Different Ectopic Endocrine Tumors on Renal Hilum Detected by 68 Ga-DOTATATE PET.

ABSTRACT: Renal hilum is a very rare location for primary adrenocortical adenoma or pheochromocytoma. We report 68 Ga-DOTATATE PET/CT findings of primary renal hilar adrenocortical adenoma in one patient and 68 Ga-DOTATATE PET/MR findings of pheochromocytoma in another patient.

Neoplastic metastases to the endocrine glands.

Endocrine organs are metastatic targets for several primary cancers, either through direct extension from nearby tumour cells or dissemination via the venous, arterial and lymphatic routes. Although any endocrine tissue can be affected, most clinically relevant metastases involve the pituitary and adrenal glands with the commonest manifestations being diabetes insipidus and adrenal insufficiency respectively. The most common primary tumours metastasing to the adrenals include melanomas, breast and lung carcinomas, which may lead to adrenal insufficiency in the presence of bilateral adrenal involvement. Breast and lung cancers are the most common primaries metastasing to the pituitary, leading to pituitary dysfunction in approximately 30% of cases. The thyroid gland can be affected by renal, colorectal, lung and breast carcinomas, and melanomas, but has rarely been associated with thyroid dysfunction. Pancreatic metastasis can lead to exo-/endocrine insufficiency with renal carcinoma being the most common primary. Most parathyroid metastases originate from breast and lung carcinomas and melanoma. Breast and colorectal cancers are the most frequent ovarian metastases; prostate cancer commonly affects the testes. In the presence of endocrine deficiencies, glucocorticoid replacement for adrenal and pituitary involvement can be life saving. As most metastases to endocrine organs develop in the context of disseminated disease, surgical resection or other local therapies should only be considered to ameliorate symptoms and reduce tumour volume. Although few consensus statements can be made regarding the management of metastases to endocrine tissues because of the heterogeneity of the variable therapies, it is important that clinicians are aware of their presence in diagnosis.

Metastatic pheochromocytoma in MEN 2A: A rare association.

A 45-year-old woman was diagnosed as having multiple endocrine neoplasia type 2A in 2014. She had bilateral pheochromocytoma, medullary thyroid carcinoma and biopsy-proven cutaneous lichen amyloidosis in the interscapular area. She underwent bilateral adrenalectomy; following which, she achieved clinical and biochemical remission. She was planned for total thyroidectomy at a later date; however, she was lost to follow-up. She presented to us again in December 2016 with abdominal pain. Examination revealed hypertension with postural drop. Positron emission tomography scan showed Ga68 and fluorodeoxyglucose (FDG)-avid suprarenal, hepatic, peritoneal and mesenteric masses with abdominal lymph nodes. Twenty-four-hour urinary metanephrines/normetanephrines were elevated. Serum calcitonin was as high as it was 2-1/2 years ago. Ultrasonography-guided fine-needle aspiration cytology (FNAC) from the liver mass revealed neuroendocrine cells that did not stain for calcitonin. Hence, a diagnosis of metastatic pheochromocytoma was made. She underwent total thyroidectomy and was started on cyclophosphamide, vincristine, dacarbazine-based chemotherapy regimen.

Imaging of metastases from breast cancer to uncommon sites: a pictorial review.

There are three types of breast cancer recurrence which can occur after initial treatment: local, regional, and distant. Distant metastases are more frequent than local and regional recurrences. It usually occurs several years after the primary breast cancer, although it is sometimes diagnosed at the same time as the primary breast cancer. Although the common distant metastases are bone, lung and liver, breast cancer has the potential to metastasize to almost any region of the body. Early detection and treatment of distant metastases improves the prognosis, therefore radiologists and clinicians should recognize the possibility of metastasis from breast cancer and grasp the imaging characteristics. In this report, we demonstrate the imaging characteristics of metastases from breast cancer to uncommon sites.

