Positive Correlation Between 18 F-FDG Uptake and Tumor-Proliferating Antigen Ki-67 Expression in Adrenocortical Carcinomas.

PURPOSE OF THE REPORT: Adrenocortical carcinoma (ACC) is an extremely rare endocrine malignancy, which cannot always be diagnosed during conventional radiology and hormonal investigations. 18 F-FDG PET could help predict malignancy, but more data are necessary to support future guidelines. METHODS: A cohort of 63 patients with histologically proven ACC (n = 55) or metastatic ACC with steroid oversecretion (n = 8) was assembled. All patients underwent an 18 F-FDG PET, and the SUV max and the adrenal-to-liver SUV max ratio were calculated. The 18 F-FDG PET parameters were compared with clinical, pathological, and outcome data. RESULTS: Fifty-six of 63 patients (89%) had an ACC with an adrenal-to-liver SUV max ratio >1.45, which was a previously defined cutoff value to predict malignancy with 100% sensitivity. Seven ACCs (11%) had a lower uptake (adrenal-to-liver SUV max <1.45), most of them with a proliferation marker Ki-67 expression level <10%. A positive correlation between 18 F-FDG PET parameters (SUV max and adrenal-to-liver SUV max ratio) and tumor size, ENSAT (European Network for the Study of Adrenal Tumors) staging, total Weiss score, and the Ki-67 was found. The strong correlation between SUV max and Ki-67 ( r = 0.47, P = 0.0009) suggests a relationship between 18 F-FDG uptake levels and tumor proliferation. No statistically significant associations between outcome parameters (progression-free or overall survival) and 18 F-FDG PET parameters were found. CONCLUSIONS: This large cohort study shows that most cases of ACC demonstrate high 18 F-FDG uptake. However, the positive correlation observed between SUV max and Ki-67 expression levels seems to explain the possibility of identifying some ACC with a low or inexistent 18 F-FDG uptake. These findings have practical implications for the management of patients with an adrenal mass.

Adrenal Mass Characterization in the Era of Quantitative Imaging: State of the Art.

Detection and characterization of adrenal lesions have evolved during the past two decades. Although the role of imaging in adrenal lesions associated with hormonal secretion is usually straightforward, characterization of non-functioning adrenal lesions may be challenging to confidently identify those that need to be resected. Although many adrenal lesions can be readily diagnosed when they display typical imaging features, the diagnosis may be challenging for atypical lesions. Computed tomography (CT) remains the cornerstone of adrenal imaging, but other morphological or functional modalities can be used in combination to reach a diagnosis and avoid useless biopsy or surgery. Early- and delayed-phase contrast-enhanced CT images are essential for diagnosing lipid-poor adenoma. Ongoing studies are evaluating the capabilities of dual-energy CT to provide valid virtual non-contrast attenuation and iodine density measurements from contrast-enhanced examinations. Adrenal lesions with attenuation values between 10 and 30 Hounsfield units (HU) on unenhanced CT can be characterized by MRI when iodinated contrast material injection cannot be performed. 18F-FDG PET/CT helps differentiate between atypical benign and malignant adrenal lesions, with the adrenal-to-liver maximum standardized uptake value ratio being the most discriminative variable. Recent studies evaluating the capabilities of radiomics and artificial intelligence have shown encouraging results.

Recurrence of a Pheochromocytoma With TNEM127 Mutation Negative on 18F-FDOPA and 18F-FDG but Positive on 123I-MIBG and 68Ga-DOTATOC Imaging.

ABSTRACT: We report the case of a 75-year-old woman with liver metastasis as a recurrence of a pheochromocytoma resected 10 years ago, with a rare germline mutation in transmembrane protein 127, falsely negative on 18F-FDOPA and 18F-FDG PET/CT scans but strongly positive on 123I-MIBG scintigraphy and on 68Ga-DOTATOC PET/CT. Functional imaging has a key role in diagnosis of pheochromocytoma and paraganglioma, especially 18F-FDOPA shows very high sensitivity and specificity. However, 18F-FDOPA might be falsely negative in some of these tumors, depending on specific mutations, and thus MIBG or 68Ga-DOTATOC imaging could be an alternative.

Indications of Peptide Receptor Radionuclide Therapy (PRRT) in Gastroenteropancreatic and Pulmonary Neuroendocrine Tumors: An Updated Review.

