Autopsy findings in cases of fatal COVID-19 vaccine-induced myocarditis.

COVID-19 vaccines have been linked to myocarditis, which, in some circumstances, can be fatal. This systematic review aims to investigate potential causal links between COVID-19 vaccines and death from myocarditis using post-mortem analysis. We performed a systematic review of all published autopsy reports involving COVID-19 vaccination-induced myocarditis through 3 July 2023. All autopsy studies that include COVID-19 vaccine-induced myocarditis as a possible cause of death were included. Causality in each case was assessed by three independent physicians with cardiac pathology experience and expertise. We initially identified 1691 studies and, after screening for our inclusion criteria, included 14 papers that contained 28 autopsy cases. The cardiovascular system was the only organ system affected in 26 cases. In two cases, myocarditis was characterized as a consequence from multisystem inflammatory syndrome. The mean age of death was 44.4 years old. The mean and median number of days from last COVID-19 vaccination until death were 6.2 and 3 days, respectively. We established that all 28 deaths were most likely causally linked to COVID-19 vaccination by independent review of the clinical information presented in each paper. The temporal relationship, internal and external consistency seen among cases in this review with known COVID-19 vaccine-induced myocarditis, its pathobiological mechanisms, and related excess death, complemented with autopsy confirmation, independent adjudication, and application of the Bradford Hill criteria to the overall epidemiology of vaccine myocarditis, suggests that there is a high likelihood of a causal link between COVID-19 vaccines and death from myocarditis.

IgG4 Antibodies Induced by Repeated Vaccination May Generate Immune Tolerance to the SARS-CoV-2 Spike Protein.

Less than a year after the global emergence of the coronavirus SARS-CoV-2, a novel vaccine platform based on mRNA technology was introduced to the market. Globally, around 13.38 billion COVID-19 vaccine doses of diverse platforms have been administered. To date, 72.3% of the total population has been injected at least once with a COVID-19 vaccine. As the immunity provided by these vaccines rapidly wanes, their ability to prevent hospitalization and severe disease in individuals with comorbidities has recently been questioned, and increasing evidence has shown that, as with many other vaccines, they do not produce sterilizing immunity, allowing people to suffer frequent re-infections. Additionally, recent investigations have found abnormally high levels of IgG4 in people who were administered two or more injections of the mRNA vaccines. HIV, Malaria, and Pertussis vaccines have also been reported to induce higher-than-normal IgG4 synthesis. Overall, there are three critical factors determining the class switch to IgG4 antibodies: excessive antigen concentration, repeated vaccination, and the type of vaccine used. It has been suggested that an increase in IgG4 levels could have a protecting role by preventing immune over-activation, similar to that occurring during successful allergen-specific immunotherapy by inhibiting IgE-induced effects. However, emerging evidence suggests that the reported increase in IgG4 levels detected after repeated vaccination with the mRNA vaccines may not be a protective mechanism; rather, it constitutes an immune tolerance mechanism to the spike protein that could promote unopposed SARS-CoV2 infection and replication by suppressing natural antiviral responses. Increased IgG4 synthesis due to repeated mRNA vaccination with high antigen concentrations may also cause autoimmune diseases, and promote cancer growth and autoimmune myocarditis in susceptible individuals.

Disseminated Multi-system Sarcoidosis Mimicking Metastases on 18F-FDG PET/CT.

A 60-year-old female with no significant medical history presented with hematuria. A computed tomography (CT) scan revealed extensive lymphadenopathy with hypodensities in the liver and spleen, and she was referred for an 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/CT (PET/CT) study to assess for malignancy of unknown primary. PET/CT revealed extensive 18F-FDG avid lymphadenopathy as well as innumerable intensely 18F-FDG avid lung, liver and splenic nodules, highly concerning for malignancy. A PET-guided bone marrow biopsy of the posterior superior iliac spine revealed several non-necrotizing, well-formed granulomas, consistent with sarcoidosis. The patient was managed conservatively and remained clinically well over the subsequent 9 years of follow-up.

Unilateral Muscle Artifacts due to Non-compliance During Uptake Phase of 18F-FDG PET/CT in an Oncologic Patient.

A 49-year-old male patient with a prior history of poor compliance with medical appointments was referred for an 18F-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) for the staging of a rectal squamous cell carcinoma. The PET/CT showed unilateral diffuse skeletal muscle 18F-FDG uptake as well as bilateral salivary gland uptake artifacts, suggestive of non-compliance with patient preparation instructions. The PET/CT nurse noted that during the 18F-FDG uptake phase, the patient appeared intoxicated, and she found two beer cans hidden in the waste disposal beside his chair just prior to imaging. The patient only admitted to eating a cookie approximately 30 minutes after the injection of 18F-FDG PET/CT and denied consuming alcohol during the uptake phase. We present the imaging findings of non-compliance with patient instructions during the uptake phase of 18F-FDG.

