Pheochromocytomas: can malignant potential be predicted?

John, Hubert; Ziegler, W. H.; Hauri, D.; Jaeger, Peter De

doi:10.1016/s0090-4295(98)00612-8

Cited by 230 publications

(144 citation statements)

References 11 publications

Supporting

Mentioning

127

Contrasting

Unclassified

Order By: Relevance

“…We found that the incidence of malignant pheochromocytomas among 152 patients with pheochromocytomas was 11.2%, in good agreement with the 8% to 12.5% previously reported [7][8][9][10][11]. We also found that the 5-year survival rate of our patients with malignant pheochromocytoma was 11.8%, which was thus somewhat lower than the 20% previously reported [12]. Although none of our patients with malignant pheochromocytomas were alive after 10 years, others have reported somewhat better results [2].…”

Section: Discussionsupporting

confidence: 90%

Predictive Characteristics of Malignant Pheochromocytoma

Park¹,

Park²,

Song³

et al. 2009

Journal of Urology

View full text Add to dashboard Cite

Purpose:The prognosis of patients with malignant pheochromocytoma is poor, but the predictive factors are not well understood. We aimed to identify the clinical characteristics predictive of malignancy after initial surgical removal in patients with pheochromocytoma. Materials and Methods:We retrospectively reviewed the records of 152 patients diagnosed with pheochromocytoma, including 5 (3.3%) with metastasis at the time of the initial surgical excision and 12 (7.9%) who developed metastasis during follow-up. To determine the factors predictive of malignancy, we compared clinical, radiographical, and urinary chemical findings between patients with benign and malignant disease. Mean follow-up was 41.5 months (range, 0.9-298 months) after surgery. Results: Malignant tumors were significantly larger than benign tumors (11.1±4.0 cm vs. 6.2±3.4 cm, p＜0.001), and postoperative persistence of arterial hypertension was more frequent after removal of malignant than benign tumors (p=0.001). Among the 147 patients without metastatic disease at diagnosis, those who developed metastasis had significantly lower concentrations of urinary catecholamine metabolites per unit of tumor, including vanillylmandelic acid (1.2 vs. 3.7 mg/day/cm, p=0.049), epinephrine (4.5 vs. 168.9 μg/day/cm, p=0.008), and norepinephrine (13.1 vs. 121.8 mg/day/cm, p ＜0.001). The overall 5-year metastasis-free survival rate was 84.4% and was significantly higher in patients with smaller tumors (≤5.5 vs. ＞5.5 cm; 90.6% vs. 81.2%, p=0.025) and higher 24-hour secretion of vanillylmandelic acid (＞2.1 vs. ≤2.1 mg/ day/cm; 94.9% vs. 70.9%, p=0.019). Conclusions: Large tumor size (＞5.5 cm) and minimally elevated 24-hour urinary vanillylmandelic acid (≤2.1 mg/day/cm) were significantly associated with a higher probability of a malignant pheochromocytoma portending a lower metastasis-free survival and mandating more rigorous follow-up after surgery.

show abstract

Section: Discussionsupporting

confidence: 90%

Predictive Characteristics of Malignant Pheochromocytoma

Park¹,

Park²,

Song³

et al. 2009

Journal of Urology

View full text Add to dashboard Cite

show abstract

“…There are no reliable distinguishing clinical parameters, except that paragangliomas are more often malignant than pheochromocytomas (1,6,8,27,28). Histopathological features usually associated with malignancy, such as nuclear atypia, pleomorphism, vascular invasion, and mitotic activity, may be seen in benign as well as malignant lesions (2,4).…”

Section: Discussionmentioning

confidence: 99%

“…Conflicting results have been reported for DNA flow cytometry (13,31,32), overexpression of the proto-oncogene products c-erb B-2 and bcl-2 (a marker of apoptosis; 16,33,34), mutations in the tumor suppressor gene p53 and its product (14,33,35), elevated plasma neuropeptide Y levels (36, 37), elevated urinary dopamine levels reflecting an immature secretion pattern (27), and absence of S-100 sustentacular cells (16,17). Immunohistochemical staining for the cell adhesion molecule E-cadherin (14), the oncogene product of HER-2/neu (14), PCNA (a marker of proliferative activity; 13), somatic mutations in the RET proto-oncogene (17), and angiogenesis assessed by high microvascular count (15) seem to have no potential diagnostic utility in this tumor type.…”