Radionuclide therapy for neuroendocrine tumors is a form of systemic radiotherapy that allows the administration of targeted radionuclides into tumor cells that express a large quantity of somatostatin receptors. The two most commonly used radio-peptides for radionuclide therapy in neuroendocrine tumors are 90Y-DOTATOC and 177Lu-DOTATATE. Radio-peptides have been used for several years in the treatment of advanced neuroendocrine tumors. Recently, the randomized Phase III study NETTER-1 compared177Lu-DOTATATE versus high-dose (double-dose) octreotide LAR in patients with metastatic midgut neuroendocrine tumors, and demonstrated its efficacy in this setting. Strong signals in favor of efficiency seem to exist for other tumors, in particular for pancreatic and pulmonary neuroendocrine tumors. This focus on radionuclide therapy in gastroenteropancreatic and pulmonary neuroendocrine tumors addresses the treatment modalities, the validated and potential indications, and the safety of the therapy.

Percutaneous thermal ablation of lung metastases from thyroid carcinomas. A retrospective multicenter study of 107 nodules. On behalf of the TUTHYREF network.

PURPOSE: To determine efficacy and safety of thermal ablation (TA) for the local treatment of lung metastases of thyroid cancer. METHODS: We retrospectively studied 47 patients from 10 centers treated by TA (radiofrequency, microwaves, and cryoablation) over 10 years. The endpoints were overall survival (OS), local efficacy, complications (CTCAE classification), and factors associated with survival. OS curves after first TA were built using the Kaplan-Meier method and compared with the log-rank test. RESULTS: A total of 107 lung metastases during 75 sessions were treated by radiofrequency (n = 56), microwaves (n = 9), and cryoablation (n = 10). Median follow-up time after TA was 5.2 years (0.2-13.3). OS was 93% at 2 years (95% confidence interval (CI): 86-94) and 79% at 3 years (95% CI: 66-91). On univariate and multivariate analysis with a Cox model, histology was the only significant factor for OS. OS at 3 years was 94% for follicular, oncocytic, or papillary follicular variant carcinomas, compared to 59% for papillary, medullary, insular or anaplastic carcinomas (P = 0.0001). The local control rate was 98.1% at 1 year and 94.8% at 2, 3, 4, and 5 years. Morbidity was low with no major complications (grade 4 and 5 CTCAE) and no complications in 29 of 75 sessions (38.7%). CONCLUSIONS: TA is a useful, safe and effective option for local treatment of lung metastases from thyroid carcinoma. Prolonged OS was obtained, especially for lung metastases from follicular, oncocytic, or papillary follicular variant carcinomas. Achieving disease control with TA delays the need for systemic treatment.

Prolonged response to 177Lu-DOTATATE therapy of a bone marrow infiltration in a refractory thymic neuro endocrine tumor.

Thymic neuro endocrine tumor (tNET) are extremely rare malignancies with poor prognosis, requiring investigation of novel therapeutic approaches. 177Lu-DOTATATE is a successful systemic treatment modality in patients with metastatic gastroenteropancreatic but it role in tNET is not yet well established. Here we report a case of a 39-year-old man with refractory bone marrow infiltration of a tNET, treated by 4 cycles of peptide receptor radionuclide therapy (PRRT) with 177Lu DOTATATE. Since the first cycle, clinical symptoms were substantially decreased, without any severe subacute haematological toxicity. Three months after the end of PRRT, both 68Ga-DOTATOC and 18F-FDG PET confirmed a partial response, already suggested by 177Lu-DOTATATE treatment scan with a significant decrease of the bone marrow uptake between the first and fourth cycle. This report highlights that PRRT could be an effective therapeutic option for advanced bone metastatic disease tNET, with the significant benefit of alleviation of bone pain and radiologic response, without severe or irreversible haematotoxicity.

MFN2-associated lipomatosis: Clinical spectrum and impact on adipose tissue.

