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  • Author: Anouk N A van der Horst-Schrivers x
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Free access

False-positive findings on 6-[18F]fluor-l-3,4-dihydroxyphenylalanine PET (18F-FDOPA-PET) performed for imaging of neuroendocrine tumors

Annika M A Berends, Michiel N Kerstens, Janne W Bolt, Thera P Links, Esther Korpershoek, Ronald R de Krijger, Annemiek M E Walenkamp, Walter Noordzij, Boudewijn van Etten, Gursah Kats-Ugurlu, Adrienne H Brouwers, and Anouk N A van der Horst-Schrivers

Background/aim

PET with 6-[18F]fluor-l-3,4-dihydroxyphenylalanine (18F-FDOPA) has been shown to be a useful imaging tool with a high sensitivity for the visualization of neuroendocrine tumors (NETs). 18F-FDOPA uptake in tumors other than NETs has been suggested previously, but data on this phenomenon are limited. We therefore studied the non-physiological, false-positive uptake of 18F-FDOPA in a large population of patients with a NET or with a high clinical suspicion of harboring a NET.

Patients and methods

Retrospective single-center study among adult patients in whom 18F-FDOPA PET scintigraphy was performed between January 2004 and December 2014. The original scan report was compared with the original pathology report corresponding with the 18F-FDOPA PET-positive lesion. In case this was inconsistent with the diagnosis of a NET, both the scan and the pathology slides were reassessed. Specimens of these non-NET tissues were immunohistochemically stained for AADC.

Results

1070 18F-FDOPA PET scans from 705 patients were evaluated. Focal or multiple 18F-FDOPA-avid lesions were described in 709 18F-FDOPA PET scans (66%). Histology of these 18F-FDOPA PET-positive lesions was present in 508 (72%) cases. In seven cases, the histopathology was not compatible with NET but showed squamous cell carcinoma of the cervix, multiple myeloma (two cases), hepatocellular carcinoma, Schwannoma, adrenocortical carcinoma and a skeletal myxoid chondrosarcoma, with positive immunohistochemical staining for AADC in 67%.

Conclusions

Pathological uptake of 18F-FDOPA does not always indicate the presence of a NET. The possibility of 18F-FDOPA uptake by tumor types other than NETs, although rare, should be considered.

Free access

The phenotype of SDHB germline mutation carriers: a nationwide study

Nicolasine D Niemeijer, Johannes A Rijken, Karin Eijkelenkamp, Anouk N A van der Horst-Schrivers, Michiel N Kerstens, Carli M J Tops, Anouk van Berkel, Henri J L M Timmers, Henricus P M Kunst, C René Leemans, Peter H Bisschop, Koen M A Dreijerink, Marieke F van Dooren, Jean-Pierre Bayley, Alberto M Pereira, Jeroen C Jansen, Frederik J Hes, Erik F Hensen, and Eleonora P M Corssmit

Objective

Succinate dehydrogenase B subunit (SDHB) gene germline mutations predispose to pheochromocytomas, sympathetic paragangliomas, head and neck paragangliomas and non-paraganglionic tumors (e.g. renal cell carcinoma, gastrointestinal stromal tumor and pituitary neoplasia). The aim of this study was to determine phenotypical characteristics of a large Dutch cohort of SDHB germline mutation carriers and assess differences in clinical phenotypes related to specific SDHB mutations.

Design

Retrospective descriptive study.

Methods

Retrospective descriptive study in seven academic centers.

Results

We included 194 SDHB mutation carriers consisting 65 (33.5%) index patients and 129 (66.5%) relatives. Mean age was 44.8 ± 16.0 years. Median duration of follow-up was 2.6 years (range: 0–36). Sixty persons (30.9%) carried the exon 3 deletion and 46 (23.7%) the c.423 + 1G > A mutation. Fifty-four mutation carriers (27.8%) had one or multiple head and neck paragangliomas, 4 (2.1%) had a pheochromocytoma and 26 (13.4%) had one or more sympathetic paragangliomas. Fifteen patients (7.7%) developed metastatic paraganglioma and 17 (8.8%) developed non-paraganglionic tumors. At study close, there were 111 (57.2%) unaffected mutation carriers. Statistical analyses showed no significant differences in the number and location of head and neck paragangliomas, sympathetic paragangliomas or pheochromocytomas, nor in the occurrence of metastatic disease or other tumors between carriers of the two founder SDHB mutations (exon 3 deletion vs c.423 + 1G > A).

Conclusions

In this nationwide study of disease-affected and unaffected SDHB mutation carriers, we observed a lower rate of metastatic disease and a relatively high number of head and neck paragangliomas compared with previously reported referral-based cohorts.

Free access

Circulating adrenomedullin and B-type natriuretic peptide do not predict blood pressure fluctuations during pheochromocytoma resection: a cross-sectional study

Annika M A Berends, Edward Buitenwerf, Ineke J Riphagen, Jacques W M Lenders, Henri J L M Timmers, Schelto Kruijff, Thera P Links, Anouk N A van der Horst-Schrivers, Coen A Stegeman, Elisabeth M W Eekhoff, Richard A Feelders, Eleonora P M Corssmit, Ronald Groote Veldman, Harm R Haak, Anneke C Muller Kobold, and Michiel N Kerstens

Background

Despite adequate presurgical management, blood pressure fluctuations are common during resection of pheochromocytoma or sympathetic paraganglioma (PPGL). To a large extent, the variability in blood pressure control during PPGL resection remains unexplained. Adrenomedullin and B-type natriuretic peptide, measured as MR-proADM and NT-proBNP, respectively, are circulating biomarkers of cardiovascular dysfunction. We investigated whether plasma levels of MR-proADM and NT-proBNP are associated with blood pressure fluctuations during PPGL resection.

