IgG4-Related Disease of the Central Nervous System: A Case Series.

IgG4-related disease (IgG4-RD) is a rare and often misdiagnosed disorder with limited literature that highlights the different neurological presentations of this treatable disease. The diagnosis of IgG4-RD could be challenging, while imaging is fundamental for the diagnosis, biopsy is considered the gold standard. Most cases respond well to steroids and immunosuppressive therapy. This is a case series study that illustrates the varied neurological presentations of IgG4-RD through three different patients that were followed at the Montreal Neurological Institute. This paper takes you through the diagnostic strategy that we followed to accurately diagnose and treat those patients.

Radioactive Iodine Therapy in Differentiated Thyroid Cancer: 2020 Update.

OBJECTIVE. The paradigm of theranostics is based on tailoring therapy for the purpose of optimizing outcomes. This principle is being applied to radioactive iodine therapy. Consequently, thyroid cancer therapy protocols are evolving. The purpose of this article is to promote a modern approach to radioiodine therapy. CONCLUSION. This article highlights guidelines and position statements, summarizes the prognostication systems of thyroid cancer, and reviews which prescribed activities of 131I.

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.

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.

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.

Comparison of Prostate-Specific Membrane Antigen-Based 18F-DCFBC PET/CT to Conventional Imaging Modalities for Detection of Hormone-Naïve and Castration-Resistant Metastatic Prostate Cancer.

UNLABELLED: Conventional imaging modalities (CIMs) have limited sensitivity and specificity for detection of metastatic prostate cancer. We examined the potential of a first-in-class radiofluorinated small-molecule inhibitor of prostate-specific membrane antigen (PSMA), N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-4-(18)F-fluorobenzyl-l-cysteine ((18)F-DCFBC), to detect metastatic hormone-naïve (HNPC) and castration-resistant prostate cancer (CRPC). METHODS: Seventeen patients were prospectively enrolled (9 HNPC and 8 CRPC); 16 had CIM evidence of new or progressive metastatic prostate cancer and 1 had high clinical suspicion of metastatic disease. (18)F-DCFBC PET/CT imaging was obtained with 2 successive PET scans starting at 2 h after injection. Patients were imaged with CIM at approximately the time of PET. A lesion-by-lesion analysis of PET to CIM was performed in the context of either HNPC or CRPC. The patients were followed with available clinical imaging as a reference standard to determine the true nature of identified lesions on PET and CIM. RESULTS: On the lesion-by-lesion analysis, (18)F-DCFBC PET was able to detect a larger number of lesions (592 positive with 63 equivocal) than CIM (520 positive with 61 equivocal) overall, in both HNPC and CRPC patients. (18)F-DCFBC PET detection of lymph nodes, bone lesions, and visceral lesions was superior to CIM. When intrapatient clustering effects were considered, (18)F-DCFBC PET was estimated to be positive in a large proportion of lesions that would be negative or equivocal on CIM (0.45). On follow-up, the sensitivity of (18)F-DCFBC PET (0.92) was superior to CIM (0.71). (18)F-DCFBC tumor uptake was increased at the later PET time point (~2.5 h after injection), with background uptake showing a decreasing trend on later PET. CONCLUSION: PET imaging with (18)F-DCFBC, a small-molecule PSMA-targeted radiotracer, detected more lesions than CIM and promises to diagnose and stage patients with metastatic prostate cancer more accurately than current imaging methods.

Value of Fluorodeoxyglucose PET/Computed Tomography Patient Management and Outcomes in Thyroid Cancer.

"Fluorodeoxyglucose (FDG) PET/computed tomography (CT) is used most frequently in the surveillance of iodine-refractory differentiated thyroid cancer with increased thyroglobulin level after therapy. This article evaluates the impact of FDG-PET/CT on clinical management and the prognostic implications of a positive scan. In the studies reviewed, FDG-PET/CT changed the course of management in 14% to 78% of patients with suspected recurrence, and a positive scan was associated with poorer survival. Similar conclusions are supported in the literature for anaplastic and medullary thyroid cancers, although these are based on fewer studies on account of the lower prevalence of these subtypes."

Clinical significance of parotid gland incidentalomas on (18)F-FDG PET/CT.

The aim of this study was to evaluate the frequency and clinical significance of incidental focal uptake of (18)F-fluorodeoxyglucose (FDG) on positron emission tomography/computed tomography (PET/CT) in the parotid glands of cancer patients. A retrospective review of 7,252 oncologic PET/CT studies was done. FDG positive parotid incidentalomas occurred in 0.4% of PET/CT scans, of which only 4% were malignant. PET/CT was unable to differentiate benign from malignant parotid lesions based on SUVmax alone. (18)F-FDG positive parotid incidentalomas can be managed conservatively, however patients with a prior history of lymphoma had a much higher risk of parotid malignancy and require further investigation.

Head and neck PET/CT: therapy response interpretation criteria (Hopkins Criteria)-interreader reliability, accuracy, and survival outcomes.

