Publications by authors named "Nicholas J Patronas"

50 Publications

Clinical findings in families with chordoma with and without T gene duplications and in patients with sporadic chordoma reported to the Surveillance, Epidemiology, and End Results program.

J Neurosurg 2020 Jun 19:1-10. Epub 2020 Jun 19.

1Division of Cancer Epidemiology & Genetics, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda.

Objective: To gain insight into the role of germline genetics in the development of chordoma, the authors evaluated data from 2 sets of patients with familial chordoma, those with and without a germline duplication of the T gene (T-dup+ vs T-dup-), which was previously identified as a susceptibility mechanism in some families. The authors then compared the patients with familial tumors to patients with sporadic chordoma in the US general population reported to the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program through 2015.

Methods: Evaluation of family members included review of personal and family medical history, physical and neurological examination, and pre- and postcontrast MRI of the skull base and spine. Sixteen patients from 6 white families with chordoma had a chordoma diagnosis at family referral. Screening MR images of 35 relatives revealed clival lesions in 6, 4 of which were excised and confirmed to be chordoma. Thus, data were available for 20 patients with histologically confirmed familial chordoma. There were 1759 patients with histologically confirmed chordoma in SEER whose race was known.

Results: The median age at chordoma diagnosis differed across the groups: it was lowest in T-dup+ familial patients (26.8 years, range 5.3-68.4 years); intermediate in T-dup- patients (46.2 years, range 11.8-60.1 years); and highest in SEER patients (57 years, range 0-98 years). There was a marked preponderance of skull base tumors in patients with familial chordoma (93% in T-dup+ and 83% in T-dup-) versus 38% in the SEER program (37% in white, 53% in black, and 48.5% in Asian/Pacific Islander/American Indian/Alaska Native patients). Furthermore, 29% of white and 16%-17% of nonwhite SEER patients had mobile-spine chordoma, versus no patients in the familial group. Several T-dup+ familial chordoma patients had putative second/multiple primary chordomas.

Conclusions: The occurrence of young age at diagnosis, skull base presentation, or multiple primary chordomas should encourage careful review of family history for patients diagnosed with chordoma as well as screening of at-risk family members by MRI for early detection of chordoma. Furthermore, given genetic predisposition in some patients with familial chordoma, identification of a specific mutation in a family will permit surveillance to be limited to mutation carriers-and consideration should be given for imaging the entire neuraxis in any chordoma patient presenting at an early age or with a blood relative with chordoma. Finally, future studies should explore racial differences in age at diagnosis and presenting site in chordoma.
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http://dx.doi.org/10.3171/2020.4.JNS193505DOI Listing
June 2020

CRH stimulation improves F-FDG-PET detection of pituitary adenomas in Cushing's disease.

Endocrine 2019 07 6;65(1):155-165. Epub 2019 May 6.

Neurosurgery Unit for Pituitary and Inheritable Diseases, National Institute of Neurological Diseases and Stroke, Bethesda, MD, USA.

Objective: In MRI-negative cases Cushing's disease (CD), surgeons perform a more extensive exploration of the pituitary gland, with fewer instances of hormonal remission. F-fluoro-deoxy-glucose (F-FDG) positron emission tomography (PET) has a limited role in detecting adenomas that cause CD (corticotropinomas). Our previous work demonstrated corticotropin-releasing hormone (CRH) stimulation leads to delayed, selective glucose uptake in corticotropinomas. Here, we prospectively evaluated the utility of CRH stimulation in improving F-FDG-PET detection of adenomas in CD.

Methods: Subjects with a likely diagnosis of CD (n = 27, 20 females) each underwent two F-FDG-PET studies [without and with ovine-CRH (oCRH) stimulation] on a high-resolution PET platform. Standardized-uptake-values (SUV) in the sella were calculated. Two blinded neuroradiologists independently read F-FDG-PET images qualitatively. Adenomas were histopathologically confirmed, analyzed for mutations in the USP8 gene and for glycolytic pathway proteins.

Results: The mean-SUV of adenomas was significantly increased from baseline (3.6 ± 1.5) with oCRH administration (3.9 ± 1.7; one-tailed p = 0.003). Neuroradiologists agreed that adenomas were visible on 21 scans, not visible on 26 scans (disagreed about 7, kappa = 0.7). oCRH-stimulation led to the detection of additional adenomas (n = 6) not visible on baseline-PET study. Of the MRI-negative adenomas (n = 5), two were detected on PET imaging (one only after oCRH-stimulation). USP8 mutations or glycolytic pathway proteins were not associated with SUV in corticotropinomas.

Conclusions: The results of the current study suggest that oCRH-stimulation may lead to increased F-FDG uptake, and increased rate of detection of corticotropinomas in CD. These results also suggest that some MRI invisible adenomas may be detectable by oCRH-stimulated FDG-PET imaging.

Clinical Trial Information: F-FDG-PET imaging with and without CRH stimulation was performed under the clinical trial NIH ID 12-N-0007 (clinicaltrials.gov identifier NCT01459237). The transsphenoidal surgeries and post-operative care was performed under the clinical trial NIH ID 03-N-0164 (clinicaltrials.gov identifier NCT00060541).
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http://dx.doi.org/10.1007/s12020-019-01944-7DOI Listing
July 2019

Origin of Syrinx Fluid in Syringomyelia: A Physiological Study.

Neurosurgery 2019 02;84(2):457-468

Surgical Neurology Branch, NINDS, National Institutes of Health, Bethesda, Maryland.

