Background The natural history of pancreatic neuroendocrine neoplasms (PNENs) in patients with Von Hippel-Lindau (VHL) disease is poorly defined. Management of patients with PNENs is challenging ...because there are no reliable preoperative criteria to detect malignant lesions, and the majority of resected tumors are found to be benign. The aim of this study was to determine whether 18-fluorodeoxyglucose-positron emission tomography (18 FDG-PET) uptake predicts growth and detects malignant VHL-associated PNENs. Study Design We performed a prospective study of 197 patients with VHL-associated pancreatic lesions. Clinical and imaging characteristics were analyzed to study the associations between FDG-PET uptake, tumor growth, and the development of metastatic disease. Results One hundred nine of 197 patients had solid pancreatic lesions and underwent both CT and18 FDG-PET scanning, which identified 165 and 144 lesions, respectively. Metastatic disease was detected by18 FDG-PET in 3 patients in whom it was not detected by CT scan and suggested non-neoplastic disease in 3 patients. Maximum standardized uptake values (SUV) on18 FDG-PET correlated with tumor size on CT (r = 0.47, p < 0.0001), and an increase in SUVmax was associated with tumor growth (r = 0.36, p = 0.0062). No association was seen between18 FDG-PET uptake and age, VHL genotype, or serum chromogranin A levels. Conclusions Scanning with FDG-PET identifies metastatic disease not detected by CT scan and avoids resection of non-PNEN lesions that have no malignant potential in patients with VHL-associated PNENs. It should be considered as a valuable functional imaging modality in the clinical management of patients with VHL-associated PNENs.
Erdheim-Chester disease (ECD) is a rare histiocytic disease that affects multiple systems in the body. While it typically targets long bones, cardiovascular structures, the retroperitoneum, and the ...central nervous system, reports of tendon and skeletal muscle involvement are scarce. This review presents 2 cases: a case of ECD involving the left Achilles tendon and left abductor hallucis, as well as an unusual manifestation of ECD in the thigh musculature. In Case 1, studies involved a 39-year-old man who initially presented with bone and pituitary involvement. An order for 18F-FDG PET/CT imaging was placed by marked swelling in the patient's left ankle and observed soft tissue fullness on foot radiographs, which revealed a soft tissue mass involving the left Achilles tendon, which arose along the tendon-muscle junction and involved the left abductor hallucis muscle. In Case 2, studies involved a 41-year-old man who initially presented with involvement of the cardiovascular system and retroperitoneum. 18F-FDG PET/CT scan showed an infiltrative right atrial mass and hypermetabolic lesion in the left external obturator muscle, extending to the left pectineus and right quadratus femoris muscle. Involvement of the Achilles tendon and skeletal muscle involvement, including left abductor hallucis muscle and medial thigh muscles, is one of the rare manifestations of ECD. Diagnostic delays were frequent due to the condition's rarity and nonspecific multisystemic symptoms. This should be considered in patients who present with myositis, tendinopathy, and bone pain and have other unexplained multisystemic problems.
Background Patients with von Hippel-Lindau disease (VHL) commonly develop pancreatic cysts and neuroendocrine neoplasms (PNENs or PNETs). Solid microcystic serous adenoma (SMSA), a rare neoplasm ...described in VHL patients, can be mistaken for PNEN on imaging. Methods Clinical, pathologic, and radiologic data were reviewed on VHL patients who underwent surgery for a preoperative diagnosis of PNEN since 1994 at 1 institution. Blinded to the pathologic diagnoses, radiologists reassessed available imaging. Results For 55 patients, 79 pancreatectomies were performed for presumed PNENs. Ten (18%) patients underwent 12 (15%) resections for neoplasms diagnosed as SMSA on final pathology. The average size of a SMSA leading to operation was 3.6 ± 0.4 cm. Four out of 11 SMSAs were still mistaken for PNENs when imaging was reassessed. The mean FDG-positron emission tomography (PET) standardized uptake value was greater for 17 PNENs (12.1 ± 1.2) compared with 6 SMSAs (4.2 ± 0.5; P = .002). The mean doubling time of SMSAs and PNENs was similar. Seven (15%) patients with pathologically proven PNENs had malignant disease. Conclusion SMSAs can mimic PNENs on nonfunctional imaging; FDG-PET may help to differentiate them. A high index of suspicion is needed to minimize operations performed for SMSA and to counsel VHL patients of their risks of undergoing operation for a lesion with no known malignant potential.
