Diagnosis of Angioimmunoblastic T Cell Lymphoma After Receiving First Dose of Pfizer/BioNTech (BNT162b2) Vaccine: A Case Report.

Pfizer/BioNTech (BNT162b2) is a messenger RNA (mRNA) vaccine that is highly effective in preventing the most severe outcomes of COVID-19 infection. Nucleoside-modified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines induce effective stimulation of T follicular helper (TFH) cells, leading to a robust germinal center B cell response. Side effects from the BNT162b2 vaccination, including significant lymphadenopathy, have been reported previously. Here, we present a case of angioimmunoblastic lymphoma (AITL), a rare, peripheral T-cell lymphoma with RHOA-G17v-mutated gene developing in a patient following BNT162B2 vaccine with a plausible explanation. A 60-year-old Asian female received her first dose of Pfizer BNT162B2 mRNA vaccine in August 2021. Right after her vaccination, she developed right axillary lymphadenopathy. She received her second vaccine dose in September 2021. Thereafter, she developed lymph node (LN) enlargement in her neck and groin. She underwent left posterior cervical and left groin LN excisional biopsy in April 2022 due to persistent palpable lymphadenopathy. Biopsy results then demonstrated benign follicular hyperplasia. For progressive B symptoms, a right axillary LN biopsy was done, which demonstrated AITL, with molecular studies revealing mutation in TET-2, IDH-2, and RHOA-G17v genes. Progression of AITL following BNT162B2 mRNA vaccine is limited in literature. Our case demonstrates a plausible correlation between the diagnosis of AITL following mRNA vaccination due to the malignant transformation of the TFH cells in patients who have a predisposing mutation of RHOA-17v. Given the rarity of AITL and the heterogeneity of molecular findings, more studies are needed to establish such an association.

A Pesky Spleen: A Painful Presentation of Extrapulmonary Sarcoidosis.

Sarcoidosis is an inflammatory and granulomatous disease of uncertain etiology that can impact various organ systems and exhibits diverse clinical presentations, which adds to the complexity of disease diagnosis and management. Pathologically, it is distinguished by the presence of noncaseating granulomas within the affected organ system. In this case report, we describe a 34-year-old Caucasian female patient with isolated splenic and possible hepatic involvement of sarcoidosis, presenting with severe abdominal pain. The absence of the typical pulmonary, cutaneous, or joint involvement posed challenges in achieving a definitive diagnosis and determining the appropriate management. Imaging studies revealed hepatic and splenic hypodensities, necessitating consideration of various differential diagnoses, including lymphoproliferative disorders, immunological disorders, environmental particle exposure, infectious causes, neoplasms, and drug reactions. The severity of symptoms in this case required hospital admission for pain and nausea control, biopsy, and eventual splenectomy with pathology that confirmed the diagnosis of splenic sarcoidosis.

GPR68 limits the severity of chemical-induced oral epithelial dysplasia.

Head and neck cancer is the sixth most common malignancy, and there is an urgent need to identify physiological processes contributing to tumorigenesis. Extracellular acidification caused by aerobic glycolysis within tumor microenvironments can stimulate proton-sensing receptors. GPR68, or ovarian cancer G protein-coupled receptor 1, responds to extracellular acidity and is highly expressed in head and neck squamous cell carcinoma (HNSCC) as well as normal esophageal tissue. To study the role of GPR68 in oral dysplasia, wild-type and GPR68-/- mice were treated with 4-Nitroquinoline N-oxide (4NQO) in drinking water for 11-13 weeks, followed by normal water for 11-12 weeks. 4NQO treatment resulted in 45 percent of GPR68-/- mice developing severe dysplasia or squamous cell carcinoma compared to only 10.5 percent of GPR68+/+ mice. This correlated with increased frequencies of regulatory T cells in the spleens of male GPR68-/- mice. Dysplastic regions of the tongue had increased CD31 staining compared to normal regions in both GPR68-/- and GPR68+/+ mice, suggesting that angiogenesis was GPR68-independent. RNA knockdown studies using HNSCC cell lines demonstrated no direct effect of GPR68 on survival or growth. Overall, we demonstrate that GPR68-deficiency worsens the severity of chemical-induced oral dysplasia, suggesting a protective role for this gene in tumorigenesis.

Sclerosing Mesenteritis: A Rare Cause of Abdominal Pain.