Methods

Study subjects participated in PRESCRIPT, a randomized controlled trial in patients undergoing PPGL resection. MR-proADM and NT-proBNP were determined in a single plasma sample drawn before surgery. Multivariable linear and logistic regression analyses were used to explore associations between these biomarkers and blood pressure fluctuations, use of vasoconstrictive agents during surgery as well as the occurrence of perioperative cardiovascular events.

Results

A total of 126 PPGL patients were included. Median plasma concentrations of MR-proADM and NT-proBNP were 0.51 (0.41–0.63) nmol/L and 68.7 (27.9–150.4) ng/L, respectively. Neither MR-proADM nor NT-proBNP were associated with blood pressure fluctuations. There was a positive correlation between MR-proADM concentration and the cumulative dose of vasoconstrictive agents (03B2 0.44, P =0.001). Both MR-proADM and NT-proBNP were significantly associated with perioperative cardiovascular events (OR: 5.46, P =0.013 and OR: 1.54, P =0.017, respectively).

Conclusions

plasma MR-proADM or NT-proBNP should not be considered as biomarkers for the presurgical risk assessment of blood pressure fluctuations during PPGL resection. Future studies are needed to explore the potential influence of these biomarkers on the intraoperative requirement of vasoconstrictive agents and the perioperative cardiovascular risk.

Free access

Long-term male fertility after treatment with radioactive iodine for differentiated thyroid carcinoma

Marloes Nies, Eus G J M Arts, Evert F S van Velsen, Johannes G M Burgerhof, Anneke C Muller Kobold, Eleonora P M Corssmit, Romana T Netea-Maier, Robin P Peeters, Anouk N A van der Horst-Schrivers, Astrid E P Cantineau, and Thera P Links

Context

Whilst radioactive iodine (RAI) is often administered in the treatment for differentiated thyroid carcinoma (DTC), long-term data on male fertility after RAI are scarce.

Objective

To evaluate long-term male fertility after RAI for DTC, and to compare semen quality before and after RAI.

Design, setting, and patients

Multicenter study including males with DTC ≥2 years after their final RAI treatment with a cumulative activity of ≥3.7 GBq.

Main outcome measure(s)

Semen analysis, hormonal evaluation, and a fertility-focused questionnaire. Cut-off scores for ‘low semen quality’ were based on reference values of the general population as defined by the World Health Organization (WHO).

Results

Fifty-one participants had a median age of 40.5 (interquartile range (IQR): 34.0–49.6) years upon evaluation and a median follow-up of 5.8 (IQR: 3.0–9.5) years after their last RAI administration. The median cumulative administered activity of RAI was 7.4 (range: 3.7–23.3) GBq. The proportion of males with a low semen volume, concentration, progressive motility, or total motile sperm count did not differ from the 10th percentile cut-off of a general population (P = 0.500, P = 0.131, P = 0.094, and P = 0.500, respectively). Cryopreserved semen was used by 1 participant of the 20 who had preserved semen.

Conclusions

Participants had a normal long-term semen quality. The proportion of participants with low semen quality parameters scoring below the 10th percentile did not differ from the general population. Cryopreservation of semen of males with DTC is not crucial for conceiving a child after RAI administration but may be considered in individual cases.

Free access

Thyroid incidentalomas in patients with multiple endocrine neoplasia type 1

Lutske Lodewijk, Pim J Bongers, Jakob W Kist, Elfi B Conemans, Joanne M de Laat, Carla R C Pieterman, Anouk N A van der Horst-Schrivers, Ciska Jorna, Ad R Hermus, Olaf M Dekkers, Wouter W de Herder, Madeleine L Drent, Peter H Bisschop, Bas Havekes, Inne H M Borel Rinkes, Menno R Vriens, and Gerlof D Valk

Objective

Currently, little is known about the prevalence of thyroid tumors in multiple endocrine neoplasia type 1 (MEN1) patients and it is unclear whether tumorigenesis of these thyroid tumors is MEN1-related. The aim of the study was to assess the prevalence of thyroid incidentalomas in MEN1 patients compared with nonMEN1 patients and to verify whether thyroid tumorigenesis is MEN1-related.

Design

A cross-sectional study.

Methods

The study included two groups: patients with MEN1 and a matched non-MEN1 control group without known thyroid disease, who underwent an ultrasound of the neck for the localization of parathyroid adenoma. Ninety-five MEN1 patients underwent ultrasound of the neck and were matched on gender and age with non-MEN1 patients. The prevalence of thyroid incidentalomas described in the ultrasound report was scored. Multinodular goiters, solitary nodes, and cysts were scored as incidentalomas. Presence of nuclear menin expression was evaluated by menin immunostaining of the thyroid tumors.

Results

In the MEN1 group, 43 (45%) patients had a thyroid incidentaloma compared with 48 (51%) in the non-MEN1 group, of which 14 (15%) and 16 (17%), respectively, were solitary nodes. Menin was expressed in the nuclei of all evaluated thyroid tumors.

Conclusions

MEN1 patients do not have a higher prevalence of thyroid incidentalomas compared with primary hyperparathyroidism patients without the diagnosis of MEN1. Menin was expressed in the thyroid tumors of MEN1 patients.