Background: The origin of syrinx fluid is controversial.

Objective: To elucidate the mechanisms of syringomyelia associated with cerebrospinal fluid pathway obstruction and with intramedullary tumors, contrast transport from the spinal subarachnoid space (SAS) to syrinx was evaluated in syringomyelia patients.

Methods: We prospectively studied patients with syringomyelia: 22 with Chiari I malformation and 16 with SAS obstruction-related syringomyelia before and 1 wk after surgery, and 9 with tumor-related syringomyelia before surgery only. Computed tomography-myelography quantified dye transport into the syrinx before and 0.5, 2, 4, 6, 8, 10, and 22 h after contrast injection by measuring contrast density in Hounsfield units (HU).

Results: Before surgery, more contrast passed into the syrinx in Chiari I malformation-related syringomyelia and spinal obstruction-related syringomyelia than in tumor-related syringomyelia, as measured by (1) maximum syrinx HU, (2) area under the syrinx concentration-time curve (HU AUC), (3) ratio of syrinx HU to subarachnoid cerebrospinal fluid (CSF; SAS) HU, and (4) AUC syrinx/AUC SAS. More contrast (AUC) accumulated in the syrinx and subarachnoid space before than after surgery.

Conclusion: Transparenchymal bulk flow of CSF from the subarachnoid space to syrinx occurs in Chiari I malformation-related syringomyelia and spinal obstruction-related syringomyelia. Before surgery, more subarachnoid contrast entered syringes associated with CSF pathway obstruction than with tumor, consistent with syrinx fluid originating from the subarachnoid space in Chiari I malformation and spinal obstruction-related syringomyelia and not from the subarachnoid space in tumor-related syringomyelia. Decompressive surgery opened subarachnoid CSF pathways and reduced contrast entry into syringes associated with CSF pathway obstruction.
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http://dx.doi.org/10.1093/neuros/nyy072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6500882PMC
February 2019

Eccrine spiradenoma mimicking a painful traumatic neuroma: case report.

J Neurosurg 2018 09 27;129(3):825-828. Epub 2017 Oct 27.

2Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health.

Diagnosing and treating patients with persistent neuropathic pain associated with peripheral nerve lesions can be challenging. The authors report the rare case of a painful eccrine spiradenoma treated as a traumatic neuroma for many years because of a history of acute trauma, the presence of a tender palpable mass, and symptoms of allodynia. Surgical excision of the neoplasm completely relieved the pain and hypersensitivity that 2 prior surgeries and other nonsurgical treatments failed to resolve. The diagnosis of eccrine spiradenoma was not established until resection and histopathological analysis of the tissue. This case highlights the need to develop and consider an extensive list of differential diagnoses, including eccrine spiradenoma, for peripheral nerve lesions that fail to respond to treatment.
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http://dx.doi.org/10.3171/2017.5.JNS162999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6087503PMC
September 2018

18F-NaF PET/CT in Extensive Melorheostosis of the Axial and Appendicular Skeleton With Soft-Tissue Involvement.

Clin Nucl Med 2017 Jul;42(7):537-539

From the *Radiology and Imaging Sciences, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, MD; †Foundation for Research and Technology Hellas, Institute of Computer Science, Computational Biomedicine Laboratory, Heraklion, Crete, Greece; ‡National Institute of Arthritis and Musculoskeletal and Skin Diseases and §PET Department, Clinical Center, National Institutes of Health, Bethesda, MD; ∥Center for Research in Computer Vision, Electrical and Computer Science Department, University of Central Florida, Orlando, FL; and ¶Department of Radiology, Medical School, University of Crete, Crete, Greece.

Melorheostosis is a rare, nonhereditary, benign, sclerotic bone dysplasia with no sex predilection, typically occurring in late childhood or early adulthood, which can lead to substantial functional morbidity, depending on the sites of involvement. We report on a patient with extensive melorheostosis in the axial and appendicular skeleton, as well as in the soft tissues, who was evaluated with whole-body F-NaF PET/CT scan. All melorheostotic lesions of the skeleton and of the ossified soft-tissue masses demonstrated intensely increased F-NaF activity, suggesting the application of this modality in assessing and monitoring the disease activity.
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http://dx.doi.org/10.1097/RLU.0000000000001647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5453819PMC
July 2017

Fibrous Dysplasia Mimicking Malignancy on 68Ga-DOTATATE PET/CT.

Clin Nucl Med 2017 Mar;42(3):209-210

From the *Radiology and Imaging Sciences, Warren Grant Magnuson Clinical Center, †PET Department; Clinical Center, and ‡Endocrine Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD; §Endocrine and Thoracic Surgery, University Hospitals of Geneva, Geneva, Switzerland; ∥Department of Radiology, Medical School, University of Crete, Greece; and ¶Center for Research in Computer Vision, Electrical and Computer Science Department, University of Central Florida, Orlando, FL.

Fibrous dysplasia of the bone is a developmental benign skeletal disorder characterized by replacement of normal bone and normal bone marrow with abnormal fibro-osseous tissue. We report on a case of a biopsy-proven fibrous dysplasia lesion in the left temporal bone, with intensely increased activity (SUVmax, 56.7) on Ga-DOTATATE PET/CT. The presented data indicate cell surface overexpression of somatostatin receptors by fibrous dysplastic cells and highlight the need of cautious management of Ga-DOTATATE-avid bone lesions, which could mimic malignancy especially in patients with history of neuroendocrine tumors.
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http://dx.doi.org/10.1097/RLU.0000000000001527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5290189PMC
March 2017

Case 1: Poor Growth With Presence of a Pituitary Lesion in an 11-year-old Boy.