Neuroendocrine tumor imaging with 68Ga-DOTA-NOC: physiologic and benign variants.

OBJECTIVE: Imaging with (68)Ga-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-octreotide analogs has become an important modality in patients with neuroendocrine tumors (NETs). In addition to high uptake in NET lesions, prominent physiologic radiotracer activity has been reported in the pituitary gland, pancreas, adrenal glands, liver, and spleen, and faint activity has been reported in the thyroid and gastrointestinal tract. This article describes previously unknown sites of 68Ga-DOTA-1-NaI3-octreotide (NOC) uptake unrelated to NETs. MATERIALS AND METHODS: One hundred eighty-two patients (96 female and 86 male patients; age range, 4-89 years) with documented (n=156) or suspected (n=26) NETs underwent 207 68Ga-DOTA-NOC PET/CT studies. Studies were retrospectively reviewed for the presence, intensity, and localization of foci of increased uptake that were further correlated with findings on additional imaging studies and clinical follow-up for a period of 4-32 months. RESULTS: Uptake of 68Ga-DOTA-NOC not identified as NET or known physiologic activity was detected in 297 sites with confirmation in 149 of 207 studies (72%). The most common location of non-NET-related 68Ga-DOTA-NOC-avid sites was in small lymph nodes, followed by prostate, uterus, breasts, lungs, brown fat, musculoskeletal system, and other sites, including oropharynx, pineal body, thymus, aortic plaque, genitalia, surgical bed, and subcutaneous granuloma. Intensity of uptake in non-NET-related 68Ga-DOTA-NOC-avid sites ranged in maximum standardized uptake value from 0.8 to 10.5. CONCLUSION: Previously unreported benign sites of 68Ga-DOTA-NOC uptake were found in the majority of studies, suggesting the presence of somatostatin receptors in physiologic variants or processes with no evidence of tumor. Knowledge of increased tracer uptake in non-NET-related sites is important for accurate interpretation and for avoiding potential pitfalls of 68Ga-DOTA-NOC PET/CT.

Navigation with use of intra-operative ultrasound in search for neoplastic lesions of endocrine glands.

UNLABELLED: The aim of the study was to evaluate the effectiveness of intraoperative ultrasonography (IOUS) during operations of endocrine glands tumors. MATERIAL AND METHODS: The study was conducted in patients who underwent endocrine operation in Department of Endocrine, General and Vascular Surgery, Medical University in Lódz in 2008-2011. RESULTS: Patients with thyroid cancer recurrences:in study group we managed shorter lesion access time (10 ± 4.47 min vs 16.78 ± 8.9 min; p=0.04). Time of surgery was also shorter in study group (75 ± 30.17 minvs 85,71 ± 38.92 min), but it was not significant (p=0.46). The use of IOUS did not affect the hospitalization time (2.91 ± 1.64 days vs 3 ± 1.66 days; p=0.820), intraoperative blood loss (45.45 ± 105.96 ml vs 40 ± 82.89 ml; p=0.972) and the rate of intraoperative complications (1/11 - 9.09% vs 2/14 - 14.29%; p=1). Patients with primary hyperparathyroidism: the time of surgery (58 ± 22.74 min vs 65 ± 19.6 min; p=0.336) and the lesion access time (13.33 ± 7,94 min vs 17.25 ± 8.19 min; p=0.169) were shorter in study group. Hospitalization time was longer in study group (6.13 ± 5.3 days vs 4.45 ± 4.58 days; p=0.079). The rate of intraoperative complications was higher in study group (3/15 - 20% vs 2/20 - 10%; p=0.631). None of this results were statistically significant (p≤0.05). Patients who underwent open adrenalectomy: in study group we managed significantly shorter time of surgery (70 ± 44.35 min vs 80.12 ± 29.60 min; p=0.033) and shorter lesion access time (12 ± 8.88 min vs 17.37 ± 7.42 min; p=0.045). The use of IOUS did not affect the hospitalization time (5.6 ± 1.65 days vs 6.35 ± 2.38 days; p=0.429), intraoperative blood loss (110 ± 164.65 ml vs 172.5 ± 226.35 ml; p=0.442) and rate of intraoperative complications (0/10 vs 1/40; p=1). Patients who underwent videoscopicadrenalectomy: in study group we managed to get shortertime of surgery (89.44 ± 27.11 min vs 109.12 ± 33.88 min; p=0.034) and shorter lesion access time (28.61 ± 14.93 min vs 45.98 ± 20.44 min; p=0.002). Intraoperative blood loss was also significantly lower in study group (86.11 ± 157 ml vs 169.27 ± 201.04 ml; p=0.037). The use of IOUS did not affect the hospitalization time (4.39 ± 3.27 days vs 3.83 ± 3.67 days; p=0.227), the rate of intraoperative complications (0/18 vs. 2/41; p=1) and the conversion rate (2/20-10% vs. 5/46- 10.87%; p=1). CONCLUSIONS: 1.During adrenalectomies this technique facilitates finding the pathological lesion shortening the time of access to the tumor and procedure duration. 2. IOUS is useful for determining the tumor relationship with the surrounding anatomical structures. 3. IOUS isa useful technique in the assessment of adrenal tumor infiltration of vena cava. 4. The use of IOUS allows the surgeon to assess anatomical relationships in the real time, after incision and retraction of tissues. 5. During operations of thyroid cancer recurrences using this technique makes easier to find a lesion in the operated area and it is possible to asses radical of surgery. 6. The use of IOUS allows to find pathological parathyroid glands inside thyroid gland. 7. IOUS is useful in the detection of thyroid pathology during parathyroidectomy.

