of the multiple myeloma . . .