Pediatr Rev 2017 Jan;38(1):44-45

Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD.

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http://dx.doi.org/10.1542/pir.2014-0135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343498PMC
January 2017

18F-FDG and 68Ga-DOTATATE PET/CT in von Hippel-Lindau Disease-Associated Retinal Hemangioblastoma.

Clin Nucl Med 2017 Mar;42(3):189-190

From the *Radiology and Imaging Sciences, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda; †PET-Department, Clinical Center, National Institutes of Health, Bethesda, MD; ‡Leeds Medical School, Leeds, UK; §Center for Research in Computer Vision, Electrical and Computer Science Department, University of Central Florida (UCF), Orlando, FL; ∥Endocrine Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD; ¶Endocrine and Thoracic Surgery, University Hospitals of Geneva, Geneva, Switzerland; and **Department of Radiology, Medical School, University of Crete, Crete, Greece.

Retinal hemangioblastomas are highly vascular benign tumors that can be encountered either sporadically or within the von Hippel-Lindau (VHL) syndrome. We report a case of a VHL patient with retinal hemangioblastoma who underwent PET/CT scans using F-FDG and Ga-DOTATATE. The tumor showed low-level F-FDG and increased Ga-DOTATATE activity, suggesting cell-surface overexpression of somatostatin receptors. The presented case indicates the clinical applications of somatostatin receptor imaging with Ga-DOTA-conjugated peptides in detection and follow-up of VHL manifestations, screening of asymptomatic gene carriers, and in diagnosis of sporadic retinal hemangioblastomas, which may have similar features on MRI with other retinal tumors.
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http://dx.doi.org/10.1097/RLU.0000000000001511DOI Listing
March 2017

Avascular Necrosis of the Hips With Increased Activity on 68Ga-DOTATATE PET/CT.

Clin Nucl Med 2017 Mar;42(3):214-215

From the *Radiology and Imaging Sciences, Warren Grant Magnuson Clinical Center (CC), Bethesda; †PET Department, Clinical Center, National Institutes of Health (NIH), Bethesda, MD; ‡Department of Radiology, Medical School, University of Crete, Crete, Greece; and §Center for Research in Computer Vision (CRCV), Electrical and Computer Science Department, University of Central Florida (UCF), Orlando, FL.

Prolonged exposure to cortisol is one of the major causes of avascular bone necrosis (AVN). We report on a case of a woman with Cushing syndrome attributed to ectopic adrenocorticotropic hormone-secreting tumor who was evaluated with whole-body PET/CT study using Ga-DOTATATE. The scan showed increased activity by both femoral heads, corresponding to the margins of bilateral AVN seen on MRI. The presented data suggests AVN-induced reactive inflammatory alterations adjacent to the necrotic segment of the bone, which can be effectively targeted using radiolabeled somatostatin (SST) analogs.
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http://dx.doi.org/10.1097/RLU.0000000000001513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5290201PMC
March 2017

Breast Fibroadenoma With Increased Activity on 68Ga DOTATATE PET/CT.

Clin Nucl Med 2017 Feb;42(2):145-146

From the *Department of Radiology and Imaging Sciences, Warren Grant Magnuson Clinical Center, †PET Department, Clinical Center, and ‡Endocrine Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD; §Endocrine and Thoracic Surgery, University Hospitals of Geneva, Geneva, Switzerland; ∥Department of Radiology, Medical School, University of Crete, Greece; and ¶Center for Research in Computer Vision, Electrical and Computer Science Department, University of Central Florida, Orlando, FL.

Fibroadenoma is the most common benign breast tumor in women of reproductive age, carrying little to no risk of breast cancer development. We report on a case of a woman with history of neuroendocrine tumor who on follow-up imaging tests underwent whole-body PET/CT study using Ga DOTATATE. The scan showed increased focal activity in the right breast, which was biopsied revealing a fibroadenoma. The presented data suggests cell surface overexpression of somatostatin receptors by this benign breast tumor. Moreover, this finding emphasizes the need for cautious interpretation of Ga DOTATATE-avid breast lesions that could mimic malignancy in neuroendocrine tumor patients.
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http://dx.doi.org/10.1097/RLU.0000000000001463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5218865PMC
February 2017

Kidney Tumor in a von Hippel-Lindau (VHL) Patient With Intensely Increased Activity on 68Ga-DOTA-TATE PET/CT.

Clin Nucl Med 2016 Dec;41(12):970-971

From the *Radiology and Imaging Sciences, Warren Grant Magnuson Clinical Center (CC), National Institutes of Health (NIH), Bethesda; †Division of Nuclear Medicine, RAD&IS, Clinical Center, National Institutes of Health (NIH), Bethesda; †Endocrine Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD; §Endocrine and Thoracic Surgery, University Hospitals of Geneva, Geneva, Switzerland; and ∥Center for Research in Computer Vision (CRCV), Electrical and Computer Science Department, University of Central Florida (UCF), Orlando, FL.

