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.

Necrosis on FDG PET/CT correlates with prognosis and mortality in sarcomas.

OBJECTIVE: The purpose of this study was to determine if there is an association between necrosis as identified on staging (18)F-FDG PET/CT and overall survival (OS) and progression-free survival (PFS) in patients with sarcoma. MATERIALS AND METHODS: Sixty-six patients with newly diagnosed limb and girdle sarcoma underwent PET/CT at our institution between June 2004 and July 2009 for sarcoma staging before treatment with curative intent. The tumor maximum standardized up-take values (SUVmax), the presence of necrosis, and the volume of necrosis were measured for each primary tumor and correlated with follow-up data. PFS and OS were analyzed using the Kaplan-Meier method. Proportional hazards models were used to estimate hazard ratios. RESULTS: Median patient age was 49 years, and 51.6% of the patients were men. Sarcomas were categorized as soft tissue (69.2%), bone (23.5%), or other (7.3%). Mean follow-up time was 33.3 months. During the follow-up interval, 53% of patients experienced disease progression, and 40.9% died. There was a statistically significant relationship between the presence of necrosis and OS (by log-rank test, p = 0.001), as well as PFS (by log-rank test, p = 0.0001). Twenty-four-month OS was 96%, 65%, and 38% in patients with tumors with absence necrosis, those with presence of necrosis, and with necrosis volume greater than 50%, respectively. Forty-eight-month OS was 81% in patients with absence of necrosis and 41% in patients with presence of necrosis. Twelve-month PFS was 96%, 60%, and 42% in patients with tumors with absence of necrosis, those with presence of necrosis, and those with necrosis volume greater than 50%, respectively. Twenty-four-month PFS was 83%, 38%, and 22%, respectively, in these groups. CONCLUSION: The presence of necrosis and the volume of necrosis, as identified on the staging FDG PET/CT and after adjusting for SUVmax, are strong independent adverse prognostic factors for disease recurrence and death in patients with limb and girdle sarcomas.

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.

Spectrum of malignant pleural and pericardial disease on FDG PET/CT.

OBJECTIVE: The purpose of this article is to illustrate a wide spectrum of malignant primary and secondary pleural and pericardial diseases imaged with (18)F-FDG PET/CT. CONCLUSION: A wide variety of malignant pleural and pericardial diseases can be detected, staged, and monitored by FDG PET/CT. Although the PET/CT findings are often nonspecific, the aim of this atlas is to show that the spectrum of pleural and pericardial disease that can be evaluated with PET/CT is much broader than current literature would suggest. PET/CT readers and oncologists should be aware of the wide variety of malignancies that can affect the pleura and pericardium and some of the patterns of FDG uptake that can be observed in these cases.

Correlating metabolic activity on 18F-FDG PET/CT with histopathologic characteristics of osseous and soft-tissue sarcomas: a retrospective review of 136 patients.

OBJECTIVE: The objective of our study was to determine whether there is a statistically significant correlation between metabolic activity of osseous and soft-tissue sarcomas as measured by the maximum standardized uptake value (SUV(max)) on (18)F-FDG PET/CT and histopathologic characteristics such as mitotic counts, the presence of necrosis, and the presence of a myxoid component. MATERIALS AND METHODS: We retrospectively evaluated 238 consecutive patients with known soft-tissue or osseous sarcoma who underwent (18)F-FDG PET/CT for initial staging or assessment for recurrence of disease. The SUV(max) of each primary or of the most intense metastatic lesion was measured and was compared with the histologic data provided in the final pathology reports. RESULTS: Histopathologic data were available for 136 sarcomas. The median SUV(max) values of sarcomas with mitotic counts of less than 2.00 (per 10 high-power fields [HPF]), 2.00-6.99, 7.00-16.24, and 16.25 or greater were 5.0, 6.6, 10.3, and 13.0, respectively (p = 0.0003). The median SUV(max) for the sarcomas with necrosis (90 patients) was 8.6 and for those without necrosis (43 patients), 6.0 (p = 0.026). The median SUV(max) for the sarcomas without a myxoid component (118 patients) was 7.7 and with a myxoid component (16 patients) was 6.2 (p = 0.28). CONCLUSION: There was a statistically significant correlation between the mitotic count and the SUV(max) as well as between the presence of tumor necrosis and the SUV(max). Although a correlation between the presence of a myxoid component and SUV(max) was shown, it was not found to be statistically significant. These findings improve on the current information in the literature regarding the use of PET/CT for guidance in sarcoma biopsy. Correlating the SUV(max) with histologic markers that also feature prominently in major sarcoma grading systems may help improve the accuracy of grading and of prognostication by allowing the SUV(max) to potentially serve as a surrogate marker in these grading systems, particularly in cases in which there is interobserver disagreement in the pathologic diagnosis or in cases in which the sarcoma cannot be properly classified on the basis of histopathologic evaluation alone.