Sclerosing mesenteritis (SM) is a rare inflammatory fibrotic disease of the small intestine mesenteric fat often discovered incidentally on a CT scan. Clinical manifestations depend on the mass effect on the viscera and vessels. The most common symptoms are abdominal pain, bloating, and nausea. SM occurs predominantly in Caucasian men, during the fifth to seventh decades of life. We present a 69-year-old woman with SM whose symptoms were thought to be from irritable bowel syndrome. A 69-year-old female with a history of fibromyalgia presented with recurrent bouts of abdominal pain across her mid-abdomen lasting 30 minutes to an hour associated with nausea, alternating constipation and diarrhea with occasional mucus, and bloating. She used bismuth subsalicylate and ondansetron with temporary relief. Upper endoscopy and colonoscopy were unrevealing. Initially, she was felt to have irritable bowel. Later she presented with nausea and right upper quadrant pain and underwent cholecystectomy. When her pain recurred, the patient had a CT abdomen and pelvis which showed multiple sub-centimeter mesenteric lymph nodes with surrounding haziness and stranding in the root of the mesentery consistent with SM. The patient had a pannus biopsy showing fat necrosis that confirmed the diagnosis. She continued to have waxing and waning symptoms over several years and in the interim was diagnosed with melanoma limited to the skin. The patient had a particularly severe episode of abdominal pain prompting a repeat CT scan with a subsequent biopsy of an enlarged left para-aortic lymph node that revealed lymphoma. Our patient's diagnosis of SM was delayed as her symptoms were mistaken for irritable bowel syndrome. Worsening symptoms should alert clinicians to an alternate diagnosis such as SM. There are characteristic radiographic findings on CT scans and biopsy of the lesions. SM's association with neoplastic diseases such as lymphoma, melanoma, colorectal, and prostate cancer is controversial, however, practitioners should be aware of this possibility and consider biopsy for any suspicious lesions.

Nodular Lymphocyte-Predominant Hodgkin Lymphoma: Review of Current Literature and Case Discussion.

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare subset of Hodgkin lymphoma (HL). It has a distinct clinical and pathological presentation. Unlike classic HL, where the predominant malignant cells are Reed Sternberg cells, the malignant cells in NLPHL are known as lymphocyte predominant (LP) cells, with their own unique immunohistochemistry antigen expression and staining pattern. Based on risk stratification and staging of the disease, treatment can range from active surveillance in asymptomatic patients with no organ compromise or bulky disease, to aggressive chemotherapeutic agents in advanced disease. Guidelines on which of these chemotherapy regimens would offer the most benefit to our patients are limited due to lack of randomized-controlled studies. Majority of the current prospective data on treatment were inclusive of both HL and NLPHL. Thus, the regimens employed in treatment of NLPHL are similar to the ones used in HL, though NLPHL is often viewed as its own distinct entity. This article aims to review the current literature and future advances on treatment of this rare disease.

Immunotherapy-Induced Sarcoid-Like Reaction: A Shrewd Imitator.

A 40-year-old male with a right-sided neck mass was diagnosed with metastatic melanoma. A repeat positron-emission tomography after treatment with combination immunotherapy demonstrated increased hypermetabolic activity in the right supraclavicular, hilar, and mediastinal regions. Immunotherapy was discontinued and a BRAF/MEK inhibitor combination was started. Repeat imaging showed a decrease in size of the neck mass; however, hilar and mediastinal lymph nodes increased in size. A fine needle aspiration of mediastinal lymph nodes was consistent with a granulomatous process. A diagnosis of a sarcoid-like reaction (SLR) was made, and he was started on steroids. A follow-up positron emission tomography showed decreased hilar and mediastinal lymph node hypermetabolic activity. We, therefore, report this rare case of immunotherapy-induced SLR to the expanding literature on immunotherapy-related adverse effects and would like to highlight that SLR can occur in conjunction with disease progression making it challenging to distinguish between the two.

Cutaneous Disease as a Rare Presentation of Follicular Lymphoma Progression.