Renal and pancreatic cysts and tumors are the most common visceral manifestations of von Hippel-Lindau (VHL) disease, a heritable multisystem cancer syndrome characterized by development of a variety of malignant and benign tumors. We report a case of a VHL patient with multiple renal cystic and complex cystic/solid lesions. The patient underwent Ga-DOTA-TATE-PET/CT showing intensely increased activity by a solid lesion which demonstrated enhancement on both CT and MRI scans, raising high suspicion for malignancy. The presented case indicates application of SSTR-imaging using Ga-DOTA-conjugated peptides in VHL-patients and emphasizes the need for cautious interpretation of renal parenchyma Ga-DOTATATE activity.
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http://dx.doi.org/10.1097/RLU.0000000000001393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5099086PMC
December 2016

Predicting clinical outcomes in chordoma patients receiving immunotherapy: a comparison between volumetric segmentation and RECIST.

BMC Cancer 2016 08 23;16(1):672. Epub 2016 Aug 23.

Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Room 13N208, Bethesda, MD, 20892, USA.

Background: The Response Evaluation Criteria in Solid Tumors (RECIST) are the current standard for evaluating disease progression or therapy response in patients with solid tumors. RECIST 1.1 calls for axial, longest-diameter (or perpendicular short axis of lymph nodes) measurements of a maximum of five tumors, which limits clinicians' ability to adequately measure disease burden, especially in patients with irregularly shaped tumors. This is especially problematic in chordoma, a disease for which RECIST does not always adequately capture disease burden because chordoma tumors are typically irregularly shaped and slow-growing. Furthermore, primary chordoma tumors tend to be adjacent to vital structures in the skull or sacrum that, when compressed, lead to significant clinical consequences.

Methods: Volumetric segmentation is a newer technology that allows tumor burden to be measured in three dimensions on either MR or CT. Here, we compared the ability of RECIST measurements and tumor volumes to predict clinical outcomes in a cohort of 21 chordoma patients receiving immunotherapy.

Results: There was a significant difference in radiologic time to progression Kaplan-Meier curves between clinical outcome groups using volumetric segmentation (P = 0.012) but not RECIST (P = 0.38). In several cases, changes in volume were earlier and more sensitive reflections of clinical status.

Conclusion: RECIST is a useful evaluation method when obvious changes are occurring in patients with chordoma. However, in many cases, RECIST does not detect small changes, and volumetric assessment was capable of detecting changes and predicting clinical outcome earlier than RECIST. Although this study was small and retrospective, we believe our results warrant further research in this area.
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http://dx.doi.org/10.1186/s12885-016-2699-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4995658PMC
August 2016

Reply: 68Ga-DOTATATE PET/CT Versus MRI: Why the Comparison of 68Ga-DOTATATE PET/CT to an Appropriate MRI Protocol Is Essential.

J Nucl Med 2017 01 4;58(1):185. Epub 2016 Aug 4.

National Institutes of Health CRC, Room 1E-3140 10 Center Dr., MSC-1109 Bethesda, MD 20892-1109 Email:

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http://dx.doi.org/10.2967/jnumed.116.180109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5219846PMC
January 2017

Adrenal cryptococcosis in an immunosuppressed patient showing intensely increased metabolic activity on F-FDG PET/CT.

Endocrine 2016 Dec 29;54(3):834-836. Epub 2016 Jul 29.

Radiology and Imaging Sciences, Warren Grant Magnuson Clinical Center (CC), National Institutes of Health (NIH), Bethesda, MD, 20892, USA.

Disseminated cryptococcosis most commonly occurs in immunosuppressed patients and can rarely affect the adrenal glands. We report on a patient with biopsy proven bilateral adrenal cryptococcosis resulting in primary adrenal insufficiency, which was evaluated with whole-body positron emission tomography/computed tomography scan using F-FDG. Both enlarged adrenal glands presented intensely increased F-FDG activity in the periphery, while central necrotic regions were photopenic. Although diagnosis was established by adrenal gland biopsy, F-FDG positron emission tomography/computed tomography scan can significantly contribute to the assessment of disease activity and monitoring of treatment response. Furthermore, fungal infections should always be considered when encountering hypermetabolic adrenal masses, especially in the setting of immunodeficient patients.
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http://dx.doi.org/10.1007/s12020-016-1040-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5107323PMC
December 2016

Epididymal Cystadenomas in von Hippel-Lindau Disease Showing Increased Activity on 68Ga DOTATATE PET/CT.

Clin Nucl Med 2016 Oct;41(10):781-2

From the *Radiology and Imaging Sciences, Warren Grant Magnuson Clinical Center, †Division of Nuclear Medicine, RADIS, Clinical Center, and ‡Endocrine Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD; §Endocrine and Thoracic Surgery, University Hospitals of Geneva, Geneva, Switzerland; and ∥Center for Research in Computer Vision, Electrical and Computer Science Department, University of Central Florida, Orlando, FL.

von Hippel-Lindau (VHL) disease is a familial cancer syndrome characterized by the development of a variety of malignant and benign tumors, including epididymal cystadenomas. We report a case of a VHL patient with bilateral epididymal cystadenomas who was evaluated with Ga DOTATATE PET/CT, showing intensely increased activity (SUVmax, 21.6) associated with the epididymal cystadenomas, indicating cell-surface overexpression of somatostatin receptors. The presented case supports the usefulness of somatostatin receptor imaging using Ga DOTA-conjugated peptides for detection and follow-up of VHL manifestations, as well as surveillance of asymptomatic gene carriers.
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http://dx.doi.org/10.1097/RLU.0000000000001314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5014623PMC
October 2016

Endolymphatic Sac Tumor Showing Increased Activity on 68Ga DOTATATE PET/CT.

