Sepsis Unveils T-cell Large Granular Lymphocytic Leukemia in the Setting of End-Stage Renal Disease: A Rare Hematologic Malignancy.

Large granular lymphocytic (LGL) leukemia is a rare chronic lymphoproliferative disorder originating from natural killer cells or T lymphocytes. In this report, we present the case of a 66-year-old female initially treated for sepsis, with methicillin-sensitive Staphylococcus aureus identified on initial blood culture prompting intravenous (IV) antibiotic therapy. The patient met systemic inflammatory response syndrome criteria upon admission due to severe neutropenia. Persistent fever led to neurological symptoms, and imaging revealed lung abnormalities along with chronic changes on the CT scan of the head. Multidisciplinary consultations were sought, resulting in treatment adjustments including antifungals and filgrastim. Flow cytometry and bone marrow biopsy confirmed the diagnosis of LGL leukemia.

Primary Effusion Lymphoma Secondary to Human Herpesvirus 8 (HHV-8) Infection in an Immunocompetent Host: A Case Report.

Primary effusion lymphoma (PEL) is a rare, aggressive, mature type of B-cell lymphoma that usually causes malignant, lymphomatous effusions in the absence of a solid mass. This is commonly seen in immunosuppressed individuals such as those with underlying malignancies, human immunodeficiency virus infection (HIV), cirrhosis, and a history of solid organ transplantation who are infected with human herpesvirus 8 (HHV-8). Clinical presentation varies depending on the extent of disease like shortness of breath, abdominal distention, and typical B symptoms like weight loss, fever, and night sweats. Morphological and immunohistochemical analysis of pleural fluid is required for diagnosis of PEL. Recent case studies are increasingly being reported with cases of PEL presenting in immunocompetent individuals infected with HHV-8. We present a case of PEL in an immunocompetent host and highlight its presentation, diagnosis, and management approaches. Due to the well-known association of PEL with immunocompromised status, the diagnosis is often overlooked in immunocompetent individuals. This case would further highlight the increasing association and the need for clinical vigilance in diagnosing PEL in immunocompetent patients.

Cyclophosphamide, Bortezomib, and Dexamethasone and Severe Systolic Heart Failure: A Case Report.

Multiple myeloma (MM) is a neoplastic proliferation of plasma cells in bone marrow. Pharmacotherapy for the management of patients with MM includes drug classes like proteasome inhibitors, monoclonal antibodies, immunomodulators, alkylating agents, steroids, etc. We present a case of new-onset heart failure with reduced ejection fraction (HFrEF) in a patient with previously normal ejection fraction after treatment with a cyclophosphamide, bortezomib, and dexamethasone (CyBorD) chemotherapeutic regimen. An echocardiogram done after the completion of nine cycles of chemotherapy in a period of about 4.5 months showed severely decreased left ventricular systolic function with an ejection fraction of only 15-20% and grade I diastolic dysfunction. Cardiac catheterization showed no angiographic evidence of vessel occlusion or epicardial disease. HFrEF was managed with the initiation of guideline-directed medical therapy with cardiology clinic follow-up, and the patient was discharged with a plan to start a lenalidomide-based chemotherapeutic regimen with oncology clinic follow-up. It is, therefore, imperative to perform a thorough cardiovascular assessment before initiation of chemotherapy, complemented by periodic and recurrent assessments of cardiovascular function during and after completion of the treatment course, for early detection and prevention of potentially severe cardiovascular toxicities in patients with MM.

Intravenous Hydration and Associated Outcomes in Patients With Sickle Cell Disease Admitted With Vaso-Occlusive Crises: A Systematic Review.

Acute painful vaso-occlusive crisis (VOC) is the common presentation of sickle cell disease (SCD) leading to emergency room visits, admissions, morbidity, mortality, and negative impacts on quality of life. Among various treatment approaches commonly employed to manage the condition, intravenous (IV) hydration is also frequently used in emergency and inpatient settings. Although helpful to overcome dehydration, IV hydration often leads to adverse outcomes like fluid overload, pulmonary edema, increased length of stay, transfer to intensive care unit, new oxygen requirement, etc. Small-scale retrospective studies are conducted to study the outcomes of IV hydration but have failed to conclusively demonstrate its benefits as well as choice of IV fluids, rate of IV fluid replacement, etc. We conduct this review as an attempt to summarize the available evidence on the role and utility of IV hydration in sickle cell crises along with reported adverse outcomes.

Cracking the Code of a Rare Colonic Mesentery Gastrointestinal Neuroendocrine Tumor Disguised as Chronic Gastroenteritis: The Critical Art of Timely Detection.