Objective: To report the functional imaging experience with a 29-year-old woman carrying a mutation in the fumarate hydratase (FH)-encoding gene and a history of a pheochromocytoma (PHEO) and ...retroperitoneal paraganglioma (PGL).Methods: The patient was found to have a splice-site mutation in the FH gene at intron 2, c.268-2A>G. To confirm this, immunohistochemical staining was performed on tumor tissue slides from the patient's previous surgeries. The patient underwent biochemical testing for PHEO/PGL, which included chromogranin A and plasma methoxytyramine. The patient's tumors were also imaged using several imaging modalities, including computed tomography (CT), magnetic resonance imaging, ultrasound, and positron emission tomography (PET)/CT studies using 18F-fluorodeoxyglucose (18F-FDG), 18F-fluorodopamine (18F-FDA), 18F-fluorodihydroxyphenylalanine (18F-FDOPA), and 68Ga-tetraazacyclododecanetetraacetic acid–Tyr3-octreotate (68Ga-DOTATATE) as tracers.Results: The patient received a comprehensive evaluation based on her symptoms and medical history. She was found to have 3 noradrenergic-secreting tumors that showed uptake on 18F-FDG-(2/3), 68Ga-DOTATATE-(2/3), 18F-FDOPA-(3/3), and 18F-FDA-(3/3) PET/CT. The patient was recommended to have the tumor sites removed (renal hilum, aortocaval, and periaortic regions) with lympadenectomies to address possible metastases. Pathology confirmed paraganglioma. Immunohistochemical staining from previous surgical slides showed negative staining for FH, consistent with a mutation in the gene.Conclusion: We share, for the first time, functional images for an FH mutation–positive PHEO/PGL patient using various PET radiopharmaceuticals. 18F-FDA- and 18F-FDOPA PET/CT served as the best imaging modalities. This case provides the appropriate selection of imaging studies and further evidence for the importance of screening for FH mutations in patients with noradrenergic PHEOs/PGLs.Abbreviations: CT = computed tomography 18F-FDA = 18F-fluorodopamine 18F-FDG = 18F-fluorodeoxyglucose 18F-FDOPA = 18F-fluorodihydroxyphenylalanine FH = fumarate hydratase 68Ga-DOTATATE = 68Ga-tetraazacyclododecanetetraacetic acid–Tyr3-octreotate MTY = methoxytyramine NIH = National Institutes of Health PET = positron emission tomography PGL = paraganglioma PHEO = pheochromocytoma SDHB = succinate dehydrogenase complex, subunit B URL = upper reference limit
Introduction There are limited data on the utility of 6-18 F-fluoro- l -3,4-dihydroxyphenylalanine (18 F-DOPA) and18 F-2-deoxy- d -glucose (18 F-FDG) in the workup of patients with pancreatic ...neuroendocrine tumors (PNETs). The aim of our study was to determine the accuracy of18 F-DOPA and18 F-FDG to detect PNETs in patients with von Hippel-Lindau disease (vHL). Methods We studied prospectively 69 patients with a diagnosis of vHL and pancreatic lesion(s) using computed tomography (CT), magnetic resonance imaging (MRI),18 F-FDG, and18 F-DOPA. Clinical, genetic, and laboratory characteristics were analyzed to determine association with imaging study results. Results In sum, 40 patients underwent evaluation by all 4 modalities; 98 PNETs and 55 PNETs were identified on CT and MRI, respectively. Only 11 of the 98 lesions (11%) were positive on18 F-DOPA and 45 of the 98 (46%) lesions were positive on18 F-FDG. There were 1318 F-DOPA and 2618 F-FDG avid extrapancreatic lesions. One patient underwent resection of an18 F-DOPA avid extrapancreatic lesion in the lung, with pathology demonstrating a NET. There was no association between18 F-DOPA and18 F-FDG avidity and tumor size, age, gender, vHL mutation, or serum chromogranin A level. Conclusion18 F-FDG and MRI may be adjuncts to CT in identifying PNETs and metastatic disease.18 F-DOPA has limited value in identifying PNETs in patients with vHL, but may be useful for identifying extrapancreatic NET lesions.
