Misleading localization by 18F-fluorocholine PET/CT in familial hypocalciuric hypercalcemia type-3: a case report.

BACKGROUND: Familial hypocalciuric hypercalcemia (FHH) is a heterogeneous autosomal-dominant disorder of calcium hemostasis that may be difficult to distinguish clinically from mild primary hyperparathyroidism. Loss-of-function mutations mainly involving Arg15 residue of the adaptor-related protein complex 2, sigma subunit 1 (AP2S1) cause a rarer, more recently recognized form of FHH, FFH type-3. Recently, 18F-fluorocholine positron emission tomography/computed tomography (FCH-PET/CT) showed superior sensitivity to conventional imaging in localizing parathyroid adenomas. We report a new FFH type-3 patient who underwent unnecessary parathyroidectomy in association with misleading FCH-PET/CT imaging. CASE PRESENTATION: A 29-year old woman was initially evaluated for parathyroid hormone (PTH)-dependent hypercalcemia in 2013. Medical history was positive only for chronic constipation and malaise with no personal or family history of hypercalcemia, kidney stones, or neck surgery. Over seven years, serum calcium level was 2.51-2.89 mmol/L with concomitant PTH level of 58.7-94.8 mmol/L. Serum phosphate levels were in the low/low normal range. Serum creatinine and magnesium levels were normal. 25-hydroxy vitamin D level was 13 nmol/L. 24-hour urine calcium level was 1.92 mmol/day but increased to 6.99 mmol/day after treatment with cholecalciferol 1000 IU daily. Bone mineral density and renal ultrasound were normal. Parathyroid ultrasound showed two hypoechoic nodules inferior to the left and right thyroid lobes; however, 99mtechnitium-sestamibi scans (2013, 2016, 2018) were negative. FCH-PET/CT (2019) showed focal uptake co-localizing with the nodule inferior to the left thyroid lobe. The patient underwent left inferior parathyroidectomy and pathology was consistent with parathyroid hyperplasia. However, postoperatively, serum calcium and PTH levels remained elevated and FCH-PET/CT and ultrasound showed persistence of the uptake/nodule. Whole exome sequencing showed Arg15Cys mutation in the AP2S1 gene characteristic of FHH type-3. CONCLUSIONS: In this new case of FHH type-3, FCH-PET/CT failed to localize to the hyperplastic parathyroid glands and localized instead to apparently a lymph node. This, together with increased urinary calcium after vitamin D supplementation, led to unnecessary parathyroidectomy. Given the increasingly lower cost of genetic testing and the cost of follow up and unnecessary surgery, it may prudent to include genetic testing for FHH early on in patients with mild PTH-dependent hypercalcemia.

Iacta Alea Est: The Inexorable Advance of Tofacitinib in the Treatment of Dermatomyositis-Associated Rapidly Progressive Interstitial Lung Disease. A Case Report.

Rapidly progressive interstitial lung disease is typically associated with clinically amyopathic dermatomyositis and the anti-melanoma differentiation associated gene 5 antibody, a condition with high mortality and resistance to classic immunosuppression. Recent reports have described the efficacy of the Janus kinase inhibitor tofacitinib in the treatment of rapidly progressive interstitial lung disease in anti-melanoma differentiation associated gene 5 antibody-positive clinically amyopathic dermatomyositis. It is uncertain, however, whether tofacitinib alters the course of rapidly progressive interstitial lung disease in other variants of dermatomyositis that are unrelated to the anti-melanoma differentiation associated gene 5 antibody and whether the early addition of the anti-fibrotic tyrosine kinase inhibitor nintedanib interferes with the development of fibrosis. To answer these questions, we present and discuss the case of an elderly woman who presented with a flare of dermatomyositis sine myositis. Based upon the detection of anti-Jo-1 antibodies and the absence of anti-melanoma differentiation associated gene 5 antibodies, anti-synthetase syndrome was diagnosed. While the cutaneous manifestations quickly resolved with prednisone, azathioprine and tacrolimus, the respiratory function paradoxically and rapidly deteriorated, and invoked the use of tofacitinib. Markedly raised ferritin levels and a severe numerical deficiency of circulating natural killer cells paralleled the acute lung inflammation, which was reflected by 18F-fluorodeoxyglucose hypermetabolism on positron emission tomography/CT. Tofacitinib lead to a prompt clinical recovery, with a reduction in oxygen requirement, correction of hyperferritinemia, reversal of the natural killer cell deficiency, and a decrease in 18F-fluorodeoxyglucose uptake in the affected lung segments. Subsequently, nintedanib was added at a point in time when inflammation subsided. Apart from cytomegalovirus reactivation no adverse events occurred. In conclusion, tofacitinib reversed the pronounced inflammatory component of anti-Jo-1 antibody-positive, anti-melanoma differentiation associated gene 5 antibody-negative rapidly progressive interstitial lung disease, confirming that Janus kinase signaling pathways are critically involved in the pathogenesis of rapidly progressive interstitial lung disease, apparently independently of the targeted autoantigen. Although some improvement in pulmonary function was observed, it seems premature to conclusively judge on reversibility or prevention of pulmonary fibrosis by pairing both kinase inhibitors for which an extended follow-up and ideally, prospective and controlled studies are needed.