Neuroendocrine tumors (NETs) typically present in the setting of metastasis from other solid organs and are considered late manifestations of the disease. Therefore, primary tumors are extremely rare. NETs of the colonic mesentery occur more than 70% of the time in the appendix, small intestine, and rectum. Here, we describe the case of a patient who presented with multiple episodes of diarrhea and abdominal pain, which was waxing and waning in occurrence, with CT findings of a rare primary NET.

Recurrent Granulosa Cell Tumor in a Postmenopausal Woman: A Case Report and Literature Review.

Ovarian cancer is among the most common types of cancer suffered by the female population. As of United States Cancer Statistics (USCS) 2019, the National Cancer Institute reports the prevalence of ovarian cancer as 11.4 cases per every 100,000 each year. The highest prevalence is in the seventh decade of life. Of all the types, sex cord-stromal tumors (SCSTs) account for 5-8% of cases. They are a heterogeneous group of rare neoplasms originating from the ovarian matrix, and nearly 90% of the hormone-producing tumors are SCSTs. Hence, patients with SCSTs are known to present with excess estrogen and androgen signs and symptoms. Many SCSTs are known for their indolent course and tendency to affect the unilateral ovary. The prognosis of the malignancy depends on the subtype of SCST, the stage of the patient's disease, and age. Among all the types, 20-50% of the ovaries' granulosa cell tumors tend to recur decades after the initial presentation, and 70% of the recurrences end up with a very poor prognosis. This case will discuss a 68-year-old woman who presented with a recurrence of an adult granulosa cell tumor after 13 years in remission. The patient had been previously diagnosed with an adult granulosa cell tumor of the right ovary at age 55 and had undergone surgical resection along with chemotherapy.

SARS-CoV-2 and chronic myeloid leukemia: a systematic review.

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus causing the coronavirus disease of 2019. The disease has caused millions of deaths since the first pandemic at the end of 2019. Immunocompromised individuals are more likely to develop severe infections. Numerous mutations had developed in SARS-CoV-2, resulting in strains (Alfa Beta Delta Omicron) with varying degrees of virulence disease severity. In CML (chronic myeloid leukemia) patients, there is a lot of controversy regarding the effect of the treatment on the patient outcome. Some reports suggested potential better outcomes among patients with CML, likely due to the use of TKI; other reports showed no significant effects. Additionally, it is unknown how much protection immunization provides for cancer patients. Method: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards, we conducted a systematic review. Retrospective, prospective studies, reviews, case series, and case reports of chronic myeloid leukemia patients aged above 18 years who had SARS-CoV-2 infection were included. English literature was screened using PubMed, SCOPUS, and Google Scholar. Search terms include chronic myeloid leukemia, chronic myelogenous leukemia, and SARS-CoV-2 and Coronavirus disease 2019 (COVID-19). We searched the reference lists of the included studies for any new articles. The search included all articles published up to April 20, 2023. The review is registered in PROSPERO (registration number CRD42022326674). Results: We reviewed 33 articles of available published literature up to April 2023 and collected data from a total of 682 CML patients with COVID-19. Most patients were in the chronic phase, seven were in the accelerated phase, and eight were in the blast phase. Disease severity was classified according to WHO criteria. Mortality was seen in 45 patients, and there were no reports of thrombotic events. Two hundred seventy-seven patients were in the era before vaccination; among them, eight were in the intensive care unit (ICU), and mortality was 30 (11%). There were 405 patients after the era of vaccination; among them, death was reported in 15 (4%) patients and ICU in 13 patients. Limitations and conclusion: The major limitation of this review is the lack of details about the use or hold of TKIs during SARS-CoV-2 infection. Additionally, after the appearance of the different variants of the SARS-CoV-2 virus, few studies mentioned the variant of the virus, which makes it difficult to compare the outcome of the other variants of the SARS-CoV-2 virus in patients with CML. Despite the limitations of the study, CML patients with COVID-19 have no significant increase in mortality compared to other hematological malignancy. Hematological cancers are associated with an increased risk of thrombosis, which is expected to increase in patients with COVID-19. However, patient with CML has not been reported to have a significant increase in thrombosis risk. The available data indicates that COVID-19's effect on patients with chronic myeloid leukemia (CML) still needs to be better understood due to the limited data. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php? RecordID:326674.