Concomitant pancreatic endocrine neoplasm and intraductal papillary mucinous neoplasm: a case report and literature review.

We report a case of concomitant pancreatic endocrine neoplasm (PEN) and intraductal papillary mucinous neoplasm (IPMN). A 74-year-old man had been followed-up for mixed-type IPMN for 10 years. Recent magnetic resonance images revealed an increase in size of the branch duct IPMN in the pancreas head, while the dilation of the main pancreatic duct showed minimal change. Although contrast-enhanced computed tomography and magnetic resonance imaging did not reveal any nodules in the branch duct IPMN, endoscopic ultrasound indicated a suspected nodule in the IPMN. A malignancy in the branch duct IPMN was suspected and we performed pylorus-preserving pancreatoduodenectomy with lymphadenectomy. The resected specimen contained a cystic lesion, 10 x 10 mm in diameter, in the head of the pancreas. Histological examination revealed that the dilated main pancreatic duct and the branch ducts were composed of intraductal papillary mucinous adenoma with mild atypia. No evidence of carcinoma was detected in the specimen. Incidentally, a 3-mm nodule consisting of small neuroendocrine cells was found in the main pancreatic duct. The cells demonstrated positive staining for chromogranin A, synaptophysin, and glucagon but negative staining for insulin and somatostatin. Therefore, the 3-mm nodule was diagnosed as a PEN. Since the mitotic count per 10 high-power fields was less than 2 and the Ki-67 index was less than 2%, the PEN was pathologically classified as low-grade (G1) according to the 2010 World Health Organization (WHO) criteria. Herein, we review the case and relevant studies in the literature and discuss issues related to the synchronous occurrence of the relatively rare tumors, PEN and IPMN.

Teratomas: a multimodality review.

Germ cell tumors (GCTs) may occur in both children and adults and include a broad array of histologic subtypes, such as teratoma, seminoma (known as dysgerminoma in the ovary and germinoma in the pineal gland), choriocarcinoma, yolk sac tumor, embryonal cell carcinoma, and mixed GCT. In adults, GCTs occur most commonly in the gonads. In children, sacrococcygeal tumors predominate. Teratomas are a common form of GCT. They are defined histologically as containing tissues derived from all 3 germ cell layers: ectoderm, mesoderm (most teratomas contain fat, an imaging hallmark, which is a mesodermal derivative), and endoderm. Teratomas are also classified as mature or immature, depending on the degree of differentiation of its components, and in adults, immature tumors are more likely to exhibit malignant behavior.