Inflammatory and Ischemic Post Liver Transplant Complications Mimic Malignancy on 18F-FDG PET/CT.

A 65-year-old male patient with a one year history of liver transplantation was referred for an 18F-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) to rule out post transplant lymphoproliferative disease. Multiple foci of intense abnormal 18F-FDG uptake were seen in the transplanted liver which were concerning for malignancy. Explantation of the liver approximately 1 month following the PET/CT revealed multiple inflammatory and ischemic changes including large bile duct necrosis, acute cholangitis, bile duct obstruction changes and periportal fibrosis, with no evidence of malignancy. We present the 18F-FDG PET/CT image findings of this case.

Primary Thyroid Lymphoma: External Beam Radiation Therapy Induced Thyroiditis Mimics Residual Disease on Serial 18F-FDG PET/CT Imaging.

A 67-year-old female patient with no prior history of benign thyroid disease was diagnosed with primary thyroid lymphoma and was staged with 18F-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT). She was treated with chemotherapy and external beam radiation therapy, and a follow-up PET/CT showed significant reduction in the size of the thyroid lymphoma with persistent intense 18F-FDG uptake, which was interpreted as partial response to therapy. However, two subsequent PET/CT studies showed no change in the persistent intense 18F-FDG uptake in the thyroid and a biopsy confirmed the presence of thyroiditis with no evidence of residual lymphoma. Follow-up PET/CTs performed over the subsequent three years showed stable intensely 18F-FDG avid thyroiditis with no evidence of lymphoma recurrence. We present the imaging characteristics of a long term radiation treatment induced thyroiditis mimicking 18F-FDG avid residual disease on PET/CT.

Primary Renal Leiomyosarcoma Presenting with Subcutaneous and Osseous Metastases: Staging and Follow-Up with 18F-FDG PET/CT.

A 60 year old woman who presented with multiple small subcutaneous nodules in the upper back and arms, was referred for an [18F] fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) after histological evaluation revealed metastatic leiomyosarcoma of unknown origin. The PET/CT showed multiple 18F-FDG-avid subcutaneous nodules, bone lesions, as well as a large left renal mass, which was biopsied to confirm a primary renal leiomyosarcoma arising from the renal parenchyma. A post therapy PET/CT showed overall progression of disease. The use of 18F-FDG PET/CT in the staging and evaluation of response to therapy of a renal leiomyosarcoma has not been previously described in the literature.

Systemic Lupus Erythematosus Associated Pitfalls on 18F-FDG PET/CT: Reactive Follicular Hyperplasia, Kikuchi-Fujimoto Disease, Inflammation and Lymphoid Hyperplasia of the Spleen Mimicking Lymphoma.

Systemic lupus erythematosus (SLE) is associated with a variety of inflammatory processes that can affect the lymph nodes, brain, kidneys, and spleen. We present two patients with SLE in whom SLE-associated conditions complicated interpretation of 18F-fluoro-2-deoxy-d-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) imaging of the lymph nodes and the spleen. The imaging findings mimicked lymphoma, but histopathological evaluation showed benign processes including reactive follicular hyperplasia in the lymph nodes, Kikuchi-Fujimoto disease in perisplenic lymph nodes, and inflammatory changes and lymphoid hyperplasia in the spleen.

Recurrent Follicular Dendritic Cell Sarcoma of the Parotid Gland Imaged with 18F-FDG PET/CT.

Follicular dendritic cell sarcoma (FDCS) is an extremely rare tumor with only 67 cases of head and neck FDCS reported in the literature. A 65-year-old female had a 6-cm follicular dendritic cell sarcoma resected from the left parotid gland with close margins. It recurred 1 year later as a 5-cm mass that was intensely [18F] fluoro-2-deoxy-D-glucose (18F-FDG) avid on positron emission tomography/computed tomography (PET/CT) and was re-excised. A follow-up PET/CT did not show any metastatic disease. The use of 18F-FDG PET/CT in the management of FDCS warrants further research. We present the 18F-FDG PET/CT imaging findings of this rare tumor.

Thyroid Incidentalomas on 18F-FDG PET/CT: Clinical Significance and Controversies.