Follicular lymphoma, the third most common lymphoid malignancy, is considered indolent but incurable non-Hodgkin lymphoma. Isolated cutaneous relapse from follicular lymphoma is very uncommon, and very few cases have been reported in the literature. In this article, we present a case of an adult patient with a history of treated follicular lymphoma who presented with a skin lesion on his face and scalp. Further workup, including biopsy, led to the diagnosis of relapsed follicular lymphoma with no progression of disease elsewhere. We reviewed cases of follicular lymphoma, which relapsed with isolated cutaneous involvement. Treatment options for relapsed follicular lymphoma include observation, anti-CD 20 antibody alone, or in combination with chemotherapy, radio-immunotherapy, and stem cell transplantation in selected patients. Increased awareness of disease evolution and prompt diagnosis of this form of relapse from follicular lymphoma will improve the effectiveness and outcome of its management.

A rare case of dual expression of CD5 and CD10 in primary central nervous system diffuse large B-cell lymphoma with prominent starry sky appearance.

This case highlights the need for both tissue biopsy for diagnosis in suspected CNS malignancy and comprehensive immune profiling for accurate subclassification.

Long-Term Treatment with Empagliflozin Attenuates Renal Damage in Obese Zucker Rat.

INTRODUCTION: Empagliflozin, a known inhibitor of sodium-glucose cotransporter type 2 (SGLT2) decreases glucose reabsorption by the renal tubules and promotes glucose excretion into the urine. While the effectiveness of Empagliflozin in the management of hyperglycemia along with associated cardiovascular and all-cause mortality has been demonstrated previously, the therapeutic benefits associated with the long-term use of this drug in obese animals have yet to be investigated. METHODS: Male 5-week-old lean and obese Zucker rats were randomly assigned to one of the 4 groups- lean control, lean treated, obese control, obese treated and treated with either Empagliflozin (10 mg/kg BW / day) or placebo for 25 weeks to investigate the therapeutic effect of Empagliflozin. RESULTS: Empagliflozin treatment in the obese animals was associated with decreased body weight, attenuated the loss of F-actin from the renal tubules and improved renal structure and function. These changes in renal function were associated with significant improvements in the glucose tolerance, and decreased non-fasting circulatory levels of glucose, amylase, and other inflammatory markers including NGAL, cystatin C, and clusterin. CONCLUSION: Long-term use of Empagliflozin in diabetic obese Zucker rats is associated with improvements in glucose tolerance and decreased loss of renal structure and function.

Prophylactic Treatment with Cerium Oxide Nanoparticles Attenuate Hepatic Ischemia Reperfusion Injury in Sprague Dawley Rats.

BACKGROUND: Hepatic ischemia reperfusion is one the main causes for graft failure following transplantation. Although, the molecular events that lead to hepatic failure following ischemia reperfusion (IR) are diverse and complex, previous studies have shown that excessive formation of reactive oxygen species (ROS) are responsible for hepatic IR injury. Cerium oxide (CeO2) nanoparticles have been previously shown to act as an anti-oxidant and anti-inflammatory agent. Here, we evaluated the protective effects of CeO2 nanoparticles on hepatic ischemia reperfusion injury. METHODS: Male Sprague Dawley rats were randomly assigned to one of the four groups: Control, CeO2 nanoparticle only, hepatic ischemia reperfusion (IR) group and hepatic ischemia reperfusion (IR) plus CeO2 nanoparticle group (IR+ CeO2). Partial warm hepatic ischemia was induced in left lateral and median lobes for 1h, followed by 6h of reperfusion. Animals were sacrificed after 6h of reperfusion and blood and tissue samples were collected and processed for various biochemical experiments. RESULTS: Prophylactic treatment with CeO2 nanoparticles (0.5mg/kg i.v (IR+CeO2 group)) 1 hour prior to hepatic ischemia and subsequent reperfusion injury lead to a decrease in serum levels of alanine aminotransaminase and lactate dehydrogenase at 6 hours after reperfusion. These changes were accompanied by significant decrease in hepatocyte necrosis along with reduction in several serum inflammatory markers such as macrophage derived chemokine, macrophage inflammatory protein-2, KC/GRO, myoglobin and plasminogen activator inhibitor-1. However, immunoblotting demonstrated no significant changes in the levels of apoptosis related protein markers such as bax, bcl2 and caspase 3 in IR and IR+ CeO2 groups at 6 hours suggesting necrosis as the main pathway for hepatocyte death. CONCLUSION: Taken together, these data suggest that CeO2 nanoparticles attenuate IR induced cell death and can be used as a prophylactic agent to prevent hepatic injury associated with graft failure.

