Malignant Pheochromocytoma with Hepatic Metastasis Diagnosed 20 Years after Resection of the Primary Adrenal Lesion.

Tanaka, Shoichi; Ito, Toshio; Tomoda, Jun; Higashi, Toshihiro; Yamada, Gotaro; Tsuji, Takao

doi:10.2169/internalmedicine.32.789

Cited by 54 publications

(34 citation statements)

References 7 publications

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“…As reported in the literature, DM can develop 20 years after surgery (Tanaka et al 1993), and only lifelong follow-up can assure that the PC is truly benign. Another limitation is the small sample number, which underlines the ultimate need for www.endocrinology-journals.org multicenter studies.…”

Section: Discussionmentioning

confidence: 94%

Microarray analysis reveals differential expression of benign and malignant pheochromocytoma

Waldmann

Fendrich²,

Holler³

et al. 2010

Endocrine-Related Cancer

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The diagnosis of a malignant pheochromocytoma (PC) can only be established by the presence of distant metastases, but a subset of apparently benign PCs develop metastases. We have employed a microarray analysis to identify a typical gene expression profile which distinguishes malignant from benign PC. Total RNA was isolated from fresh-frozen tissue of five benign and five malignant PCs. The reference consisted of laser microdissected tissue from normal adrenal medulla. After generating Cy3-and Cy5-fluorescently labeled cDNAs, F-chips containing 11 540 spots were hybridized. Data were analyzed with the IMAGENE 3.0 software. Gene expression levels were validated by real-time (RT)-PCR and immunohistochemistry (IHC). The analysis revealed a more than twofold difference in expression between benign and malignant PCs in 132 genes: 19 were up-regulated and 113 were down-regulated. Expression differences of six genes (calsequestrin, NNAT, neurogranin, secreted protein acidic and rich in cysteine (SPARC), EGR2, and MAOB) were confirmed by RT-PCR in 25 PCs. IHC for calsequestrin revealed an overexpression in malignant PCs (7/10 vs 1/10, PZ0.03). Comparative analysis by microarray of all ten PCs (benign/malignant) versus normal adrenal medulla revealed a more than twofold expression difference in 455/539 and 491/671 genes respectively. Several of these genes are known to participate on adrenal tumorigenesis, potential tumor suppressor genes, and oncogenes. Comprehensive gene expression analysis of malignant and benign PCs revealed different gene profiles, which could be used to discriminate between malignant and benign PCs. Based on these findings, the strategy for further follow-up and treatment could be modified accordingly.

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Section: Discussionmentioning

confidence: 94%

Microarray analysis reveals differential expression of benign and malignant pheochromocytoma

Waldmann

Fendrich²,

Holler³

et al. 2010

Endocrine-Related Cancer

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“…Metastatic disease in pheochromocytoma may be present at the time of initial diagnosis or may only become evident after surgical removal of the primary tumor, usually within 5 years, but sometimes 16 or more years later (Baba et al 1985, Tanaka et al 1993, Lenders et al 2002. Because there is currently no effective cure for malignant pheochromocytoma, most treatments are palliative, but in some cases may reduce tumor burden and prolong survival.…”

Section: Current Therapymentioning

confidence: 99%

“…Because metastases may be microscopic at the time of initial surgery, and therefore may not present as malignant disease until many years later, biochemical screening should continue at yearly intervals (Baba et al 1985, Tanaka et al 1993, Lenders et al 2002. Again, however, there is a lack of consensus regarding the duration of follow-up and in what form follow-up screening should take.…”