OBJECTIVE: The purpose of the current study is to examine the incidence and clinical significance of unexpected focal uptake of 18F-fluorodeoxyglucose (18F-FDG) on positron emission tomography/computed tomography (PET/CT) in the thyroid gland of oncology patients, the maximum standardized uptake value (SUVmax) of benign and malignant thyroid incidentalomas in these patients, and review the literature. METHODS: Seven thousand two hundred fifty-two 18F-FDG PET/CT studies performed over four years, were retrospectively reviewed. Studies with incidental focal 18F-FDG uptake in the thyroid gland were further analyzed. RESULTS: Incidental focal thyroid 18F-FDG uptake was identified in 157 of 7252 patients (2.2%). Sufficient follow-up data (≥12 months) were available in 128 patients, of whom 57 (45%) had a biopsy performed and 71 had clinical follow-up. Malignancy was diagnosed in 14 of 128 patients (10.9%). There was a statistically significant difference between the median SUVmax of benign thyroid incidentalomas (SUVmax 4.8) vs malignant (SUVmax 6.3), but the wide range of overlap between the two groups yielded no clinically useful SUVmax threshold value to determine malignancy. CONCLUSION: 18F-FDG positive focal thyroid incidentalomas occurred in 2.2% of oncologic PET/CT scans, and were malignant in 10.9% of 128 patients. This is the lowest reported malignancy rate in a North American study to date, and significantly lower than the average malignancy rate (35%) reported in the literature. Invasive biopsy of all 18F-FDG positive thyroid incidentalomas, as recommended by some studies, is unwarranted and further research to determine optimal management is needed. There was no clinically useful SUVmax cut-off value to determine malignancy and PET/CT may not be a useful imaging modality to follow these patients conservatively.

Composite Cutaneous Lymphoma (Iatrogenic Immunodeficiency-Associated Lymphoproliferative Disorder) in a Patient with Rheumatoid Arthritis Treated with Methotrexate: Staging and Evaluation of Response to Therapy with 18F-FDG PET/CT.

A 67 year old woman with a 10 year history of rheumatoid arthritis (RA) treated with methotrexate and prednisone, presented with a 2 year history of worsening multiple cutaneous plaques of variable appearance. Two distinct skin lesions were biopsied to reveal a composite cutaneous lymphoma, possibly caused by long term methotrexate therapy. An [18F] fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) was performed to stage the malignancy, and was later repeated to evaluate response to chemotherapy, which guided subsequent management. We present the PET/CT imaging findings of this very rare iatrogenic (methotrexate induced) immunodeficiency-associated lymphoproliferative disorder.

Clinical Significance of 18F-Fluorodeoxyglucose Avid Prostate Gland Incidentalomas on Positron Emission Tomography/Computed Tomography.

OBJECTIVE: The aim of this study was to evaluate the clinical significance of incidental focal uptake of 18F-fluorodeoxyglucose (18F-FDG) on positron emission tomography/computed tomography (PET/CT) in the prostate glands of cancer patients. METHODS: A retrospective review of 3122 consecutive male patients who underwent 18F-FDG PET/CT studies with an oncologic indication, over the course of four years, was performed. Studies with incidental 18F-FDG uptake in the prostate gland were further analyzed. RESULTS: Incidental 18F-FDG uptake in the prostate gland was identified in 65/3122 men (2.1%). Sufficient follow-up data (≥12 months) were available in 53 patients, of whom 11 had a biopsy and 42 had clinical and imaging follow-up. Malignancy was histologically diagnosed in 4 out of 53 patients (7.5%). There was no statistically significant difference in 18F-FDG uptake values between benign prostate lesions [maximum standardized uptake value (SUVmax) 7.3] and malignant ones (SUVmax 7.2, p=0.95). There was a statistically significant difference between the serum prostate specific antigen (PSA) of the benign group (n=24, PSA=2.7 ng/mL) and the malignant group (n=4, PSA=9.2 ng/mL, p<0.001). There was a direct correlation between SUVmax and Gleason score. CONCLUSION: 18F-FDG positive prostate incidentalomas were detected in 2.1% of oncologic PET/CT scans and of these 7.5% were malignant. SUVmax was not useful for distinguishing between benign and malignant incidental prostate lesions. 18F-FDG avid prostate incidentalomas on PET/CT should prompt a recommendation for obtaining a serum PSA and further investigation if serum PSA is elevated.

Follicular lymphoma transforming into diffuse large B-cell lymphoma in spleen: Simultaneous appearance of both on 18F-FDG PET/CT and histology.

