Aplastic anemia secondary to adjuvant Osimertinib therapy: a case report and a review of literature.

Aplastic anemia is a rare hematological disorder characterized by suppressed hematopoiesis and pancytopenia. Although several drugs have been associated with aplastic anemia, its occurrence in response to Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is extremely rare. We present a case report of a 63-year-old patient with locally advanced non-small cell lung cancer (NSCLC) who developed aplastic anemia following adjuvant treatment with Osimertinib. Extensive investigations ruled out infectious etiology, and the absence of bone marrow involvement or other identifiable causes suggested a drug-induced etiology, specifically Osimertinib. This case report emphasizes the importance of recognizing this adverse event and considering it as a potential complication of Osimertinib therapy. Vigilant monitoring and prompt management are essential for optimizing patient outcomes. Further studies are needed to better understand the risk factors, underlying mechanisms, and management strategies for Osimertinib-induced aplastic anemia in the adjuvant settings.

Co-infection of Cytomegalovirus and Epstein-Barr Virus in an Immunocompetent Patient: A Case Series and Literature Review.

Cytomegalovirus (CMV) infection or Epstein-Barr virus (EBV) infection in immunocompetent patients usually resolves without treatment. However, it can cause severe symptoms that can last for several weeks, especially in immunocompromised patients. Indications for antiviral immunocompetent individuals with CMV disease are not well-established. Here, we report two cases who had concomitant CMV-EBV infection. The first patient ultimately received anti-CMV therapy with significant improvement in symptoms and labs. The second patient had a milder disease course and was treated conservatively.

Recurrent sideroblastic anemia during pregnancy.

Sideroblastic anemia is a heterogeneous group of disorders typified by the presence of ring sideroblasts in the bone marrow and has congenital and acquired types. Sideroblastic anemia is a rare event in pregnancy. We report a case of a 32-year-old female patient, gravida 4 para 3, 27th weeks pregnant, who presented to the emergency department complaining of palpitation and generalized weakness for 2 weeks. She was found to have severe normochromic normocytic anemia, with hemoglobin of 4.2 g/dl, and low reticulocytes count of 13 × 103/µl. She gave a history of recurrent anemia, which had only occurred during pregnancy. Her bone marrow aspirate showed many ring sideroblasts concluding the diagnosis of sideroblastic anemia (SA). Further investigation revealed a significantly low pyridoxine level (vitamin B6) of (8 nmol/L). The Hb level improved with vitamin B6 replacement, without any transfusion support.

Assessing Bone Marrow Activity with [18F]FLT PET in Patients with Essential Thrombocythemia and Prefibrotic Myelofibrosis: A Proof of Concept.

Objectives: This study aims to assess the value of FLT-PET as a non-invasive tool to differentiate between patients with ET and Pre-PMF. This study is a pilot study to have a proof of concept only. Methods: This is a prospective, interventional study where a total of 12 patients were included. Each patient underwent FLT PET imaging as well as bone marrow examination (gold standard). In addition, semi-quantitative (SUVmax and SUVmean) measurements of FLT uptake in the liver, spleen, and Lspine, SUVmean, as well as the Total Lesion Glycolysis (TLG) of the Lspine were performed. Results from the two patient cohorts were compared using = Kruskal-Wallis statistical test. A P-value of <.05 is considered to be statistically significant. Results: The differences in FLT SUVmax and SUVmean measurements in the three organs (liver, spleen, and LSpine) between the ET and Pre-PMF patients were not statistically significant (P > .05). In contrast, TLG measurements in the LSpine were statistically different (P = .013), and therefore, compared to gold standard bone marrow results, TLG can separate ET and Pre-PMF patients. Conclusion: This study is a proof of concept about the potential to discriminate between ET and pre-PMF patients in a non-invasive way. TLG of the LSpine in FLT PET images is a potential quantitative parameter to distinguish between ET and pre-PMF patients.

Heterotopic pregnancy after a spontaneous conception a case report with a review of clinical, laboratory and imaging findings.

