An Unusual Case of Hashimoto's Thyroiditis Presenting as Impending Cardiac Tamponade in a Patient with Acquired Immune Deficiency Syndrome (AIDS).

BACKGROUND Cardiac tamponade is a life-threatening pericardial compressive disorder that is a common downstream manifestation of infections, malignancy, and metabolic disorders. Hypothyroidism is a rare cause of tamponade that is attributed to the slow accumulation of effusive fluid into the intrapericardial space. In individuals living with HIV/AIDS, tamponade is commonly associated with infection or malignancy. To our knowledge, this is the first reported case of a patient with HIV/AIDS to have been identified with tamponade secondary to hypothyroidism. CASE REPORT Herein, we describe the case of a 52-year-old male patient with a history of AIDS, who presented with nausea, vomiting, diarrhea, and episodic gastrointestinal discomfort for the past several weeks, in conjunction with progressive fatigue. At initial presentation, he had no hemodynamic or clinical signs of tamponade, but pericardial effusion was incidentally found on imaging. Further investigations revealed an undiagnosed Hashimoto's thyroiditis as a function of restored immunocompetency, which ultimately led to the impending tamponade in this patient. We describe his clinical course through diagnosis of autoimmune hypothyroidism, review cardiac tamponade and hypothyroidism in the context of people living with HIV/AIDS, and discuss this rare manifestation of restored immunocompetency. CONCLUSIONS Hypothyroidism should be ruled out in all patients presenting with pericardial effusions or cardiac tamponade, even in people living with HIV/AIDS or those with a history of immune deficiencies.

Rare Causes of Isolated and Progressive Splenic Lesions: Challenges in Differential Diagnosis, Evaluation, and Treatment of Primary Splenic Lymphomas.

The spleen is among the most common extranodal sites for Hodgkin and non-Hodgkin lymphomas (NHLs); however, among lymphomas arising from the spleen, primary splenic lymphomas (PSLs) are rare. The group of PSLs includes primary splenic diffuse large B-cell lymphoma (PS-DLBCL), splenic red pulp small B-cell lymphoma, splenic marginal zone lymphoma (SMZL), and a splenic hairy cell leukemia variant. Delineating between the PSL variants can be challenging, especially as fine-needle aspirate and core needle biopsy of the spleen are not routinely offered at most medical centers. Herein, we describe the clinical course of 2 representative patients who presented with non-specific gastrointestinal symptoms, the first who was diagnosed with PS-DLBCL and the second who was diagnosed with SMZL. We review and contrast the clinical presentations, imaging techniques, and laboratory findings of these discrete lymphoma variants and offer strategies on how to delineate between these varied splenic processes. We also examine the use of splenectomy and splenic needle biopsy as diagnostics and, in the case of splenectomy, a therapeutic tool. Finally, we also briefly review treatment options for these varied lymphoma sub-types while acknowledging that randomized trials to guide best practices for PSLs are lacking.

B-cell acute lymphoblastic leukemia in an elderly man with plasma cell myeloma and long-term exposure to thalidomide and lenalidomide: a case report and literature review.

BACKGROUND: The advent of the immunomodulatory imide drugs (IMiDs) lenalidomide and thalidomide for the treatment of patients with plasma cell myeloma (PCM), has contributed to more than a doubling of the overall survival of these individuals. As a result, PCM patients join survivors of other malignancies such as breast and prostate cancer with a relatively new clinical problem - second primary malignancies (SPMs) - many of which are a result of the treatment of the initial cancer. PCM patients have a statistically significant increased risk for acute myeloid leukemia (AML) and Kaposi sarcoma. IMiD treatment has also been associated with an increased risk of myelodysplastic syndrome (MDS), AML, and squamous cell carcinoma of the skin. However, within these overlapping groups, acute lymphoblastic leukemia (ALL) is much less common. CASE PRESENTATION: Herein, we describe an elderly man with PCM and a 14-year cumulative history of IMiD therapy who developed persistent pancytopenia and was diagnosed with B-cell acute lymphoblastic leukemia (B-ALL). He joins a group of 17 other patients documented in the literature who have followed a similar sequence of events starting with worsening cytopenias while on IMiD maintenance for PCM. These PCM patients were diagnosed with B-ALL after a median time of 36 months after starting IMiD therapy and at a median age of 61.5 years old. CONCLUSIONS: PCM patients with subsequent B-ALL have a poorer prognosis than their de novo B-ALL counterparts, however, the very low prevalence rate of subsequent B-ALL and high efficacy of IMiD maintenance therapy in PCM should not alter physicians' current practice. Instead, there should be a low threshold for bone marrow biopsy for unexplained cytopenias.

New Human Chromosomal Sites with "Safe Harbor" Potential for Targeted Transgene Insertion.

This study identified 35 new sites for targeted transgene insertion that have the potential to serve as new human genomic "safe harbor" sites (SHS). SHS potential for these 35 sites, located on 16 chromosomes, including both arms of the human X chromosome, and for the existing human SHS AAVS1, hROSA26, and CCR5 was assessed using eight different desirable, widely accepted criteria for SHS verifiable with human genomic data. Three representative newly identified sites on human chromosomes 2 and 4 were then experimentally validated by in vitro and in vivo cleavage-sensitivity tests, and analyzed for population-level and cell line-specific sequence variants that might confound site targeting. The highly ranked site on chromosome 4 (SHS231) was further characterized by targeted homology-dependent and -independent transgene insertion and expression in different human cell lines. The structure and fidelity of transgene insertions at this site were confirmed, together with analyses that demonstrated stable expression and function of transgene-encoded proteins, including fluorescent protein markers, selectable marker cassettes, and Cas9 protein variants. SHS-integrated transgene-encoded Cas9 proteins were shown to be capable of introducing a large (17 kb) gRNA-specified deletion in the PAX3/FOXO1 fusion oncogene in human rhabdomyosarcoma cells and as a Cas9-VPR fusion protein to upregulate expression of the muscle-specific transcription factor MYF5 in human rhabdomyosarcoma cells. An engineering "toolkit" was developed to enable easy use of the most extensively characterized of these new human sites, SHS231, located on the proximal long arm of chromosome 4. The target sites identified here have the potential to serve as additional human SHS to enable basic and clinical gene editing and genome-engineering applications.