First clinical evidence that imaging with somatostatin receptor antagonists is feasible.

UNLABELLED: Preclinical studies have indicated that somatostatin receptor (sst)-expressing tumors demonstrate higher uptake of radiolabeled sst antagonists than of sst agonists. In this study, we evaluated whether imaging with sst antagonists was feasible in patients. METHODS: Biodistribution and tumor uptake of the sst antagonist (111)In-DOTA-pNO(2)-Phe-c(DCys-Tyr-DTrp-Lys-Thr-Cys)DTyrNH(2) ((111)In-DOTA-BASS) were studied in 5 patients with metastatic thyroid carcinoma or neuroendocrine tumors. Findings were compared with (111)In-pentetreotid ((111)In-DTPA-octreotide) scan. RESULTS: No adverse effects of (111)In-DOTA-BASS (20 µg) were observed. (111)In-DOTA-BASS detected 25 of 28 lesions, whereas (111)In-DTPA-octreotide detected only 17 of 28 lesions. In the same patient, (111)In-DOTA-BASS showed higher tumor and lower renal uptake than (111)In-DTPA-octreotide (3.5 ± 2.8 percentage injected activity [%IA] vs. 1.0 ± 0.99%IA and 1.5 ± 0.3 %IA vs. 2.3 ± 0.7 %IA) at 4 h after injection. CONCLUSION: Imaging of neuroendocrine tumors with sst antagonists is clinically feasible. The favorable human biodistribution data suggest that sst antagonists could significantly affect peptide receptor-mediated imaging and therapy.

Total 18F-dopa PET tumour uptake reflects metabolic endocrine tumour activity in patients with a carcinoid tumour.

PURPOSE: Positron emission tomography (PET) using 6-[18F]fluoro-L-dihydroxyphenylalanine (18F-dopa) has an excellent sensitivity to detect carcinoid tumour lesions. 18F-dopa tumour uptake and the levels of biochemical tumour markers are mediated by tumour endocrine metabolic activity. We evaluated whether total 18F-dopa tumour uptake on PET, defined as whole-body metabolic tumour burden (WBMTB), reflects tumour load per patient, as measured with tumour markers. METHODS: Seventy-seven consecutive carcinoid patients who underwent an 18F-dopa PET scan in two previously published studies were analysed. For all tumour lesions mean standardised uptake values (SUVs) at 40% of the maximal SUV and tumour volume on 18F-dopa PET were determined and multiplied to calculate a metabolic burden per lesion. WBMTB was the sum of the metabolic burden of all individual lesions per patient. The 24-h urinary serotonin, urine and plasma 5-hydroxindoleacetic acid (5-HIAA), catecholamines (nor)epinephrine, dopamine and their metabolites, measured in urine and plasma, and serum chromogranin A served as tumour markers. RESULTS: All but 1 were evaluable for WBMTB; 74 patients had metastatic disease. 18F-dopa PET detected 979 lesions. SUVmax on 18F-dopa PET varied up to 29-fold between individual lesions within the same patients. WBMTB correlated with urinary serotonin (r=0.51) and urinary and plasma 5-HIAA (r=0.78 and 0.66). WBMTB also correlated with urinary norepinephrine, epinephrine, dopamine and plasma dopamine, but not with serum chromogranin A. CONCLUSION: Tumour load per patient measured with 18F-dopa PET correlates with tumour markers of the serotonin and catecholamine pathway in urine and plasma in carcinoid patients, reflecting metabolic tumour activity.