BACKGROUND: Multiple symmetric lipomatosis (MSL) is characterized by upper-body lipomatous masses frequently associated with metabolic and neurological signs. MFN2 pathogenic variants were recently implicated in a very rare autosomal recessive form of MSL. MFN2 encodes mitofusin-2, a mitochondrial fusion protein previously involved in Charcot-Marie-Tooth neuropathy. OBJECTIVE: To investigate the clinical, metabolic, tissular, and molecular characteristics of MFN2-associated MSL. METHODS: We sequenced MFN2 in 66 patients referred for altered fat distribution with one or several lipomas or lipoma-like regions and performed clinical and metabolic investigations in patients with positive genetic testing. Lipomatous tissues were studied in 3 patients. RESULTS: Six patients from 5 families carried a homozygous p.Arg707Trp pathogenic variant, representing the largest reported series of MFN2-associated MSL. Patients presented both lipomatous masses and a lipodystrophic syndrome (lipoatrophy, low leptinemia and adiponectinemia, hypertriglyceridemia, insulin resistance and/or diabetes). Charcot-Marie-Tooth neuropathy was of highly variable clinical severity. Lipomatous tissue mainly contained hyperplastic unilocular adipocytes, with few multilocular cells. It displayed numerous mitochondrial alterations (increased number and size, structural defects). As compared to control subcutaneous fat, mRNA and protein expression of leptin and adiponectin was strikingly decreased, whereas the CITED1 and fibroblast growth factor 21 (FGF21) thermogenic markers were strongly overexpressed. Consistently, serum FGF21 was markedly increased, and 18F-FDG-PET-scan revealed increased fat metabolic activity. CONCLUSION: MFN2-related MSL is a novel mitochondrial lipodystrophic syndrome involving both lipomatous masses and lipoatrophy. Its complex neurological and metabolic phenotype justifies careful clinical evaluation and multidisciplinary care. Low leptinemia and adiponectinemia, high serum FGF21, and increased 18F-FDG body fat uptake may be disease markers.

Adrenalectomy for incidentaloma: lessons learned from a single-centre series of 274 patients.

BACKGROUND: Adrenal incidentalomas are increasingly diagnosed and include a wide spectrum of lesions from benign adenomas to secreting or malignant lesions. The aim of the present study is to report a large single-institution experience of patients undergoing surgery for adrenal incidentaloma with particular attention to their diagnosis and post-operative course and the evolution of surgical practice over time. METHODS: From 1993 to 2013, 274 patients underwent adrenalectomy for incidentaloma. All patients underwent standardized clinical, hormonal and imaging assessments. RESULTS: Patients were mainly female (63.1%; n = 173), and the median age of patients was 56.5 years. After a complete hormonal evaluation, 47.9% (n = 129) of incidentalomas were classified as secreting tumours, including 24.4% (n = 67) subclinical cortisol-secreting adenomas and 18.9% (n = 52) pheochromocytomas. Adrenocortical carcinomas represented 9.5% (n = 26) of incidentalomas, and the risk of malignancy was significantly correlated with tumour size. The conversion rate after laparoscopic adrenalectomy (90.9%; n = 249) was 3.2% (n = 8). The overall morbidity rate was 13.9%, which included a 4.4% rate of severe morbidity (Clavien-Dindo ≥3). From 2008 onwards, there was a significant decrease (P < 0.001) in the use of surgical approaches for non-secreting adenomas. CONCLUSION: After a complete work-up, half of the incidentalomas were classified as subclinical oversecreting adrenal lesions and 10% proved to be malignant adrenocortical carcinomas. The debatable use of surgical approaches for benign nonfunctioning adenomas significantly decreased over time.

Restoring Radioiodine Uptake in BRAF V600E-Mutated Papillary Thyroid Cancer.

This image illustrates a multimodal therapeutic strategy for an iodine-refractory BRAF-mutated metastatic papillary thyroid carcinoma with reversed radioiodine resistance using BRAF inhibitors.

Long-term outcome after adrenalectomy for incidentally diagnosed subclinical cortisol-secreting adenomas.

BACKGROUND: The management of subclinical cortisol-secreting adenomas (SCSAs) is controversial, and available evidence to assess the superiority of an operative versus a nonoperative approach is lacking. The aim of this work was to report the postoperative results and the long-term outcomes for patients with incidentally diagnosed SCSAs and to compare the results with those of patients who underwent an operation for cortisol-secreting adenomas (CSAs). METHODS: From 1994-2011, 107 consecutive patients underwent laparoscopic unilateral adrenalectomy for either an SCSA (n = 39) or a CSA (n = 68). Preoperatively, all patients underwent standardized clinical, hormonal, and imaging assessments. Patients were followed up for ≥2 years with serial assessments of body weight, blood pressure, and glycated hemoglobin, HbA1c. RESULTS: Operative resection of SCSAs and CSAs did not significantly differ regarding operative time, conversion rate, overall operative and medical morbidity, and duration of stay. For SCSAs, the comparison between preoperative status and 2-year assessment showed a median weight loss of 6% (P < .001), a decrease in the median HbA1c of 15% (P < .001), and an improvement or normalization of blood pressure in 50% of the patients. The same significant beneficial metabolic effects of the operation with even greater improvement were observed in patients with CSAs. CONCLUSION: Laparoscopic unilateral adrenalectomy for SCSA is associated with low morbidity, no mortality, and significant improvement of various aspects of metabolic syndrome. Until additional evidence from prospective randomized controlled studies is obtained, laparoscopic unilateral adrenalectomy should be considered a valid option in the care of patients with SCSA.

