Hidden treasures: Incidental findings in two cases of chronic subdural hematoma.

Background: Extramedullary hematopoiesis (EMH) and plasmacytomas occurring within the cranium are rare entities. Case Description: We review two cases in which patients presented with subdural hematoma and underwent evacuation. On routine histopathologic examination of their membranes, both patients were subsequently found to have focal EMH, as well as a clonal plasma cell proliferation in one case. Conclusion: EMH is rare and usually found in individuals with profound and chronic anemia. However, this entity may be more common in chronic subdural hematomas. Solitary extraosseous plasmacytoma is exceedingly rare in the cranium, and its presence in chronic subdural hematoma membranes is of uncertain significance. The cytokine milieu that promotes organization of chronic subdural hematomas may play a role in the establishment of both of entities in this location.

Leukoerythroblastosis in a Sickle Cell Patient With Pregnancy: An Interesting Peripheral Blood Smear Finding.

The global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has shaken the entire world. The social, health and financial impacts of this pandemic are beyond words. We have learnt a lot about this new disease in a short period of time, but still a long road to go to fully determine its pathogenic effect. The primary target of this virus is angiotensin-converting enzyme 2 (ACE2) receptor, which is prevalent in endothelial cells throughout the body. Immunocompromised patients such as patients with sickle cell disease are more vulnerable to severe respiratory infections, including infection with SARS-CoV-2. In addition, sickle cell disease patients are prone to vaso-occlusive crisis, and theoretically SARS-CoV-2 can worsen the situation as it also can cause endothelial dysfunction and thrombosis. Herein, we are sharing an interesting peripheral blood smear finding of an asymptomatic 31-year-old multigravida pregnant female with a history of sickle cell disease and found to have a positive COVID-19 polymerase chain reaction (PCR) test during her third trimester of pregnancy at a routine clinic visit. Two weeks after the initial positive test, she developed nausea, vomiting, constipation and a pain crisis affecting her extremities while her COVID-19 PCR test was still positive. She was hemodynamically stable, and lab workup revealed chronic anemia, leukocytosis with neutrophilia and lymphopenia. Morphologic examination of the peripheral blood smear showed a marked leukoerythroblastosis: rare myeloblasts, sickle cells, markedly abundant nucleated red blood cells (RBCs), metamyelocytes, and many large and giant platelets were seen. In this context, her previous peripheral blood smears (prior to positive COVID-19 test) did not show leukoerythroblastosis. She was managed conservatively with hydration and pain control and delivered at 36 weeks via cesarean section due to pre-term labor and intrauterine growth retardation. The unusual finding of leukoerythroblastosis in a pregnant sickle cell disease patient with an asymptomatic COVID-19 infection indicates further studies to determine its effect on hematopoietic system and elucidate its clinical significance.

Polyclonal CD5+/CD19+ B1a lymphocytes after allogeneic stem cell transplantation: a potential diagnostic pitfall.

In adults, B-lymphocytes comprise approximately 10% of circulating lymphocytes. The majority of peripheral B cells are B2 cells ("Mature" B-cells), which function as part of the humoral adaptive immune system. B1 cells ("Innate-like" B cells) are another sub-class of B lymphocytes, considered as innate immune cells with a characteristic phenotype (CD20+, CD27+, CD43+, CD70-, CD11b+, sIgM++, sIgD+) which can be divided into two subtypes; B1a (CD5+): spontaneously produce broadly reactive natural IgM, and B1b (CD5-): can generate T-cell independent, long-lasting IgM. There is very limited data available, indicating a correlation between allogeneic bone marrow transplantation and an increase in B1a cells. Here we present a case of a 17-year-old female with homozygous sickle cell disease (HbSS disease) who underwent hematopoietic stem cell transplant (HSCT). Approximately seven months post-transplant, she was found to have 16% immature mononuclear cells on complete blood count (CBC)-differential report. A follow-up peripheral blood flow cytometry showed that these cells were polyclonal CD5+/CD20+ B-cells, and comprised 66% of lymphocytes. Further workup and follow up failed to reveal any lymphoproliferative disorders. It is important not to misdiagnose these cells as an atypical CD5+ lymphoproliferative disorder. The presence of B1a cells has not been widely reported in non-neoplastic post-stem cell transplanted patients. This case also adds to and expands our knowledge regarding the presence of increased circulating B1a cells after stem cell transplant in a patient with no history of hematological malignancy.

