Low level of superoxide dismutase activity in pheochromocytoma

A copper-zinc superoxide dismutase found in the cytosol and intermembrane space of mitochondria, and a manganese superoxide dismutase detected in the mitochondria were determined in pheochromocytomas and normal adrenal tissues. Manganese superoxide dismutase activity in pheochromocytomas was lower than that in the normal adrenal tissues but copper-zinc superoxide dismutase activity was almost identical. The total catecholamine content in pheochromocytomas was greater than that in the normal adrenal tissues, and negative relationships were noted between superoxide dismutase activities and total catecholamine content in pheochromocytomas alone. The low level of manganese superoxide dismutase activity might be a characteristic of pheochromocytomas and the decrease in manganese superoxide dismutase activity may not be attributed solely to a decrease in the amount of mitochondria but to a nonspecific abnormality in mitochondrial enzymes.     

Malignant pheochromocytoma. A case report and comments on a rare pathology

Pheochromocytomas and functioning paragangliomas are rare tumors arising from the primitive neural crest, and found in the adrenal medulla or elsewhere within the sympathetic paraganglion axis. Clinical symptoms are related to catecholamine production or less frequently to dopamine or other neuropeptides secretion. Malignant pheochromocytomas are very rare tumors comprising between 5-35%, but this value is uncertain because the usual criteria for malignancy, such as mitotic activity, nuclear pleomorphism, are not suitable to discern benign from malignant pheochromocytomas. A specific diagnosis of malignancy requires evidence of invasion of the adjacent organs and the occurrence of metastases. Personal experience is presented with 92 patients affected by: adrenal pheochromocytomas (51 cases), cervical paragangliomas (32 cases), and extra-adrenal paragangliomas (9 cases). Malignant forms were observed in a 23-year-old young woman affected by malignant pheochromocytoma with lymphatic para-aortic metastases (1.9%), and in 2 patients affected by cervical paragangliomas (1 CBT, 1 VBT) with lymph nodal metastases. Careful follow-up of all patients with measurement of the urinary catecholamine is necessary to detect metachronous neoplasm and later metastases, identified with RMN and 131I-MIBG scintiscan.     

Should pheochromocytoma size influence surgical approach? A comparison of 90 malignant and 60 benign pheochromocytomas

BACKGROUND: Diagnostic tests cannot reliably distinguish malignant from benign pheochromocytomas. Laparoscopic adrenalectomy for pheochromocytomas >6 cm is controversial because of a perceived increased risk of malignancy that is based on anecdotal reports and small series. The aim of this study was to determine if pheochromocytoma size should affect the choice of surgical approach. METHODS: Malignant pheochromocytomas in the Surveillance Epidemiology and End Results (SEER) database (1988-2000) were compared to benign pheochromocytomas in our institutional database (1993-2003). The sensitivity, specificity and likelihood ratio for tumor size to predict malignancy were calculated for both groups. RESULTS: Ninety malignant and 60 benign pheochromocytomas were compared. Overall, malignant pheochromocytomas were larger than benign pheochromocytomas (7.6 +/- 4.2 cm vs 5.3 +/- 2.3 cm). However, tumor size was not significantly different between malignant pheochromocytomas without local invasion or metastases and benign pheochromocytomas (6.1 +/- 3.1 cm vs 5.3 +/- 2.3 cm). In pheochromocytomas with local disease only, maximum likelihood ratio to predict malignancy was at a tumor size of greater than 8 cm (2.84). CONCLUSIONS: Although risk of malignancy increases with size for all pheochromocytomas, size does not reliably predict malignancy in pheochromocytomas with local disease only. Regardless of tumor size, laparoscopic adrenalectomy for pheochromocytoma should be converted to open adrenalectomy for difficult dissection, invasion, adhesions, or surgeon inexperience.     

