Automated feathered edge blood smear analysis: early diagnosis of carcinocythemia in a case of disseminated intravascular coagulation with multi-organ failure.

Carcinocythemia, known as the presence of circulating tumor cells in the peripheral blood, is difficult to detect when the carcinoma cells are minimally present. We describe a case of a 56-year-old patient presenting with disseminated intravascular coagulation (DIC) and multiple organ failure. Despite initial suspicion of sepsis, a peripheral blood smear showed the presence of atypical cells, mainly located at the feathered edge, leading to a presumptive diagnosis of carcinocythemia of unknown primary origin. The presence of a high-fluorescent cell population detected by our hematology analyzer (Sysmex XN-9100) and immunohistochemical staining with pancytokeratin AE1/AE3 confirmed the carcinoma cell origin. The patient died 4 days after referral to our hospital. Postmortem examination revealed a pleomorphic lobular breast carcinoma (triple-negative, androgen receptor-negative). Given the clinical acuity of patients with carcinocythemia, early diagnosis is essential to guide management. This case underscores the importance of optimizing current workflows relying on complex flagging algorithms and enhanced digital imaging to aid in the early detection of such rare condition. When patients present with DIC of unknown origin and high fluorescent signals are detected on the hematology analyzer, carcinocythemia should actively be ruled out by extensive microscopic peripheral blood examination.

MYH9-related disease with a normal platelet count.

MYH9-related disease (MYH9-RD) is characterized by congenital macrothrombocytopenia, progressive kidney failure, and sensorineural hearing loss. We describe a patient with MYH9-RD and a normal platelet count. A 13-year-old boy with a normal platelet count presented with proteinuria and hematuria and underwent a kidney biopsy. Light microscopy showed mild mesangial matrix expansion. Electron microscopy showed thinning of the glomerular basement membrane and splitting of the lamina densa. A tentative diagnosis of Alport syndrome was made. Unexpectedly, genetic analysis revealed a de novo MYH9 gene variant (p.Gln1068_Leu1074dup). A peripheral blood smear examination showed giant platelets and leukocyte inclusion bodies, confirming a diagnosis of MYH9-RD. In summary, we described a patient with MYH9-RD without thrombocytopenia who showed glomerular basement membrane abnormalities similar to Alport syndrome. Peripheral blood smear examinations may be helpful for an appropriate diagnosis of MYH9-RD, even in patients with proteinuria and a normal platelet count.

Bone marrow metastasis in nonhematological malignancies: A study from tertiary care center.

Introduction: Metastatic cancer presents a treatment challenge to clinicians, particularly for patients with bone marrow infiltration. For tumor staging, therapy selection, and prognosis risk stratification, the status of the bone marrow should be known for the presence or absence of metastasis. The study aimed to evaluate the hematological findings and comprehensive analysis of bone marrow in cases of nonhematological malignancies with bone marrow metastasis. Materials and Methods: This retrospective study comprised a record retrieval of the departmental archives for the past 6 years. A total of 331 patients with nonhematological malignancies were found, of whom 31.42% (104/331) showed bone marrow metastasis. An integrated clinical approach with bone marrow examination findings and immunohistochemistry whenever necessary was used to achieve a definitive diagnosis of bone marrow metastasis. Results: Among the study population, 31.42% (104/331) of patients had nonhematological malignancies that metastasized to the bone marrow. Most of the patients with bone marrow metastasis had anemia, which was found in 77.88% (81/104) of the cases. Leukoerythroblastic reaction was noted in 31.73% (33/104) of the cases, and thrombocytopenia was found in 25% (26/104) of the cases. The most common malignancy with bone marrow metastasis in adults was prostatic adenocarcinoma (28.1%) (9/32) and in pediatric cases, neuroblastoma (53.9%) (52/98). Conclusions: It is essential to diagnose nonhematological malignancies that have metastasized to the bone marrow since this necessitates tumor staging, therapy selection, and prognosis risk stratification. To conclude, not a single hematological parameter is predictive of bone marrow metastasis; however, unexplained anemia, a leukoerythroblastic blood picture, and thrombocytopenia in peripheral blood should raise suspicion for bone marrow metastasis in cases of nonhematological malignancies.

