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.

Uncommon Haematological Transformation: Chronic Myeloid Leukaemia Transitioning Into Plasma Cell Leukaemia in a Single Patient.

A 40-year-old male patient who was a known case of chronic myeloid leukaemia (CML) was diagnosed two years back on tab imatinib 400 mg/day; he came with complaints of easy fatigability, syncopal attacks, and bone pain associated with low-grade fever for 15 days. Repeat haematological profile and a peripheral smear of the patient suggested features of plasma cell leukaemia (PCL)/plasma cell dyscrasia (PCD). A definitive treatment protocol of lenalidomide, bortezomib, and dexamethasone for PCL was prescribed to the patient. This medical case study emphasizes the rare possibility of the transformation of CML into PCL and the possible trigger of tyrosine kinase inhibitor for the same.

Clinicopathological Parameters of Haemophilia Patients at a Tertiary Care Centre in Northern India.

INTRODUCTION: Haemophilia affects a large number of people all over the world, yet very little is known about the clinical manifestations and diagnostic protocols of the condition in areas with limited access to resources in developing countries. Understanding the clinical spectrum and diagnostic approach will help with the design of measures to address the situation in these places. The primary objective of this study was to examine the clinicopathological parameters of haemophiliac patients. MATERIALS AND METHODS: From the departmental archive, a thorough history of each patient was retrieved, including values of bleeding time, prothrombin time, activated partial prothrombin time, and percentage of specific factor activity. RESULTS: Out of a total of 385 cases over the period of six years, 86.75% were classified as haemophilia A and 13.25% of cases were diagnosed as haemophilia B. In terms of the severity of the disease, 44.93% were classified as severe, 42.08% as moderate, and 12.99% as mild. Joint bleeding was the first and most typical clinical manifestation of the disease, accounting for 34.80% of cases, followed by ecchymosis (23.12%), post-traumatic bleeding (12.73%), epistaxis (12.20%), and gum bleeding (8.05%). 1.56% of patients had a positive screening test for the hepatitis C virus, followed by 1.30% for HIV and 0.78% for hepatitis B surface antigen. CONCLUSION: In the presence of joint bleeding, ecchymosis, and post-traumatic bleeding in an otherwise healthy individual, a clinician should be alerted to the possibility that the patient has haemophilia and should request a work-up for the bleeding disorder.

Immune-dysregulation in subacute sclerosing panencephalitis: An exploratory case-control study.

Subacute sclerosing panencephalitis (SSPE) is a chronic progressive neurological condition caused by a defective measles virus. It is postulated that immune-dysregulation might result in persistent infection (immune evasion) as well as initiation of autoimmune phenomenon (via natural killer cells) leading to panencephalitis. The primary objective of this case-control study was to analyse the pattern of immune dysregulation in cases with SSPE. The secondary objective was to assess the correlation between the measured immunological variables and disability/death at 6 months. This was an exploratory case-control study conducted at a tertiary-care referral-facility from January 2020 to September 2021. Thirty consecutive patients fulfilling the Dyken's criteria for SSPE and 30 age-and-sex-matched healthy controls were enrolled. Immunological profile constituted by lymphocyte subset analysis, immunoglobulin levels and complement levels were done in all cases and controls. Cases were staged as per Jabbour's system; disability was assessed using the modified Rankin Scale (mRS). Patients with SSPE had a mean age of 14.76 years (±6.9 years). There were 25 males and 5 females; 6.7% cases belonged to Jabbour's first stage, 40% to second stage and 53.3% to third stage. At least 1/4th had evidence of measles vaccination. Levels of absolute lymphocyte count, B-cells, T cells, helper T-cells, and cytotoxic T-cells were significantly higher in cases. IgG, IgM, and IgE levels were significantly higher while IgD levels were significantly lower in cases. At baseline, 13.3% of cases had a mRS score of 0-2 and 86.7% had a score of 3-6; at 6 months 10% had a mRS score 0-2 (favorable outcome) while 90% had a mRS score 3-6 (poor outcome). Higher IgE levels were found to correlate significantly with favorable outcome. Immune-dysregulation may play a significant role in shaping one's response to measles infection as well as in determining vaccine-efficacy.

Reed Sternberg-Like Cells in Non-Hodgkin Lymphoma: A Diagnostic Challenge.

