HEMOGLOBIN C TRAIT PRESENTING WITH BILATERAL CENTRAL RETINAL VEIN OCCLUSION.

PURPOSE: To report a case of bilateral sequential, central retinal vein occlusion (CRVO) in a man with newly diagnosed hemoglobin C trait. METHODS: A 67-year-old man presented with a one-month history of declining visual acuity. He was diagnosed with left CRVO. Bilateral temporal retinal ischemia and arteriovenous anastomoses on fluorescein angiography suggestive of sickle cell retinopathy prompted a systemic work-up. Hemoglobin electrophoresis revealed an underlying hemoglobin C trait. Six-months after his initial presentation, the patient developed symptomatic right CRVO. RESULTS: The initial left CRVO was complicated by optic disc swelling and macular edema. Intravitreal antiangiogenic therapy was initiated and the macular edema resolved. The left eye subsequently developed an epiretinal membrane which was surgically removed. Macular edema in the right eye also resolved after intravitreal antiangiogenic therapy. CONCLUSION: This is the first reported case of bilateral CRVO in a case of hemoglobin C trait. It is possible that erythrocyte inflexibility, caused by hemoglobin C-induced dehydration and crystallization, acted concomitantly with hypertension to produce occlusive microangiopathy. This case highlights the need for further investigation in patients presenting with central retinal vein occlusion, especially when bilateral, or when retinal angiography reveals bilateral pathology.

B-lymphoblastic leukemia/lymphoma with MYC and BCL2 gene rearrangements shows evidence for clonal evolution and mitotic recombination.

BACKGROUND: B-lymphoblastic leukemia/lymphomas (B-ALL/LBL) are uncommon neoplasms that may be associated with a variety of cytogenetic and molecular changes. The mechanisms by which these changes arise have not been fully described. AIMS/PURPOSE: This report describes an unusual case of B-ALL/LBL with complex clonal evolution that includes BCL2 and MYC gene rearrangements. METHODS: Immunophenotyping was performed by immunohistochemistry and flow cytometry. Traditional G-band karyotyping was accompanied by fluorescence in-situ hybridization (FISH) using break-apart and dual fusion probes. Single nucleotide polymorphisms were assessed using a high-density DNA microarray. RESULTS: The karyotype of the blasts showed reciprocal translocation of chromosomes 4 and 18, reciprocal translocation of chromosomes 8 and 14 with two copies of the oncogenic translocation derivative(14)t(8;14), and no normal chromosome 14. FISH studies showed complex IGH-BCL2 and IGH-MYC fusion signals. CONCLUSIONS: A clonal evolution model involving multiple chromosomal translocations and mitotic recombination is postulated to account for the karyotype, FISH, and microarray results but leaves unresolved the exact order of the evolutionary changes.

Acquired hemophilia A.

Acquired inhibitors of coagulation are a group of rare but potentially life-threatening blood disorders characterized by the presence of autoantibodies directed against clotting factor. Autoantibody against factor VIII is the most common form of clotting factor inhibitor, a condition also known as acquired hemophilia A. We present a clinical series of nine patients diagnosed and treated for acquired hemophilia A at our institution. Among these nine patients, there were five men and four women with a median age of 64 years. All patients presented with bleeding diathesis. Factor eight inhibitor bypassing agent and/or recombinant factor VIIa were predominantly used for control of active bleeding. For elimination of autoantibodies, either steroids alone or the combination of steroids with rituximab or oral cyclophosphamide was used. Despite aggressive measures, two of the patients had a poor outcome; seven of the nine patients (77%) had a good clinical outcome. Acquired hemophilia A should be strongly suspected in any patient presenting with bleeding and a prolonged activated partial thromboplastin time. Early initiation of factor bypassing agents such as activated prothrombin complex concentrates or recombinant factor VIIa, along with the use of immunosuppressive agents, can be lifesaving.

Hemophagocytic lymphohistiocytosis in adults.