Hormonal, Radiological, NP-59 Scintigraphy, and Pathological Correlations in Patients With Cushing's Syndrome Due to Primary Pigmented Nodular Adrenocortical Disease (PPNAD).

CONTEXT: Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of ACTH-independent Cushing's syndrome that may occur in an isolated form or as part of Carney complex. The diagnosis of this disease can be difficult preoperatively because computed tomography (CT) scan can be normal or suggest unilateral adrenal lesion, which can impede the correct diagnosis of bilateral adrenal disease. OBJECTIVE: The aim of our study was to describe the results of preoperative imaging (adrenal [6ß-(131)I]iodomethyl-19-norcholesterol] [NP-59] scintigraphy and standard adrenal CT scan) and their correlations with clinical, pathological, and genetics investigations in patients with PPNAD. PATIENTS AND METHODS: Seventeen patients with ACTH-independent syndrome due to PPNAD were investigated with a standard adrenal CT scan and NP-59 scintigraphy. Hormonal, pathological, and genetics data were analyzed. RESULTS: Four males and 13 females (median age, 27 y) were included. PPNAD was isolated in 11 patients (with PRKAR1A mutation, n = 7; and without PRKAR1A mutation, n = 4) and was associated with extra-adrenal manifestations of Carney complex in six patients (with PRKAR1A mutation, n = 4; and without PRKAR1A mutation, n = 2). Standard adrenal CT scan revealed micronodules in 11 patients, macronodules in three patients, and was normal in three patients. All patients demonstrated bilateral adrenal radiocholesterol uptake. Adrenal uptake was asymmetrical in 10 of 17 patients (59%). Asymmetrical uptake correlated with the presence of macronodules at pathological analysis (P = .03). CONCLUSION: Standard adrenal CT scan most often reveals micronodules but there is no specific CT imaging. NP-59 scintigraphy always shows a bilateral adrenal uptake confirming the bilateral nature of the disease, but asymmetrical scintigraphic uptake can be observed in patients with macronodules.

Value of 18-F-FDG PET/CT and CT in the Diagnosis of Indeterminate Adrenal Masses.

The purpose of this paper was to study the value of 18-FDG PET/CT and reassess the value of CT for the characterization of indeterminate adrenal masses. 66 patients with 67 indeterminate adrenal masses were included in our study. CT/MRI images and 18F-FDG PET/CT data were evaluated blindly for tumor morphology, enhancement features, apparent diffusion coefficient values, maximum standardized uptake values, and adrenal-to-liver maxSUV ratio. The study population comprised pathologically confirmed 16 adenomas, 19 metastases, and 32 adrenocortical carcinomas. Macroscopic fat was observed in 62.5% of the atypical adenomas at CT but not in malignant masses. On 18F-FDG PET/CT, SUVmax and adrenal-to-liver maxSUV ratio were significantly lower in adenomas than in malignant tumors. An SUVmax value of less than 3.7 or an adrenal-to-liver maxSUV ratio of less than 1.29 is highly predictive of benignity.

Peritoneal implantation of pheochromocytoma following tumor capsule rupture during surgery.