类肝素酶-1和血管内皮生长因子在嗜铬细胞瘤中的表达及其相关性

目的通过检测类肝素酶-1（HPA）、血管内皮生长因子（VEGF）在良、恶性嗜铬细胞瘤中的表达情况,探讨HPA、VEGF能否成为预测恶性嗜铬细胞瘤的指标,并阐明二者间的关系。方法选取1986年10月～2006年8月住院经手术治疗,且具有完整的临床、病理和随访资料的嗜铬细胞瘤患者存档石蜡标本38例,其中良性嗜铬细胞瘤21例,恶性嗜铬细胞瘤17例。恶性嗜铬细胞瘤组中首次手术确诊为嗜铬细胞瘤后随访28～179个月;良性嗜铬细胞瘤组中首次手术确诊为嗜铬细胞瘤后随访93～264个月。另取20例因良性肾疾患行肾切除时获取的同侧正常肾上腺组织作为对照组。采用免疫组织化学技术,检测良、恶性嗜铬细胞瘤及20例正常肾上腺髓质组织中HPA和VEGF的表达情况。结果HPA在恶性嗜铬细胞瘤中高表达（76．47％）,在良性嗜铬细胞瘤中表达较低（28．57％）,在正常肾上腺髓质组织中无表达,恶性嗜铬细胞瘤组与良性嗜铬细胞瘤组及恶性嗜铬细胞瘤组与正常。肾上腺髓质组织组之间HPA的表达有显著性差异（P〈0．05）。VEGF在恶性嗜铬细胞瘤中呈高表达,阳性率为82．40％,在良性嗜铬细胞瘤和正常。肾上腺髓质组织中的阳性率分别为23．80％、5．00％,VEGF在恶性嗜铬细胞瘤中的表达与在良性嗜铬细胞瘤和正常肾上腺髓质组织中的表达有显著性差异（P〈0．05）。在嗜铬细胞瘤中HPA与VEGF的表达呈正相关。结论HPA和VEGF有望成为预测恶性嗜铬细胞瘤的指标。     

Pheochromocytomas: can malignant potential be predicted?

OBJECTIVES: The presence of metastatic lesions is the only acceptable fact to confirm malignant pheochromocytoma. Patients with malignant pheochromocytomas, however, have a very poor survival rate. The aim of our study was to postulate predictive values for malignant pheochromocytomas. METHODS: We evaluated symptoms, diagnostic modalities, treatment, and long-term follow-up of 86 patients with 85 benign and 10 malignant pheochromocytomas. Parameters from the benign were compared with those of the malignant pheochromocytomas. RESULTS: Preoperative 24-hour urinary dopamine was in the normal range for benign pheochromocytomas but increased in malignant pheochromocytomas (P<0.0001). Vanillylmandelic acid was elevated in both benign and malignant pheochromocytomas but higher in malignant than in benign tumors (P = 0.01). No differences could be shown in urinary epinephrine and norepinephrine samplings. Tumor location was divided into 77 adrenal (81%) and 18 extra-adrenal (19%) sites. Malignant pheochromocytomas were located more often at extra-adrenal sites (P = 0.03). There was no increased incidence of malignancy in patients with familial bilateral pheochromocytomas or multiple endocrine neoplasia. Tumors greater than 80 g in weight corresponded to malignancy (P<0.0001). Dopamine tumor concentration was higher in malignant than in benign pheochromocytomas (P = 0.01). Persistent arterial hypertension occurred in 9 (13%) of 72 benign and 6 (60%) of 10 malignant pheochromocytomas (P = 0.001). The 10-year survival rate was 94% for benign pheochromocytomas. All patients with malignant pheochromocytomas died within this period (P = 0.0001). CONCLUSIONS: High preoperative 24-hour urinary dopamine levels, extra-adrenal tumor location, high tumor weight, elevated tumor dopamine concentration, and postoperative persistent arterial hypertension are all factors that increase the likelihood of malignant pheochromocytoma. Patients with these characteristics should have more frequent follow-up evaluations to identify malignancy at earlier states.     

Extra-adrenal pheochromocytoma.

Extra-adrenal pheochromocytomas may arise in any portion of the paraganglion system, although they most commonly occur below the diaphragm. The most common site of occurrence of extra-adrenal pheochromocytoma is the superior para-aortic region between the diaphragm and lower renal poles. Although the traditional teaching has been that 10% of all pheochromocytomas are at extra-adrenal sites, this may be an underestimation. Extra-adrenal pheochromocytomas probably represent at least 15% of adult and 30% of childhood pheochromocytomas. They may be malignant in up to 40% of the cases, although conflicting data add to the uncertainty of this point. Patients with tumors arising at extra-adrenal sites commonly present with headache, palpitations, sweating and hypertension. The diagnosis is most often confirmed by demonstrating increased catecholamine production, usually by measurement of urinary catecholamines and/or their metabolites. CT scanning is presently the imaging procedure of choice for localization. The roles of MRI and 131I-MIBG scintigraphy in the localization process are still being determined. Thorough preoperative pharmacological preparation, attentive intraoperative monitoring and aggressive surgical therapy all have an important role in achieving the safest and most successful outcome. Complete surgical excision is the treatment of choice for primary extra-adrenal pheochromocytoma as well as recurrent or metastatic disease. When residual tumor cannot be resected, medical therapy for symptomatic relief is preferred, since radiotherapy and chemotherapy have limited effectiveness. Extra-adrenal pheochromocytomas are more likely to recur and to metastasize than their adrenal counterparts, making lifelong followup with annual determinations of catecholamine production essential.     

