To investigate the value of tumor biomarkers of CA125, CA153, CA 19-9, CEA, human epididymis protein 4 (HE4) and ROMA index in combination for the diagnosis of epithelial ovarian tumors. Patients with epithelial ovarian tumors were retrospectively enrolled in comparison with healthy controls. The venous blood samples were tested and analyzed. The CA 19-9 value was significantly (P < 0.05) greater in borderline tumors than in ovarian cancers, benign tumors or healthy controls, and significantly (P < 0.05) greater in benign tumors than in healthy controls. Compared with the borderline tumors, the ovarian cancer in stages III and IV had significantly (P < 0.05) greater CA 125, CA 153, HE 4, ROMA 1 and ROMA 2 but significantly (P < 0.05) smaller CA 19-9. Stage-II ovarian cancer also had significantly (p < 0.05) greater CA 153 but smaller CA 19-9 than borderline tumors. The CA 19-9 value was significantly greater in the epithelial mucous cancer (50.15) or the borderline non-mucinous (22.90) or mucinous (47.55) tumor than in the non-mucinous cancer (12.15), benign tumors (14.80), or healthy controls (9.40). CA 125, CA 19-9, HE 4, ROMA 1, ROMA 2 and CA 153 had larger AUC and Youden indexes for diagnosing borderline tumors, and CA 125, CA 153, HE 4, ROMA 1 and ROMA 2 had larger AUC and Youden indexes for diagnosing ovarian cancers. For epithelial borderline tumors, CA 125, HE 4, ROMA 1, and ROMA 2 may have higher diagnostic value, especially ROMA 2 and CA 125. For ovarian cancer, ROMA 2, CA125, ROMA 1, HE4, and CA153 may have the highest clinical application value. CA 19-9 elevation may indicate mucinous ovarian cancer or mucinous borderline tumor. Elevated CA153 also has certain application value.
Serum iron is a routinely ordered test for assessing iron metabolism. Among colorimetric assays, Ferrozine- and Ferene S-based methods are widely used; however, analytical differences may compromise result comparability across platforms. This study evaluated the analytical transferability of serum iron results between these two methods performed on different analyzers. In accordance with the CLSI EP09-A3 guideline, 40 serum samples were analyzed in duplicate using two colorimetric methods: Ferrozine on the Roche Cobas Integra 400+ and Ferene S on the DiaSys Respons 920. Method agreement was assessed using Passing-Bablok regression, Bland-Altman analysis, and clinical concordance analysis. Mean serum iron concentrations were slightly higher with the Ferene S method than with the Ferrozine method, with a statistically significant paired difference (p = 0.001) and very high clinical concordance (κ = 0.91). The two methods were strongly correlated (r = 0.992; p < 0.001) and showed a constant bias of -0.845 (95% CI: -1.672 to -0.043). Bland-Altman analysis demonstrated a mean bias of -0.99 μmol/L with narrow limits of agreement (-2.08 to +0.09 μmol/L). The relative bias (-6.15 %) remained well below the predefined analytical tolerance threshold. Ferrozine and Ferene S based assays showed satisfactory analytical transferability and can be used comparably for serum iron measurement under the evaluated conditions.
Gaucher disease is a rare, autosomal recessive lysosomal storage disorder caused by a deficiency of acid beta-glucocerebrosidase (Enzyme Commission 3.2.1.45). Its clinical presentation is polymorphic, dominated by hepatosplenomegaly and cytopenias, and may mimic a malignant hematologic disorder or a chronic infection. This is a clinical case report compiled in the pediatrics department of the Yalgado Ouédraogo University Hospital Center. The patient was a four-year-old boy with a history of chronic malnutrition and multiple hospitalizations in various hospitals across the country. He was admitted for abdominal distension that had been present for two years, associated with recurrent epistaxis and severe bicytopenia. Clinical signs on admission included good general condition, pallor of the skin and mucous membranes, and hepatosplenomegaly. Laboratory findings revealed bicytopenia on the complete blood count and hyperproteinemia. The progression to pancytopenia led to the performance of a myelogram, which revealed numerous foam cells resembling Gaucher cells, raising suspicion of a constitutional lysosomal storage disorder. Enzyme assay confirmed a glucocerebrosidase deficiency, leading to a diagnosis of Gaucher disease type 1. Treatment was symptomatic, and the patient died the day before the enzyme assay results were received, eighty-four days after his initial admission to our hospital. This case illustrates the difficulties and consequences of delayed diagnosis in countries with limited resources and technical capabilities.
