Primary effusion lymphoma (PEL) is a rare, aggressive B-cell lymphoma that usually localizes to serous body cavities to subsequently form effusions in the absence of a discrete mass. Although some tumors can develop in extracavitary locations, the areas most often affected include the peritoneum, pleural space, and the pericardium. PEL is associated with the presence of human herpesvirus 8 (HHV8), also called the Kaposi sarcoma-associated herpesvirus (KSHV), with some variability in transformation potential suggested by frequent coinfection with the Epstein-Barr virus (EBV) (~80%), although the nature of the oncogenesis is unclear. Most patients suffering with this disease are to some degree immunocompromised (e.g., Human immunodeficiency virus (HIV) infection or post-solid organ transplantation) and, even with aggressive treatment, prognosis remains poor. There is no definitive guideline for the treatment of PEL, although CHOP-like regimens (cyclophosphamide, doxorubicin, vincristine, and prednisone) are frequently prescribed and, given the rarity of this disease, therapeutic focus is being redirected to personalized and targeted approaches in the experimental realm. Current clinical trials include the combination of lenalidomide and rituximab into the EPOCH regimen and the treatment of individuals with relapsed/refractory EBV-associated disease with tabelecleucel.

Hematopoietic stem cell aging, through the acquisition of somatic mutations, gives rise to clonal hematopoiesis (CH). While a high prevalence of CH has been described in otherwise healthy older adults, CH confers an increased risk of both hematologic and non-hematologic diseases. Classification of CH into clonal hematopoiesis of indeterminate potential (CHIP) and clonal cytopenia of undetermined significance (CCUS) further describes this neoplastic myeloid precursor state and stratifies individuals at risk of developing clinically significant complications. The sequential acquisition of driver mutations, such as DNMT3A, TET2, and ASXL1, provide a selective advantage and lead to clonal expansion. Inflammation, microbiome signatures, and external selective pressures also contribute to clonal evolution. Despite significant progress in recent years, the precise molecular mechanisms driving CH transformation to hematologic neoplasms are not well defined. Further understanding of these complex mechanisms may improve risk stratification and introduce therapeutic interventions in CH. Here we discuss the genetic drivers underpinning CH, mechanisms for clonal evolution, and transformation to hematologic neoplasm.

Nucleophosmin (NPM1) is a multifunctional protein with both proliferative and growth-suppressive roles in the cell. In humans, NPM1 is involved in tumorigenesis via chromosomal translocations, deletions, or mutation. Acute myeloid leukemia (AML) with mutated NPM1, a distinct diagnostic entity by the current WHO Classification of myeloid neoplasm, represents the most common diagnostic subtype in AML and is associated with a favorable prognosis. The persistence of NPM1 mutation in AML at relapse makes this mutation an ideal target for minimal measurable disease (MRD) detection. The clinical implication of this is far-reaching because NPM1-mutated AML is currently classified as being of standard risk, with the best treatment strategy (transplantation versus chemotherapy) yet undefined. Myeloid neoplasms with NPM1 mutations and <20% blasts are characterized by an aggressive clinical course and a rapid progression to AML. The pathological classification of these cases remains controversial. Future studies will determine whether NPM1 gene mutation may be sufficient for diagnosing NPM1-mutated AML independent of the blast count. This review aims to summarize the role of NPM1 in normal cells and in human cancer and discusses its current role in clinical management of AML and related myeloid neoplasms.

Cytogenetic evolution (CGE) in patients with myeloid neoplasms who relapsed after an allogeneic (allo) hematopoietic cell transplantation (HCT) has been evaluated by only few studies. The effect of the CGE on survival of relapsed allo-HCT recipients is not clear. The effect of previously received chemotherapy to induce CGE in this patient population has not been studied. The aims of our study are to (1) characterize the patterns of cytogenetic change in patients with myeloid neoplasms who relapsed after an allo-HCT, (2) evaluate the effect of CGE on survival, and (3) explore the association of CGE with previous chemotherapy (including the lines of salvage therapy, type of induction, and conditioning therapy). Of 49 patients with a myeloid malignancy (27 acute myeloid leukemia [AML], 19 myelodysplastic syndrome [MDS]/myeloproliferative neoplasm [MPN], and 3 chronic myelogenous leukemia) who relapsed after an allo-HCT, CGE was observed in 25 (51%), whereas 24 patients had unchanged cytogenetic findings at relapse. The CGE group carried more cytogenetic abnormalities at original diagnosis. The most frequent cytogenetic change was the acquisition of 3 or more new chromosomal abnormalities followed by acquisition of unbalanced abnormalities, aneuploidy, and emergence of apparently new clones unrelated to the original clone. The CGE cohort had higher proportion of MDS and MPN and fewer patients with de novo AML. Disease risk assessment category showed a trend to higher frequency of high-risk patients in the CGE group, though the difference was not statistically significant. Time from diagnosis to transplantation and time from transplantation to relapse were not different between the CGE and non-CGE groups. CGE and non-CGE cohorts had similar exposures to salvage therapy and to induction chemotherapy, as well as similar conditioning regimens; thus, no particular type of chemotherapy emerged as a predisposing factor to CGE. CGE was associated with significantly shortened post-transplantation and postrelapse survival when compared with those of the non-CGE group (P = .004 and P < .001, respectively). Our results underscore the significance of CGE in progression of myeloid malignancies after an allo-HCT.

Context.—: The pathologic diagnosis of pulmonary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) is challenging. Objective.—: To evaluate the diagnostic usefulness and limitations of current diagnostic strategies for pulmonary MALT lymphoma. Design.—: A retrospective review of 120 cases of pulmonary MALT lymphoma from 2014 through 2021 was performed. Results.—: Clinicoradiologic presentations overlapped with previous observations in patients with MALT lymphoma, such as a wide age range, female predominance, frequent association with autoimmune disease or immunodeficiency, and broad imaging findings. The histopathologic diagnosis was based on a combination of morphology, immunohistochemistry, and demonstration of B-cell lineage clonality. Two-thirds (76 of 113) of MALT lymphomas had lymphoplasmacytoid cytomorphology. Occasionally, MALT lymphomas were associated with granulomas/giant cells (29%, 35 of 120) or immunoglobulin deposition disease (21%, 25 of 120), including light chain/heavy chain deposition disease, amyloidosis, and/or crystal storing histiocytosis. While CD5, CD10, Bcl-2, and Bcl-6 rarely revealed aberrancies, aberrant CD43 expression either on B-cells or on plasma cells was detected in 42% (27 of 64) of cases, including cases for which proof of clonality could not be obtained. κ/λ in situ hybridization was particularly useful for tumors with lymphoplasmacytoid morphology but performed poorly in lymphomas having no plasmacytic differentiation. κ/λ immunohistochemistry showed no additional usefulness when applied together with κ/λ in situ hybridization. Immunoglobulin gene rearrangement studies by polymerase chain reaction achieved high detection rates of clonality in all cytomorphologic subgroups. Conclusions.—: Our study offers a practical evaluation of common diagnostic tests in pulmonary MALT lymphoma. We offer recommendations for a diagnostic workup that takes into consideration the usefulness and the specific limitations of the various diagnostic strategies.