Reed-Sternberg cells are distinguishing features of classical Hodgkin lymphoma. However, they are seen infrequently, in both B and T cells Non-Hodgkin lymphomas with a comparable morphology and immunophenotype. These cells are known as Reed-Sternberg-like cells. The characteristic background milieu of classical Hodgkin lymphoma is typically not present in Non-Hodgkin lymphomas, and Reed-Sternberg-like cells are typically present as dispersed cells or in tiny clusters. They are positive for CD30, show variable expression of B cell lineage markers and are negative for CD45/LCA in Non-Hodgkin lymphomas. Reed-Sternberg-like cells have phenotypes that are remarkably similar to those of conventional Reed-Sternberg cells. In this interesting case report, we discuss a case of disseminated B-cell Non-Hodgkin lymphoma with Reed-Sternberg-like cells that presented as a diagnostic challenge. It is essential to distinguish between classical Hodgkin lymphoma and Non-Hodgkin lymphomas due to distinct therapy protocols and prognosis. The presence of large CD30 positive Reed-Sternberg like cells may mimic Hodgkin's Lymphoma. However, monomorphic background population with CD20 positivity should always raise the suspicious of B-cell Non-Hodgkin lymphoma. Immunohistochemical detection of a panel of targets should always be applied to correctly diagnose these rare cases of B-cell Non-Hodgkin lymphoma with Reed-Sternberg like cells.

A cross-sectional study on thrombopoietin levels in immune thrombocytopenia and its correlation with platelet count, megakaryocytes, and treatment response.

INTRODUCTION: Thrombopoietin (TPO) being the major regulator of megakaryopoiesis is expected to show a compensatory increase in immune thrombocytopenia (ITP), however, it is not so observed. This study was undertaken to measure TPO levels in ITP and assesses its association with platelet count, megakaryocytes, and response to steroid therapy. MATERIALS AND METHODS: A total of 41 cases of ITP and twenty controls with normal platelet count were enrolled in this prospective study. Complete blood count, bone marrow examination, and ELISA for serum TPO were measured. Response to steroid therapy was evaluated for thirty cases. RESULTS: The TPO levels were increased in 80.5% of patients in comparison to the controls. The degree of rise, however, was variable. On analyzing low, normal, and high TPO levels with reference to platelet and megakaryocyte count no statistically significant difference was observed. Raised TPO levels were seen with significant lowering of functional megakaryocytes. The mean TPO levels in nonresponders were higher than responders but highly variable and statistically nonsignificant. CONCLUSION: Quantitative alterations in TPO are in a way regulated by qualitative efficacy of megakaryocytes rather than platelet or megakaryocyte count. Nonresponders with markedly increased TPO levels (due to qualitative megakaryocyte injury) are less likely to respond to TPO receptor agonist.

Prevalence of primary immunodeficiency syndromes in tuberculous meningitis: A case-control study.

BACKGROUND: Only a proportion of patients with tuberculosis develop tuberculous meningitis. We hypothesize that inherent abnormalities in the host's innate or adaptive immune system may affect the outcome in tuberculous meningitis. In this study, we evaluated the proportion of underlying primary immunodeficiency in patients with tuberculous meningitis and its impact on the outcome. METHODS: Newly-diagnosed cases with tuberculous meningitis and healthy controls were included. Patients with HIV disease were excluded. Blood specimen were subjected to immunological assessment to detect primary immunodeficiency syndrome/s. We estimated serum levels of IgG, IgA, IgM, IgE and IgD along with complement C3, C4, and C5 assay. Absolute lymphocyte count was obtained from an automated three-part cell counter. Flow cytometry was used to enumerate the following lymphocyte subsets: T Cell (CD3, CD4, CD8), B cell (CD19/CD20), and Natural killer cells (CD16 and CD56). Cases were followed for 6 months. Modified Barthel Index was used as a measure of disability. RESULTS: We included 55 cases with tuberculous meningitis and 30 healthy controls. We notedthat among immune parameters, absolute lymphocyte count and CD4 T-cell count in the tuberculous meningitis group was lower; higher serum IgG levels were noted in the poor outcome group. On multivariate regression analysis, none of the immunological, clinical or radiological features were found to predict a poor outcome. CONCLUSION: Host's immune factors contribute to the pathogenesis of tuberculous meningitis. Absolute lymphocyte count and CD4+ T-cell count were lower in tuberculous meningitis cases. Higher serum IgG levels may be associated with a poor outcome. A study with a larger sample size is needed to confirm our findings.

Bleeding Versus Thrombotic Tendency in Young Children With Beta-Thalassemia Major.

