Long-term prognosis of patients with pediatric pheochromocytoma

被引：94

作者：

Bausch, Birke ^{[1
]}

Wellner, Ulrich ^{[2
]}

Bausch, Dirk ^{[2
]}

Schiavi, Francesca ^{[3
,4
]}

Barontini, Marta ^{[5
]}

Sanso, Gabriela ^{[5
]}

Walz, Martin K. ^{[6
]}

Peczkowska, Mariola ^{[7
]}

Weryha, Georges ^{[8
]}

Dall'Igna, Patrizia ^{[9
]}

Cecchetto, Giovanni ^{[9
]}

Bisogno, Gianni ^{[10
]}

Moeller, Lars C. ^{[11
]}

Bockenhauer, Detlef ^{[12
]}

Patocs, Attila ^{[13
]}

Racz, Karoly ^{[13
]}

Zabolotnyi, Dmitry ^{[14
]}

Yaremchuk, Svetlana ^{[14
]}

Dzivite-Krisane, Iveta ^{[15
]}

Castinetti, Frederic ^{[16
]}

Taieb, David ^{[17
]}

Malinoc, Angelica ^{[18
]}

von Dobschuetz, Ernst ^{[19
]}

Roessler, Jochen ^{[20
]}

Schmid, Kurt W. ^{[21
]}

Opocher, Giuseppe ^{[3
,4
]}

Eng, Charis ^{[22
,23
]}

Neumann, Hartmut P. H. ^{[18
]}

机构：

[1] Univ Freiburg, Dept Med 2, D-79106 Freiburg, Germany

[2] Univ Hosp Schleswig Holstein, Dept Surg, Lubeck, Germany

[3] Univ Padua, Familial Canc Clin, Dept Med, Padua, Italy

[4] Univ Padua, Padua, Italy

[5] Hosp Ninos Dr Ricardo Gutierrez, Ctr Endocrinol Invest CEDIE, Buenos Aires, DF, Argentina

[6] Kliniken Essen Mitte, Ctr Minimally Invas Surg, Dept Surg, Essen, Germany

[7] Inst Cardiol, Dept Hypertens, Warsaw, Poland

[8] Univ Lorraine, Dept Endocrinol, Nancy, France

[9] Univ Hosp Padova, Dept Pediat, Div Pediat Surg, Padua, Italy

[10] Univ Hosp Padova, Dept Pediat, Div Hematol & Oncol, Padua, Italy

[11] Univ Duisburg & Essen, Univ Med Ctr, Dept Endocrinol, Essen, Germany

[12] Hosp Great Ormond St, Dept Pediat, London, England

[13] Semmelweis Univ, Dept Internal Med 2, H-1085 Budapest, Hungary

[14] NAMS Ukraine, Inst Otorhinolaryngol, Kiev, Ukraine

[15] Univ Riga, Dept Endocrinol, Riga, Latvia

[16] Aix Marseille Univ, La Timone Hosp, Dept Endocrinol, Marseille, France

[17] Univ Hosp Timone, Dept Nucl Med, Marseilles, France

[18] Univ Freiburg, Dept Nephrol & Gen Med, Sect Prevent Med, D-79106 Freiburg, Germany

[19] Univ Freiburg, Dept Visceral Surg, D-79106 Freiburg, Germany

[20] Univ Freiburg, Dept Pediat, D-79106 Freiburg, Germany

[21] Univ Duisburg & Essen, Univ Med Ctr, Dept Pathol, Essen, Germany

[22] Cleveland Clin, Lerner Res Inst, Genom Med Inst, Cleveland, OH 44106 USA

[23] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA

来源：

关键词：

pheochromocytoma; long-term follow-up; relapse; germline mutations; HEREDITARY PHEOCHROMOCYTOMA; PARAGANGLIOMA; MUTATIONS; CHILDREN; CHILDHOOD; SURGERY; RISK; SDHB;

D O I：

10.1530/ERC-13-0415

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

A third of patients with paraganglial tumors, pheochromocytoma, and paraganglioma, carry germline mutations in one of the susceptibility genes, RET, VHL, NF1, SDHAF2, SDHA, SDHB, SDHC, SDHD, TMEM127, and MAX. Despite increasing importance, data for long-term prognosis are scarce in pediatric presentations. The European-American-Pheochromocytoma-Paraganglioma-Registry, with a total of 2001 patients with confirmed paraganglial tumors, was the platform for this study. Molecular genetic and phenotypic classification and assessment of gene-specific long-term outcome with second and/or malignant paraganglial tumors and life expectancy were performed in patients diagnosed at < 18 years. Of 177 eligible registrants, 80% had mutations, 49% VHL, 15% SDHB, 10% SDHD, 4% NF1, and one patient each in RET, SDHA, and SDHC. A second primary paraganglial tumor developed in 38% with increasing frequency over time, reaching 50% at 30 years after initial diagnosis. Their prevalence was associated with hereditary disease (P=0.001), particularly in VHL and SDHD mutation carriers (VHL vs others, P=0.001 and SDHD vs others, P=0.042). A total of 16 (9%) patients with hereditary disease had malignant tumors, ten at initial diagnosis and another six during follow-up. The highest prevalence was associated with SDHB (SDHB vs others, P<0.001). Eight patients died (5%), all of whom had germline mutations. Mean life expectancy was 62 years with hereditary disease. Hereditary disease and the underlying germline mutation define the long-term prognosis of pediatric patients in terms of prevalence and time of second primaries, malignant transformation, and survival. Based on these data, gene-adjusted, specific surveillance guidelines can help effective preventive medicine.

引用

页码：17 / 25

页数：9