Heterotopic pregnancy (HP) describes the simultaneous presence of two pregnancies at different implantation sites. Usually, one pregnancy is intrauterine and the other one is ectopic. The incidence of HP after assisted reproductive technologies reaches 1:3900, but is very rare after a spontaneous pregnancy, with a reported incidence of 1 to 30,000 pregnancies. Due to its rarity, complex clinical picture, and laboratory findings, it is challenging to diagnose HP. We present a case of spontaneous HP diagnosed in the first trimester by ultrasound (US) and magnetic resonance imaging (MRI) and subsequently managed successfully. We present an analysis of the clinical and laboratory findings as well as imaging, including MRI that we used to diagnose the condition. Additionally, we performed a literature review. CONCLUSIONS: HP is a very rare condition frequently faced in obstetrics, gynecology, and emergency departments that requires a high index of clinical suspicion. US remains the imaging modality of choice in diagnosing a HP, however, in some cases, an MRI with a reported safety in the first trimester, can be used to provide additional information over US.

P190 BCR-ABL1 in a Patient with Philadelphia Chromosome Positive T-Cell Acute Lymphoblastic Leukemia: A Rare Case Report and Review of Literature.

T-acute lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL/LBL) is rare and aggressive leukemia. Philadelphia chromosome positive (Ph+) is the most common cytogenetic abnormality in chronic myeloid leukemia (CML) and B-acute lymphoblastic leukemia (B-ALL). Ph+ T-ALL is exceeding rare and has a therapeutic and prognostic significance. The incidence and outcome of Ph+ T-ALL are unknown. Differentiation between Ph+ T-ALL/LBL and T-cell lymphoblastic crises of CML may be difficult. We report a rare case of adult de novo T-ALL with significant monocytosis, having Ph+ with (P190 BCR-ABL1) as a cytogenetic abnormality. He was treated with ALL induction chemotherapy and imatinib and achieved complete remission, then relapsed twice and expired shortly after the last CNS relapse.

Ovarian Dysgerminoma in Pregnant Women with Viable Fetus: A Rare Case Report.

Dysgerminoma is an uncommon malignant tumor arising from the germ cells of the ovary. Its association with pregnancy is extremely rare, with a reported incidence of about 0.2-1 per 100,000 pregnancies. Women in the reproductive age group are more commonly affected. It can be extremely rare to conceive naturally, without assisted reproductive interventions, in cases with ovarian dysgerminoma. If a pregnancy does occur with a concurrent dysgerminoma, it is even more unusual to carry the pregnancy to viability or childbirth without fetal or maternal compromise. We report a case of right ovarian dysgerminoma in a young female with a viable intrauterine pregnancy at 10 weeks, which is rarely diagnosed and managed at this gestational age. Numerous factors played a role in her favorable outcome, including early suspicion by ultrasound and presenting history, surgery, histopathological assessment, imaging, and involvement of the multidisciplinary oncology team. Ovarian neoplasms may rapidly increase in size within a short period with little or no symptoms. This poses a diagnostic challenge for obstetricians and oncologists. Hence, we aimed to evaluate the role of imaging in pregnancy using ultrasound as an imaging modality for both early detection of ovarian neoplasms and for follow-up. In conclusion, patients with ovarian dysgerminoma in pregnancy can have favorable outcomes. Treatment should be individualized on a case-to-case basis, depending on many factors; cancer stage, previous reproductive history, the impact of imaging in staging or follow-up of tumor on the fetus, fetal gestational age, and whether termination of the pregnancy can improve survival or morbidity for the mother.

Fatal temozolomide induced aplastic anemia in a female with Glioblastoma multiforme : A case report and literature review.

When seeing patients on Temozolomide with pancytopenia, aplastic anemia secondary to the drug should be considered early in the differentials to avoid permanent hematological suppression.

COVID-19 unfolding filariasis: The first case of SARS-CoV-2 and Wuchereria bancrofti coinfection.

With the evolution of the Coronavirus Disease 2019 (COVID-19) pandemic, the number of patients brought to medical attention has increased. This has led to the unmasking of many coexisting occult infections and comorbidities such as tuberculosis, dengue, human immunodeficiency viral infection, diabetes, and hypertension. We report the first case of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, unveiling the diagnosis of asymptomatic filariasis. A 37-year-old gentleman presented with shortness of breath, fever, and cough. He was found to have COVID-19 pneumonia. During his stay, microfilaria of Wuchereria bancrofti was detected incidentally on a blood smear exam. Consequently, the patient received appropriate treatment for both conditions. In order not to miss relevant concomitant diagnoses, it is prudent to keep a broad differential diagnosis when faced with SARS-CoV-2-infected patients; this is especially true when atypical symptoms are present or in areas endemic with other infections.