Polyclonal CD5+/CD19+ B1a lymphocytes after allogeneic stem cell transplantation: a potential diagnostic pitfall

In adults, B-lymphocytes comprise approximately 10% of circulating lymphocytes. The majority of peripheral B cells are B2 cells ("Mature" B-cells), which function as part of the humoral adaptive immune system. B1 cells ("Innate-like" B cells) are another sub-class of B lymphocytes, considered as innate immune cells with a characteristic phenotype (CD20+, CD27+, CD43+, CD70-, CD11b+, sIgM++, sIgD+) which can be divided into two subtypes; B1a (CD5+): spontaneously produce broadly reactive natural IgM, and B1b (CD5-): can generate T-cell independent, long-lasting IgM. There is very limited data available, indicating a correlation between allogeneic bone marrow transplantation and an increase in B1a cells. Here we present a case of a 17-year-old female with homozygous sickle cell disease (HbSS disease) who underwent hematopoietic stem cell transplant (HSCT). Approximately seven months post-transplant, she was found to have 16% immature mononuclear cells on complete blood count (CBC)-differential report. A follow-up peripheral blood flow cytometry showed that these cells were polyclonal CD5+/CD20+ B-cells, and comprised 66% of lymphocytes. Further workup and follow up failed to reveal any lymphoproliferative disorders. It is important not to misdiagnose these cells as an atypical CD5+ lymphoproliferative disorder. The presence of B1a cells has not been widely reported in non-neoplastic post-stem cell transplanted patients. This case also adds to and expands our knowledge regarding the presence of increased circulating B1a cells after stem cell transplant in a patient with no history of hematological malignancy.

Acquired Elliptocytosis as a Manifestation of Myelodysplastic Syndrome with Ring Sideroblasts and Multilineage Dysplasia.

Acquired elliptocytosis is a known but rarely described abnormality in the myelodysplastic syndromes (MDS). Here we report the case of an elderly male who was admitted to the hospital with chest pain, dyspnea, and fatigue and was found to be anemic with an elliptocytosis that had only recently been noted on peripheral smears of his blood. After bone marrow biopsy he was diagnosed with MDS with ring sideroblasts and multilineage dysplasia and acquired elliptocytosis. Here we report a rare case of acquired elliptocytosis cooccurring with MDS with ring sideroblasts and multilineage dysplasia.

PAX5-Negative Classical Hodgkin Lymphoma: A Case Report of a Rare Entity and Review of the Literature.

Classical Hodgkin lymphoma (CHL) is recognized as a B-cell neoplasm arising from germinal center or postgerminal center B-cells. The hallmark of CHL is the presence of CD30 (+) Hodgkin and Reed-Sternberg (HRS) cells with dim expression of PAX5. Nearly all of the HRS cells are positive for PAX5. However, a small minority of HRS cells may lack PAX5 expression, which can cause a diagnostic dilemma. Herein we describe two cases of PAX5-negative CHL and review of the English literature on this very rare entity. It is crucial to be aware of this phenomenon, which in some cases may lead to misdiagnosis and may ultimately adversely affect patient's management.

An extremely rare case of concurrent BRAF V600E mutation driven hairy cell leukemia and melanoma: case report and review of literature.

BRAF protein is a serine/threonine kinase with 766 amino acids. Approximately 15% of human cancers harbor BRAF mutations as well as other BRAF anomalies (amplifications, fusions). Somatic mutations mainly occur in the catalytic kinase domain (CR3), and the predominant mutation is p.V600E which is the substitution of glutamic acid (E) for valine (V) as result of a mutation at codon 600 of the kinase domain. To our knowledge, the vast majority of the cancers have non-germline BRAF mutations. Here we describe a case of a 60-year-old female with a history of hairy cell leukemia (HCL) who presented with aphasia and forgetfulness. A follow-up Brain CT scan showed three distinct brain lesions which were found to be diagnostic of melanoma (confirmed by immunohistochemistry) with no evidence of a concurrent brain involvement by a B-cell neoplasm. Molecular studies confirmed the same BRAF p.V600E mutation in both malignancies (hairy cell leukemia and melanoma). Thereafter the patient was started on BRAF inhibitor treatment and is now symptom-free after one year of follow up. Having two concurrent malignancies with a shared BRAF mutation is extremely rare and makes this an excellent example of a genomic marker-driven treatment in two histologically and immunophenotypically distinct tumors.