Introduction Bleeding and thrombotic events are known to occur in beta-thalassemia major (BTM) patients and have been attributed to hepatic iron overload associated with multiple blood transfusions. We evaluated hemostatic parameters in children with BTM who had no previous history of bleeding or thrombotic episodes. Materials and Methods Hemostatic parameters including prothrombin time (PT), activated partial thromboplastin time (APTT), platelet aggregation, protein C and S, iron profile, and liver function tests were evaluated in 54 children (median age = 12 months, age range = 4-144 months) with BTM and 15 age and sex-matched controls. Results The mean PT and APTT of patients were significantly higher (P=0.016 and P <.001) than that of controls. Mean protein C, protein S activity and platelet aggregability with adenosine 5-diphosphate (ADP) as an agonist in patients were significantly lower (P <.001, P <.001 and P=0.007, respectively) than that in controls. Mean serum ferritin in BTM children was not significantly elevated to be associated with hepatic dysfunction. Conclusion Deranged hemostatic parameters indicative of bleeding and thrombotic tendencies are observed in BTM children from an early age and may not be solely due to hyperferritinemia-associated hepatic dysfunction. Despite the presence of deranged hemostatic parameters, a state of balance exists between bleeding and thrombosis, and an imbalance may lead to bleeding or thrombotic events at a later age.

A Cross Sectional Study on T Cells and Subsets in Chronic Lymphocytic Leukemia and their Association with Clinical Phenotype.

T cells in B chronic lymphocytic leukaemia (CLL) have been reported to show qualitative and quantitative alterations, thereby regulating the antitumor immune response. We evaluated the absolute count, percentages of T cells and subsets and their association with disease parameters in Indian patients. 45 treatment naïve CLL cases and 10 healthy controls were evaluated for CD3 + Tcells, CD4 + T cells, CD8 + T cells percentage by flowcytometry. The absolute counts were obtained by multiplication with absolute lymphocyte counts obtained on cell counter. The clinical characteristics (age, sex, Rai stage, B symptoms, CD38 expression) were analysed for any association with alteration of these cells (percentages, absolute counts, ratio with monoclonal B cell count) and CD4: CD8 ratio. The mean absolute count of CD3 + T cell, CD4 + T cell and CD8 + T cells was significantly higher (p < 0.05) in CLL patients as compared to healthy controls. CD4:CD8 ratio was variable (normal, increased and decreased). The mean CD8 + T cells count was higher in advanced disease stage, and CD38 positive cases (p > 0.05). Younger CLL patients (< 55 years) had greater increase in CD8 + T cells (p > 0.05). Significant alterations in T cells and their subsets were observed in CLL. A trend towards advanced stage, CD38 expression, presentation an early age was seen with increase in CD8 + T cell counts.

Epstein-Barr Virus Expression in Classic Hodgkin Lymphoma in an Indian Cohort and its Association with Clinical and Histomorphological Parameters.

Epstein Barr virus (EBV) associated Hodgkin lymphoma (HL) has been defined as cases with clonal EBV infection, EBV genome and gene products in the Reed Sternberg cells. We evaluated the prevalence and clinico-pathological association of EBV in North Indian HL patients. Eighty-eight cases of histologically confirmed classic HL were evaluated for EBV by both IHC expression of LMP1 and real time PCR on formalin fixed lymph node tissue. The expression pattern was analyzed for any association with clinical and histomorphological parameters. Nodular sclerosis subtype was seen in 79.5% patients and mixed cellularity was seen in the remaining patients. Ninety percent of the cases were positive for EBV. The detection rate of EBV by IHC was higher. The EBV positive cases presented with higher disease stage (p < 0.05). The presence of histomorphological features like granuloma formation (5/5), atypical lymphocytes (8/8), histiocyte clusters (26/28), large area of necrosis (11/12), less prominent inflammatory response (25/27) was associated with EBV positivity (p > 0.05). In our study population a high proportion of HL cases showed positivity for EBV indicating a pathogenic role. The positivity was independent of age, gender and histological subtype. Further evaluation of EBV positivity in modulation of tumor immunity may provide insights into variable treatment outcome in EBV positive cases.

Essential Thrombocythemia Presenting with Recurrent Priapism: A Case Report and Review of Literature.