Clin Nucl Med 2016 Oct;41(10):783-4

From the *Radiology and Imaging Sciences, Warren Grant Magnuson Clinical Center, †Division of Nuclear Medicine, RAD&IS, Clinical Center, and ‡Endocrine Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD; §Endocrine and Thoracic Surgery, University Hospitals of Geneva, Geneva, Switzerland; and ∥Center for Research in Computer Vision, Electrical and Computer Science Department, University of Central Florida, Orlando, FL.

Endolymphatic sac tumors (ELSTs) are rare tumors arising from the epithelium of the endolymphatic sac and duct that can be either sporadic or associated with von Hippel-Lindau (VHL) disease. We report a case of a VHL patient with histologically proven residual ELST who underwent Ga DOTATATE PET/CT showing increased activity (SUVmax, 6.29) by the ELST. The presented case of a VHL-associated ELST with increased Ga DOTATATE uptake indicates cell-surface expression of somatostatin receptors by this tumor, suggesting the potential application of somatostatin receptor imaging using Ga DOTA-conjugated peptides in the workup and management of these patients.
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http://dx.doi.org/10.1097/RLU.0000000000001315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5014707PMC
October 2016

Resources Required for Semi-Automatic Volumetric Measurements in Metastatic Chordoma: Is Potentially Improved Tumor Burden Assessment Worth the Time Burden?

J Digit Imaging 2016 06;29(3):357-64

Department of Radiology and Imaging Sciences, Clinical Center, NIH, Bethesda, MD, USA.

The Response Evaluation Criteria in Solid Tumors (RECIST) is the current standard for assessing therapy response in patients with malignant solid tumors; however, volumetric assessments are thought to be more representative of actual tumor size and hence superior in predicting patient outcomes. We segmented all primary and metastatic lesions in 21 chordoma patients for comparison to RECIST. Primary tumors were segmented on MR and validated by a neuroradiologist. Metastatic lesions were segmented on CT and validated by a general radiologist. We estimated times for a research assistant to segment all primary and metastatic chordoma lesions using semi-automated volumetric segmentation tools available within our PACS (v12.0, Carestream, Rochester, NY), as well as time required for radiologists to validate the segmentations. We also report success rates of semi-automatic segmentation in metastatic lesions on CT and time required to export data. Furthermore, we discuss the feasibility of volumetric segmentation workflow in research and clinical settings. The research assistant spent approximately 65 h segmenting 435 lesions in 21 patients. This resulted in 1349 total segmentations (average 2.89 min per lesion) and over 13,000 data points. Combined time for the neuroradiologist and general radiologist to validate segmentations was 45.7 min per patient. Exportation time for all patients totaled only 6 h, providing time-saving opportunities for data managers and oncologists. Perhaps cost-neutral resource reallocation can help acquire volumes paralleling our example workflow. Our results will provide researchers with benchmark resources required for volumetric assessments within PACS and help prepare institutions for future volumetric assessment criteria.
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http://dx.doi.org/10.1007/s10278-015-9846-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879033PMC
June 2016

68Ga-DOTATATE PET/CT in the Localization of Head and Neck Paragangliomas Compared with Other Functional Imaging Modalities and CT/MRI.

J Nucl Med 2016 Feb 12;57(2):186-91. Epub 2015 Nov 12.

Program in Adult and Reproductive Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland

Unlabelled: Pheochromocytomas/paragangliomas overexpress somatostatin receptors, and recent studies have already shown excellent results in the localization of sympathetic succinate dehydrogenase complex, subunit B, mutation-related metastatic pheochromocytomas/paragangliomas using (68)Ga-DOTATATE PET/CT. Therefore, the goal of our study was to assess the clinical utility of this functional imaging modality in parasympathetic head and neck paragangliomas (HNPGLs) compared with anatomic imaging with CT/MRI and other functional imaging modalities, including (18)F-fluorohydroyphenylalanine ((18)F-FDOPA) PET/CT, currently the gold standard in the functional imaging of HNPGLs.

Methods: (68)Ga-DOTATATE PET/CT was prospectively performed in 20 patients with HNPGLs. All patients also underwent (18)F-FDOPA PET/CT, (18)F-FDG PET/CT, and CT/MRI, with 18 patients also undergoing (18)F-fluorodopamine ((18)F-FDA) PET/CT. (18)F-FDOPA PET/CT and CT/MRI served as the imaging comparators.

Results: Thirty-eight lesions in 20 patients were detected, with (18)F-FDOPA PET/CT identifying 37 of 38 and CT/MRI identifying 23 of 38 lesions (P < 0.01). All 38 and an additional 7 lesions (P = 0.016) were detected on (68)Ga-DOTATATE PET/CT. Significantly fewer lesions were identified by (18)F-FDG PET/CT (24/38, P < 0.01) and (18)F-FDA PET/CT (10/34, P < 0.01).

Conclusion: (68)Ga-DOTATATE PET/CT identified more lesions than other imaging modalities. With the results of the present study, and the increasing availability and use of DOTA analogs in the therapy of neuroendocrine tumors, we expect that (68)Ga-DOTATATE PET/CT will become the preferred functional imaging modality for HNPGLs in the near future.
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http://dx.doi.org/10.2967/jnumed.115.161018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4738157PMC
February 2016

Multiple Endocrine Neoplasia, Type 1: Imaging Solutions to Clinical Questions.