Immunoglobulin D (IgD) multiple myeloma is a rare entity, accounting for 1 to 2% of myelomas, characterized by aggressive progression and frequent renal involvement. Its diagnosis is often delayed due to the low serum concentration of IgD and the absence of a monoclonal peak on serum protein electrophoresis. We report the case of a 56-year-old patient with no significant medical history who was hospitalized for severe renal failure associated with profound anemia. Renal biopsy revealed myelomatous nephropathy with tubular deposits of lambda light chains on immunofluorescence. Serum protein electrophoresis revealed hypogammaglobulinemia with an increase in the beta-2-globulin fraction. Serum immunofixation identified a monoclonal IgD lambda immunoglobulin associated with monoclonal free light chains (FLC) of lambda isotype. Serum FLC measurement confirmed a massive excess of lambda chains. The diagnosis was made in accordance with the 2014 International Myeloma Working Group (IMWG) criteria. This observation illustrates the diagnostic pitfalls of this entity and highlights the major importance of extended immunofixation, serum FLC measurement, and renal biopsy for early identification.
Hemoglobin G-Philadelphia is an alpha-globin chain variant resulting from the substitution of asparagine by lysine at position 68 [α68(E17) Asn→Lys]. This hemoglobin (Hb) variant is generally clinically silent; however, its identification may be challenging, particularly when present in the homozygous state and co-inherited with the -α3.7 deletion. We report the case of a 28-year-old woman from southeastern Morocco presenting with refractory hypochromic microcytic anemia (Hb 10,6 g/dL, MCV 60.5 fL, MCH 20.3 pg). Owing to a family history of type 2 diabetes mellitus, HbA1c testing was performed and revealed a hemoglobin variant eluting in the D window (87.44 %) on the Bio-Rad D-100 HPLC system. Further laboratory investigations (HPLC Variant II, capillary electrophoresis, and acid pH gel electrophoresis) confirmed the presence of homozygous Hb G-Philadelphia. Molecular analysis confirmed the variant and demonstrated its association with mild α-thalassemia. Family study revealed that the daughter is a heterozygous carrier of Hb G-Philadelphia and a cis -α3.7 α-thalassemia trait.
Organs-on-a-Chip (OoC) are innovative models designed to reproduce an architecture close to in vivo physiology, by recreating the specific microenvironment of each organ. They represent a promising advance in the process of developing new drugs, aimed at improving the prediction of adverse effects in preclinical studies and reducing the use of laboratory animals. However, a lack of validated standards governing these technologies currently limits their acceptance by regulatory authorities, who rely on guidelines to judge the admissibility of non-clinical studies. This is particularly the case for assessing the risk of cardiac damage using in silico, in vitro and in vivo tests. However, animal models are not always able to accurately detect adverse effects in humans. OoC are additional tools that could improve the assessment of drug cardiac toxicity. According to data in the literature, the results of studies with OoC overlap with those of conventional models. What's more, in some cases, OoC offer better prediction via the detection of biomarkers such as alpha-actin and troponin T. These results could lead to their integration into the regulatory process for preclinical drug evaluation.
Genomic instability is a major driver of clinical heterogeneity and treatment resistance in B-cell malignancies. In chronic lymphocytic leukemia (CLL) complex karyotype (CK) and disruption of the TP53 pathway are key markers of poor prognosis. Here we investigated whether interphase nuclear abnormalities - nucleoplasmic bridges (NPB) and nuclear buds (NBUD) - visible on routine blood smears could serve as cytological surrogates of dicentric chromosomes and structural genomic instability. We analyzed 29 patients with indolent B-cell malignancies: CLL (n = 15) and splenic marginal zone lymphoma (SMZL) (n = 14) enriched for dicentric chromosomes. A semi-quantitative Cytological Instability Score (CIS; 0-3) was developed from the systematic evaluation of 200 lymphoid cells per smear, incorporating NPB ≥ 2%, NBUD ≥ 10%, and multinucleated pleomorphic forms. Genomic instability was measured cytogenetically as the Charge of Genomic Instability (CGI). NPB frequency correlated with CGI (Spearman rho = 0.89, p < 0.0001), while NBUD correlated with the total number of chromosomal aberrations (rho = 0.85, p < 0.0001). Increasing CIS categories were associated with progressively complex cytogenetic architectures. Within this dicentric-enriched pilot cohort, cases displaying the highest CIS values generally corresponded to the most rearranged karyotypic patterns. These findings support the concept that specific interphase nuclear morphologies observable on routine cytology may reflect ongoing breakage-fusion-bridge cycles and underlying structural genomic instability; the CIS could be regarded as an exploratory morphology-based framework for assessing cytological manifestations of genomic instability in B-cell malignancies. Larger validation studies including broader cytogenetic profiles will be required to determine its reproducibility and potential clinical utility.
