A Rare Case of Spindle Cell Sarcoma With Rare Asymptomatic Cerebellar Metastasis.

Sarcomas are one of the rarest cancers, occurring in less than 1% of all adult malignancies. Spindle cell sarcomas are one subset of soft tissue sarcomas that are even less commonly reported in the literature due to the scarcity of cases, especially with the presence of brain metastases. We present a case of an adult male who presented with non-specific exertional dyspnea and chest pain, which was found to have spindle cell sarcoma with cerebellar metastasis.

Rituximab in the Treatment of Acquired Angioedema Secondary to Marginal Zone Lymphoma of the Spleen.

Angioedema occurs in less than 1-2% of the population and amongst these cases, those with acquired angioedema are less prevalent than hereditary angioedema. Amongst cases of acquired angioedema, studies have shown that they were highly linked with an associated lymphoproliferative disorder, suspected secondary to the production of neutralizing autoantibodies from pathological B cell proliferation. We present a case of a patient who presented with recurrent episodes of angioedema and was found to have low C4 and C1 esterase function, initially concerning for a hereditary angioedema variant, who was subsequently found to have marginal B cell lymphoma mimicking hereditary angioedema.

Reintroduction of 5-Fluorouracil Post-cardiac Arrest Secondary to Chemotherapy-Induced Cardiotoxicity.

5-fluorouracil (5-FU) has been known to have cardiotoxic side effects, including coronary vasospasm, myocardial infarctions, heart failure, arrhythmias, and cardiac arrest. These cases have been reported in patients with either known coronary disease or known risk factors. In cases of acute cardiotoxicity, cessation of fluoropyrimidines is recommended, and reintroduction of the medication is generally avoided. We present a case of a young patient with no known risk factors for coronary disease, who presented with an acute cardiac arrest suspected secondary to vasospasm from the administration of 5-FU for the treatment of rectal cancer and was successfully maintained on treatment with 5-FU post-arrest after transitioning from an infusion to bolus administration.

Pancytopenia with Development of Persistent Neutropenia Secondary to COVID-19.

Viral infections have long been linked to hematologic dysfunction. With the rapid spread of COVID-19, various hematologic manifestations have emerged. While there have been several reports of immune thrombocytopenic purpura from SARS-CoV-2, concurrent lymphopenia and anemia have sparse. We describe a case of COVID-induced pancytopenia that presented months after initial COVID infection that initially responded to IVIG and steroids, but now with persistent neutropenia.

A Unique Case of Cardiac Hypereosinophilia With Recurrent Valve Thrombosis After Mechanical Mitral Valve Replacement in the Setting of a Supratherapeutic International Normalized Ratio.

Hypereosinophilia (HES) is a rare, but highly fatal, disease that results in excess eosinophils causing multiorgan damage, mainly manifesting as extensive inflammation contributing to fibrosis. Notably, cardiac involvement occurs in almost half the cases and can often lead to thrombus development. This is a unique case of HES contributing to recurrent cardiac thrombus formation on a mechanical mitral valve in the setting of a patient who had a supratherapeutic international normalized ratio (INR) while on coumadin. The rarity of this case is also displayed in the patient's negativity for one of the fusion genes that are highly suggestive of cardiac HES, the demographics of her female gender, and her first objective sign being T-wave inversions versus the usual heart failure signs and symptoms. This case raises awareness of the disorder but also the importance of keeping its potential exacerbations on the differential, even in the setting of atypical presentations. With this, it also begs the question of whether coumadin is the proper anticoagulant of choice in these patients and whether other parameters should be considered.

A Rare Case of Splenic and Pulmonary Metastases From Renal Cell Carcinoma.

Renal cell carcinoma commonly spreads to the lungs, bones, and liver, but splenic involvement has been rare. When metastasis does occur, patients are usually asymptomatic but may present with weight loss, fatigue, or abdominal pain. We present a case of a patient who had known renal cell cancer status post-total nephrectomy who, due to COVID, had delayed surveillance scans and was found to have a recurrent mass in the nephrectomy bed with splenic and pulmonary metastasis.

Right Atrial Tumor Invasion: A Rare Presentation of Hepatocellular Carcinoma.

Metastatic hepatocellular carcinoma has been associated with a poor prognosis. Common areas of spread include the lungs, portal vein, and portal lymph nodes. Affected patients often have coexisting comorbidities, including cirrhosis, chronic hepatitis, and nonalcoholic fatty liver disease. Our case discusses a rare presentation of hepatocellular carcinoma that had spread to the right atrium, manifesting as acute heart failure in a patient with no history of liver disease. This case highlights the importance of recognizing unusual presentations of advanced hepatocellular carcinoma, as earlier detection can lead to improved patient outcomes.

Junctional adhesion molecule A: expression in the murine epididymal tract and accessory organs and acquisition by maturing sperm.