Adrenal Oncocytoma: An Incidental Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Findings with Magnetic Resonance Imaging Correlation.

A good percentage of adrenal masses in patients with known malignancy may be benign; thus, noninvasive characterization is important in preventing unnecessary biopsy. This case report represents a patient with papillary thyroid carcinoma and known lung metastasis for which she was followed up with whole-body fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) postradioactive iodine therapy. During the follow-up, she had developed an adrenal mass lesion seen by FDG PET/CT and further characterized by magnetic resonance imaging (MRI). This case demonstrates the potential importance of combining the molecular characterization by FDG PET/CT with the data derived from MRI in narrowing the differential diagnosis of an adrenal mass and suggesting the next diagnostic step in reaching the definitive diagnosis.

Cardiac and pericardial tumors: A potential application of positron emission tomography-magnetic resonance imaging.

Cardiac and pericardial masses may be neoplastic, benign and malignant, non-neoplastic such as thrombus or simple pericardial cysts, or normal variants cardiac structure can also be a diagnostic challenge. Currently, there are several imaging modalities for diagnosis of cardiac masses; each technique has its inherent advantages and disadvantages. Echocardiography, is typically the initial test utilizes in such cases, Echocardiography is considered the test of choice for evaluation and detection of cardiac mass, it is widely available, portable, with no ionizing radiation and provides comprehensive evaluation of cardiac function and valves, however, echocardiography is not very helpful in many cases such as evaluation of extracardiac extension of mass, poor tissue characterization, and it is non diagnostic in some cases. Cross sectional imaging with cardiac computed tomography provides a three dimensional data set with excellent spatial resolution but utilizes ionizing radiation, intravenous iodinated contrast and relatively limited functional evaluation of the heart. Cardiac magnetic resonance imaging (CMR) has excellent contrast resolution that allows superior soft tissue characterization. CMR offers comprehensive evaluation of morphology, function, tissue characterization. The great benefits of CMR make CMR a highly useful tool in the assessment of cardiac masses. (Fluorine 18) fluorodeoxygluocse (FDG) positron emission tomography (PET) has become a corner stone in several oncological application such as tumor staging, restaging, treatment efficiency, FDG is a very useful imaging modality in evaluation of cardiac masses. A recent advance in the imaging technology has been the development of integrated PET-MRI system that utilizes the advantages of PET and MRI in a single examination. FDG PET-MRI provides complementary information on evaluation of cardiac masses. The purpose of this review is to provide several clinical scenarios on the incremental value of PET and MRI in the evaluation of cardiac masses.

Analysis of metastatic involvement in bone using anatomical and functional information from 18F-FDG PET/CT.