High-Grade Epstein-Barr Virus-Negative Biphenotypic Lymphoma with Expression of B- and T-Cell Markers and Leukemia Presentation: Case Report and Literature Review.

Lymphomas are presently categorized according to their origin from B or T lymphocytes. The co-expression of CD3 in B-cell lymphomas or CD20 in T-cell lymphomas has been rarely reported. Immature and less often mature lymphomas may incorporate the rearrangements of both B- and T-cell antigen receptor genes (dual genotype or bigenotype). Lymphoma cells with a sole genotype hardly concurrently express both B- and T-cell markers (biphenotypic lymphomas). We describe a 63-year-old female who was presented with obstructive jaundice and epigastric pain of 10 days. Initial CBC revealed 43×103/µL white blood cells, 11.2 g/dL hemoglobin, and 88x103/µL platelets. CT abdomen revealed hepatomegaly and suspected pancreatic mass with large retroperitoneal lymph nodal mass. Peripheral smear showed 56% lymphoid cells with blast morphology. The bone marrow (BM) aspirate smear was infiltrated by 83% immature-looking cells. BM biopsy showed interstitial to diffuse extensive infiltration by primitive-looking cells, positive for pan-B-cell antigens CD20, CD79, and PAX5 as well as the T-cell antigen CD4, CD5, CD3, while negative for all immaturity markers (CD34, TdT, and CD1a). In situ hybridization for Epstein-Barr virus (EBV)-encoded small RNA (EBER) was negative. Flow cytometry on BM aspirate showed an abnormal population (50%) expressing the B-cell antigens (CD19, CD20, CD79, CD22) and CD10, and showed lambda light chain restriction as well as the T-cell antigens cCD3 and CD4 with partial CD5. The analysis showed, also, another abnormal population of lambda restricted monotypic B cells (8%) with dimmer CD45 (blast gate) and showed the same immunophenotype (expressing the B-cell antigens), but negative for CD10, cCD3, CD5, and CD4. Conventional cytogenetic revealed complex karyotype. Molecular studies revealed rearrangements of the immunoglobulin heavy chain region consistent with a clonal B-cell population. TCR gene rearrangement analysis was equivocal concerning clonality but was not conclusive for clonal T-cell disease. Our final diagnosis was peripheral blood and BM involvement by EBV-negative high-grade lymphoid neoplasm (in leukemic phase with blast morphology) and an ambiguous immunophenotype with a differential diagnosis that may include the rare entity of bigenotypic lymphoma or an unusual case of high-grade B-cell lymphoma with aberrant expression of T-cell markers (biphenotypic lymphomas).

A study of 18F-FLT positron emission tomography/computed tomography imaging in cases of prefibrotic/early primary myelofibrosis and essential thrombocythemia.

The objectives of this research project are to study in patients with primary myelofibrosis (PMF) and Essential Thrombocythemia (ET); (1) the uptake patterns of FLT-PET (FLT-PET) and its value in diagnosing, staging, and treatment response monitoring of malignant hematopoiesis, (2) compare imaging findings from FLT-PET with bone marrow biopsy (standard of care), and (3) associate FLT-PET uptake patterns with genetic makeup such as JAK2 (Janus kinase 2), CALR (Calreticulin), MPL (myeloproliferative leukemia protein), Triple negative disease, and allele burden.This trial is registered in ClinicalTrials.gov with number NCT03116542. Protocol version: Mar 2017.

Chronic Lymphocytic Leukemia Concomitant with COVID 19: A Case Report.

BACKGROUND COVID-19 is a newly emerging disease that is not yet fully understood. It is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel virus that is easily transmitted from human to human through the respiratory route. Usually, it presents with fever, headache, fatigue accompanied by respiratory symptoms like cough and dyspnea, and other systemic involvements. Chronic lymphocytic leukemia (CLL) is a common lymphoproliferative neoplasm characterized by absolute lymphocytosis and demonstration of clonality unlike other causes of lymphocytosis. Patients with CLL are considered immunocompromised because of impaired humoral immunity (mainly) and cellular immunity. Therefore, they are vulnerable to various infections including COVID-19. Little is known about the COVID-19 infection when it unmasks CLL. CASE REPORT A 49-year-old man with no significant previous illnesses, and an unremarkable family history, presented with a moderate COVID-19 infection. He initially presented to the emergency department with fever and mild shortness of breath. A complete blood count showed a high white blood cell count with absolute lymphocytosis. Flow cytometry revealed the clonality of the lymphocytes confirming the diagnosis of CLL. Despite having CLL, he developed a moderate COVID-19 infection and recovered in a few days. To the best of our knowledge, this is the first report of CLL, which presented with a COVID-19 infection as the initial presentation. CONCLUSIONS Lymphocytosis is an unexpected finding in patients diagnosed with COVID-19 infection and the elevated lymphocytes may be indicative of other conditions. Secondary causes of lymphocytosis like malignancy or other infections should be considered in these cases.