CONTEXT: Patients with pheochromocytoma (PH) or paraganglioma (PGL) may suffer from tumor persistence or recurrence after resection of the primary tumor. Malignancy and genetic determinants account for the vast majority of these cases, but tumor recurrence or persistence may also arise from tumor spillage during primary resection, followed by peritoneal implantation. We report here five such cases. MATERIALS AND METHODS: Thirty-nine of the 181 patients referred to our unit for a PH experienced tumor persistence or recurrence as a result of malignant disease (n = 12), new PGL in a context of genetic determinants (n = 18) or incomplete primary surgical resection (n = 4). Another five patients presenting with adrenal PH could not be categorized into these three groups. RESULTS AND DISCUSSION: All five patients (age range 45-63 years) presented evidence of tumor capsule rupture documented upon macroscopic examination or in the surgical report. Initial diagnostic examinations provided no evidence of malignancy. All had a period of apparent remission, lasting from 24 to 106 months. The principal site of recurrence was invariably the peritoneum or the retroperitoneum. Two patients suffered solid organ metastasis, involving the liver (n = 2), bones (n = 1), and lung (n = 1). Therapeutic management involved a combination of (131)I-metaiodobenzylguanidine therapy and surgery. Two patients died due to tumor progression. One patient experienced tumor progression despite surgery. Two patients are currently in a satisfactory condition. CONCLUSION: Tumor rupture during surgical resection, with subsequent peritoneal and retroperitoneal dissemination, is a potentially lethal complication of primary pheochromocytoma resection. Even in cases of apparently benign disease, it may lead to peritoneal carcinomatosis and metastatic disease. Complete primary surgery is, therefore, crucial for a good prognosis in PH patients. Furthermore, in cases of tumor rupture, careful follow-up is mandatory, because recurrences may occur after long periods of apparent remission.

[Update in adrenal imaging]. / Nouveautés en imagerie surrénalienne.

Subclinical adrenocortical adenomas are the most frequent cause of adrenal incidentalomas that are present in 5 % of adult abdominal imaging. Pheochromocytomas and adrenocortical carcinomas, less often encountered tumors, should be diagnosed at an early stage. Unenhanced density with computed tomography below 10 Hounsfield Units (HU) is in favor of an adrenocortical adenoma. Higher unenhanced density should lead to a characterization of the vascularization with contrast-enhanced washout study. Some adrenal masses remain indeterminate after computed tomography scanning. Further diagnostic imaging performed by a multidisciplinary team is required. Progress has been made recently in the characterization of adrenal mass with nuclear medicine imaging. Flurodeoxyglucose positron emission tomography scan is a useful tool to suspect malignancy. Up-to-date imaging allows in the majority of cases to properly diagnose an adrenal tumor.

Imaging work-up for screening of paraganglioma and pheochromocytoma in SDHx mutation carriers: a multicenter prospective study from the PGL.EVA Investigators.

CONTEXT: Recommendations have not been established concerning imaging to screen SDHx mutation carriers for paraganglioma and pheochromocytoma. OBJECTIVE: Our objective was to compare the performance of gadolinium-enhanced magnetic resonance angiography, contrast-enhanced computed tomography, and [(123)I]metaiodo-benzylguanidine and somatostatin receptor scintigraphies for detecting head and neck and thoracic-abdominal-pelvic paragangliomas in SDHx mutation carriers. DESIGN AND SETTING: We conducted a prospective, multicenter study from June 2005 to December 2009 at 23 French medical centers. PATIENTS: A total of 238 index cases or relatives carrying mutations in SDHD, SDHB, or SDHC genes were included. INTERVENTION: Images obtained by each technique were analyzed blind, without knowledge of results from other tests, first in each local center and then centrally. MAIN OUTCOME MEASURES: We evaluated sensitivity, specificity, and likelihood ratios for individual and combinations of tests, the gold standard being the consensus of an expert committee. RESULTS: Two hundred two tumors were diagnosed in 96 subjects. At local assessment, the sensitivity of anatomical imaging for detecting all tumors was higher (85.7%) than that of both scintigraphic techniques (42.7% for [(123)I]metaiodo-benzylguanidine and 69.5% for somatostatin receptor scintigraphy), except for thoracic localizations where somatostatin receptor scintigraphy was more sensitive (61.5 vs. 46.2% for anatomical imaging and 30.8% for [(123)I]metaiodo-benzylguanidine scintigraphy). The best diagnostic performance during local assessment was obtained by combining anatomical imaging tests and somatostatin receptor scintigraphy (sensitivity 91.7%). Central assessment significantly increased the sensitivity (98.6%) of tests in combination. CONCLUSIONS: In routine practice, the imaging work-up for screening SDHx mutation carriers should include thoraco-abdomino-pelvic computed tomography, head and neck magnetic angiography, and somatostatin receptor scintigraphy. Expert centralized image assessment is recommended.