Performance of (18)fluorodeoxyglucose-positron emission tomography and somatostatin receptor scintigraphy for high Ki67 (≥10%) well-differentiated endocrine carcinoma staging.

OBJECTIVE: The purpose of this prospective study was to compare the performance of (111)In-octreotide somatostatin receptor scintigraphy (SRS) and (18)fluorodesoxyglucose positron emission tomography (FDG-PET) in aggressive well-differentiated endocrine carcinoma (WDEC) defined by a high Ki67 (≥10%). METHODS: Eighteen consecutive patients explored in a single hospital between November 2003 and 2008 for high Ki67 (≥10%) WDEC were prospectively included. WDEC were sporadic in 17 cases and secreting in 16 cases. FDG-PET, SRS, and computed tomography (CT) were performed within a maximum of 3 months and reviewed by two independent readers. For each patient, an analysis per organ and lesion was performed. Both the results of conventional imaging and the highest number of metastatic organs and distinct lesions visualized by all imaging methods including SRS, FDG-PET, and thoraco-abdomino-pelvic CT were considered for the determination of the standard. Correlation between tumor slope and maximum standardized uptake value, Ki67 value, and grade of uptake at SRS was evaluated. RESULTS: FDG-PET, SRS, and CT showed at least one lesion in 18 (100%), 15 (83%), and 17 (94%) patients, respectively. A total of 254 lesions were diagnosed in 59 organs. FDG-PET, SRS, and CT detected 195 (77%), 109 (43%), and 195 (77%) lesions in 53 (90%), 30 (51%), and 39 (66%) organs, respectively. FDG-PET, compared to SRS, detected more, the same as, and less lesions in 14 (78%), one (6%), and three (17%) patients, respectively. A statistical trend was found between Ki67 value and tumor slope (P = 0.07). Median survival after diagnosis was 25 months (range, 6-71 months). CONCLUSION: These results suggest that FDG-PET is more sensitive than the SRS for high Ki67 WDEC staging.

Poorly differentiated endocrine carcinoma of the pancreas responded to gemcitabine: Case report.

Poorly differentiated endocrine carcinoma (PDEC) of the pancreas is a rare and aggressive tumor. First-line treatment is commonly a combination of etoposide and cisplatin, but there is no consensus regarding further treatment recommendations. In this report, we describe a case of pancreatic PDEC treated with gemcitabine as third-line chemotherapy. A 62-year-old man with pancreatic PDEC was administered etoposide plus cisplatin as first-line treatment; he then received irinotecan for tumor relapse. However, because irinotecan induced ileus in this patient, we chose gemcitabine as third-line chemotherapy. After two cycles of gemcitabine (1000 mg/m(2) on days 1, 8 and 15 every 4 wk), a partial tumor response was noted by computed tomography (approximately 68% reduction in tumor size). Our patient survived for 15 mo after diagnosis. This is a rare case of unresectable pancreatic PDEC, which showed a partial response to gemcitabine after the failure of two other regimens. Gemcitabine could be an effective treatment option for pancreatic PDEC that is resistant to other treatments.

Imaging findings in a case of mixed acinar-endocrine carcinoma of the pancreas.

Mixed acinar-endocrine carcinoma (MAEC) of the pancreas is extremely uncommon. We report here a rare case of MAEC of the pancreas presenting as watery diarrhea. This is the first report in the English-language literature that describes the imaging findings of MAEC of the pancreas, including computed tomography (CT), magnetic resonance (MR) imaging, and MR cholangiopancreatography features.

PET and PET/CT in endocrine tumours.

Functional information provided by PET tracers together with the superior image quality and the better data quantification by PET technology had a changing effect on the significance of nuclear medicine in medical issues. Recently introduced hybrid PET/CT systems together with the introduction of novel PET radiopharmaceuticals have contributed to the fact that nuclear medicine has become a growing diagnostic impact on endocrinology. In this review imaging strategies, different radiopharmaceuticals including the basic mechanism of their cell uptake, and the diagnostic value of PET and PET/CT in endocrine tumours except differentiated thyroid carcinomas will be discussed.