Warfarin Failure in a Patient With Chronic Thromboembolic Pulmonary Hypertension: A Case Report and Literature Review.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a form of pulmonary hypertension caused by chronic venous thromboembolism (VTE). Venous thromboembolism (VTE) manifests as deep vein thrombosis (DVT), progressing to pulmonary embolism (PE). Pulmonary endarterectomy (PEA) is the preferred therapeutic option as it provides vascular disobliteration. Long-term anticoagulation with warfarin or direct oral anticoagulants (DOACs) is recommended for patients at risk for recurrent DVT in poor surgical candidates. However, treatment failure remains a concern. We present a patient who had VTE despite long-term anticoagulation with warfarin who had failed treatment and developed VTE with a therapeutic dilemma to continue anticoagulation despite supratherapeutic international normalized ratio (INR).

Abscess or Tumor? When a Retroperitoneal Mass on Computerized Tomography Turns Out to Be a Rare Soft Tissue Growth.

A retroperitoneal finding on a computerized tomography scan, in a symptomatic patient, can harbor the clinician to many differential diagnoses from infectious to malignancy. Desmoid fibromatosis (DF), a relatively innocuous mass that can spread locally, can be found in that anatomical region. Even for a rare tumor such as DF, our patient did not meet the usual benchmarks of this cancer, being an elderly female and having it appear as an abscess radiologically. Timely clinical response with radiotherapy and tamoxifen allowed our patient's DF to regress and resolved her symptoms.

A Case of Multiple Myeloma Presenting as Streptococcus pneumoniae Meningitis with Candida auris Fungemia.

Multiple myeloma (MM), a plasma cell neoplasm, has a typical presenting pattern consisting of bone pain, renal failure, anemia, and/or hypercalcemia. Even though MM is a cancer that impairs the immune system, rarely is a systemic infection the first sign of disease. In this case report, our patient presented with altered mental status due to meningitis and was later diagnosed with MM. Furthermore, we display a case of a rare but emerging and serious fungus, Candida auris, that the patient developed during his inpatient stay. This is the first such record of C. auris in an MM patient.

Renal Medullary Carcinoma with an Aggressive Clinical Course: A Case Report and Review of the Literature.

Renal medullary carcinoma (RMC) is a rare, yet aggressive malignancy of the kidney that is found predominantly in young patients with African descent and sickle cell hemoglobinopathies and most specifically sickle cell trait. Due to its aggressive nature, most cases have metastasis or local invasion at the time of diagnosis. Prognosis is extremely poor with survival less than 1 year after diagnosis. Here we present a case of metastatic RMC in a 29-year-old African female. Despite chemotherapy with cisplatin, gemcitabine, and paclitaxel, and initial shrinkage of the tumor, the patient died 5 months after diagnosis.

Quantification of IGF-1 Receptor May Be Useful in Diagnosing Polycythemia Vera-Suggestion to Be Added to Be One of the Minor Criterion.

Endogenous erythroid colony (EEC) formation is one of the minor criteria for diagnosing polycythemia vera (PV) according to 2008 WHO diagnostic criteria. But EEC requires bone marrow aspiration and sophisticated laboratory procedures; therefore, practically it is rarely used to diagnose PV. Insulin-like growth factor 1 receptor (IGF-1R) was found to be constitutively phosphorylated and was responsible for the EEC formation in PV; therefore, we measured IGF-1R levels in the peripheral blood of 26 PV patients and compared them with those of 33 patients with secondary polycythemia and 29 normal controls. Among the PV patients, 16 were treated with only phlebotomy, 9 received hydroxyurea, and 1 was treated with ruxolinitinib. We found that PV patients treated with only phlebotomy had significantly higher IGF-1R levels than did those PV patients treated with hydroxyurea or ruxolinitinib. None of the secondary PV patients or normal controls had elevated IGR-1R levels, while 14 of 16 (87%) PV patients had significantly elevated IGF-1R levels. The new 2016 WHO has eliminated EEC as a minor criterion for diagnosing PV, but there are still some cases that cannot be definitively diagnosed by the current criteria. Therefore, we suggest that quantifying the IGF-1R level in peripheral blood by flow cytometry to replace EEC as the minor criterion for diagnosing PV.

Small bowel adenocarcinoma presenting with refractory iron deficiency anemia - case report and review of literature.

Cancers of the small bowel are relatively rare and account for approximately 1-2% of all gastrointestinal neoplasms. The most common histologic subtype - adenocarcinoma - constitutes 40% of all cases. These cancers generally present with vague abdominal discomfort and are often diagnosed at a late stage and carry a poor prognosis. The treatment of choice of early-stage small bowel adenocarcinoma is surgical resection. No standard treatment protocol has been defined for unresectable or metastatic disease. Here, we report a case of a 56-year-old woman who presented with unexplained iron deficiency anemia. Extensive initial studies with serial CT scans of the abdomen, esophagogastroduodenoscopy, small bowel capsule endoscopy and colonoscopy were noncontributory. She was later found to have a metastatic small bowel adenocarcinoma and treated with palliative chemotherapy. She achieved a modest response to the treatment. Interestingly, in our case, the sole presentation was unexplained iron deficiency anemia. Physician's awareness regarding the possibility of small bowel cancer especially in the setting of iron deficiency and its workup has been emphasized. This enhances the chance of early detection and hence better survival.