Hemophagocytic lymphohistiocytosis (HLH) is an underrecognized disorder due to the variability of its presentation and the fact that in adults, its diagnosis is based on cumbersome, pediatric-based criteria. Data regarding demographics, underlying causes, clinical features, laboratory results, complications, treatments received, and clinical outcomes were collected and analyzed in 41 patients who were diagnosed and treated at University of Arkansas for Medical Sciences between 2007 and 2019. In this group, 51% were male, the median age at diagnosis was 47 years, and 85% (35/41) met the HLH-2004 diagnostic criteria (5/8 variables). When evaluating seven extended variables easily obtained by routine laboratory test, 93% (38/41) of patients met 8 out of 15 criteria. The overall mortality in our patient population was 54% (22/41). The 30-day and 1-year overall survival estimates were 0.73 (95% confidence interval 0.56, 0.84) and 0.46 (95% confidence interval 0.29, 0.62), respectively. Thirty-five patients (85.4%) received HLH-directed therapy, and 19 patients (46.3%) achieved remission. The most common regimen for treating HLH was dexamethasone plus etoposide (53.7%). The patients with malignancy-related HLH had a worse prognosis than those without underlying malignancy, with a 73.33% (11/15) vs 34.62% (9/26) mortality (P = 0.02). In conclusion, despite increasing recognition, HLH remains an enigmatic disorder with increased mortality, even more so with malignancy-associated HLH.

Acquired Amegakaryocytic Thrombocytopenia Misdiagnosed as Immune Thrombocytopenia: A Case Report.

INTRODUCTION: Acquired amegakaryocytic thrombocytopenia (AATP) is a rare bleeding disorder that causes severe thrombocytopenia with preserved hematopoiesis of other cell lineages. Many cases are misdiagnosed and treated as immune thrombocytopenia. CASE PRESENTATION: We report a case of AATP, in a 50-year-old man, that was treated as immune thrombocytopenia for years with no clinical response. The disorder later was diagnosed as AATP after bone marrow biopsy and was successfully treated with cyclosporine. DISCUSSION: The exact mechanism of AATP remains unclear; it is suspected to be an immune-mediated process. Patients with AATP present with severe bleeding and thrombocytopenia, which is usually unresponsive to high-dose corticosteroids. There are no standard treatment guidelines for AATP. Cyclosporine and antithymocyte globulin are found to be effective in some cases. The prompt diagnosis of AATP is vital because it carries high mortality because of excessive bleeding, and it can progress into aplastic anemia or myelodysplastic syndrome.

Tumor-associated antigens and their antibodies in the screening, diagnosis, and monitoring of esophageal cancers.

Despite the advances in the treatment and management, esophageal cancers continue to carry a dismal prognosis with an overall 5-year survival rate ranging from 15 to 25%. Delayed onset of symptoms and lack of effective screening methods and guidelines for diagnosis of the early disease contribute to the high mortality rate of esophageal cancers. Detection of esophageal cancer at their early stage is really a challenge for physicians including primary care physicians, gastroenterologists and oncologists. Although imaging, endoscopy and biopsy have been proved to be useful diagnostic tools for esophageal cancers, their diagnostic accuracy is unsatisfactory. In addition, expensive costs, invasiveness and special training operator have limited the clinical application of these tools. Recently, tumor-associated antigens (TAAs) and their antibodies have been reported to be potential markers in esophageal cancer screening, diagnosis, monitoring and prognostication. Because TAAs and their antibodies have the advantages of inexpensive cost, noninvasiveness and easy access, they have attracted much attention as an affordable option for early esophageal cancer diagnosis. In this review, we summarized the advances in TAAs and their antibodies in esophageal cancer screening, diagnosis, monitoring and prognostication.

Vitamin B12 deficiency mimicking acute leukemia.

Vitamin B12 deficiency can cause extensive hematologic alterations such as pancytopenia, macrocytosis, hypersegmentation of neutrophils, and hypercellular bone marrow with blastic differentiation. These dysplastic changes can sometimes be so profound that they mimic myelodysplastic syndromes or even acute leukemia, leading to extensive workup and aggressive treatment measures. We present a patient who was referred to our tertiary care medical center for treatment of suspected acute myeloid leukemia on the basis of peripheral smear and bone marrow biopsy findings, and induction chemotherapy was considered. However, the patient was found to have vitamin B12 deficiency, with improvement in pancytopenia and blastic changes with parenteral vitamin B12 supplementation. This highlights the importance of recognizing that dysplastic changes in patients with vitamin B12 deficiency could be misleading.