Advances in Hematology Analyzers Technology.

The evolution of complete blood count (CBC) methodology from manual calculations to sophisticated high throughput hematology analyzers is the focus of this article. In recent years, hematology testing has greatly benefitted from the combination of various technologies with automated neural networks. In addition to an increasing complexity of the laboratory instrumentation, there is a demand on point of care CBC testing with its benefits and drawbacks. This article highlights exciting advancements of hematology testing from the past to the present and into the future.

Applications of Flow Cytometry in Diagnosis and Evaluation of Red Blood Cell Disorders.

Clinical flow cytometry plays a vital role in the diagnosis and monitoring of various red blood cell disorders. The high throughput, precision, and automation potential of this technique allows for cost-effective and timely analysis compared to older and more manual test methods. Flow cytometric analysis serves as the gold standard diagnostic method for multiple hematological disorders, especially in clinical scenarios where an assay needs to have high sensitivity, high specificity, and a short turnaround time. In this review, we discuss the role of flow cytometric analysis in paroxysmal nocturnal hemoglobinuria, fetal-maternal hemorrhage, and hereditary spherocytosis.

Advances in Hemoglobinopathies and Thalassemia Evaluation.

Hemoglobin (Hb) disorders are among the most prevalent inherited diseases. Despite a limited number of involved genes, these conditions represent a broad clinical and prognostic spectrum. The menu of laboratory tests is extensive. From widely available modalities, for example, complete blood count to rather sophisticated molecular technologies, the investigation of Hb disorders recapitulates an increasing complexity of laboratory workup in other medical fields. This review highlights a current state of biochemical and molecular investigation of Hb disorders and offers a glimpse on technologies that are yet to be fully embraced in clinical practice.

Chronic Myelomonocytic Leukemia and Atypical Chronic Myeloid Leukemia: A National Analysis.

BACKGROUND: Myelodysplastic/myeloproliferative overlap syndromes (MDS/MPN) are rare blood cancers characterized by concomitant myeloid hyperplasia and dysplasia. These heterogenous disorders include chronic myelomonocytic leukemia (CMML) and atypical chronic myeloid leukemia (aCML). METHODS: Using two large national cancer databases to examine a total of 15,704 CMML and 702 aCML patients, we report the largest study to date on the incidence, survival and demographic characteristics of CMML and aCML in the United States. RESULTS: Overall age-adjusted incidence of CMML and aCML was 0.63 per 100,000 Americans per year and 0.03 per 100,000 per year, respectively. CMML incidence in the U.S. was noted to rise steadily in the years between 2001 and 2019. Median patient age was 75 and 72 years for CMML and aCML, and the majority of CMML and aCML patients were male (62.9% and 62.0%) and White (90.1% and 86.3%). Median OS was 17.4 months for CMML, and 15.2 months for aCML. Multivariate Cox regression demonstrated features associated with reduced survival, including increasing age, comorbidities, Medicaid insurance status, and low-income residential zip code, highlighting survival disparities in underinsured and socioeconomically disadvantaged patients. In CMML, Black race was associated with inferior survival, while female sex, management at an academic center, and later calendar-year of diagnosis were associated with improved OS. CONCLUSION: These findings underscore the need to better understand the biological basis for such differences in survival and reflect the importance of access to specialized care for patients with these rare disorders.

How I diagnose systemic mastocytosis.

OBJECTIVES: Systemic mastocytosis (SM) is a neoplasm of mast cells (MCs) characterized by their proliferation in extracutaneous organs. Systemic mastocytosis includes several entities with different clinical courses and prognoses. The rarity of this disease and the diversity of clinical and morphologic presentation make the diagnosis of SM very challenging. The aim of this review is to share our approach to the diagnosis of SM. METHODS: We present 4 cases that highlight the spectrum of clinical and laboratory features of SM and outline the diagnostic process with an emphasis on morphology. RESULTS: Pathology and laboratory medicine play a key role in investigation of SM, as correct diagnosis requires integration of morphologic, molecular, and serologic findings. In addition to awareness of microscopic findings in SM, a pathologist must keep abreast with an expanding menu of ancillary studies, particularly molecular testing. CONCLUSIONS: Systemic mastocytosis is a challenging diagnosis that requires not only a demonstration of a clonal proliferation of MCs but also a correct subclassification based on the recently updated criteria.

Granulomas in bone marrow biopsies: clinicopathological significance and new perspectives.

