Malignant pheochromocytoma with remarkable response to CVD chemotherapy--a case report

A 60-year-old man was admitted to our hospital with the chief complaint of a left upper abdominal mass. 131I-MIBG scintiscan revealed a left upper abdominal mass, and the patient's serum catecholamine level was very high. Our diagnosis was pheochromocytoma of the left adrenal gland. On Oct. 19, 1995, a left nephrectomy and adrenectomy were performed. The serum catecholamine level then decreased and blood pressure was normalized. Two years later, it became difficult to control the patient's hypertension, and multiple metastatic liver cancer was found by an abdominal CT scan. The diagnosis of malignant pheochromocytoma was confirmed by the accumulation of 131I-MIBG in the liver. We started CVD chemotherapy. After 10 cycles of this chemotherapy, the serum catecholamine level was almost normalized and the metastatic liver cancer was reduced to one-third in size.     

Malignant pheochromocytoma with ganglioneuroblastoma elements in a patient with von Recklinghausen's disease

A 14-year-old girl with numerous café-au-lait spots in her skin was hospitalized because of fever, weight loss, and a mass of the right upper quadrant of the abdomen. Despite intensive chemotherapy, she died 6 months after admission. The autopsy revealed a right adrenal tumor with metastases to liver, lungs, vertebrae, and lymph nodes. Histologically the tumor was a pheochromocytoma with small foci of ganglioneuroblastoma. The catecholamine contents of the tumor were markedly elevated, as confirmed by the catecholamine fluorescence technique. Electron microscopically, the tumor cells contained intracytoplasmic membrane-bound chromaffin granules of varying sizes and shapes. This may be the first report of the concomitant occurrence of malignant catecholamine-secreting pheochromocytoma with ganglioneuroblastoma elements in a patient with von Recklinghausen's disease.     

恶性嗜铬细胞瘤骨转移--附髂骨转移1例报告

目的报告1例恶性嗜铬细胞瘤髂骨转移患者的临床资料。方法回顾性分析1999年我院骨科收治的1例27岁女性恶性嗜铬细胞瘤患者的临床资料,包括手术前后血儿茶酚胺的测定,骨骼影像学资料和手术病理资料,并进行有关文献复习。结果该患者在右侧肾上腺嗜铬细胞瘤手术后10年诊断左侧髂骨恶性嗜铬细胞瘤转移性复发。手术切除左侧髂骨转移肿瘤,术后1周血压和血生化检查均恢复正常,术后7年存活。结论恶性嗜铬细胞瘤髂骨转移较为罕见,临床表现隐匿,导致诊断较晚,但积极手术切除治疗效果较好。     

Malignant pheochromocytoma. Severe clinical exacerbation and release of stored catecholamines during lymphoma chemotherapy

The association of malignant pheochromocytoma and poorly differentiated lymphocytic lymphoma has not previously been reported. A case is presented of a 58-year old man with a 20-year history of malignant pheochromocytoma well controlled on Dibenzyline who was found to have poorly differentiated lymphocytic lymphoma. During lymphoma chemotherapy with cyclophosphamide, vincristine and prednisone (VCP) he developed tachycardia and syncope accompanied by severe hypertension. During the next course of chemotherapy one month later, 24-hour urinary VMA, metanephrine and catecholamine values were determined before, during and after the chemotherapy and were found to have increased two- to ten-fold. This suggests that VCP caused tumor lysis with release of catecholamines into the circulation.     

Hereditary pheochromocytoma and paraganglioma

Hereditary pheochromocytomas (pheo) and paragangliomas (pgl) are caused by identifiable germline mutations. The previously well-known associated syndromes include neurofibromatosis type 1, multiple endocrine neoplasia 2 A and B, and von Hippel-Lindau syndrome. Newly discovered mutations in the succinate dehydrogenase gene complex have been identified as a cause of inherited pgls and pheos. It is now clear that up to 30% of patients presenting with sporadic pheos/pgls harbor a recognizable germline mutation, and therefore directed genetic testing is recommended for many of these patients. J. Surg. Oncol. 2012; 106:580-585. ? 2012 Wiley Periodicals, Inc.     