Serum free light chains (FLC) are key biomarkers for the diagnosis and monitoring of plasma cell dyscrasias. Current International Myeloma Working Group (IMWG) recommendations are based on Freelite™ assays. This study aimed to evaluate the analytical performance and clinical concordance of Diazyme κ and λ FLC assays on the Roche Cobas® platform in comparison with Freelite™. A total of 660 serum samples from patients with multiple myeloma, MGUS/smoldering myeloma, Waldenström macroglobulinemia, AL amyloidosis, and other gammopathies were analyzed. Precision, reference intervals, and method comparison were assessed according to CLSI EP05-A3 and EP09-A3 guidelines. Statistical analyses included Passing-Bablok regression, Bland-Altman analysis, Pearson correlation, and evaluation of clinical concordance. Within-run and total imprecision showed coefficients of variation ≤ 6%. Reference intervals for the κ/λ ratio were 0.22-2.25 in healthy individuals and 0.30-2.75 in patients with renal insufficiency. Method comparison demonstrated strong agreement with Freelite™ for κ (y = 0.95x + 0.34, R² = 0.96), λ (y = 0.90x + 4.1, R² = 0.91), and κ/λ ratio (r = 0.92). Overall clinical concordance was 96%, with discrepancies mainly observed near decision thresholds. Diazyme κ and λ FLC assays on the Cobas® platform show excellent analytical performance and high clinical concordance with Freelite™, supporting their use in routine laboratory practice, with applicability to IMWG-based interpretation.
In multiple myeloma, the measurement of serum free light chains (sFLC) is an essential biomarker for establishing the diagnosis, assessing the risk of disease progression and monitoring treatment response. However, analytical techniques are not yet standardized and results obtained with different analyzer/reagent combinations are not interchangeable. Moreover, an excess of antigen (the hook effect) may lead to an underestimation of the true concentrations. We report the case of a female patient with IgG kappa multiple myeloma, admitted to the emergency department for general deterioration following a clinical relapse. The measurement of (sFLC) performed by immunoturbidimetric method (Diazyme®) on a Cobas c311® analyzer yielded low values that were inconsistent with the clinical findings and the results of serum protein electrophoresis. Reassessment using the Optilite® analyzer with Freelite® reagents provided results consistent with the patient's clinico-biological status. This observation highlights the analytical limitations of certain assay systems and emphasizes the importance of interpreting results in the light of clinical and biological data.
The aim of our institutional project is to make ecological transition an integrated issue at all levels. We wanted to measure the carbon footprint of the automated shared platform known as IBCore following its renewal (Roche, Meylan, France). This platform performs all emergency and high-volume analyses in biochemistry, pharmacology, and toxicology. In 2025, IBCore performed more than 4 million analyses. The total emissions of the analytical platform were estimated at 657.4 tons of CO₂eq/year. The five main sources of emissions account for 93% of total annual emissions: purchases of reagents/consumables (69.6%); energy consumption (8.8%); platform equipment (7.4%); sample transport (4.7%); and employee commuting (2.6%). An "average" biological analysis, corresponding to a weighted average, represents approximately 0.16 kgCO₂eq. The gain from the upgrade (cobas® 8000 to cobas® pro) has been estimated at 9.2 tons CO₂eq/year, representing a reduction of 1.3%. Future improvements include sample transport by drone, with a potential gain estimated at 27.9 tons CO₂eq/year, and the consolidation of serology analyses on the IBCore platform, with a gain of 2.1 tons CO₂eq/year. Finally, we believe that our measurement of the CO₂ footprint per test is a new argument that can be used to engage physicians in a more rational ordering of biology tests.