Section: Discussionmentioning

confidence: 99%

KI-67 AND hTERT Expression Can Aid in the Distinction between Malignant and Benign Pheochromocytoma and Paraganglioma

et al. 2003

View full text Add to dashboard Cite

The clinical and histopathological distinction between benign and malignant pheochromocytomas and paragangliomas is difficult, and reliable diagnostic markers are lacking. Here we have evaluated the prognostic value of human telomerase reverse transcriptase (hTERT) gene expression detected by reverse transcription PCR (RT-PCR); telomerase activity (TA) measured by TRAP (telomeric repeat amplification protocol) assay; immunohistochemical staining for Ki-67/MIB-1; and the mRNA expression of matrix metalloproteinase (MMP)-2 and EMMPRIN (extracellular matrix metalloproteinase inducer) analyzed by in situ hybridization in 32 primary pheochromocytomas or abdominal paragangliomas. hTERT was expressed in 7/11 malignant tumors (defined as presence of metastasis and/or extensive local invasion) as compared with in 2/21 benign tumors. All of the benign tumors showed <1% proliferative activity, as measured by Ki-67/MIB-1 staining. In all three patients with malignant tumors who developed metastases and/or invasive local recurrence during follow-up, the tumors were positive for either hTERT expression or Ki-67/MIB-1 immunoreactivity. TA was not a significant discriminator between benign and malignant tumors, and the value of EMMPRIN and MMP-2 as predictive markers was limited. In conclusion, the findings imply that the combined use of Ki-67/ MIB-1 and hTERT, in addition to histopathology, provides a highly specific tool to identify benign pheochromocytoma and abdominal paraganglioma cases that are not at risk of developing recurrent or metastatic disease.

show abstract

“…High preoperative 24 h urinary dopamine levels, extra-adrenal tumour location, high tumour weight, elevated tumour dopamine concentration and postoperative persistent arterial hypertension are all factors that increase the likelihood of malignant phaeochromocytoma. 10,11 Adherence to the recommendation to only report results for urinary noradrenaline and adrenaline resulted in di⁄culty in reaching a diagnosis for our patient because the dopamine excretion was ¢rst measured in 1998 but not noted to be signi¢cantly high until almost two years later. It has been suggested that 3-methoxytyramine may also be a useful diagnostic and monitoring parameter for catecholamine-secreting carotid body tumours.…”

Section: Discussionmentioning

confidence: 97%

Increased urinary dopamine excretion in association with bilateral carotid body tumours - clinical, biochemical and genetic findings

Jeffery

Devendra

Farrugia³

et al. 2006

Ann Clin Biochem

View full text Add to dashboard Cite

This report describes a rare case of a patient with increased urinary dopamine excretion in association with bilateral carotid body tumours. Excretion of adrenaline, noradrenaline, metadrenaline, normetadrenaline and 4-hydroxy-3-methoxymandelic acid (HMMA) were within the reference ranges, and an 123 I-meta-iodobenzylguanidine (MIBG) scan showed uptake in the neck masses, with no other abnormal uptake anywhere else in the body. The patient is being managed conservatively as the tumours are not amenable to resection on account of their size and vascularity. There are only four previous case reports of dopamine-secreting tumours of the carotid body described in the literature, all of whom were women. The tumours were unilateral in three cases and bilateral in the fourth case. Familial cases of carotid body tumours have a higher prevalence of bilateral tumours than nonfamilial cases. Recent reports in the literature have suggested that a significant number of patients with extra-adrenal catecholamine-secreting paragangliomas have a genetic mutation in one of the identified susceptibility genes for catecholamine-secreting tumours, despite having no other affected family members, and a mutation has been found in the succinate dehydrogenase gene for this patient. 2006; 43: 156-160 Case report Ann Clin BiochemA 61-year-old gentleman with a long-standing history of hypertension presented with syncopal episodes to the casualty department in December 1999. The initial diagnosis was thought to be recurrent transient ischaemic attacks in association with bilateral carotid bruits. Following a neck ultrasound scan, carotid angiography revealed bilateral large carotid body tumours encircling each common carotid artery with splaying of the internal and external carotid arteries; a characteristic benign tumour blush was seen (Figure1). The masses in the neck (Figure 2) were ¢rst commented on by an Ear, Nose and Throat (ENT) surgeon when the patient underwent a tonsillectomy 20 years ago to alleviate sleep apnoea. Due to recurrence of this problem, a trachaeostomy was carried out, and due to episodes of collapse ascribed to asystole as a result of carotid sinus baroreceptor hypersensitivity secondary to his carotid body tumours, a permanent pacemaker was inserted. 1 Although these interventions brought about signi¢-cant improvement in the clinical condition of the patient, his blood pressure and heart rate showed large variations on 24 h monitoring (70/41--219/102 mmHg, 14--98 bpm). The patient is not currently receiving any medical management for his labile hypertension.Baseline laboratory investigations were normal (urea. As his blood pressure remained labile, urinary catecholamines were requested. Dopamine excretion was signi¢cantly elevated at 20,679 nmol/24 h (upper limit of reference range 4440 nmol/24 h); excretion of the dopamine metabolite homovanillic acid (HVA) was also increased at 13.1mmol/mol creatinine (upper limit of reference range 5 mmol/mol creatinine). Excretion of noradrenaline, adrenaline, normetadrenalin...

show abstract

Pheochromocytomas: can malignant potential be predicted?

Cited by 230 publications

References 11 publications

Predictive Characteristics of Malignant Pheochromocytoma

Predictive Characteristics of Malignant Pheochromocytoma

KI-67 AND hTERT Expression Can Aid in the Distinction between Malignant and Benign Pheochromocytoma and Paraganglioma

Increased urinary dopamine excretion in association with bilateral carotid body tumours - clinical, biochemical and genetic findings

Contact Info

Product

Resources

About