PURPOSE: Although the overall incidence of bone metastasis is not known, over one-half of the people who die of cancer in the USA every year are thought to have bone involvement. In this study we have developed a method to quantify the metabolic and anatomic changes induced by different types of bone metastases in cancer patients using PET/CT images. PATIENTS AND MATERIALS: Seventy-three cancer patients with no previous history of chemotherapy or radiotherapy who had definite bone metastases documented by PET/CT and other conventional modalities were selected for this study. PET and computed tomography (CT) images were resampled to the same pixel size. Thereafter, the bone structure was segmented using thresholding. The 50% of the maximum standardized uptake value within the bone mask was used to identify bone lesions in each slice. Using the final regions of interest defined at 70% of the maximum, the lesion characteristics including the mean Hounsfield Units were computed from the PET/CT images. The lesions were subjected to visual confirmation by an experienced physician who also categorized them on the basis of the appearances in CT as lytic, sclerotic, mixed, or no-change type. The lesion characteristics were compared using statistical methods. RESULTS: In all, 340 bony lesions in 73 patients with different cancer types were analyzed. The lesions were further categorized into four groups on the basis of their anatomical location. The spine hosts the largest number of lesions. The lumbar bones are the most preferential sites within the spine. Statistical comparison of CT values indicated that the difference between no-change and lytic types was significant. Uptake period did not seem to have a significant impact on no-change and sclerotic types. Quantitatively, maximum standardized uptake value for lytic, no change, mixed, and sclerotic lesions were 7.4, 6.1, 8.2, and 7.2, respectively. CONCLUSION: A quantitative method provides a convenient way that may serve as a useful tool in monitoring and assessing the response to therapy.

Comparison of 18F-FDG PET/CT scan and 99mTc-MDP bone scintigraphy in detecting bone metastasis in head and neck tumors.

PURPOSE: The aim of this study was to evaluate the efficacy of fluorine-18 fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) compared with bone scan in detecting bone metastases in patients with head and neck cancer. MATERIALS AND METHODS: A total of 319 patients with head and neck cancer were identified in our database who had undergone F-FDG PET/CT, from January 2006 until June 2007. Of them 156 patients (age range 15-100 years) met our inclusion criteria - namely, biopsy-proven head and neck cancer, and bone scan and F-FDG PET/CT within 30 days. Comparison was made on a lesion-by-lesion analysis. MRI, multidetector CT, and the clinical course of the patients were our references. RESULTS: F-FDG PET/CT identified (n=213) bone lesions in 18 patients, in addition to distant metastases in solid organs such as the liver and lung, lymphadenopathy above and below the diaphragm, and adrenal glands in 12 patients. However, bone scan identified (n=198) 16 patients. Bone scan missed two patients with confirmed bone metastases by means of biopsy in one patient and radiologically in the second. F-FDG PET/CT showed true-positive results in 18 patients, whereas bone scan showed true-positive results in 16 patients. F-FDG PET/CT showed true-negative results in 138 patients, whereas bone scan showed true-negative results in 134 patients. F-FDG PET/CT showed no false-positive or false-negative results. However, bone scan had two false-positive and two false-negative results. The overall sensitivity, specificity, and accuracy was 100% for F-FDG PET/CT and 88, 98, and 96%, respectively, for bone scan. CONCLUSION: F-FDG PET/CT is superior to Tc-methylene diphosphonate bone scan in detecting bone metastases in head and neck cancer.

Case report of severe Cushing's syndrome in medullary thyroid cancer complicated by functional diabetes insipidus, aortic dissection, jejunal intussusception, and paraneoplastic dysautonomia: remission with sorafenib without reduction in cortisol concentration.