Bone marrow granulomas in trephine biopsies are a rare and usually incidental finding. Possible causes include infectious (especially tuberculous and rarer non-tuberculous mycobacteria, but also many other bacterial, viral, fungal and parasitic agents) and non-infectious causes (especially medications, autoimmune disease, sarcoidosis, haematological and non-haematological malignancy). Necrotising granulomas are generally suggestive of an infectious aetiology (tuberculosis being the most common), whereas fibrin ring granulomas are associated with Q-fever and Epstein Barr Virus, although exceptions are possible. Every case suspicious for infectious aetiology should undergo further analysis like special staining (Ziehl-Neelsen for acid-fast rods) or molecular studies. The histomorphology should always be clinically correlated. In cases in which no infectious cause can be identified, untargeted metagenomics may represent a valid diagnostic tool that may become standard in the near future for bone marrow diagnostics. In this review, we have analysed the published data from 1956 up to today, and we report aspects of epidemiology, aetiology, diagnostic algorithms, differential diagnosis and the role of metagenomics in bone marrow biopsies with granulomas.

Molecular diagnosis of hereditary hemolytic anemias: Recent updates.

Hereditary hemolytic anemia (HHA) is a heterogeneous group of disorders due to genetically caused defects in red blood cell membrane structure, enzymes, heme and globin synthesis, erythroid proliferation, and differentiation. Traditionally, the diagnostic process is complex and includes a plethora of tests from routine to highly specialized ones. The inclusion of molecular testing has significantly improved the diagnostic yield. The value of molecular testing is broader than just rendering the correct diagnosis, as it may also guide therapeutic decisions. As more molecular modalities become available for clinical use, it is imperative to understand their benefits and disadvantages pertaining to the HHA diagnostics. Re-evaluation of the traditional diagnostic workflow may also bring forth additional benefits. This review focuses on the current state of molecular testing for HHA.

Lymphoid aggregates in bone marrow: a diagnostic pitfall.

Lymphoid aggregates in bone marrow specimens are a relatively frequent finding that may pose a diagnostic challenge for a pathologist. The distinction between reactive and neoplastic aggregates has significant clinical relevance. Although many testing modalities such as immunohistochemistry, flow cytometry and molecular studies are currently available in clinical laboratories, the appropriate utilisation of these modalities and the awareness of their potential pitfalls are important. When a neoplastic process is ruled out, the significance of benign lymphoid aggregates in bone marrow is often unclear, as they may be associated with a broad spectrum of conditions including infections, autoimmune disorders, medications, or may even be idiopathic.This review focuses on evidence-based criteria that can aid in making the distinction between benign and malignant lymphoid aggregates and discusses the advantages, disadvantages and limits of ancillary tests used for this purpose. Finally, the most common aetiologies of benign lymphoid aggregates and their associations with specific diseases are discussed.

δ-Globin Chain Variants Associated with Decreased Hb A2 Levels: A National Reference Laboratory Experience.

High prevalence of hemoglobin (Hb) disorders mandates national programs for screening and genetic counseling in many countries. Increased Hb A2 levels are commonly associated with ß-thalassemias, however, various disorders including alteration of δ chains may result in decreased production of Hb A2, thus hindering the diagnosis of ß-thalassemias. The reported data reflect the experience of a large reference laboratory in the United States. In the current study, we have attempted to assess the prevalence and also tried to characterize the identified mutations in the HBD gene resulting in decreased Hb A2 levels. In our cohort, 1.6% of 6486 patients were found to have Hb A2 values of <1.9%. Bidirectional sequencing of the HBD gene demonstrated mutations in 20 cases (19.0% of the individuals with decreased Hb A2). In addition to the previously reported variants, one novel mutation (Hb A2-Utah or HBD: c.46T>C).

Nodular Lymphocyte Predominant Hodgkin Lymphoma versus T-Cell/Histiocyte-Rich Large B-Cell Lymphoma: A Diagnostic Challenge.

Lymphomas with overlapping histological features of two distinct entities cause difficulty in classification. Their classification is of particular significance when the two alternatives require different treatment modalities. We present a diagnostically challenging case of a nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) with features of T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL). Our patient is a 39-year-old woman who presented with painless subclavicular and axillary lymphadenopathy. The biopsied lymph node showed diffuse architectural effacement and scattered large neoplastic cells with large irregular nuclei and prominent nucleoli. These cells were positive for CD20 and Bcl-6 and negative for CD15, CD30, IgD, and Bcl-2. The background cells were predominantly T lymphocytes, whereas B cells were markedly depleted. The lymph node was interpreted as NLPHL, consistent with THRLBCL-like variant. NLPHL, especially THRLBC-like variant, and de novo THRLBCL are characterized by significant morphologic and immunophenotypic overlap. Our case demonstrates a rare predominance of background T-cells in NLPHL and emphasizes the importance of thorough evaluation of multiple morphologic and immunophenotypic features as an essential approach for arriving at the correct diagnosis.

Parotid gland abscess caused by Haemophilus paraphrophilus: a case report.

Human diseases caused by Haemophilus paraphrophilus (H.paraphrophilus) are unusual. The following case report describes a 67-year-old man who presented with pain and swelling of the right side of the face. Fine needle aspiration suggested a parotid gland abscess. Microbiological studies identified H.paraphrophilus. This is the first time a parotid abscess has been found to be caused by this organism.