An extremely rare case of concurrent BRAF V600E mutation driven hairy cell leukemia and melanoma: case report and review of literature

BRAF protein is a serine/threonine kinase with 766 amino acids. Approximately 15% of human cancers harbor BRAF mutations as well as other BRAF anomalies (amplifications, fusions). Somatic mutations mainly occur in the catalytic kinase domain (CR3), and the predominant mutation is p.V600E which is the substitution of glutamic acid (E) for valine (V) as result of a mutation at codon 600 of the kinase domain. To our knowledge, the vast majority of the cancers have non-germline BRAF mutations. Here we describe a case of a 60-year-old female with a history of hairy cell leukemia (HCL) who presented with aphasia and forgetfulness. A follow-up Brain CT scan showed three distinct brain lesions which were found to be diagnostic of melanoma (confirmed by immunohistochemistry) with no evidence of a concurrent brain involvement by a B-cell neoplasm. Molecular studies confirmed the same BRAF p.V600E mutation in both malignancies (hairy cell leukemia and melanoma). Thereafter the patient was started on BRAF inhibitor treatment and is now symptom-free after one year of follow up. Having two concurrent malignancies with a shared BRAF mutation is extremely rare and makes this an excellent example of a genomic marker-driven treatment in two histologically and immunophenotypically distinct tumors.

Optimal Molecular Methods in Detecting p190 (BCR-ABL) Fusion Variants in Hematologic Malignancies: A Case Report and Review of the Literature.

Patients with BCR-ABL1 positive hematologic malignancies and Philadelphia-like B-lymphoblastic leukemia (B-ALL) are potential candidates for targeted therapy with tyrosine kinase inhibitors (TKI). Before TKIs, patients with B-ALL had a much worse prognosis and current treatments with targeted TKI therapy have improved outcomes. Thus, the detection of BCR-ABL1 is crucial and a false negative BCR-ABL1 result may adversely affect patient care. We report a case of a 76-year-old male with a new diagnosis of B-ALL who was initially found to be BCR-ABL1 negative by quantitative polymerase chain reaction (PCR). A concurrent qualitative PCR was performed which detected a positive BCR-ABL1 result that was confirmed by a next generation sequencing (NGS) based assay and identified as the rare fusion variant e1a3 of p190(BCR-ABL). Based on this result, the patient was placed on dasatinib as a targeted therapy. In the era of molecular diagnostic medicine and targeted therapy, it is essential to have an understanding of the limitations of molecular assays and to follow a comprehensive diagnostic approach in order to detect common abnormalities and rare variants. Incorporating NGS methods in an algorithmic manner into the standard diagnostic PCR-based approach for BCR-ABL1 will aid in minimizing false negative results.

Translocation (6;15)(q12;q15): A Novel Mutation in a Patient with Therapy-Related Myelodysplastic Syndrome.

Most myelodysplastic syndromes (MDS) present with loss or gain of chromosomal material and less commonly show translocations as a sole abnormality. In addition, certain translocations are more commonly seen in MDS than others, but to our knowledge, the presence of t(6;15) has not been reported in MDS, specifically therapy-related MDS (t-MDS) cases. Patients with t-MDS, a group of heterogeneous stem cell related disorders resulting as a latent complication of cytotoxic and/or radiation therapy, generally tend to have a poorer prognosis than de novo MDS. We present a unique case of a patient who initially presented with acute myeloid leukemia (AML) with a normal karyotype and FLT3-ITD and NPM1 mutations. The patient was successfully treated with chemotherapy and an autologous bone marrow transplant but subsequently developed a new FLT3-ITD negative t-MDS with a unique translocation, t(6;15)(q12;q15), three years after transplant. To our knowledge, this unique sole translocation has never been reported in MDS or t-MDS and given her successful response to treatment and remission, presence of this translocation may have some prognostic value.

Extraocular muscle enlargement leading to the diagnoses of Burkitt lymphoma and acquired immune deficiency syndrome.

Orbital involvement in nonendemic Burkitt lymphoma is rare. The authors report a unique case of a patient who sought treatment for extraocular muscle enlargement without a concurrent orbital mass, which subsequently led to the diagnoses of Burkitt lymphoma and acquired immune deficiency syndrome in an adult patient. The case report adhered to the principles of the Declaration of Helsinki and Health Insurance Portability and Accountability Act compliance. This single case report was institutional review board exempt, given that it does not meet the definition of human subjects' research.

B-cell lymphoma line (Raji) viability and surface marker expression minimally affected by 20- and 25-gauge vitrectomy systems analyzed by flow cytometry.