UNLABELLED: There has been no established qualitative system of interpretation for therapy response assessment using PET/CT for head and neck cancers. The objective of this study was to validate the Hopkins interpretation system to assess therapy response and survival outcome in head and neck squamous cell cancer patients (HNSCC). METHODS: The study included 214 biopsy-proven HNSCC patients who underwent a posttherapy PET/CT study, between 5 and 24 wk after completion of treatment. The median follow-up was 27 mo. PET/CT studies were interpreted by 3 nuclear medicine physicians, independently. The studies were scored using a qualitative 5-point scale, for the primary tumor, for the right and left neck, and for overall assessment. Scores 1, 2, and 3 were considered negative for tumors, and scores 4 and 5 were considered positive for tumors. The Cohen κ coefficient (κ) was calculated to measure interreader agreement. Overall survival (OS) and progression-free survival (PFS) were analyzed by Kaplan-Meier plots with a Mantel-Cox log-rank test and Gehan Breslow Wilcoxon test for comparisons. RESULTS: Of the 214 patients, 175 were men and 39 were women. There was 85.98%, 95.33%, 93.46%, and 87.38% agreement between the readers for overall, left neck, right neck, and primary tumor site response scores, respectively. The corresponding κ coefficients for interreader agreement between readers were, 0.69-0.79, 0.68-0.83, 0.69-0.87, and 0.79-0.86 for overall, left neck, right neck, and primary tumor site response, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of the therapy assessment were 68.1%, 92.2%, 71.1%, 91.1%, and 86.9%, respectively. Cox multivariate regression analysis showed human papillomavirus (HPV) status and PET/CT interpretation were the only factors associated with PFS and OS. Among the HPV-positive patients (n = 123), there was a significant difference in PFS (hazard ratio [HR], 0.14; 95% confidence interval, 0.03-0.57; P = 0.0063) and OS (HR, 0.01; 95% confidence interval, 0.00-0.13; P = 0.0006) between the patients who had a score negative for residual tumor versus positive for residual tumor. A similar significant difference was observed in PFS and OS for all patients. There was also a significant difference in the PFS of patients with PET-avid residual disease in one site versus multiple sites in the neck (HR, 0.23; log-rank P = 0.004). CONCLUSION: The Hopkins 5-point qualitative therapy response interpretation criteria for head and neck PET/CT has substantial interreader agreement and excellent negative predictive value and predicts OS and PFS in patients with HPV-positive HNSCC.

Electroencephalographic and fluorodeoxyglucose-positron emission tomography correlates in anti-N-methyl-d-aspartate receptor autoimmune encephalitis.

IMPORTANCE: Anti-N-methyl-d-aspartate receptor (anti-NMDAR) autoimmune encephalitis is an increasingly recognized cause of limbic encephalitis (LE). Prolonged LE and limbic status epilepticus (LSE) share many features. The ability to distinguish between the two is crucial in directing appropriate therapy because of the potential iatrogenesis associated with immunosuppression and anesthetic-induced coma. OBSERVATIONS: A 34-year-old woman with recurrent LE developed behavioral changes, global aphasia, and repetitive focal and generalized tonic-clonic seizures. Because asymmetric rhythmic delta patterns recurred on electroencephalography (EEG) despite treatment with nonsedating antiepileptic drugs followed by anesthetic-induced coma, an investigation to distinguish LSE from LE was undertaken. Implanted limbic/temporal lobe depth electrodes revealed no epileptiform activity. Brain single-photon emission computerized tomography (SPECT) showed no hyperperfusion, and brain fluorodeoxyglucose-positron emission tomography (FDG-PET) showed hypermetabolism in the left frontal, temporal, and parietal cortices. Anti-N-methyl-d-aspartate receptor autoimmune encephalitis was diagnosed based detection of anti-NMDAR antibody in the cerebrospinal fluid (CSF). With chronic immunosuppression, the resolution of brain FDG-PET abnormalities paralleled clinical improvement. CONCLUSIONS AND RELEVANCE: This case of anti-NMDAR autoimmune encephalitis illustrates the challenges of distinguishing prolonged LE from LSE. We discuss the parallels between these two conditions and propose a management paradigm to optimize evaluation and treatment.

Gastric neuroendocrine carcinoma staged and followed with (18)F-FDG PET/CT--a report of 3 cases.

Gastric neuroendocrine carcinomas (NEC) are very rare, aggressive tumors of the stomach that are distinct from the more benign neuroendocrine tumors, sometimes referred to as "gastric carcinoids." We present 3 cases of gastric NEC representing various histological subtypes that were successfully staged and followed with F-FDG PET/CT, impacting therapeutic management in each case.

Infectious and inflammatory complications of surgical management of cancer patients imaged with 18F-FDG PET/CT: a pictorial essay.

The aim of this pictorial essay was to highlight the usefulness of fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in evaluating incidental infection or inflammation in cancer patients, related to surgical management. A retrospective review of 10,985 consecutive oncologic PET/CTs was done, and nine cases with suspected FDG positive infectious or inflammatory processes were selected for further review. PET/CT helped identify infections and inflammatory processes related to surgical management of cancer patients, define the extent of infection or inflammation, guide the management and, in some cases, evaluate response to therapy.

Spectrum of malignant renal and urinary bladder tumors on 18F-FDG PET/CT: a pictorial essay.

A wide variety of malignant renal and urinary bladder diseases can be detected on (18)F-FDG PET/CT. Although the PET/CT findings are often nonspecific, the aim of this atlas was to demonstrate that the spectrum of renal and urinary bladder malignancy that can be evaluated with PET/CT is much broader than current medical literature would suggest. PET/CT readers and oncologists should be aware of the variety of urological tumor types that can be detected on PET/CT and some of the patterns of (18)F-FDG uptake that can be observed in these cases.

Spectrum of gastric malignancy on 18F-FDG PET/CT: a pictorial essay.

A wide variety of malignant gastric diseases can be detected, staged, and followed on (18)F-FDG PET/CT. Although the PET/CT findings are often nonspecific and some can be seen in certain benign gastric diseases, the aim of this atlas was to demonstrate that the wide histological spectrum of gastric tumors that can be evaluated, staged, and followed with PET/CT is much broader than current medical literature would suggest. PET/CT readers and oncologists should be aware of the utility of PET/CT in these tumors and the imaging characteristics and patterns of (18)F-FDG uptake that can be demonstrated in these cases.