Curr Probl Diagn Radiol 2016 Jul-Aug;45(4):278-83. Epub 2015 Sep 11.

Uniformed Services University of the Health Sciences, Bethesda, MD.

The common clinical presentations of multiple endocrine neoplasia, type 1 (MEN1) often lead to predictable clinical questions that can be answered with imaging. From pituitary adenomas to parathyroid adenoms and pancreaticoduodenal neuroendocrine tumors, the multiple faces of MEN1 require an understanding of the basic disease characteristics and an understanding of multiple imaging modalities. We attempt to provide the reader with a basic understanding of the common clinical questions raised by patients with MEN1 and how radiologists can provide critical management information.
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http://dx.doi.org/10.1067/j.cpradiol.2015.08.010DOI Listing
May 2017

Pituitary abnormalities in patients with Fanconi anaemia.

Clin Endocrinol (Oxf) 2016 Feb 22;84(2):307-309. Epub 2015 Sep 22.

Program on Developmental Endocrinology and Genetics, National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD, USA.

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http://dx.doi.org/10.1111/cen.12883DOI Listing
February 2016

Talc Pleurodesis With Intense 18F-FDG Activity But No 68Ga-DOTA-TATE Activity on PET/CT.

Clin Nucl Med 2015 Oct;40(10):819-20

From the *Radiology and Imaging Sciences, Warren Grant Magnuson Clinical Center; †Division of Nuclear Medicine, RAD&IS, Clinical Center, National Institutes of Health; ‡Center for Research in Computer Vision, University of Central Florida, Orlando, FL; and §Section on Endocrinology and Genetics, Program on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (NIH), Bethesda, MD.

Talc pleurodesis (TP) is a technique, widely employed in the management of patients with persistent pleural effusions or pneumothoraces not amenable to other treatment options. It is well documented that talc deposits produce areas of highly increased F-FDG uptake, because of talc-induced inflammation. We present a case of a patient with history of TP who was evaluated with both F-FDG and Ga-DOTA-TATE. The hypermetabolic area seen on F-FDG-PET-CT in the region of talc placement showed no uptake by Ga-DOTA-TATE, suggesting the potential role of Ga-DOTA-TATE-PET-CT in elucidating F-FDG-postitive lesions in patients with history of both neuroendocrine malignancy and TP.
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http://dx.doi.org/10.1097/RLU.0000000000000807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4564300PMC
October 2015

Ectopic ACTH and CRH Co-secreting Tumor Localized by 68Ga-DOTA-TATE PET/CT.

Clin Nucl Med 2015 Jul;40(7):576-8

From the *Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD; †Center for Research in Computer Vision (CRCV), University of Central Florida, Orlando, FL; ‡Endocrine Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD; and §Section on Endocrinology and Genetics, Program on Developmental Endocrinology & Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (NIH), Bethesda, MD.

Diagnosis of ectopic adrenocorticotropic hormone (ACTH) and corticotropin-releasing hormone (CRH) co-secreting tumors causing Cushing syndrome (CS) is challenging because these tumors are rare and their diagnosis is frequently confused with Cushing disease (CD), caused by the effect of CRH on the pituitary. We report a case of a 21-year-old male patient who was referred to our institution with persistent hypercortisolemia and CS after undergoing unnecessary transsphenoidal surgery (TSS). ⁶⁸Ga-DOTA-TATE PET/CT revealed increased tracer uptake in the thymus, which was histologically proven to be a neuroendocrine tumor (NET) that stained positive for ACTH and CRH. Imaging with ¹⁸F-FDG PET/CT was not diagnostic.
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http://dx.doi.org/10.1097/RLU.0000000000000806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4459884PMC
July 2015

Preoperative Imaging Features are Associated with Surgical Complications Following Carotid Body Tumor Resection.

World J Surg 2015 Aug;39(8):2084-9

Thoracic and GI Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA,

Background: Surgical resection remains the treatment of choice for carotid body tumors (CBTs). Although perioperative complications such as carotid artery injury and neurological deficits occur infrequently, they can be devastating. The aim of this study was to evaluate whether clinical factors or preoperative imaging findings can accurately predict perioperative complications.

Methods: Twenty CBTs were resected from 19 patients. Preoperative computed tomography (CT) and magnetic resonance imaging (MRI) of the neck were used to measure the degree of circumferential involvement of the CBT to the internal carotid artery (ICA), carotid artery narrowing, tumor length, tumor volume, and the distance from the tip of the C2 dens to the superior aspect of the CBT (dens-CBT). Operative reports and Shamblin classification (I-III) of each tumor were independently reviewed. Preoperative imaging features were compared to perioperative cranial nerve injury (CNI), rates of carotid artery injury, and major carotid artery repairs, as well as Shamblin classifications≥II.

Results: CNI was associated with a high-lying CBT (dens-CBT=1.8 vs. 2.9 cm, p<0.01). All four patients with CNI had a dens-CBT of <3 cm. Neither tumor length and tumor volume nor the involvement of the ICA (≥180° as measured by CT or MRI) was associated with CNI, carotid artery injury, major carotid artery repair, or Shamblin II or III classification. No carotid artery narrowing was observed in any of the cases.

Conclusions: Preoperative measurement of the dens-CBT is helpful in identifying CBTs at risk for CNI after surgical resection.
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http://dx.doi.org/10.1007/s00268-015-3058-9DOI Listing
August 2015

Combined PET/CT by 18F-FDOPA, 18F-FDA, 18F-FDG, and MRI correlation on a patient with Carney triad.