BACKGROUND: Normalization of cortisol concentration by multikinase inhibitors have been reported in three patients with medullary thyroid cancer-related Cushing's syndrome. Aortic dissection has been reported in three patients with Cushing's syndrome. Diabetes insipidus without intrasellar metastasis, intestinal intussusception, and paraneoplastic dysautonomia have not been reported in medullary thyroid cancer. CASE PRESENTATION: An adult male with metastatic medullary thyroid cancer presented with hyperglycemia, hypernatremia, hypokalemia, hypertension, acne-like rash, and diabetes insipidus (urine volume >8 L/d, osmolality 190 mOsm/kg). Serum cortisol, adrenocorticoitropic hormone, dehydroepiandrostenedione sulfate, and urinary free cortisol were elevated 8, 20, 4.4, and 340 folds, respectively. Pituitary imaging was normal. Computed tomography scan revealed jejunal intussusception and incidental abdominal aortic dissection. Sorafenib treatment was associated with Cushing's syndrome remission, elevated progesterone (>10 fold), normalization of dehydroepiandrostenedione sulfate, but persistently elevated cortisol concentration. Newly-developed proximal lower limb weakness and decreased salivation were associated with elevated ganglionic neuronal acetylcholine receptor (alpha-3) and borderline P/Q type calcium channel antibodies. CONCLUSION: Extreme cortisol concentration may have contributed to aortic dissection and suppressed antidiuretic hormone secretion; which combined with hypokalemia due cortisol activation of mineralocorticoid receptors, manifested as diabetes insipidus. This is the first report of paraneoplastic dysautonomia and jejunal intussusception in medullary thyroid cancer, they may be related to medullary thyroid cancer's neuroendocrine origin and metastasis, respectively. Remission of Cushing's syndrome without measurable reduction in cortisol concentration suggests a novel cortisol-independent mechanism of action or assay cross-reactivity. Normalization of dehydroepiandrostenedione sulfate and elevation of progesterone suggest inhibition of 17-hydroxylase and 21-hydroxylase activities by sorafenib.

Pulmonary epitheloid hemangioendothelioma PET CT findings and review of literature.

We describe a case of pulmonary epitheloid hemangioendothelioma (PEH) in a 13 years old girl, the aggressive nature of the tumor in this particular case and the PET CT findings. PEH are rare tumors of vascular origin, first described by Dial and Liebow in 1975. This is an uncommon pulmonary neoplasm, 4 times more common in young women. This tumor can affect multiple organs (lung, liver, bones and soft tissue, skin, heart, central nervous system). However lung and liver represent 2 main locations. Clinical manifestations are variable; typically patients are asymptomatic, and PEH is detected on routine chest radiographs as bilateral small (1 cm or less) nodules in the lungs Diagnosis usually requires a surgical lung biopsy. The prognosis is very unpredictable, with life expectancy ranging from 1 to 15 years. The tumor is usually considered as low to intermediate grade sarcoma. There is no single effective treatment however spontaneous remissions and aggressive behavior has been described.

The relationship between coronary artery calcification and myocardial perfusion in asymptomatic women.

BACKGROUND AND OBJECTIVES: No data are available in Saudi Arabia on the relationship between coronary artery calcification (CAC) and myocardial perfusion scintigraphy (MPS) in asymptomatic women, for determining subclinical coronary artery disease (CAD). The main objective of this study was to investigate the relationship between the presence of CAC and stress-induced myocardial ischemia by MPS in asymptomatic women. DESIGN AND SETTING: Single-center retrospective study over a 2-year period. METHODS: One hundred and one women (mean [SD] age, 56 [11] years) without known CAD underwent both MPS and CAC scanning within 3 months. The frequency of ischemia by MPS was compared with the presence or absence of CAC and the number of CAD risk factors. RESULTS: The prevalence of ischemic MPS was 22% (22/101). Among the 22 patients with ischemic MPS, the CAC score was 0 in 5 patients of 22 (23%), 1 to 200 in 4 patients of 22 (18%), and more than 200 in 13 patients of 22 (59%) (P=.0001). In contrast, among the 79 patients with normal MPS, the CAC score was 0 in 44 of 79 (56%) patients, 1 to 200 in 25 of 79 (32%), and more than 200 in 10 of 79 (13%). The presence or absence of CAC was the single most important predictor of the MPS result (P=.0001). CONCLUSIONS: Moderate to severe CAC is associated with ischemic MPS in more than 50% of asymptomatic women with 2 or more CAD risk factors. Abnormal MPS is rarely associated with a 0 CAC score. Normal MPS does not exclude subclinical CAD. Therefore, CAC screening is an appropriate initial screening test for CAD in asymptomatic women.

Propionic acidemia associated with visual hallucinations.