[Somatostatin receptor-based imaging and therapy of digestive endocrine tumors]. / Imageries et traitements basés sur les récepteurs à la somatostatine dans les tumeurs endocrines digestives.

The management of gastroenteropancreatic endocrine tumors is greatly linked to the localization of primary tumor. Morphological imaging methods are thus necessary. However, the expression of somatostatin receptors in endocrine tumors makes their detection possible thanks to radiolabeled somastotatin analogs. [(111)In-DTPA] octreotide is the main radiolabeled analog for somatostatin receptor scintigraphy. Positron emission tomography uses other tracers and currently allows improvement of the diagnosis and the tumoral staging. It also allows to affect the therapeutic management. A further step is about to be taken as far as the therapy of endocrine tumors is concerned with the peptide receptor radionuclide therapy. Those therapies are now being offered in some European and American centers for progressive metastatic tumors. Their place in the therapeutic strategy has to be defined, especially in comparison to targeted therapy. The sudden and delayed adverse events as well as the current legislation on the use of radioactive therapy-aimed products have limited their development in France so far.

Clinical value of 18F-fluorodihydroxyphenylalanine positron emission tomography/computed tomography (18F-DOPA PET/CT) for detecting pheochromocytoma.

PURPOSE: In detecting pheochromocytoma (PHEO), positron emission tomography (PET) with the radiolabelled amine precursor (18)F-fluorodihydroxyphenylalanine ((18)F-DOPA) offers excellent specificity, while computed tomography (CT) provides high sensitivity and ability to localize lesions; therefore, the combination of these modalities could be advantageous in this setting. The aim of this study was to investigate whether combined (18)F-DOPA PET/CT more accurately detects and localizes PHEO lesions than does each modality alone. METHODS: (18)F-DOPA PET, CT and (18)F-DOPA PET/CT images of 25 consecutive patients undergoing diagnostic scanning of suspected sporadic or multiple endocrine neoplasia type 2 syndrome-associated PHEO were reviewed retrospectively in randomized sequence. Two blinded observers scored the images regarding the likelihood of PHEO being present and localizable. Results were correlated with subsequent clinical history and, when available, histology. RESULTS: Of the 19 lesions detected by all three modalities, PET identified each as positive for PHEO, but was unable to definitively localize 15 of 19 (79%). CT could definitively localize all 19 lesions, but could not definitively diagnose or exclude PHEO in 18 of 19 (95%) lesions. Furthermore, CT falsely identified as negative for PHEO one lesion which was judged to be positive for this tumor by both PET and PET/CT. Only in PET/CT scans were all 19 lesions accurately characterized and localized. On a per-patient basis, the sensitivity of (18)F-DOPA PET/CT for PHEO was 100% and the specificity 88%, with a 100% positive predictive value and an 88% negative predictive value. CONCLUSION: (18)F-DOPA PET/CT more accurately diagnoses and localizes adrenal and extra-adrenal masses suspicious for PHEO than do (18)F-DOPA PET or CT alone.

Endocrine tumors: the evolving role of positron emission tomography in diagnosis and management.

Endocrine tumors comprise a range of benign and malignant conditions that produce a spectrum of clinical symptoms and signs depending on the specific hormones they produce. The symptoms and presentations of these tumors are often independent of their size and location. Because of their expression of cell membrane receptors or production of specific types of hormones or peptides, endocrine tumors can be identified with functional radionuclide imaging much more readily compared to standard cross-sectional imaging. In recent years, 18F-fluoro-deoxy- D-glucose positron emission tomography (18F-FDG-PET) has emerged as a useful tool for diagnosing and assessing many tumors. In this review we describe how PET, using 18F-FDG and other radiopharmaceuticals can be useful in the diagnosis and management of a wide range of endocrine tumors.