PURPOSE: The purpose of this study was to evaluate the effect of 20-gauge (20-G) and 25-gauge (25-G) vitrectomy on cell viability and diagnostic yield (surface marker expression) using flow cytometry and human lymphoma cells in culture. METHODS: Cultured human Burkitt lymphoma cells (Raji B-cell lymphoma line) were allocated into five study groups in Roswell Park Memorial Institute media. By using manual aspiration, cells were then processed by aspiration alone, by 20-G vitrectomy at 600 cuts per minute (cpm) and 1,500 cpm, or by 25-G vitrectomy at both 600 and 1,500 cpm. To assess cell viability and cell surface marker expression, samples underwent standard flow cytometry analysis for suspected lymphoma using 7-amino-actinomycin D and antibodies against CD45, CD19, lambda, and kappa light chains. RESULTS: Twenty-five samples were processed after being divided into four vitrectomy groups and one nonvitrectomy group (control). The mean cell viability was 98.5 for both the nonvitrectomized and vitrectomized specimens. The percentage of cells positive for CD45 or kappa light chain was the same in the nonvitrectomized and vitrectomized groups. In addition, the level of expression of these molecules was not significantly different in all five groups. Similarly, no difference was seen for these markers between 20-G and 25-G vitrectomy at either a cut rate of 600 or 1,500 cpm. The percentage positive for CD19 was significantly lower for the 20-G vitrectomy at 1,500 cpm compared with the 25-G vitrectomy at both 600 and 1,500 cpm. Percentage of CD19 cells was greater for the 25-G vitrectomy at 600 cpm than the nonvitrectomy group. CONCLUSION: Compared with simple aspiration, both 20-G and 25-G vitrectomy seem to have no significant effect on cell viability or diagnostic yield for B-cell lymphoma cells (Raji cell line) in suspension based on flow cytometry. Further studies need to be conducted to study and compare 20-G versus 25-G vitrectomy on lymphoma cells in human vitreous or in an animal model.

Transfusion-related acute lung injury (TRALI): current clinical and pathophysiologic considerations.

Transfusion-related acute lung injury (TRALI) is a rare transfusion reaction presenting as respiratory distress during or after transfusion of blood products. TRALI varies in severity, and mortality is not uncommon. TRALI reactions have equal gender distributions and can occur in all age groups. All blood products, except albumin, have been implicated in TRALI reactions. TRALI presents as acute respiratory compromise occurring in temporal proximity to a transfusion of a blood product. Other causes of acute lung injury should be excluded in order to definitively diagnose TRALI. Clinically and pathologically, TRALI mimics acute respiratory distress syndrome (ARDS), with neutrophil-derived inflammatory chemokines and cytokines believed to be involved in the pathogenesis of both entities. Anti-HLA and anti-neutrophil antibodies have been implicated in some cases of TRALI. Treatment for TRALI is supportive; prevention is important. It is suspected that TRALI is both underdiagnosed and underreported. One of the difficulties in the evaluation of potential TRALI reactions is, until recently, the lack of diagnostic criteria. A group of transfusion medicine experts, the American-European Consensus Conference (AECC), recently met and developed diagnostic criteria of TRALI, as well as recommendations for management of donors to prevent future TRALI reactions. In light of the AECC consensus recommendations, we report an incident of TRALI in an oncology patient as an example of the potential severity of the lung disease and the clinical and laboratory evaluation of the patient. We also review the literature on this important complication of blood transfusion that internists may encounter.

A red blood cell autoantibody with mimicking anti-E specificity.

BACKGROUND: Uncommonly, antibodies that appear to exhibit antigenic specificity on red blood cell (RBC) panels fail to maintain specificity following alloadsorption (i.e., they mimic antigenic specificity). Understanding both the pitfalls and the proper pathways to establish the diagnosis and to interpret the clinical significance of these mimicking antibodies is important for patient management. CASE REPORT: A 68-year-old woman was admitted with dyspnea, anemia, bilateral pulmonary emboli, and metastatic ovarian cancer. Blood bank evaluation identified anti-E reactivity in the patient's plasma sample and a positive direct antiglobulin test (DAT). RESULTS: The DAT was positive for immunoglobulin G and negative for C3b. An eluate of the RBCs showed E-antigen specificity on a RBC antibody panel. Repeat serologic testing with RBC antibody panels with adsorbed patient plasma showed removal of apparent anti-E reactivity with either E-antigen-positive or E-antigen-negative RBC stroma. CONCLUSION: A mimicking autoantibody with apparent E-antigen specificity was identified in the plasma sample of a woman with newly diagnosed ovarian cancer. Despite their relative low frequency, mimicking antibodies, whether auto- or alloantibodies, may interfere with the timely issuance of compatible blood products and may confuse laboratory and clinical staff. Determining the clinical significance of the antibody, by taking into account the RBC phenotype of the patient and the antigen prevalence in the general population, guides the extent of workup required to best utilize resources while assuring patient safety.