Background. Kaposi sarcoma herpesvirus (KSHV) is the cause of Kaposi sarcoma (KS), primary effusion lymphoma (PEL), and a form of Castleman disease (KSHV-MCD). Recently a KSHV-associated inflammatory ...cytokine syndrome (KICS) distinct from KSHV-MCD was reported. Methods. We prospectively characterized the clinical, laboratory, virologic and immunologic features of KICS by evaluating symptomatic adults with KSHV using a prespecified definition. These features and overall survival were compared with controls from 2 prospectively characterized human immunodeficiency virus (HIV)-infected cohorts, including 1 with KSHV coinfection. Results. All 10 KICS subjects were HIV infected males; 5 had HIV viral load (VL) suppressed <50 copies mL (median 72, range <50–74 375); all had KS and 2 also had PEL. All had multiple severe symptoms attributable to KICS: median number of symptoms 8 (6–11), median grade of worst symptom 3 (2–4). These included gastrointestinal disturbance (present in 9); edema (9); respiratory (6); and effusions (5). Laboratory abnormalities included anemia (all); hypoalbuminemia (all) and thrombocytopenia (6). None developed KSHV-MCD; 6 died with median survival from KICS diagnosis 13.6 months. KICS subjects compared with controls had more severe symptoms; lower hemoglobin and albumin; higher C-reactive protein; higher KSHV VL; elevated interleukin (IL)-6 and IL-10; and an increased risk of death (all P < .05). Anemia and hypoalbuminemia at presentation were independently associated with early death. Conclusions. KICS subjects demonstrated diverse severe symptoms, a high rate of KSHV-associated tumors, high mortality, and a distinct IL-6/IL-10 signature. KICS may be an important unrecognized cause of morbidity and mortality, including symptoms previously ascribed to HIV. Exploration of KSHV-directed therapy is warranted.
Background Screening for neuroendocrine tumors (NETs) in patients with multiple endocrine neoplasia type 1 (MEN1) is recommended to detect primary and metastatic tumors, which can result in ...significant morbidity and mortality. The utility of somatostatin receptor imaging68 Gallium-DOTATATE PET/CT in patients with MEN1 is not known. The aim of this study was to prospectively determine the accuracy of68 Gallium-DOTATATE PET/CT vs111 In- pentetreotide single-photon emission CT (SPECT)/CT and anatomic imaging in patients with MEN1. Study Design We performed a prospective study comparing68 Gallium-DOTATATE PET/CT,111 In-pentetreotide SPECT/CT, and triphasic CT scan to clinical, biochemical, and pathologic data in 26 patients with MEN1. Results68 Gallium-DOTATATE PET/CT detected 107 lesions;111 In-pentetreotide SPECT/CT detected 33 lesions; and CT scan detected 48 lesions. Lesions detected on68 Gallium-DOTATATE PET/CT had high standard uptake value (SUV)max (median SUVmax = 72.8 range 19 to 191). In 7 of the 26 patients (27%),68 Gallium-DOTATATE PET/CT was positive, with a negative111 In-pentetreotide SPECT/CT, and in 10 patients (38.5%), additional metastases were detected (range 0.3 cm to 1.5 cm). In 8 of the 26 patients (31%), there was a change in management recommendations as a result of the findings on68 Gallium-DOTATATE PET/CT that were not seen on111 In-pentetreotide SPECT/CT and CT scan. Conclusions68 Gallium-DOTATATE PET/CT is more sensitive for detecting NETs than111 In-pentetreotide SPECT/CT and CT scan in patients with MEN1. This imaging technique should be integrated into radiologic screening and surveillance of patients with MEN1 because it can significantly alter management recommendations.
Pheochromocytoma and paraganglioma (PHEO/PGL) are rare neuroendocrine tumors which may cause potentially life-threatening complications, with about a third of cases found to harbor specific gene ...mutations. Thus, early diagnosis, treatment, and meticulous monitoring are of utmost importance. Because of low incidence of succinate dehydrogenase complex subunit A (
)-related metastatic PHEO/PGL, currently there exists insufficient clinical information, especially with regards to its diagnostic and treatment characteristics.