Résumé Introduction: Le cancer métastatique présente un défi de traitement pour les cliniciens, en particulier pour les patients présentant une infiltration de moelle osseuse. Pour la stadification tumorale, la sélection du traitement et la stratification du risque de pronostic, l'état de la moelle osseuse doit être connu pour la présence ou l'absence de métastases. L'étude visait à évaluer les résultats hématologiques et l'analyse complète de la moelle osseuse dans les cas de tumeurs malignes non hématologiques avec métastases de la moelle osseuse. Matériel et méthodes: Cette étude rétrospective comprenait une récupération des archives ministérielles des 6 dernières années. Un total de patients atteints de tumeurs malignes non hématologiques ont été trouvés, dont 31,42% (104/331) présentaient des osmétastases médullaires. Une approche clinique intégrée avec les résultats de l'examen de la moelle osseuse et l'immunohistochimie chaque fois que nécessairea été utilisé pour établir un diagnostic définitif de métastases médullaires. Résultats: Dans la population étudiée, 31,42 % (104/331) des patients présentaient des tumeurs malignes non hématologiques qui se métastasaient à la moelle osseuse. La plupart des patients atteints de métastases de la moelle osseuse présentaient une anémie, qui a été trouvée dans 77,88% (81/104) des cas. Une réaction leucoérythroblastique a été observée dans 31,73 % (33/104) des cas, et une thrombocytopénie a été observée dans 25 % (26/104) des cas. La tumeur maligne la plus fréquente associée aux métastases de la moelle osseuse chez l'adulte était l'adénocarcinome de la prostate (28,1 %) (9/32) et, chez les enfants, le neuroblastome (53,9 %) (52/98). Conclusions: Il est essentiel de diagnostiquer les tumeurs malignes non hématologiques qui ontmétastasé à la moelle osseuse car cela nécessite une stadification tumorale, une sélection thérapeutique et une stratification du risque de pronostic. Pour conclure, pas un seul paramètre hématologique n'est prédictif des métastases de la moelle osseuse; Cependant, une anémie inexpliquée, une image sanguine leucoérythroblastique et une thrombocytopénie dans le sang périphérique devraient faire suspecter des métastases de la moelle osseuse en cas de tumeurs malignes non hématologiques. Mots-clés: Aspiration de moelle osseuse, biopsie de la moelle osseuse, métastases de la moelle osseuse, résultats hématologiques, immunohistochimie, tumeurs malignes non hématologiques, frottis sanguin périphérique.

Immune-mediated thrombocytopenia and IL-6-mediated thrombocytosis observed in idiopathic multicentric Castleman disease.

Idiopathic multicentric Castleman disease (iMCD) is a rare haematological disorder characterized by generalized lymphadenopathy with atypical histopathological features and systemic inflammation caused by a cytokine storm involving interleukin-6 (IL-6). Three clinical subtypes are recognized: thrombocytopenia, anasarca, fever, renal dysfunction, organomegaly (iMCD-TAFRO); idiopathic plasmacytic lymphadenopathy (iMCD-IPL), involving thrombocytosis and hypergammaglobulinaemia; and iMCD-not otherwise specified (iMCD-NOS), which includes patients who do not meet criteria for the other subtypes. Disease pathogenesis is poorly understood, with potential involvement of infectious, clonal and/or autoimmune mechanisms. To better characterize iMCD clinicopathology and gain mechanistic insights into iMCD, we analysed complete blood counts, other clinical laboratory values and blood smear morphology among 63 iMCD patients grouped by clinical subtype. Patients with iMCD-TAFRO had large platelets, clinical severity associated with lower platelet counts and transfusion-resistant thrombocytopenia, similar to what is observed with immune-mediated destruction of platelets in immune thrombocytopenic purpura. Conversely, elevated platelet counts in iMCD-IPL were associated with elevated IL-6 and declined following anti-IL-6 therapy. Our data suggest that autoimmune mechanisms contribute to the thrombocytopenia in at least a portion of iMCD-TAFRO patients whereas IL-6 drives thrombocytosis in iMCD-IPL, and these mechanisms likely contribute to disease pathogenesis.

Homozygous SPTA1-associated hereditary pyropoikilocytosis presenting as hydrops fetalis.

INTRODUCTION: Hereditary pyropoikilocytosis (HPP) is a heterogeneous inherited disorder of red blood cell (RBC) membrane and cytoskeletal proteins that leads to hemolytic anemia. HPP is characterized by marked poikilocytosis, microspherocytes, RBC fragmentation, and elliptocytes on peripheral blood smear. Mutations in SPTA1 can cause HPP due to a quantitative defect in α-spectrin and can lead to profound fetal anemia and nonimmune hydrops fetalis, which can be managed with intrauterine transfusion. CASE PRESENTATION: We present a case of a 26-year-old G4P2102 woman of Amish-Mennonite ancestry with a pregnancy complicated by fetal homozygosity for an SPTA1 gene variant (SPTA1c.6154delG) as well as severe fetal anemia and hydrops fetalis, which was managed with four intrauterine transfusions between 26 and 30 weeks gestation. Pre-transfusion peripheral smears from fetal blood samples showed RBC morphology consistent with HPP. The neonate had severe hyperbilirubinemia at birth, which has resolved, but remains transfusion-dependent at 6 months of life. DISCUSSION/CONCLUSION: To our knowledge, this is the first report that correlates homozygosity of the SPTA1c.6154delG gene variant with RBC dysmorphology and establishes the diagnosis of HPP.

Hematocytological Clues of Peripheral Blood in Different Clinical Presentations of COVID-19.