Clin Nucl Med 2015 Jan;40(1):70-2

From the *Section on Endocrinology and Genetics, Program on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, †Department of Radiology and Imaging Sciences, Warren Grant Magnuson Clinical Center, and ‡Division of Nuclear Medicine, Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD; and §Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.

Carney triad is a rare syndrome involving gastrointestinal stromal tumor, pulmonary chondroma, and extra-adrenal paraganglioma. We present a 21-year-old woman with the complete triad who was evaluated with MRI, F-FDOPA, F-FDA, and F-FDG. F-FDOPA best demonstrated the paraganglioma, whereas hepatic metastases noted by MRI demonstrated increased uptake only by F-FDG.
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http://dx.doi.org/10.1097/RLU.0000000000000616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260990PMC
January 2015

Ectopic adrenocorticotropic hormone and corticotropin-releasing hormone co-secreting tumors in children and adolescents causing cushing syndrome: a diagnostic dilemma and how to solve it.

J Clin Endocrinol Metab 2015 Jan;100(1):141-8

Section on Endocrinology and Genetics (A.S.K., J.B., M.F.K., C.L., M.B.L., C.A.S.), Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892; Section of Radiology and Imaging Sciences (G.Z.P., N.J.P.), Clinical Center, National Institutes of Health, Bethesda, Maryland 20892; Laboratory of Pathology (M.M.Q., M.M.), Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892; Thoracic and Gastrointestinal Oncology Branch (D.S.S.), Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892; Endocrine Oncology Branch (E.K.), Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892; Randall Children's Hospital at Legacy Emanuel (M.K.H.), Children's Diabetes and Endocrine Center, Portland, Oregon 97227; Department of Pediatrics (M.R.A., L.P.K., A.E.B.), Section of Diabetes and Endocrinology, Baylor College of Medicine, Houston, Texas 77030.

Context: Ectopic ACTH/CRH syndrome is a rare cause of Cushing syndrome (CS), especially in children. The localization, work-up, and management of ACTH/CRH-secreting tumors are discussed.

Setting: A retrospective study was conducted of patients under 21 years of age evaluated at the National Institutes of Health (NIH) for CS and diagnosed with ectopic ACTH/CRH-secreting tumors during the period 2009-2014.

Patients: Seven patients with ectopic ACTH/CRH CS are included in this study with a median age 13.6 years (range 1-21), and 3 are female.

Measurements: Clinical, biochemical, radiological features, treatment, and histological findings are described.

Results: Seven patients were found to have ACTH/CRH-secreting tumors, all with neuroendocrine features. The site of the primary lesion varied: pancreas (3), thymus (2), liver (1), right lower pulmonary lobe (1). PATIENTS underwent biochemical evaluation for CS, including diurnal serum cortisol and ACTH levels, urinary free cortisol levels (UFC), and CRH stimulation tests. All patients underwent radiological investigations including MRI, CT, and PET scan; imaging with octreotide and 68 gallium DOTATATE scans were performed in individual cases. Five patients underwent inferior petrosal sinus sampling; 4 patients had sampling for ACTH and CRH levels from additional sites. Three patients underwent trans-sphenoidal surgery (TSS), and 3 patients required bilateral adrenalectomy. Three patients (43%) died due to metastatic disease, demonstrating the high mortality rate. One of the unique findings in these seven patients is that in each case, their neuroendocrine tumors were ultimately proven to be co-secreting ACTH and CRH. This explains the enigmatic presentation, in which 3 patients initially thought to have Cushing's disease (CD) with corresponding pituitary hyperplasia underwent TSS prior to the correct localization of the causative tumor.

Conclusions: Ectopic ACTH/CRH co-secreting tumors are extremely rare in children and adolescents. The diagnosis of this condition is frequently missed and is sometimes confused with CD due to the effect of CRH on the pituitary.
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http://dx.doi.org/10.1210/jc.2014-2945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4283025PMC
January 2015

Multifocal dysembryoplastic neuroepithelial tumours associated with refractory epilepsy.

Epileptic Disord 2014 Sep;16(3):328-32

Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda.

Dysembryoplastic neuroepithelial tumours (DNET) are a common cause of tumour-associated epilepsy, and are usually located in the temporal lobes. We present a case of multifocal DNETs in both infra- and supra-tentorial locations, in a 23-year-old man with a coincident Type I Chiari malformation, presenting with medically refractory focal seizures. The extensive anatomical distribution of the lesions suggests a genetic component in their tumourigenesis.
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http://dx.doi.org/10.1684/epd.2014.0680DOI Listing
September 2014

Early-onset stroke and vasculopathy associated with mutations in ADA2.

N Engl J Med 2014 Mar 19;370(10):911-20. Epub 2014 Feb 19.

The authors' affiliations are listed in the Appendix.

Background: We observed a syndrome of intermittent fevers, early-onset lacunar strokes and other neurovascular manifestations, livedoid rash, hepatosplenomegaly, and systemic vasculopathy in three unrelated patients. We suspected a genetic cause because the disorder presented in early childhood.

Methods: We performed whole-exome sequencing in the initial three patients and their unaffected parents and candidate-gene sequencing in three patients with a similar phenotype, as well as two young siblings with polyarteritis nodosa and one patient with small-vessel vasculitis. Enzyme assays, immunoblotting, immunohistochemical testing, flow cytometry, and cytokine profiling were performed on samples from the patients. To study protein function, we used morpholino-mediated knockdowns in zebrafish and short hairpin RNA knockdowns in U937 cells cultured with human dermal endothelial cells.