Ten patients with
-related metastatic PHEO/PGL were followed-up prospectively and/or retrospectively between January 2010-July 2018. They underwent biochemical tests (
= 10),
I-MIBG (
= 9) scintigraphy, and multiple whole-body positron emission tomography/computed tomography (PET/CT) scans with
Ga-DOTATATE (
= 10),
F-FDG (
= 10), and
F-FDOPA (
= 6).
Our findings suggest that these tumors can occur early and at extra-adrenal locations, behave aggressively, and have a tendency to develop metastatic disease within a short period of time. None of our patients had a family history of PHEO/PGL, making them appear sporadic. Nine out of 10 patients showed abnormal PHEO/PGL-specific biochemical markers with predominantly noradrenergic and/or dopaminergic phenotype, suggesting their utility in diagnosing and monitoring the disease. Per patient detection rates of
Ga-DOTATATE (
= 10/10),
F-FDG (
= 10/10),
F-FDOPA (
= 5/6) PET/CT, and
I-MIBG (
= 7/9) scintigraphy were 100, 100, 83.33, and 77.77%, respectively. Five out of 7
I-MIBG positive patients had minimal
I-MIBG avidity or detected very few lesions compared to widespread metastatic disease on
F-FDG PET/CT, implying that diagnosis and treatment with
I-MIBG is not a good option.
Ga-DOTATATE PET/CT was found to be superior or equal to
F-FDG PET/CT in 7 out of 10 patients and hence, is recommended for evaluation and follow-up of these patients. All 7 out of 7 patients who received conventional therapies (chemotherapy, somatostatin analog therapy, radiation therapy,
I-MIBG, peptide receptor radionuclide therapy) in addition to surgery showed disease progression.
In our cohort of patients,
-related metastatic PHEO/PGL followed a disease-course similar to that of
-related metastatic PHEO/PGL, showing highly aggressive behavior, similar imaging and biochemical phenotypes, and suboptimal response to conventional therapies. Therefore, we recommend careful surveillance of the affected patients and a search for effective therapies.
Summary
In animals, defective brown adipogenesis leads to bone loss. Whether brown adipose tissue (BAT) mass relates to bone mineral density (BMD) in humans is unclear. We determined the relationship ...between BAT mass and BMD by cold-stimulated positron-emission tomography (PET) and dual-energy X-ray absorptiometry (DXA) in healthy volunteers. Higher BAT mass was associated with higher BMD in healthy women, but not in men, independent of age and body composition.
Introduction
Contrary to the traditional belief that BAT is present only in infants, recent studies revealed significant depots of BAT present in adult humans. In animals, defective brown adipogenesis leads to bone loss. While white adipose tissue mass is a known determinant of BMD in humans, the relationship between BAT and BMD in humans is unclear. We thus examined the relationship between BAT and BMD in healthy adults.
Methods
BAT volume (ml) and activity (standard uptake value) were determined by
18
F-fluorodeoxyglucose PET after overnight mild cold exposure at 19 °C, and BMD was determined by DXA.
Results
Among 24 healthy adults (age 28 ± 1 years,
F
= 10), BAT volumes were 82.4 ± 99.5 ml in women and 49.7 ± 54.5 ml in men. Women manifested significantly higher BAT activity, by 9.4 ± 8.1 % (
p
= 0.03), than men. BAT volume correlated positively with total and spine BMD (
r
2
= 0.40 and 0.49, respectively,
p
< 0.02) in women and remained a significant predictor after adjustment for age, fat, and lean body mass (
p
< 0.05). Total and spine BMD were higher in women who harbored visually detectable BAT on PET images than those without by 11 ± 2 % (
p
= 0.02) and 22 ± 2 % (
p
< 0.01), respectively. No associations were observed between BAT parameters and BMD in men.
Conclusions
This study demonstrated higher BMD among healthy women with more abundant BAT, independent of age and other body compositional parameters. This was not observed in men. The data suggest that brown adipogenesis may be physiologically related to modulation of bone density.
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