Pregnancy is associated with physiological changes, particularly with regard to vitamins and trace elements. Crucial nutrients for optimal fetal development include vitamins B9 and B12, as well as minerals such as iron, zinc, copper, selenium, and iodine. Pregnant women with a history of bariatric surgery require special attention. Supplementation adjustment is mainly based on biological monitoring. Unfortunately, there are no validated reference values for the French population. The BIOMAT group of the SFBC aims to establish reference values for some of these parameters, in order to facilitate the detection of deficiencies and ensure appropriate monitoring of supplementation. The proposal for reference values is one of the objectives of the NUMASURG project. In the previous part of this article, the main physiological changes in organs, metabolism, hematology, and hormones during pregnancy were detailed. This second part of the article focuses on micronutrients, highlighting the potential risks associated with their deficiency during pregnancy.
The ANOFEL/LABAC recommendations aim to standardize the methods used for the biological diagnosis of malaria in France in accordance with the NF EN ISO 15189 standard. Any fever after returning from a malaria-endemic area should raise suspicion of malaria and prompt urgent testing for Plasmodium. Biological diagnosis is based on detecting parasites or their DNA using a sensitive technique, such as rapid molecular biology or a thick smear. If the result is positive, a thin blood smear is performed to identify the parasite species and stages and estimate parasitemia. A rapid diagnostic test (RDT) for detecting plasmodial proteins is a supplementary diagnostic tool and should not be used alone. The result must confirm or rule out malaria, and if malaria is confirmed, it must specify the species involved and the parasitemia. Biologists play an active role in rapidly communicating results and in the medical management of patients. They collaborate with clinicians, interpret results, identify serious cases, and contextualize findings. In the event of indigenous malaria, they participate in mandatory reporting (MR) to the regional health agency (ARS). CNR- or LBMR-qualified malaria laboratories may be consulted for expertise in severe or complex cases. Operator competence and reagent performance control are essential to ensuring the reliability of the results produced.
Despite major advances in molecular diagnostics, morphological examination of blood and bone marrow remains fundamental in the evaluation of diverse malignancies. This five-case series illustrates how subtle and often overlooked morphological clues can be decisive in diagnostically challenging settings. The aim of this study is to demonstrate that morphological assessment should extend beyond isolated cytologic features to include spatial distribution of cells, functional behavior, and bone marrow microenvironmental context. The reported cases comprise: (1) bone marrow infiltration by dedifferentiated melanoma mimicking a hematologic neoplasm, with melanin-laden macrophages providing a critical clue; (2) carcinocythemia revealing metastatic melanoma, with neoplastic cells confined to smear edges; (3) an anaplastic IgA multiple myeloma with striking cytological atypia; (4) acute monoblastic leukemia with a rapidly fatal course; and (5) myelodysplastic syndrome with SF3B1 mutation, characterized by prominent erythroblastic islands and subtle dysplasia. Key findings highlight that atypical spatial localization of tumor cells, functional features such as hemophagocytosis, and microenvironmental alterations may provide decisive diagnostic information. In conclusion, a structured, contextual morphological approach remains central to the accurate diagnosis of aggressive malignancies and serves as an essential complement to immunophenotypic and molecular techniques.
The management of HIL indices (Hemolysis, Icterus, Lipemia) remains heterogeneous among clinical chemistry laboratories, despite their major impact on result interpretation. Based on recommendations from the IFCC and the EFLM, a review of the literature, and expert opinions, the French Collège National de Biochimie des Hôpitaux (CNBH) proposes in this document a structured framework aimed at harmonizing practices. These recommendations address the three phases of the total testing process: (1) pre-analytical measures intended to prevent interferences related to sample collection, transport, and preparation; (2) analytical guidelines to better understand the limitations of measurement methods, strengthen quality control, and secure the interpretation of HIL indices; and (3) a standardized post-analytical strategy integrating the definition of thresholds based on potential clinical impact and harmonized communication of results. This document aims to support laboratory professionals in rationalizing and securing the management of HIL indices, thereby improving result quality and clinical management.