Results: All nine patients carried recessively inherited mutations in CECR1 (cat eye syndrome chromosome region, candidate 1), encoding adenosine deaminase 2 (ADA2), that were predicted to be deleterious; these mutations were rare or absent in healthy controls. Six patients were compound heterozygous for eight CECR1 mutations, whereas the three patients with polyarteritis nodosa or small-vessel vasculitis were homozygous for the p.Gly47Arg mutation. Patients had a marked reduction in the levels of ADA2 and ADA2-specific enzyme activity in the blood. Skin, liver, and brain biopsies revealed vasculopathic changes characterized by compromised endothelial integrity, endothelial cellular activation, and inflammation. Knockdown of a zebrafish ADA2 homologue caused intracranial hemorrhages and neutropenia - phenotypes that were prevented by coinjection with nonmutated (but not with mutated) human CECR1. Monocytes from patients induced damage in cocultured endothelial-cell layers.

Conclusions: Loss-of-function mutations in CECR1 were associated with a spectrum of vascular and inflammatory phenotypes, ranging from early-onset recurrent stroke to systemic vasculopathy or vasculitis. (Funded by the National Institutes of Health Intramural Research Programs and others.).
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http://dx.doi.org/10.1056/NEJMoa1307361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4193683PMC
March 2014

State of art imaging of the pituitary tumors.

J Neurooncol 2014 May 17;117(3):395-405. Epub 2013 Dec 17.

, Bethesda, MD, USA,

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http://dx.doi.org/10.1007/s11060-013-1307-zDOI Listing
May 2014

Pituitary stalk lesion in a 13-year-old female.

J Pediatr Endocrinol Metab 2014 Mar;27(3-4):359-62

Germinomas presenting with a pituitary stalk lesion and panhypopituitarism are rare in children, and their definite diagnosis is challenging. An invasive diagnostic approach, such as a transsphenoidal biopsy, is often required prior to establishing a treatment regimen. A 13-year-old female presented with 1 year of secondary amenorrhea, fatigue, and progressive thirst with polyuria. Laboratory work-up revealed panhypopituitarism (central hypothyroidism, hypogonadotropic hypogonadism, adrenal insufficiency and central diabetes insipidus). α-Fetoprotein and β-human chorionic gonadotropin were not elevated in serum nor in cerebrospinal fluid. The magnetic resonance imaging (MRI) of the pituitary region showed an enhancing infundibular lesion, extending into the hypothalamus, and infiltrating the pituitary gland. A transsphenoidal biopsy of the infundibular lesion confirmed the diagnosis of germinoma (germ-cell tumor). After appropriate hormone replacement therapy, chemotherapy and low-dose radiation therapy, the patient achieved complete resolution of the pituitary stalk lesion on the MRI.
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http://dx.doi.org/10.1515/jpem-2013-0274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4727445PMC
March 2014

The complex of myxomas, spotty skin pigmentation and endocrine overactivity (Carney complex): imaging findings with clinical and pathological correlation.

Insights Imaging 2013 Feb 12;4(1):119-33. Epub 2013 Jan 12.

Department of Radiology and Medical Imaging, University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, 68100, Greece,

The complex of myxomas, spotty skin pigmentation and endocrine overactivity, or Carney complex (CNC), is a familial multiple endocrine neoplasia and lentiginosis syndrome. CNC is inherited in an autosomal dominant manner and is genetically heterogeneous. Its features overlap those of McCune-Albright syndrome and other multiple endocrine neoplasia (MEN) syndromes. Spotty skin pigmentation is the major clinical manifestation of the syndrome, followed by multicentric heart myxomas, which occur at a young age and are the lethal component of the disease. Myxomas may also occur on the skin (eyelid, external ear canal and nipple) and the breast. Breast myxomas, when present, are multiple and bilateral among female CNC patients, an entity which is also described as "breast-myxomatosis" and is a characteristic feature of the syndrome. Affected CNC patients often have tumours of two or more endocrine glands, including primary pigmented nodular adrenocortical disease (PPNAD), an adrenocorticotropin hormone (ACTH)-independent cause of Cushing's syndrome, growth hormone (GH)-secreting and prolactin (PRL)-secreting pituitary adenomas, thyroid adenomas or carcinomas, testicular neoplasms (large-cell calcifying Sertoli cell tumours [LCCSCT]) and ovarian lesions (cysts and cancinomas). Additional infrequent but characteristic manifestations of CNC are psammomatous melanotic schwannomas (PMS), breast ductal adenomas (DAs) with tubular features, and osteochondromyxomas or "Carney bone tumour". Teaching Points • Almost 60 % of the known CNC kindreds have a germline inactivating mutations in the PRKAR1A gene. • Spotty skin pigmentation is the major clinical manifestation of CNC, followed by heart myxomas. • Indicative imaging signs of PPNAD are contour abnormality and hypodense spots within the gland. • Two breast tumours may present in CNC: myxoid fibroadenomas (breast myxomatosis) and ductal adenomas. • Additional findings of CNC are psammomatous melanotic schwannomas (PMSs) and osteochondromyxomas.
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http://dx.doi.org/10.1007/s13244-012-0208-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3579989PMC
February 2013