STUDY QUESTION: Is junctional adhesion molecule A (JAM-A), a sperm protein essential for normal motility, expressed in the murine post-testicular pathway and involved in sperm maturation? SUMMARY ANSWER: JAM-A is present in the prostate and seminal vesicles and in all three regions of the epididymis where it is secreted in epididymosomes in the luminal fluid and can be delivered to sperm in vitro. WHAT IS KNOWN ALREADY: JAM-A shares with the plasma membrane Ca2+ATPase 4 (PMCA4, the major Ca2+ efflux pump in murine sperm) a common interacting partner, CASK (Ca2+/CaM-dependent serine kinase). JAM-A, like PMCA4, plays a role in Ca2+ regulation, since deletion of Jam-A results in significantly elevated intracellular Ca2+ levels and reduced sperm motility. Recently, PMCA4 was reported to be expressed in the epididymis and along with CASK was shown to be in a complex on epididymosomes where it was transferred to sperm. Because of the association of JAM-A with CASK in sperm and because of the presence of PMCA4 and CASK in the epididymis, the present study was performed to determine whether JAM-A is expressed in the epididymis and delivered to sperm during their maturation. STUDY DESIGN, SIZE, DURATION: The epididymides, prostate and seminal vesicles were collected from sexually mature C57BL/6J and Institute for Cancer Research mice and antibodies specific for JAM-A and Ser285 -phosphorylated JAM-A (pJAM-A) were used for the analysis. Tissues, sperm and epididymal luminal fluid (ELF) were studied. Epididymosomes were also isolated for study. Caput and caudal sperm were co-incubated with ELF individually to determine their abilities to acquire JAM-A in vitro. PARTICIPANTS/MATERIALS, SETTING, METHODS: Sections of all three regions of the epididymis were subjected to indirect immunofluorescence analysis. Epididymal tissues, fluid, sperm, prostate and seminal vesicle tissues were analyzed for JAM-A and/or pJAM-A via western blotting analysis. The relative amounts of JAM-A and pJAM-A among epididymal tissues, ELF and sperm were detected by western blot via quantification of band intensities. Epididymosomes were isolated by ultracentrifugation of the ELF after it was clarified to remove cells and tissue fragments, and the proteins western blotted for JAM-A and pJAM-A, and exosomal biochemical markers. FACS analysis was used to quantify the amount of JAM-A present on caput and caudal sperm, as well as the amount of JAM-A acquired in vitro after their co-incubation with ELF. MAIN RESULTS AND THE ROLE OF CHANCE: Western blots revealed that JAM-A is expressed in all three regions of the epididymis, the prostate and seminal vesicles. As confirmed by indirect immunofluorescence, a western blot showed that JAM-A has a higher expression in the corpus and caudal regions, where it is significantly (P < 0.01) more abundant than in the caput. Both JAM-A and Ser285-phosphorylated JAM-A (pJAM-A) are secreted into the ELF where it is highest in the distal regions. In the ELF, both JAM-A and pJAM-A were detected in epididymosomes. Western blotting of sperm proteins showed a significant (P < 0.01) increase of JAM-A and pJAM-A in caudal, compared with caput, sperm. Flow-cytometric analysis confirmed the increase in JAM-A in caudal sperm where it was 1.4-fold higher than in caput ones. Co-incubation of caput and caudal sperm with ELF demonstrated ~2.3- and ~1.3-fold increases, respectively, in JAM-A levels indicating that epididymosomes transfer more JAM-A to caput sperm that are less saturated with the protein than caudal ones. LARGE SCALE DATA: Not applicable. LIMITATIONS, REASONS FOR CAUTION: First, although the ELF was clarified prior to ultracentrifugation for epididymosome isolation, we cannot rule out contamination of the epididymosomal proteins by those from epididymal epithelial cells. Second, the JAM-A detected in the prostate and seminal vesicles might not necessarily be secreted from those organs and may only be present within the tissues, where it would be unable to impact sperm in the ejaculate. WIDER IMPLICATIONS OF THE FINDINGS: Although performed in the mouse the study has implications for humans, as the highly conserved JAM-A is a signaling protein in human sperm. There is physiological significance to the finding that JAM-A, which regulates sperm motility and intracellular Ca2+, exists in elevated levels in the cauda where sperm gain motility and fertilizing ability. The study suggests that the acquisition of JAM-A in the epididymal tract is involved in the mechanism by which sperm gain their motility during epididymal maturation. This increased understanding of sperm physiology is important for aspects of ART. STUDY FUNDING AND COMPETING INTEREST(S): The work was supported by NIH-RO3HD073523 and NIH-5P20RR015588 grants to P.A.M.-D. The authors declare there are no conflicts of interests.

Hyaluronidase 2: a novel germ cell hyaluronidase with epididymal expression and functional roles in mammalian sperm.

To initiate the crucial cell adhesion events necessary for fertilization, sperm must penetrate extracellular matrix barriers containing hyaluronic acid (HA), a task thought to be accomplished by neutral-active hyaluronidases. Here we report that the ~57 kDa hyaluronidase 2 (HYAL2) that in somatic tissues has been highly characterized to be acid-active is present in mouse and human sperm, as detected by Western blot, flow cytometric, and immunoprecipitation assays. Immunofluorescence revealed its presence on the plasma membrane over the acrosome, the midpiece, and proximal principal piece in mice where protein fractionation demonstrated a differential distribution in subcellular compartments. It is significantly more abundant in the acrosome-reacted (P = 0.04) and soluble acrosomal fractions (P = 0.006) (microenvironments where acid-active hyaluronidases function) compared to that of the plasma membrane where neutral hyaluronidases mediate cumulus penetration. Using HA substrate gel electrophoresis, immunoprecipitated HYAL 2 was shown to have catalytic activity at pH 4.0. Colocalization and coimmunoprecipitation assays reveal that HYAL2 is associated with its cofactor, CD44, consistent with CD44-dependent HYAL2 activity. HYAL2 is also present throughout the epididymis, where Hyal2 transcripts were detected, and in the epididymal luminal fluids. In vitro assays demonstrated that HYAL2 can be acquired on the sperm membrane from epididymal luminal fluids, suggesting that it plays a role in epididymal maturation. Because similar biphasic kinetics are seen for HYAL2 and SPAM1 (Sperm adhesion molecule 1), it is likely that HYAL2 plays a redundant role in the catalysis of megadalton HA to its 20 kDa intermediate during fertilization.