Background: To gain insight into the pathogenesis and clinical course of COVID-19 from a historical perspective, we reviewed paraclinical diagnostic tools of this disease and prioritized the patients with a more severe form of disease admitted to intensive care units (ICUs). The objective was to better predict the course and severity of the disease by collecting more paraclinical data, specifically by examining the relationship between hematological findings and cytological variation of blood neutrophils and monocytes. Methods: This retrospective study was conducted on 112 patients with confirmed COVID-19 admitted to Imam Hossein Hospital (Tehran, Iran) from August to September 2020. Peripheral blood smears of these patients were differentiated according to several cytological variations of neutrophils and monocytes, and the correlation to the severity of the disease was specified. Results: The mean percentages of degenerated monocytes, degenerated granulocytes, and spiky biky neutrophils were significantly different among critical and non-critical patients (P<0.05). Degenerated monocytes and granulocytes were higher in critical patients as opposed to spiky biky neutrophils, which were higher among non-critical ones. Comparing the peripheral blood smears of COVID-19 patients (regarding pulmonary involvement in chest computed tomography [CT] scans [subtle, mild, moderate, and severe groups]), the twisted form of neutrophils was significantly higher in the subtle group than in the mild and moderate groups (P=0.003). Conclusion: Different cytological morphologies of neutrophils and monocytes, including degenerated monocytes, degenerated granulocytes, and spiky biky and twisted neutrophils, could help to predict the course and severity of the disease.

DSCNet: Deep Skip Connections-Based Dense Network for ALL Diagnosis Using Peripheral Blood Smear Images.

Acute lymphoblastic leukemia (ALL) is a life-threatening hematological malignancy that requires early and accurate diagnosis for effective treatment. However, the manual diagnosis of ALL is time-consuming and can delay critical treatment decisions. To address this challenge, researchers have turned to advanced technologies such as deep learning (DL) models. These models leverage the power of artificial intelligence to analyze complex patterns and features in medical images and data, enabling faster and more accurate diagnosis of ALL. However, the existing DL-based ALL diagnosis suffers from various challenges, such as computational complexity, sensitivity to hyperparameters, and difficulties with noisy or low-quality input images. To address these issues, in this paper, we propose a novel Deep Skip Connections-Based Dense Network (DSCNet) tailored for ALL diagnosis using peripheral blood smear images. The DSCNet architecture integrates skip connections, custom image filtering, Kullback-Leibler (KL) divergence loss, and dropout regularization to enhance its performance and generalization abilities. DSCNet leverages skip connections to address the vanishing gradient problem and capture long-range dependencies, while custom image filtering enhances relevant features in the input data. KL divergence loss serves as the optimization objective, enabling accurate predictions. Dropout regularization is employed to prevent overfitting during training, promoting robust feature representations. The experiments conducted on an augmented dataset for ALL highlight the effectiveness of DSCNet. The proposed DSCNet outperforms competing methods, showcasing significant enhancements in accuracy, sensitivity, specificity, F-score, and area under the curve (AUC), achieving increases of 1.25%, 1.32%, 1.12%, 1.24%, and 1.23%, respectively. The proposed approach demonstrates the potential of DSCNet as an effective tool for early and accurate ALL diagnosis, with potential applications in clinical settings to improve patient outcomes and advance leukemia detection research.

A Rare Concurrence of Myelodysplastic Neoplasia and Tetrasomy 8 in a 3-Year-Old Bahraini Male.

Myelodysplastic neoplasia (MDS) is a group of stem cell disorders involving ineffective hematopoiesis. It can be associated with an increased risk of progression toward acute myeloid leukemia (AML). In Bahrain, MDS is the fifth most common primary hematologic malignancy. MDS has an annual incidence of up to 4 million cases. Some of the presenting signs and symptoms of MDS are often nonspecific, such as fatigue, pallor, malaise, fevers, bleeding, bruising, weight loss, and anorexia. Approximately 40% of patients with MDS progress to AML. This paper outlines a case of a 3-year-old Bahraini male (known to have sickle cell trait) who presented to the emergency department of Salmaniya Medical Complex with a five-day history of fever, congested throat, left ear pain, and abdominal pain. He had one episode of vomiting gastric content the previous day. He had previously gone to a private clinic with similar symptoms. Physical examination revealed a short neck and short stature, which was found to be below the 5th percentile. He had generalized pallor and hepatosplenomegaly. A blood smear showed leukopenia and normochromic normocytic anemia. There were excessive blasts found which consisted of 17% of nucleated cells and few granulopoietic cells. Erythropoiesis was active with a few showing mild megaloblastic changes. There were rare megakaryocytes noted. Moreover, the bone marrow aspirate showed two populations on dim CD45. The first population consisted of 3.15% on dim CD45 comprising of hematogones which brightly expressed CD19, HLA-DR, CD79a, and dim CD10. The second population consisted of 14.85% on dim CD45 which expressed CD34, CD13, CD117, HLA-DR, and dim CD7. Based on the peripheral blood smear and bone marrow immunophenotyping findings, a diagnosis of myelodysplastic syndrome with excessive blasts was made, which soon transformed into a diagnosis of AML. Furthermore, increased levels of dysplastic changes and percentage of blasts in the peripheral blood smear and bone marrow lead to a higher possibility of transformation into AML. As per the WHO classification, a diagnosis of MDS needs evaluation of the morphology of blood and bone marrow.