Patient with inoperable pheochromocytoma

Malignant pheochromocytoma is a tumour with a very low incidence that occurs sporadically or in the presence of multiple endocrine neoplasia. We present the case of a woman with a sporadic occurrence of pheochromocytoma diagnosed in the phase of multiple dissemination in the abdominal cavity and overexpressing adrenaline, noradrenaline, and dopamine. Local transarterial chemoembolization and systemic treatment with lanreotide resulted in a very good response, a decrease in the production of catecholamines for 12 months and a partial decrease for another 8 months, with stabilization of disease determined by imaging.Systemic treatment with tegafur resulted in disease stabilization lasting 50 months, after which the drug was discontinued because of adverse effects. Maintenance therapy with lanreotide continues, and no disease progression has been observed for 4 months.The treatment algorithm for such patients is multidisciplinary and must always take into account the current scope of the disease, intercurrence, and the general condition of the patient.     

Bladder pheochromocytoma encountered on sonography

Pheochromocytomas of the bladder are rare neoplasms, constituting <0.06% of all vesical tumours. Common presenting features of this tumour include episodes of sweating, hypertension, haematuria and postmicturition syncope. We describe a case of bladder pheochromocytoma in a 66‐year‐old man whose only symptom of macroscopic haematuria was initially assessed with ultrasonography. Clinical presentation highlights the need for a high index of suspicion during sonographic evaluation of bladder neoplasms because such tumours might present without symptoms of adrenergic excess.     

肾上腺嗜铬细胞瘤的临床病理特征分析

目的探讨肾上腺嗜铬细胞瘤(PCC)的临床病理特征。方法收集22例PCC患者的临床病历资料,分析临床表现、病理特征、免疫组织化学特征、鉴别诊断、治疗和预后。结果患者中位年龄46岁(23~67岁);男性13例、女性9例;临床常见症状包括高血压、腹胀腹痛;Ⅰ期10例、Ⅱ期12例;中位随访时间为72.5个月(14.9~117.7个月),其中1例复发、1例转移,其余患者均未发生复发及转移;CgA、Syn和CD56阳性表达率分别为95.2%、95.2%、100.0%,CK、Melan-A阴性表达率分别为90.5%和100.0%,Ki-67增殖指数低于10%,S100阳性表达率为76.2%。结论肾上腺PCC发病率低,但有转移和复发的可能,需要定期随访。     

Imaging of pheochromocytoma and paraganglioma

Paragangliomas are tumours that arise within the sympathetic nervous system originating from the neural crest. These tumours can be found anywhere from the neck to the pelvis in locations of sympathetic ganglions. Although in the majority of paragangliomas the diagnosis is based on measuring catecholamines and metabolites in plasma or urine, imaging plays an important preoperative role. Today, there are several morphological and radionuclide imaging methods available that predict tumour localisation and tumour extent and give anatomic information to the surgeon. MRI is the morphological imaging modality of choice in localising pheochromocytomas and extra-adrenal paragangliomas. It provides excellent anatomic detail and has the advantage of lacking ionising radiation. The overall accuracy of computed tomography (CT) in detecting primary adrenal pheochromocytomas is very high, but CT lacks in specificity as difficulties may occur in distinguishing between paragangliomas and other tumour entities. The major advantages of radionuclide imaging are very high specificity and routinely performed whole-body scanning. Furthermore, metabolic imaging is not influenced by artifacts like scar tissue or metallic clips in post-surgical follow-up. Currently, a reported specificity of 99% and a cumulative sensitivity of about 90% in paragangliomas make ¹²³I-MIBG the most important nuclear imaging method. However, ¹⁸F-DOPA-PET seems to be a very promising procedure which offers higher accuracy. The higher spatial resolution of PET-scanners enables the detection of small lesions not visualised with ¹²³I-MIBG. Both use of radiolabelled somatostatin analogue like ¹¹¹In-pentetreotide and ¹⁸F-FDG is limited due to low specificity of the tracers and should be restricted to MIBG- and F-DOPA-negative cases.     