Propionic acidemia, an autosomal recessive disorder, is a common form of organic aciduria resulting from the deficiency of propionyl-CoA carboxylase. It is characterized by frequent and potentially lethal episodes of metabolic acidosis often accompanied by hyperammonemia. A wide range of brain abnormalities have been reported in propionic acidemia. We report recurrent visual hallucinations in 2 children with propionic acidemia. Four visual hallucination events were observed in the 2 patients. Three episodes were preceded by an intercurrent illness, and 2 were associated with mild metabolic decompensation. The 2 events in one patient were associated with a seizure disorder with abnormal electroencephalogram. Brain magnetic resonance imaging showed abnormal basal ganglia and faint temporo-occipital swelling bilaterally. This is probably the first report of visual hallucinations in propionic acidemia and should alert the treating clinicians to look for visual hallucinations in patients with organic acidurias, especially in an unusually anxious child.

Coronary artery calcification detected by PET/CT scan as a marker of myocardial ischemia/coronary artery disease.

BACKGROUND: There have been no data with regard to the relationship between coronary artery calcification (CAC) detected with positron emission tomography (PET)/computed tomography (CT), as incidental findings, and myocardial perfusion single photon computed tomography (MPS) results in patients with cancer. OBJECTIVES: The main objective of this study was to investigate the relationship between CAC detected on the CT component of PET/CT and abnormal MPS in patients with cancer before oncologic surgery. METHOD: A total of 157 patients without known coronary disease and clinically proven indication for PET/CT underwent PET/CT and MPS as a routine preoperative workup. PET/CT and MPS were performed within 3 months. The frequency of abnormal MPS was compared with the presence or absence of CAC. CAC was evaluated visually. RESULTS: Among 81 patients with no CAC, MPS results were normal in 71 patients (88%). Only 10 patients (20%) with no CAC had abnormal MPS (P<0.005) results. However, in the total patient population with visually detectable CAC (76 patients), MPS results were normal in 36 patients (47%) and abnormal in 40 patients (53%) with no statistically significant value. CAC and diabetes mellitus were the most potent predictors of abnormal MPS by multivariable analysis. CONCLUSIONS: Visual detection of CAC in the CT component of PET/CT is a strong predictor of MPS results. The presence of CAC is associated with a high likelihood of abnormal MPS, but the absence of CAC is rarely associated with abnormal MPS. These findings imply a potential role for applying routine visual CAC detection in the CT component of PET/CT and might obviate unnecessary MPS indications in the preoperative evaluation in patients with cancer.

Clinical use of combined positron emission tomography and computed tomography in thymoma recurrence.

The aim of this study is to evaluate the efficacy of hybrid fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) for surveillance and follow-up of thymoma patients to detect recurrent disease. A retrospective chart review was performed on 37 thymoma patients who underwent FDG-PET/CT-scans during postoperative follow-up. The following information was obtained: clinical indication for FDG-PET/CT, the results of the FDG-PET/CT, particularly with regard to the additional diagnostic imaging information, the localization of the disease and subsequent clinical patient management. A total of 51 CT-scans were performed on 37 patients providing sensitivity and specificity for thymoma recurrence of 71% and 85%, respectively. Forty-five FDG-PET/CT-scans were performed on the same group of patients with an overall sensitivity and specificity of 82% and 95%, respectively. Notably, FDG-PET/CT sensitivity when employed for diagnosis of thymoma recurrence in the anterior mediastinum has reached 100% (CT has shown only 55% sensitivity for the detection of anterior mediastinal thymoma recurrence). Our preliminary study demonstrates that during follow-up after thymoma excision, FDG-PET/CT is superior to computed tomography alone in the detection and localization of mediastinal recurrence. In particular, the combined structural and metabolic information of FDG-PET/CT enhances the diagnostic confidence in lesion characterization.

The diagnostic value of fused positron emission tomography/computed tomography in the localization of adrenocorticotropin-secreting pituitary adenoma in Cushing's disease.