BACKGROUND Priapism is rarely reported as a complication in patients with essential thrombocythemia at presentation. We could find very few such cases of essential thrombocythemia while searching the literature. A combined modality of treatment is used in the form of chemotherapy and procedures like repeated aspiration and instillation of phenylephrine to treat essential thrombocythemia presenting with recurrent priapism. CASE REPORT A 31-year-old man presented to the Urology Department with priapism for the last 24 h. He had previously had multiple similar episodes in the last 20 days and 1 episode of prolonged penile erection 5 months ago. On examination, his penis was erect, swollen, and painful. There was no organomegaly. The priapism was managed with repeated aspiration and instillation of phenylephrine. Routine investigations showed marked thrombocytosis. Subsequent investigations done in the Clinical Hematology Department revealed increased megakaryocytes in bone marrow and presence of JAK2V617F mutation. After confirmation of diagnosis, cytoreductive therapy (hydroxyurea 500 mg twice a day) and acetyl salicylic acid 75 mg once a day was initiated. With this treatment, the platelet count normalized over a period of 2 months and no further episodes of priapism were noted; however, the patient developed erectile dysfunction. CONCLUSIONS Essential thrombocythemia can present with priapism as the first manifestation. Early suspicion, diagnosis, and management is needed to prevent erectile dysfunction. Erectile dysfunction is usually irreversible after long-standing priapism.

A case of Philadelphia chromosome-positive acute myeloid leukaemia with missense mutation R132c (c.394 c>t) and single nucleotide polymorphism rs11554137(G105G) in isocitrate dehydrogenase 1 gene.

Acute myeloid leukaemia (AML) is a heterogeneous disease due to its variable clinical, morphological and genetic features. New chromosomal and molecular abnormalities are being studied to evaluate novel treatment options and prognostic implications. We report a patient with AML who was Philadelphia chromosome-positive along with IDH1R132 mutation and SNP rs11554137(IDH1105GGT). Due to limited reports regarding these aberrations in patients with AML, there is no consensus regarding their prognostic implications. To the best of our knowledge, the presence of Philadelphia chromosome, IDH1R132 and SNP rs11554137 in a single AML patient with good prognosis is a novel finding.

Prothrombotic state in HIV: A study on protein C, protein S, homocysteine and correlation with CD4 counts.

Introduction: Human immunodeficiency virus (HIV) may result in variable haematological manifestations. Thrombotic events are more common among HIV-infected persons than the general population, possibly due to the increased inflammatory/hypercoagulable state and presence of concurrent comorbidities. Aims and Objectives: (1) Screen for coagulation abnormalities in HIV-infected patients. (2) Detect certain prothrombotic factors such as deficiency of protein C and protein S and elevation of homocysteine as possible precursors of coagulation defects in HIV patients. (3) Correlation of coagulation abnormalities with CD4 counts. Methods: A pilot study of 1-year duration conducted in the Department of Pathology in collaboration with ART centre, KGMU Lucknow. All diagnosed HIV-seropositive patients (n = 30) who were not taking Vitamin K, antithrombotic and antiplatelet drugs including aspirin, oral contraceptives and not having known protein C/S deficiency were included in the present study as cases. Apart from this, 30 age- and sex-matched healthy individuals were also included in the present study. Assessment of the bleeding time, prothrombin time and activated partial thromboplastin time, complete blood count was done. Protein C and S were measured by calorimetric assay. Serum homocysteine was measured by the semi-automated method. CD4 count was done by flow cytometry. Results: The findings of the present study suggest a relationship between HIV, its complications and thrombosis. The HIV-seropositive patients have reduced levels of haemoglobin, CD4 counts, platelet counts, mean platelet volume, protein C and S activity as compared to the healthy individuals. Thrombophilic abnormality in the form of hyperhomocysteinaemia is more frequent in HIV-infected patients. All these parameters have a definite correlation with CD4 count.

Hypertriglyceridemia thalassemia syndrome.

Background Hypertriglyceridemia thalassemia syndrome is a rare entity with an unknown pathogenetic link. Case presentation We report a case of an 8-month-old female with thalassemia major and increased triglyceride (TG) levels. The clinical features were as in classical thalassemia except for a white discoloration of the plasma. After exclusion of familial triglyceridemia and secondary causes (hypothyroidism, nephrotic syndrome, drugs etc.), a diagnosis of hypertriglyceridemia thalassemia syndrome was made. Conclusions The high levels of TG in these patients are associated with oxidative stress and higher risk of acute pancreatitis and coronary diseases. An early recognition is thus essential. In our patient, the levels reduced after a transfusion therapy similar to previous reports.