Emerging therapies in the treatment of locally advanced squamous cell cancers of head and neck.

Head and neck squamous cell cancers (HNSCCs) represent 4 to 5% of all solid malignancies. Despite improvements in diagnostic techniques, 60% of patients will present with locally advanced HNSCCs with a median survival of about 12 months and 5-year overall survival of approximately 10-40%. Recent clinical trials have altered the treatment landscape by refining existing forms of radiation, incorporation of IMRT, choice of chemotherapeutic agents, introduction of biological and targeted therapy, immunotherapy and gene therapy. Cetuximab, a monoclonal antibody directed against the human epidermal growth factor receptor (EGFR), has recently been approved in combination with RT in patients with locally advanced HNSCCs. Antiangiogenic therapies and tyrosine kinase inhibitors (gefitinib and erlotinib) have also shown promise in the clinical trials. Vandetanib, an antagonist of both vascular endothelial growth factor receptor (VEGFR) and the EGFR is currently being tested in phase II trial. New patents on hypoxia-inducible factor 1 alpha, mesenchymal-epithelial transition factor, insulin-like growth factor or the PI3K/AKT/mTOR pathway, farnesyl transferase inhibitors have shown promise in the management of HNSCCs. Nevertheless, identification of predictive biomarkers of resistance or sensitivity to these therapies remains a fundamental challenge in the optimal selection of patients most likely to benefit from them. However, increase in efficacy comes at the cost of increased toxicity. The current review focuses on insight into recent patents and updates on the clinical trials using new investigational agents in the management for HNSCCs.

Dual-Positive (CD4+/CD8+) Acute Adult T-Cell Leukemia/Lymphoma Associated with Complex Karyotype and Refractory Hypercalcemia: Case Report and Literature Review.

We describe a rare case of adult T-cell leukemia characterized by an expansion of CD4+ CD8+ double-positive lymphocytes associated with human T-lymphotropic virus type 1 (HTLV-1) and a complex karyotype in a 43-year-old Caribbean male who was initially admitted to our hospital with significant lethargy, visual disturbances, dysphagia, right facial palsy and numbness in both feet for 3 days. He was found to have severe hypercalcemia (15.6 mg/dl). Peripheral blood smear showed multilobulated clover-shaped nuclei. Bone marrow and CSF flow cytometries revealed abnormal monoclonal expansion of T cells positive for CD4, CD5, CD8 and CD25 but negative for CD7, CD20, CD56, CD68 and terminal deoxynucleotidyl transferase. The polymerase chain reaction analysis showed a distinct band of the T-cell receptor γ gene, revealing T-cell clonal integration of the proviral DNA of HTLV-1, thus confirming the diagnosis of acute adult T-cell leukemia/lymphoma. Cytogenetic study revealed a male karyotype with monosomy 12, unbalanced translocation 5q and 13q and additional material on 5q, 7q, 14q and 17q. The patient underwent prednisone (EPOCH) chemotherapy followed by autologous transplantation with BEAM regimen. Although patients with a rare mixed CD4+ CD8+ immunophenotype usually present with an aggressive clinical course and have a poor prognosis, our patient was able to survive for 2.5 years.

Inhibition of human CD24 binding to platelet-bound P-selectin by monoclonal antibody.

P-selectin, an adhesive molecule present on the surface of activated platelets, participates in the interactions between platelets and a variety of cells, including cancer cells. Such interaction is an important step toward the establishment of thriving secondary tumors during blood-borne metastasis. CD24, one of the mucin-type ligands of P-selectin, is expressed in various adenocarcinomas and may mediate the interaction between platelets and cancer cells. To demonstrate the involvement and specificity of P-selectin and/or CD24 in the interaction, we adapted a fluorometric binding procedure to assay the binding of calcein AM-labeled platelets to DU145 cells grown on 96-well microplates in the presence or absence of antibodies against CD24 or P-selectin. The platelet binding on DU145 cells was inhibited by anti-P-selectin antibody (GA-6) by 83.6% (p<0.01). The similar inhibition seen with anti-CD24 (FL80) antibody, (68%, p<0.01), was preventable by preincubating with a cognate CD24 peptide. In conclusion, our results indicate that P-selectin ligand CD24 mediates the binding of platelets to prostate cancer line DU145 cells in vitro. The fluorometric assay for platelet binding may have a promising role in further defining parameters of the interaction.