Despite the high resolution of magnetic resonance imaging (MRI) of the pituitary gland, up to 40% of cases of Cushing's disease (CD) have normal MRI. Fused images of positron emission tomography and computed tomography (PET-CT) may have a potential diagnostic role in CD in general and in such cases in particular. Objective of this study is to explore the diagnostic potential of PET-CT for localization of adrenocorticotropin-secreting pituitary adenomas in CD. PET-CT was performed in 12 cases with de novo (7 cases) or persistent CD (5 cases) that were proven to have CD on biochemical, radiological and/or histopathological findings. These cases had a definite CD confirmed on histopathological and immunostaining examination of the subsequent transphenoidal surgical specimens (10 cases) and/or bilateral inferior petrosal sinus sampling (IPSS, 4 cases). PET-CT was positive in 7 of the 12 cases of CD (58%) showing a focal area of uptake in the pituitary gland. In these seven cases, MRI was positive in six (85.7%) but negative in one case (14.3%). In the other five cases with negative PET-CT, MRI was positive in two and negative in three cases. Of four cases with negative MRI, PET-CT was positive in one case (25%). We conclude that PET-CT is positive in around 60% of the cases of CD. Although the majority of cases with positive PET-CT had positive MRI, PET-CT may detect some cases with negative MRI and thus provides important diagnostic information. If these findings are confirmed in larger studies, PET-CT might become an important diagnostic technique, especially when the more invasive and technically demanding procedure of IPSS is not available or inconclusive.

The role of F-18-fluorodeoxyglucose positron emission tomography in the postoperative evaluation of differentiated thyroid cancer.

OBJECTIVES: The objective of the study was to compare F-18-fluorodeoxyglucose position emission tomography (FDG-PET) with diagnostic whole body scanning (DxWBS) and post-ablation radioiodine whole body scanning (TxWBS) and to assess its prognostic value in newly diagnosed differentiated thyroid cancer (DTC) patients, hypothesizing that FDG-PET is more likely to disclose locoregional and distant metastases. PATIENTS AND METHODS: DxWBS and FDG-PET scanning were performed in 26 newly diagnosed DTC patients who underwent thyroidectomy and TxWBS in 24 cases who had radioactive iodine ablation. The results of the FDG-PET scans were correlated with the stage of the disease and the long-term outcome of DTC. RESULTS: Overall, 18 FDG-PET scans (69.2%) were positive showing a total of 40 foci while 8 scans (30.8%) were negative. The corresponding 26 DxWBS were all positive and showed a total of 47 foci. DxWBS and TxWBS showed similar foci in the 24 patients who had ablation therapy. In contrast to the FDG-PET scans that showed uptake of 26 foci (65%) outside the thyroid bed, 45 foci (95.7%) on DxWBS were in the thyroid bed while 2 foci (4.3%) were in cervical lymph nodes and no focus was seen outside the neck area (P=0.000). There was a clear correlation between the FDG-PET results, the stage of the disease and long-term outcome; seven of the eight negative FDG-PET scans were in stage 1, while all patients with disease higher than stage 1 (six patients) had positive scans. Over a median of 30 months (10-48), seven out of eight patients (87.5%) with negative FDG-PET scans were in remission compared with only eight patients (44.4%) with positive FDG-PET (P=0.04). CONCLUSIONS: In the postoperative evaluation of DTC, compared with DxWBS and TxWBS, FDG-PET scans are more likely to reveal uptake outside the thyroid bed and to correlate with the stage of the disease and long-term outcome.

18F-FDG imaging: pitfalls and artifacts.

18F-FDG PET is emerging as a useful tool in the staging and restaging of many malignant neoplasms, such as lymphoma, lung cancer, colorectal cancer, head and neck cancer, breast cancer, and melanoma. To accurately interpret 18F-FDG findings one must be familiar with the normal physiologic distribution of the tracer, frequently encountered physiologic variants, and benign pathologic causes of 18F-FDG uptake that can be confused with a malignant neoplasm. The objectives of this article are to (a) describe the mechanism of 18F-FDG uptake, (b) list the patient preparation and pertinent patient history before 18F-FDG imaging, (c) describe the whole-body physiologic distribution of 18F-FDG, (d) list and discuss normal physiologic variants, and (e) list and discuss benign pathologic causes of 18F-FDG uptake.