A Case of Fulminant Liver Failure in a 24-Year-Old Man with Coinfection with Hepatitis B Virus and SARS-CoV-2.

BACKGROUND Coronavirus disease 2019 (COVID-19) is a newly emerging disease that is still not fully characterized. It is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel virus that can be transmitted easily from human to human mainly by the respiratory route. Currently, there is no specific treatment for COVID-19 or a vaccine for prevention. The disease has various degrees of severity. It often presents with nonspecific symptoms such as fever, headache, and fatigue, accompanied by respiratory symptoms (e.g., cough and dyspnea) and other systemic involvement. Severe disease is associated with hemophagocytic syndrome and cytokine storm due to altered immune response. Patients with severe disease are more likely to have increased liver enzymes. The disease can affect the liver through various mechanisms. CASE REPORT We report an unusual case of SARS-CoV-2 infection in a 24-year-old man with no previous medical illness, who presented with mild respiratory involvement. He had no serious lung injury during the disease course. However, he experienced acute fulminant hepatitis B infection and cytokine release syndrome that led to multiorgan failure and death. CONCLUSIONS It is uncommon for SARS-CoV-2 infection with mild respiratory symptoms to result in severe systemic disease and organ failure. We report an unusual case of acute hepatitis B infection with concomitant SARS-CoV-2 leading to fulminant hepatitis, multiorgan failure, and death.

A Rare Case of Severe Copper Deficiency in an Infant with Exclusive Breast Feeding Mimicking Myelodysplastic Syndrome.

An 11-month-old full-term female infant was referred to the hematology clinic due to marked anemia and neutropenia. She was almost exclusively breastfed and rejecting all trials for supplementary food including artificial formulas. Bone marrow aspirate revealed cytoplasmic vacuolization in precursors of the myeloid and erythroid series with significant dysgranulopoiesis and dyserythropoiesis and ringed sideroblasts. Flow cytometry analysis revealed increased hematogones with aberrant loss/downregulation of CD33 on granulocytes and monocytes (sign of dysmyelopoiesis). Laboratory investigation revealed low serum copper and ceruloplasmin. Administration of a multivitamin including a high concentration of copper for only 1 week improved her hemoglobin and absolute neutrophil count up to 1.9 × 103/µL, then dropped to 0.3 103/µL after she stopped taking the copper multivitamin. Her blood counts improved till total normalization and up to the time this report is issued. The probable role of unrecognized copper deficiency in causing anemia in infants more than 6 months of age is discussed, and the importance of serum copper examination in refractory anemia and neutropenia is emphasized. This case shows that copper deficiency should be an integral part of the differential diagnosis of refractory anemia including sideroblastic anemia and dysplasia. To the best of our knowledge, no such case has previously been described in the literature.

Case Report: Papillary Thyroid Cancer in a Patient with Celiac Disease and Thalassemia Trait.

Thyroid cancer is the most frequent endocrine neoplasm in the general population. Common risk factors include gender, radiation exposure, and genetic backgrounds. The association of papillary thyroid cancer and celiac disease has frequently been reported in the literature; however, the association of papillary thyroid cancer and thalassemia trait is rare. Likewise, the association of thalassemia major and celiac disease is also rare. We hereby report a unique case of papillary thyroid cancer in a patient with celiac disease and thalassemia trait.

A Rare Case of Hairy Cell Leukemia with Unusual Loss of CD123 Associated with COVID-19 at the Time of Presentation.