Enkephalin degradating enzymes in pheochromocytoma patients

Adrenal gland as a major source of enkephalins on the periphery can be affected by a rare adrenal gland tumor, adrenal pheochromocytoma. It has been demonstrated that this tumor might be associated with altered concentration of enkephalin-like peptides. The effect of these peptides can be either prolonged or abbreviated by two neutrophil membrane bound enzymes; aminopeptidase N (APN) and neutral endopeptidase (NEP). We assumed that altered enkephalin level in pheochromocytoma patients (but not in patients with non-functional adenomas or tumors of different origin) might result in differently regulated APN and/or NEP activity. We measured APN and NEP activity on surface of neutrophils, level of lipid peroxidation (LPO) in plasma and enkephalin concentration in plasma in patients with pheochromocytomas, non-functional adenomas, malignant renal tumors and healthy controls. Catheholamines and vanyllmandelic acid (VMA) were measured in 24-h urine of pheochromocytoma patients. NEP and APN activity on neutrophils from all pheochromocytoma patients was significantly increased as compared with healthy controls, non-functional adenomas and malignant renal tumors. In all pheochromocytoma patients NEP activity was reduced almost to the control level after surgery. At the same time APN activity was in some patients up- and in others down-regulated. In comparison, elevated levels of cateholamines and VMA were found after multiple determinations in 6 out of 10 pheochromocytoma patients. Although preliminary, this study has shown specifically and consistently up-regulated NEP activity on neutrophils from pheochromocytoma patients, and uniformly decreased NEP activity in these patients after adrenalectomy.     

Evolving concepts in pheochromocytoma and paraganglioma

PURPOSE OF REVIEW: The pheochromocytoma field has recently undergone a paradigm shift. This review will highlight some of these novel findings, including their impact on our understanding of the disease biology and influence on clinical management. RECENT FINDINGS: Identification of novel susceptibility loci and recognition of a high rate of germline mutations in pheochromocytomas indicate that their genetic diversity is broader and more complex than previously estimated. Further, increased risk of tumor malignancy and aggressiveness in certain patients with succinate dehydrogenase subunit B(SDHB) mutations suggest that they may have prognostic value as predictors of pheochromocytoma behavior. Finally, discovery of a shared activation of the hypoxic response in pheochromocytomas with mutations in VHL and SDH genes and uncovering of a common JunB-mediated apoptosis defect in the major hereditary groups of pheochromocytoma have provided a mechanistic basis for the clinical similarities between these distinct syndromes. SUMMARY: The notion that 'sporadic'-appearing tumors may in fact be components of one of multiple hereditary syndromes has a major impact on surveillance and follow-up of patients and their at-risk family members. Likewise, the ability to predict tumor malignancy has the potential to improve the prognosis of these patients. Importantly, insights into the biology of pheochromocytomas have provided clues on pathway interactions in cancers and have laid the ground for generation of new hypotheses on the cell-of-origin of these tumors. Pheochromocytomas have therefore emerged as key models for understanding cancer biology and for paving the way for future designer treatment in this and other cancers.     

Arterial embolization for ruptured adrenal pheochromocytoma

Background

Spontaneous rupture of adrenal pheochromocytoma is an extremely rare condition that can be lethal. Optimal treatment in these cases is still unclear.

Methods

We conducted a comprehensive review of medline articles on ruptured pheochromocytomas to locate all research done on this topic. Based on the literature review and one additional case at European Gaza Hospital, we analyzed clinical presentations, hemorrhage site, tumour side, mortality rate, and treatment options.

Results

In addition to our case, we identified 53 cases of ruptured pheochromocytoma. A review of all 53 cases revealed that 17 (32%) of the patients died, and that no mortality occurred among the 12 patients who received an alpha-blocker (to control high blood pressure) and fluid infusion therapy before surgery. Only 3 patients, including our case, underwent elective surgery after transcatheter arterial embolization (tae).

Conclusions

Surgical treatment should be considered for ruptured pheochromocytoma. Surgical approaches involve either emergency or elective surgery. It has been reported that emergency surgery is commonly associated with a high mortality rate; no deaths were reported in patients who underwent elective surgery. We therefore consider that, if a patient has hemodynamic instability, tae can be an effective and a safe procedure for achieving hemostasis and maintaining the patient in good condition until surgery can be performed.     

Further studies of a transplantable rat pheochromocytoma

Additional histopathological and immunocytological studies were completed on the serially transplanted Warren rat pheochromocytoma. Special efforts were made to characterize features of the primary tumor common to pheochromocytomas, as well as features of the primary tumor commonly found in neuroblastoma. In summary this study found evidence for a composite primary tumor exhibiting a dual differentiative expression of both pheochromocytoma and neuroblastoma. We feel this reflects a possibility that this primary tumor arose from a common progenitor cell in the neural crest.     

Model systems in SDHx-related pheochromocytoma/paraganglioma

Cancer and Metastasis Reviews - Pheochromocytoma (PHEO) and paraganglioma (PGL) (together PPGL) are tumors with poor outcomes that arise from neuroendocrine cells in the adrenal gland, and...