Low grade lymphoma may transform into a more aggressive lymphoma and this transformation is usually associated with a poor outcome. A 65year old man presented with two metabolically active splenic lesions on a staging [18F] fluoro-2-deoxy-d-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT). Histologic evaluation post splenectomy confirmed the presence of two clonally related lymphomas: a follicular lymphoma (FL) and a diffuse large B-cell lymphoma (DLBCL). Molecular genetic studies confirmed that the DLBCL lesions arose from a pre-existing FL. We present the 18F-FDG PET/CT imaging characteristics of both lymphoma types which were simultaneously present in the spleen.

131I-MIBG Therapy in a Metastatic Small Bowel Neuroendocrine Tumor Patient Undergoing Hemodialysis.

Systemic radioisotope therapy with I-metaiodobenzylguanidine (I-MIBG) is an effective form of targeted therapy for neuroendocrine tumors. One of the absolute contraindications to administering I-MIBG therapy listed in the 2008 European Association of Nuclear Medicine guidelines is renal insufficiency requiring dialysis, although this contraindication is not evidence based. We describe a 68-year-old woman with a metastatic small bowel neuroendocrine tumor who developed renal insufficiency requiring hemodialysis. Imaging and dosimetry with I-MIBG were performed and showed that the radiation doses to the whole body and lungs were within safe limits. She was treated with 1820 MBq of I-MIBG with no short-term adverse reactions.

Pleomorphic spindle cell sarcoma (PSCS) (formerly known as malignant fibrous histiocytoma, MFH) of the spleen, mimics an atypical haemangioma on 99mTc-RBC, CT and Ultrasound: staging with 18F-FDG PET/CT.

A 63-year-old male was found to have a 7.5-cm splenic mass that had imaging appearances of an atypical haemangioma on CT, ultrasound and a 99mTc-RBC scan, and he was followed conservatively with serial ultrasounds. Sixteen months later, however, the splenic lesion grew and he developed numerous new liver masses which were biopsy confirmed to be a pleomorphic spindle cell sarcoma (PSCS), formerly known as malignant fibrous histiocytoma (MFH). A staging 18F-FDG PET/CT was performed and showed innumerable, mostly necrotic hepatic and splenic masses. The patient passed away a few days after the PET/CT, before a treatment program could be implemented. The use of 18F-FDG PET/CT in the staging of splenic PSCS has not been previously described. We present the 99mTc-RBC and 18F-FDG PET/CT image characteristics of a patient with splenic PSCS.

Klippel-Feil Syndrome With Spinal Dysraphism: Diastematomyelia on 18F-NaF Bone PET, CT, and MRI Imaging.

A 49-year-old woman with known Klippel-Feil syndrome had a CT scan for staging of stage IIIA invasive carcinoma of the left breast. She was found to have cervicothoracic spinal dysraphism with diastematomyelia. An F-NaF bone PET done as part of the metastatic workup showed the characteristic sagittal bone spur, and MRI demonstrated a complete split of the cervical and upper thoracic spinal cord, previously unknown to the patient.

Metastatic Insulinoma Pancreatic Neuroendocrine Tumor Treated With 177Lu-DOTATATE Induction and Maintenance Peptide Receptor Radionuclide Therapy: A Suggested Protocol.

A 70-year-old woman presented with frequent episodes of hypoglycemia. Imaging revealed a 6-cm pancreatic mass with several liver lesions. The pancreatic mass was resected and confirmed to be a well-differentiated insulinoma. Surgery improved but did not resolve her hypoglycemic episodes, and she was referred for peptide receptor radionuclide therapy with 177Lu-DOTATATE to treat her residual disease. A modified protocol with a continuous IV dextrose infusion was used, and the treatments were well tolerated. After 4 induction and 2 maintenance treatments, her hypoglycemic symptoms resolved completely and her disease stabilized. She has been progression free for 24 months.

Chest X-ray Artifact Caused by Bilateral 99mTc-Antimony Trisulfite Injection for Sentinel Node Imaging in a Patient With Breast Cancer.

A 52-year-old woman diagnosed with invasive ductal carcinoma of both breasts had a chest x-ray for preoperative assessment. A striking artifact was noted by the x-ray technologist, who, as a result, became very concerned about radiation exposure from the patient. The patient had undergone bilateral sentinel lymph node injections in the nuclear medicine department with Tc-antimony trisulfite colloid just 2 hours before the chest x-ray. Radiation exposure to the x-ray technologist was determined to be similar to 8 hours of naturally occurring background radiation (∼2.96 µSv).