Section: Diagnostic and Prognostic Markersmentioning

confidence: 99%

Malignant pheochromocytoma: current status and initiatives for future progress

Eisenhofer

Bornstein

Brouwers

et al. 2004

Endocr Relat Cancer

305

226

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Pheochromocytomas are rare catecholamine-producing neuroendocrine tumors that are usually benign, but which may also present as or develop into a malignancy. Predicting such behavior is notoriously difficult and there are currently no curative treatments for malignant tumors. This report follows from a workshop at the Banbury Conference Center, Cold Spring Harbor, New York, on the 16th-18th November 2003, held to review the state of science and to facilitate future progress in the diagnosis and treatment of malignant pheochromocytoma. The rarity of the tumor and the resulting fragmented nature of studies, typically involving small numbers of patients, represent limiting factors to the development of effective treatments and diagnostic or prognostic markers for malignant disease. Such development is being facilitated by the availability of new genomics-based tools, but for such approaches to succeed ultimately requires comprehensive clinical studies involving large numbers of patients, stringently collected clinical data and tumor samples, and interdisciplinary collaborations among multiple specialist centers. Nevertheless, the well-characterized hereditary basis and the unique functional nature of these neuroendocrine tumors provide a useful framework that offers advantages for establishing the pathways of tumorigenesis and malignancy. Such findings may have relevance for understanding the basis of other more common malignancies where similar frameworks are not available. As the relevant pathways leading to pheochromocytoma are established it should be possible to take advantage of the new generation of drugs being developed to target specific pathways in other malignancies. Again the success of this will require well-designed and coordinated multicenter studies.

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“…1 These can appear up to 20 years after the initial resection. 2 In our case, the discovery of hepatic and bone metastases occurred 3 years after the adrenal resection. Since the initial tumour was large (Ͼ50 mm), relapse was more likely in our case as also occurs when the tumour is bilateral or from outside the adrenal.…”

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confidence: 60%

Metastatic phaeochromocytoma: risks of diagnostic needle puncture and treatment by arterial embolisation

et al. 2001

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A 62-year-old man had an acute episode of hypertension 72 h after fine needle aspiration biopsy of an intrahepatic nodule. The patient had been operated 3 years previously for a right adrenal phaeochromocytoma with no evidence of metastases at that time. Thus, a relapse of the tumour was postulated and confirmed by raised levels of urinary metanephrines. The extent of the metastases precluded surgical intervention and thus localised embolisation was proposed and permitted a clinical Keywords: phaeochromocytoma; metastases; fine needle aspiration biopsy; embolisation A 62-year-old man was hospitalised 72 h after a fine needle aspiration biopsy of a hepatic nodule with headache, sweats, palpitations and vertigo. He was found to have a very high blood pressure (200/100 mm Hg). Three years previously, he had had several hypertensive crises with blood pressure rising to 240/140 mm Hg, with similar symptoms. The diagnosis of a right sided adrenal phaeochromocytoma was established by urinary metanephrine levels (87 mol/24 h, normal Ͻ4.2) and by abdominal CT scan which showed a heterogeneous right adrenal mass (80 × 70 mm) (Figure 1). There was no evidence of spread of the tumour to other sites. After the introduction of treatment with labetolol at 200 mg/day the patient underwent total resection of the right adrenal tumour. Histological examination confirmed an adrenal phaeochromocytoma of 181 grams with areas of haemorrhagic necrosis and no evidence of extension beyond the capsule. The post-operative period was uneventful and the patient was asymptomatic without any treatment. Follow-up was limited to an annual abdominal ultrasound examination and nothing abnormal was found until the discovery 3 years after the original intervention of two nodules in the segment VI of the liver. It was following a fine needle aspiration biopsy of one of these nodules that the patient was hospitalised in our unit for a hypertensive crisis. The histological and cytological examination of the samples showed only normal liver tissue. The diagnosis of metastasis from a phaeochromocytoma was postulated and confirmed by the levels of urinary metanephrines (23 mol/24 h). A CT scan of the abdomen (Figure 2) demonstrated three hepatic lesions in segments VI and VII, the largest being 50 × 40 mm. Thoracic CT scan was normal and total body scan by metaiodobenzylguanidine (MIBG) showed uptake not only in the liver but also in the

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Malignant Pheochromocytoma with Hepatic Metastasis Diagnosed 20 Years after Resection of the Primary Adrenal Lesion.

Cited by 54 publications

References 7 publications

Microarray analysis reveals differential expression of benign and malignant pheochromocytoma

Microarray analysis reveals differential expression of benign and malignant pheochromocytoma

Malignant pheochromocytoma: current status and initiatives for future progress

Metastatic phaeochromocytoma: risks of diagnostic needle puncture and treatment by arterial embolisation

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