Extraovarian primary peritoneal carcinoma: staging with 18F-FDG PET/CT.

A 69-year-old woman who presented with left lower quadrant abdominal pain and elevated serum cancer antigen 125 (CA-125) levels was referred for an MRI and an (18)F-FDG PET/CT to evaluate a suspicious abdominal mass seen on ultrasound. PET/CT showed extensive, intensely FDG-avid, omental and pelvic peritoneal thickening with no suspicious ovarian or colon masses. Based on the PET/CT results, the patient had extensive debulking surgery and histopathological evaluation revealed an extraovarian primary peritoneal carcinoma (EOPPC). (18)F-FDG PET/CT may be useful in differentiating EOPPC from other types of peritoneal carcinomatosis, and in determining the extent of the disease to better guide surgical management and improve long term outcomes.

Chondromyxoid fibroma of the rib mimics a chondrosarcoma on 18F-FDG PET/CT.

Chondromyxoid fibroma (CMF) is a rare benign bone tumor of chondroid origin that occurs mostly in the metaphyses of long bones. CMF can occasionally mimic a chondrosarcoma on CT, and the literature on the 18F-FDG PET/CT imaging characteristics of CMF tumors is limited. In the presented case, a large histologically proven CMF chest wall mass was initially misinterpreted as a chondrosarcoma. This case highlights a potential pitfall in the PET/CT evaluation of these rare benign bone tumors.

Plasmablastic lymphoma of the oral cavity in an HIV-positive patient: staging with 18F-FDG PET/CT.

Plasmablastic lymphoma of the oral cavity is a very rare and only recently recognized entity that has been identified almost exclusively in HIV-infected individuals. It has a predilection for the oral cavity, often exhibits very aggressive behavior and has a poor prognosis. The use of 18F-FDG PET/CT in the evaluation of HIV-associated lymphomas is a recent development, and its use in the staging of plasmablastic lymphoma of the oral cavity has not been previously reported. This rare report highlights the usefulness of 18F-FDG PET/CT in the staging of plasmablastic lymphoma of the oral cavity.

Necrotic pseudotumor caused by a metal-on-metal total hip prosthesis: imaging characteristics on (18)F-FDG PET/CT and correlative imaging.

Necrotic pseudotumor is a complication of metal-on-metal arthroplasty that has been reported with increasing frequency in the last 5 years. It is believed to be the result of a hypersensitivity reaction to metal ions such as nickel, cobalt, or chromium that are released in large quantities from these prostheses. The imaging appearance of a necrotic pseudotumor caused by a metal-on-metal prosthesis, on (18)F-FDG PET/CT or (99m)Tc-MDP bone scan has not been previously described in the literature. Our case demonstrates that a necrotic pseudotumor can be detected incidentally in oncologic patients referred for an (18)F-FDG PET/CT or a (99m)Tc-MDP bone scan, and recognizing this process is vital in preventing further tissue necrosis and patient morbidity, as the offending prosthesis must be promptly removed. The imaging characteristics of a necrotic pseudotumor on PET/CT and bone scan may also mimic a malignant process such as a necrotic sarcoma, and can represent a potential pitfall leading to a false positive diagnosis in an oncologic patient.

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.

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.

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.

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.

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.