Coronavirus disease 2019 (COVID-19) pandemic has been a serious threat and has been reported with different presentations and complications. Older age, along with comorbidities such as diabetes, hypertension, or cardiac disease, increases the risk factors for COVID-19 severity and death [N Engl J Med. 2020;382(18):1708-20 and Lancet Respir Med. 2020 05;8(5):475-81]. It is proposed that cancer patients have a significantly higher incidence of severe incidents including admission to the intensive care unit, the necessity for assisted ventilation, and even death after catching the virus compared with non-cancer patients [Lancet Oncol. 2020;21(3):335-7]. It is also described that cancer patients appear to be twice as likely to contract infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) [JAMA Oncol. 2020;6(7):1108-10]. Hairy cell leukemia (HCL) is a rare B-cell lymphoproliferative disorder, with patients typically presenting with cytopenias, marked splenomegaly in 80-90% of patients, circulating leukemia cells, bone marrow infiltration and the presence of BRAF V600E somatic mutation [Indian J Hematol Blood Transfus. 2014;30(Suppl 1):413-7]. Leukemic cells classically have central nuclei and abundant cytoplasm with hairy-like projections and express CD11c, CD25, CD103, and CD123 [Indian J Hematol Blood Transfus. 2014;30(Suppl 1):413-7]. Loss of CD123 in HCL has been rarely reported in the literature [Am J Hematol. 2019;94(12):1413-22]. We describe a unique case of a COVID-19-positive male who presented with severe respiratory symptoms, deteriorated quickly, and was intubated. Workup of severe progressive pancytopenia and bone marrow examination revealed HCL without splenomegaly and with atypical unusual loss of CD123. To our knowledge, this is the first case of CD123-negative HCL without splenomegaly associated with COVID-19 infection as the initial presentation.

A Challenging Case of Gamma Delta T-Cell Lymphoma with Precursor T-Cells and Marked Eosinophilia: A Case Report.

Gamma-delta (γδ) T-cell lymphomas are very rare and aggressive neoplasms. We describe here a challenging case of γδ T-cell neoplasm composed of γδ mature T-cells and γδ precursor T-cells with marked eosinophilia that is inapplicable to the current 2016 World Health Organization (WHO) classification. A 3-year-old female child who was presented with fever and marked leukocytosis. Peripheral blood smear showed marked lymphocytosis, marked eosinophilia, neutrophilia, monocytosis, and 5% circulating blasts. CT scan showed anterior mediastinal mass, lymphadenopathy, and hepatosplenomegaly. The patient underwent a bone marrow examination and a biopsy taken from the mediastinal mass. Peripheral blood and bone marrow findings were consistent with a γδ T-cell neoplasm with increased blasts and eosinophilia. The patient was sequentially treated with imatinib (tyrosine kinase inhibitor), acute lymphoblastic leukemia protocol (BFM 2009) then shifted to lymphoma protocol (LMP 96). In conclusion, we report a unique rare case of γδ T-cell neoplasm with a combination of mature and immature γδ T-cells and eosinophilia that is inapplicable to the current 2016 WHO classifications. This case raises a challenging concept of a mature T-cell lymphoma arising in an immature T-cell neoplasm. It also highlights the need to target all neoplastic components to eradicate the disease.

Role of Imaging in Diagnosis of a Rare Hepatosplenic Gamma Delta T-Cell Lymphoma during Pregnancy: A Case Report and Review of Literature.

Hepatosplenic γδ T-cell lymphoma (HSTCL) is a very rare peripheral T-cell lymphoma characterized by extranodal infiltration of mature malignant post-thymic T-lymphocytes into sinusoids of the liver and spleen without lymphadenopathy and significant cytopenias. It is an aggressive form of lymphoma, resistant to the conventional chemotherapy. We report a case of HSTCL in pregnancy. Because this condition is an extremely aggressive and rare entity, data from these cases can help confirm the most suitable treatment regimen and timing of initiation. The role of ultrasound and magnetic resonance imaging in the diagnosis has been discussed. HSTCL is a rare entity of T-cell lymphoma, uncommon in female patients and very rarely reported during pregnancy.

An uncommon case of chronic myeloid leukemia with variant cytogenetic.

Chronic Myeloid Leukemia (CML) is myeloproliferative neoplasm characterized by Philadelphia chromosome which is a balanced translocation between chromosome 9 and 22 in 90% of cases. However, variant cytogenetic still happens in 5-10 % of cases, the importance of which is controversial as well as its response to therapy, prognosis and progression to acute leukemias. Here we report a male patient with CML and variant cytogenetic who responded to low dose of Dasatinib (50 mg daily).