The diagnosis and management of suspected lymphoma in general practice.

With rapid advancements in diagnosis and treatment of malignancies, the gap between generalists and subspecialists continues to widen, particularly in cancers like lymphoma where the spectrum of disease varies from indolent to rapidly progressive. Prior to establishing with a hematologist/oncologist, patients must be accurately and comprehensively diagnosed and managed for lymphoma in the generalist setting. In the following manuscript, we review the common clinical presentations in which should raise concern for lymphoma. We summarize the literature regarding the role of laboratory studies including complete blood count and peripheral blood flow cytometry, the recommendations for lymph node sampling, the role and selection of imaging modalities, and ideal patient monitoring for high-risk clinical syndromes that may be encountered in lymphoma.

Clinical outcomes of patients referred for asymptomatic neutropenia: A focus on racial disparities in hematology.

BACKGROUND: Asymptomatic neutropenia is a common hematology referral, though standardized reference ranges and published clinical outcomes are lacking. METHODS: In our retrospective analysis, we evaluated demographics, laboratory, and clinical outcomes of adult patients referred to an academic hematology practice for evaluation of neutropenia from 2010 to 2018. Primary and secondary outcomes included incidence of hematologic disorders and rates of Duffy-null positivity by race, respectively. In a separate analysis, we reviewed absolute neutrophil count (ANC) reference ranges from publicly available Association of American Medical Colleges Medical School Member laboratory directories to assess institutional variations. RESULTS: In total, 163 patients were included, with disproportionate number of Black patients referred compared to local demographics. Twenty-three percent of patients (n = 38) were found to have a clinically relevant hematologic outcome (mean ANC of 0.59 × 109 /L), and only six were identified with ANC ≥1.0 × 109 /L. Incidence of hematologic outcomes was lowest among Black patients (p = .05), and nearly all Blacks who underwent Duffy-null phenotype testing were positive (93%), compared to 50% of Whites (p = .04). In separate review of laboratory directories, we confirmed wide variation in ANC lower limit of normal (0.91-2.40 × 109 /L). CONCLUSION: Hematologic disorders were rare in patients with mild neutropenia and among Blacks, highlighting the need to standardize hematological ranges representative of non-White communities.

Mixed Adenosquamous Cell Carcinoma of the Prostate with Paired Sequencing on the Primary and Liver Metastasis.

This report aims to shed light on the intricate challenges encountered during the diagnosis and treatment of an uncommon variant of prostate cancer-mixed adenosquamous cell carcinoma of the prostate. Prostate cancers of this nature pose distinctive diagnostic and therapeutic dilemmas due to their rarity and complex histological composition. We present a case of a 63-year-old man with metastatic prostate cancer, featuring adenocarcinoma with squamous cell differentiation, who underwent a multimodal treatment approach. The patient responded to first-line carboplatin, docetaxel, and androgen deprivation therapy, followed by androgen receptor pathway inhibitor (ARPI) maintenance. However, disease progression led to radiation therapy and a subsequent switch to Lutetium (177Lu) vipivotide tetraxetan after chemotherapy challenges. Comprehensive genetic profiling revealed shared mutations in the prostate and liver lesions, emphasizing the role of targeted therapies. Prostate-specific membrane antigen (PSMA)-targeted therapy resulted in a notable PSA decline. This case highlights the evolving treatment landscape for rare prostate cancers, integrating genetic insights for tailored interventions. In conclusion, squamous cell carcinoma (SCC) of the prostate is rare, emphasizing the imperative for enhanced comprehension in diagnosis and management. Our case suggests the potential efficacy of ARPI and PSMA-targeted therapies. Our findings advocate for a more nuanced approach to the management of this rare prostate cancer variant, leveraging genomic insights for personalized treatment strategies. This exploration serves as a foundation for further research and clinical considerations in addressing the challenges posed by mixed adenosquamous cell carcinoma of the prostate.

Building on Foundations: Venetoclax-Based Combinations in the Treatment of Acute Myeloid Leukemia.

Frontline acute myeloid leukemia (AML) treatment is determined by a combination of patient and genetic factors. This includes patient fitness (i.e., comorbidities that increase the risk of treatment-related mortality) and genetic characteristics, including cytogenetic events and gene mutations. In older unfit patients, the standard of care treatment is typically venetoclax (VEN) combined with hypomethylating agents (HMA). Recently, several drugs have been developed targeting specific genomic subgroups of AML patients, enabling individualized therapy. This has resulted in investigations of doublet and triplet combinations incorporating VEN aimed at overcoming known resistance mechanisms and improving outcomes in older patients with AML. These combinations include isocitrate dehydrogenase-1/2 (IDH1/2) inhibitors (i.e., ivosidenib and enasidenib), fms-like tyrosine kinase 3 (FLT3) inhibitors (i.e., gilteritinib), anti-CD47 antibodies (i.e., magrolimab), mouse double minute-2 (MDM2) inhibitors, and p53 reactivators (i.e., eprenetapopt). This review summarizes ongoing trials aimed at overcoming known VEN resistance mechanisms and improving outcomes beyond that observed with HMA + VEN combinations in the treatment of AML.

Case Report: ASXL1, RUNX1, and IDH1 mutation in tyrosine kinase-independent resistant chronic myeloid leukemia progressing to chronic myelomonocytic leukemia-like accelerated phase.

Although the majority of patients with chronic myeloid leukemia (CML) enjoy an excellent prognosis tyrosine kinase inhibitor (TKI) therapy, resistance remains a significant clinical problem. Resistance can arise from mutations in the kinase domain of ABL preventing drug binding, or due to ill-defined kinase-independent mechanisms. In this case report, we describe the case of a 27-year-old woman with a long-standing history of chronic phase (CP) CML who developed kinase-independent resistance with mutations in ASXL1 and RUNX1. As a consequence of uncontrolled disease, she progressed to a chronic myelomonocytic leukemia-like (CMML) accelerated phase (AP) disease with the acquisition of a mutation in IDH1. This disease progression was associated with the development of an inflammatory serositis, a phenomenon that has been described in CMML but not in AP-CML. This case presents key features of kinase-independent resistance with insight into potential mechanisms, highlights management challenges, and describes a novel systemic inflammatory response that occurred in this patient upon disease progression.