A family with pheochromocytoma-paraganglioma inherited tumour syndrome

Summary

Aim: Hereditary pheochromocytoma-paraganglioma syndromes are characterized by multiple pheochromocytomas (PCC) and paragangliomas (PGLs), inherited in an autosomal dominant manner. Early detection and removal of tumours may prevent or minimize complications related to mass effects and malignant transformation. Having confirmed the diagnosis, it is important to localize the tumours and reveal their extent preoperatively. This study aimed to introduce ¹⁸F-DOPA PET/CT as a highly sensitive noninvasive diagnostic tool for early detection of mass lesions in patients with pheochromocytoma-paraganglioma inherited tumour syndrome and to report about its impact on patient management. Patients, methods: We are currently supervising one of the largest documented families in Germany with genetically determined SDHD gene mutation. We performed ¹⁸F-DOPA PET/CT in order to detect tumours in asymptomatic gene carriers and enable subsequent surgical therapy. Results: In seven patients undergoing 12 ¹⁸F-DOPA PET/CT scans 17 lesions have been detected. Three of these lesions, located in the head and neck region, have had no morphologic correlate in CT and one had also no morphologic correlate in MRI. Of the six histologically analyzed lesions five have been tumors (PGL or PCC) and one has been a nodular hyperplasia. This means the ¹⁸F-DOPA PET/CT scan in our study group had a sensitivity of 83%. ¹⁸F-DOPA PET/CT investigations lead to change in the management in 5/7 studied patients (70%). Conclusion: The benefits of PET/ CT in detection of pheochromocytoma and paraganglioma are well documented, but we are the first to use this technique for screening of a rare hereditary disease (estimated prevalence 0.3/100 000).

Zusammenfassung

Das autosomal-dominant vererbte Phäochromozytom-Paragangliom-Syndrom ist gekennzeichnet durch das Auftreten multipler Phäochromozytome (PCC) und Paragangliome (PGLs). Durch die Früherkennung solcher Tumore und operative Entfernung können Komplikationen verhindert oder minimiert werden. Nach Diagnosestellung ist es für die Therapieplanung von großer Bedeutung Tumore genau zu lokalisieren und ihre Ausbreitung festzustellen. Ziel dieser Studie war es, ¹⁸F-DOPA-PET/CT als ein hochsensitives, nicht-invasives diagnostisches Verfahren zur Früherkennung von Tumoren bei Patienten mit hereditärem Phäochromozytom-Paragangliom-Syndrom einzusetzen und dessen Einfluss auf die weitere Therapieplanung zu dokumentieren. Patienten, Methoden: Wir betreuen eine der größten dokumentierten Familien in Deutschland mit genetisch nachgewiesener SDHD-Genmutation. Bei den Mitgliedern dieser Familie führten wir ¹⁸F-DOPA-PET/CT-Untersuchungen als nicht-invasives und zuverlässiges Screening zur Früherkennung von Tumoren in asymptomatischen Mutationsträgern und zur weiteren Therapieplanung durch. Ergebnisse: In 12 ¹⁸F-DOPA-PET/ CT-Untersuchungen an sieben Patienten entdeckten wir 17 Läsionen, von denen drei, die im Kopf-Hals-Bereich lokalisiert waren, kein morphologisches Korrelat im CT zeigten und eine ebenfalls nicht im MRT. Von den sechs histologisch untersuchten Läsionen handelte es sich bei fünf um Tumorgewebe, in einer dieser Läsionen war kein Tumorgewebe nachweisbar (noduläre Hyperplasie). Die ¹⁸F-DOPA- PET/CT-Untersuchung in unserer Studiengruppe zeigte eine Sensitivität von 83%. Die Ergebnisse der ¹⁸F- DOPA-PET/CT- Untersuchungen führte zu einer Änderung der Therapiestrategie in 5/7 Patienten unserer Studiengruppe (70%). Schlussfolgerung: Die Vorteile des PET/CT bei der Diagnostik von Phäochromozytomen und Paragangliomen sind gut dokumentiert. Wir sind die ersten, die diese Technik als Screening bei einer seltenen (Prävalenz 0,3/100 000) Erbkrankheit erfolgreich einsetzten.

Keywords

¹⁸F-DOPA PET/CT - pheochromocytoma - paraganglioma - screening - inherited tumour syndrome - SDHD mutation

Schlüsselwörter

¹⁸F-DOPA PET/CT - Phäochromozytom - Paragangliom - Screening - familiäres Tumorsyndrom - SDHD-Genmutation

^* Authors contributed equally to this manuscript.

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