Effect of cold water-induced stress on immune response, pathology and fertility in mice during Chlamydia muridarum genital infection.

Genital infection by Chlamydia trachomatis is the most common bacterial sexually transmitted disease worldwide. It causes serious reproductive health complications, including pelvic inflammatory disease and infertility. Stress is implicated as a risk factor for various infections; however, its effect on chlamydia genital infection is unknown. We previously showed that repeated exposure of mice to cold water results in increased severity of chlamydia genital infection. In this study, cold water-induced stress resulted in (i) elevated levels of norepinephrine (NE) and epinephrine in the spleen and genital tract of stressed mice; (ii) elevated IL-1ß, TNF-α, IL-6 and nitric oxide production in macrophage-rich peritoneal cells of mice; (iii) supplement of NE in vitro exerts an immunosuppressive effect on splenic T-cell production of cytokines; (iv) decreased C. muridarum shedding in the genital tract of ß1Adr/ß2Adr receptor KO mice; and (v) a higher rate of infertility in infected mice. These results suggest that cold water stress induces the production of catecholamines, which may play a critical role in the modulation of the immune system leading to increased intensity of C. muridarum genital infection.

Same difference: A pilot study of cyclin D1, bcl-2, AMACR, and ALDH-1 identifies significant differences in expression between primary colon adenocarcinoma and its metastases.

Tumor heterogeneity implies the possibility of significantly different expression of key pathways between primary and metastatic clones. Colon adenocarcinoma is one of the few tumors where current practice includes resection of primary and isolated organ metastases simultaneously without neoadjuvant therapy. We performed a pilot study on 28 cases of colon adenocarcinoma resected simultaneously with metastases in patients with no history of neoadjuvant therapy. We assayed matched primary and metastatic tumors from each patient with common diagnostic antibodies to Bcl-2, Cyclin D1, AMACR, and ALDH-1 by immunohistochemistry with semi-quantitative interpretation on archived formalin fixed, paraffin embedded samples. We were powered for large, consistent differences between primary and metastatic expression, and found 21 of 28 had a significant difference in expression of at least one of the four proteins, accounting for multiplicity of testing. Cyclin D1 had significantly more cases with differential metastatic:primary expression than would be expected by chance alone (p-value 0.0043), favoring higher expression in the metastatic sample. Bcl-2 and ALDH-1 had trends in this direction (p-value 0.078 each). Proportionately more cases with significant differences were identified when a liver metastasis was tested. We conclude differences in expression between metastatic and primary colon adenocarcinoma within the same patient exist, and may have therapeutic and biomarker testing consequences.

Role of leukotrienes in N-(3,5-dichlorophenyl)succinimide (NDPS) and NDPS metabolite nephrotoxicity in male Fischer 344 rats.

The agricultural fungicide N-(3,5-dichlorophenyl)succinimide (NDPS) can induce marked nephrotoxicity in rats following a single intraperitoneal (ip) administration of 0.4mmol/kg or greater. Although NDPS induces direct renal proximal tubular toxicity, a role for renal vascular effects may also be present. The purpose of this study was to examine the possible role of vasoconstrictor leukotrienes in NDPS and NDPS metabolite nephrotoxicity. Male Fischer 344 rats (4 rats/group) were administered diethylcarbamazine (DEC; 250 or 500mg/kg, ip), an inhibitor of LTA(4) synthesis, 1h before NDPS (0.4mmol/kg, ip), N-(3,5-dichlorophenyl)-2-hydroxysuccinimide (NDHS, 0.1, 0.2, or 0.4mmol/kg, ip), or N-(3,5-dichlorophenyl)-2-hydroxysuccinamic acid (2-NDHSA, 0.1mmol/kg, ip) or vehicle. In a separate set of experiments, the LTD(4) receptor antagonist LY171883 (100mg/kg, po) was administered 0.5h before and again 6h after NDHS (0.1mmol/kg, ip) or 2-NDHSA (0.1mmol/kg, ip) or vehicle. Renal function was monitored for 48h post-NDPS or NDPS metabolite. DEC markedly reduced the nephrotoxicity induced by NDPS and its metabolites, while LY171883 treatments provided only partial attenuation of NDHS and 2-NDHSA nephrotoxicity. These results suggest that leukotrienes contribute to the mechanisms of NDPS nephrotoxicity.