CONTEXT: Mutations of the gene encoding succinate dehydrogenase subunit B (SDHB) predispose to malignant paraganglioma (PGL). Recognition of the SDHB phenotype in apparently sporadic PGL directs appropriate treatment and family screening. OBJECTIVE: The objective of the study was to assess mutation-specific clinical and biochemical characteristics of SDHB-related PGL. DESIGN: The study design was retrospective descriptive. PATIENTS: PATIENTS included 29 patients (16 males) with SDHB-related abdominal or thoracic PGL. INTERVENTION: There was no intervention. MAIN OUTCOME MEASURES: Clinical presentations, plasma and urine concentrations of catecholamines and O-methylated metabolites, and genotype-phenotype correlations were measured. RESULTS: Mean +/- sd age at diagnosis was 33.7 +/- 15.7 yr. Tumor-related pain was among the presenting symptoms in 54% of patients and was the sole symptom in 14%. Seventy-six percent had hypertension, and 90% lacked a family history of PGL. All primary tumors but one originated from extraadrenal locations. Mean +/- sd tumor size was 7.8 +/- 3.7 cm. In this referral-based study, 28% presented with metastatic disease and all but one eventually developed metastases after 2.7 +/- 4.1 yr. Ten percent had additional head and neck PGLs. The biochemical phenotype was consistent with hypersecretion of both norepinephrine and dopamine in 46%, norepinephrine only in 41%, and dopamine only in 3%. Ten percent had normal catecholamine (metabolite) levels, consistent with biochemically silent PGL. No obvious genotype-phenotype correlations were identified. CONCLUSIONS: SDHB-related PGL often presents as apparently sporadic PGL with symptoms related to tumor mass effect rather than to catecholamine excess. The predominant biochemical phenotype consists of hypersecretion of norepinephrine and/or dopamine, whereas 10% of tumors are biochemically silent. The clinical expression of these tumors cannot be predicted by the genotype.
CONTEXT: Mutations of the gene encoding succinate dehydrogenase subunit B (SDHB) predispose to malignant paraganglioma (PGL). Recognition of the SDHB phenotype in apparently sporadic PGL directs appropriate treatment and family screening. OBJECTIVE: The objective of the study was to assess mutation-specific clinical and biochemical characteristics of SDHB-related PGL. DESIGN: The study design was retrospective descriptive. PATIENTS: PATIENTS included 29 patients (16 males) with SDHB-related abdominal or thoracic PGL. INTERVENTION: There was no intervention. MAIN OUTCOME MEASURES: Clinical presentations, plasma and urine concentrations of catecholamines and O-methylated metabolites, and genotype-phenotype correlations were measured. RESULTS: Mean +/- sd age at diagnosis was 33.7 +/- 15.7 yr. Tumor-related pain was among the presenting symptoms in 54% of patients and was the sole symptom in 14%. Seventy-six percent had hypertension, and 90% lacked a family history of PGL. All primary tumors but one originated from extraadrenal locations. Mean +/- sd tumor size was 7.8 +/- 3.7 cm. In this referral-based study, 28% presented with metastatic disease and all but one eventually developed metastases after 2.7 +/- 4.1 yr. Ten percent had additional head and neck PGLs. The biochemical phenotype was consistent with hypersecretion of both norepinephrine and dopamine in 46%, norepinephrine only in 41%, and dopamine only in 3%. Ten percent had normal catecholamine (metabolite) levels, consistent with biochemically silent PGL. No obvious genotype-phenotype correlations were identified. CONCLUSIONS:SDHB-related PGL often presents as apparently sporadic PGL with symptoms related to tumor mass effect rather than to catecholamine excess. The predominant biochemical phenotype consists of hypersecretion of norepinephrine and/or dopamine, whereas 10% of tumors are biochemically silent. The clinical expression of these tumors cannot be predicted by the genotype.
Authors: Ingo Janssen; Elise M Blanchet; Karen Adams; Clara C Chen; Corina M Millo; Peter Herscovitch; David Taieb; Electron Kebebew; Hendrik Lehnert; Antonio T Fojo; Karel Pacak Journal: Clin Cancer Res Date: 2015-04-14 Impact factor: 12.531
Authors: Ivana Jochmanova; April Melody T Abcede; Ruby Jane S Guerrero; Chandy Lou P Malong; Robert Wesley; Thanh Huynh; Melissa K Gonzales; Katherine I Wolf; Abhishek Jha; Marianne Knue; Tamara Prodanov; Naris Nilubol; Leilani B Mercado-Asis; Constantine A Stratakis; Karel Pacak Journal: J Cancer Res Clin Oncol Date: 2020-02-15 Impact factor: 4.553
Authors: Hans K Ghayee; Bas Havekes; Eleonora P M Corssmit; Graeme Eisenhofer; Stephen R Hammes; Zahid Ahmad; Alexander Tessnow; Ivica Lazúrová; Karen T Adams; Antonio T Fojo; Karel Pacak; Richard J Auchus Journal: Endocr Relat Cancer Date: 2008-12-15 Impact factor: 5.678
Authors: Edwin W Lai; Shiromi M Perera; Bas Havekes; Henri J L M Timmers; Frederieke M Brouwers; Beverly McElroy; Karen T Adams; Shoichiro Ohta; Robert A Wesley; Graeme Eisenhofer; Karel Pacak Journal: Endocrine Date: 2008-11-04 Impact factor: 3.633