Experience with extra-adrenal pheochromocytoma

From 1955 to 1985, 20 patients presented with a total of 22 extra-adrenal pheochromocytomas (2 had multiple tumors and 2 had a malignant extra-adrenal pheochromocytoma). There were 13 male and 7 female patients, and the highest incidence was in the second decade. Although most patients presented with symptoms typical of pheochromocytoma, several presented with unusual features related to the anatomical location, such as mediastinal mass (chest tumor), upper airway obstruction (neck tumor) or gross hematuria (bladder tumor). In 5 of 6 patients in whom plasma catecholamine levels were fractionated epinephrine levels were elevated. The most common tumor location was the superior para-aortic region (13 patients). In 16 patients the location of tumors was established before treatment. Computerized tomography (9 patients) was the most accurate imaging study for tumor localization. A total of 19 patients underwent complete excision of all pheochromocytomas. Postoperative followup information (median interval 120 months) was available for 15 of these patients. Three patients had recurrent pheochromocytoma that was treated successfully. One patient had essential hypertension. No patient had metastatic disease. The low incidence of malignancy suggests a benign course for extra-adrenal pheochromocytoma and represents a departure from the previously reported higher incidence of malignancy with extra-adrenal pheochromocytoma.     

Dihydroxyphenylglycol in Pheochromocytoma: Its Diagnostic Use for Norepinephrine Dominant Tumor

Purpose

To discern whether the 3,4-dihydroyphenylglycol produced in adrenal medulla is associated with altered urinary excretion, we compared the tissue and urinary levels of this catecholamine metabolite, epinephrine and norepinephrine in 23 patients with pheochromocytoma and 26 subjects with renal cell carcinoma.

Materials and Methods

Tissue and urine concentrations of dihydroyphenylglycol, epinephrine and norepinephrine were determined by catechol-O-methyl-transferase-based radioenzymatic method and high performance liquid chromatography with electrochemical detection.

Results

Contents of dihydroyphenylglycol, epinephrine and norepinephrine in pheochromocytomas were higher than those in normal adrenal medullae. Removal of pheochromocytomas lowered urinary excretion of these catecholamines and dihydroxyphenylglycol. Norepinephrine content correlated closely with dihydroxyphenylglycol content in normal adrenal medullae and pheochromocytomas but not with epinephrine content in either tissue. Contents of norepinephrine and dihydroxyphenylglycol correlated significantly with urinary norepinephrine excretion and dihydroxyphenylglycol excretion in patients with pheochromocytoma but not in subjects with renal cell carcinoma. The norepinephrine-to-dihydroxyphenylglycol ratio in a 24-hour preoperative urine collection from patients with pheochromocytoma was higher than that from subjects with renal cell carcinoma, which was almost similar to that of epinephrine dominant pheochromocytomas.

Conclusions

Our study suggests that dihydroxyphenylglycol in urine in subjects with renal cell carcinoma is predominantly of a neuronal origin and urinary dihydroxyphenylglycol in patients with pheochromocytoma is of tumor origin. A high level of norepinephrine-to-dihydroxyphenylglycol ratio in urine can be used to determine the diagnosis of the norepinephrine dominant type pheochromocytoma. Measurement of at least a few markers is preferable for precise biochemical diagnosis of pheochromocytoma.     

复发性嗜铬细胞瘤

目的提高复发性嗜铬细胞瘤的诊断水平。方法总结１９７０～１９９６年术后复发的嗜铬细胞瘤１１例，占同期嗜铬细胞瘤的９．３％。经手术及病理证实复发原因是恶性肿瘤的转移及良性肿瘤的多发。结果肾上腺外嗜铬细胞瘤易多发或转移，转移部位多在无嗜铬组织的部位，而多发部位常在肾上腺外。结论复发肿瘤是良性还是恶性应结合诸多因素综合判断。复发嗜铬细胞瘤不都是恶性肿瘤，但因恶性倾向较大应密切观察，定期复查。尤其对原发或复发在肾上腺外的肿瘤更应如此。作者还就复发嗜铬细胞瘤诊断进行讨论。     

Differential heparanase-1 expression in malignant and benign pheochromocytomas

INTRODUCTION: Extracellular matrix (ECM) degradation is an essential step that allows tumor cells to penetrate a tissue barrier and become metastatic. Heparanase-1 (HPR) is an endoglycosidase that specifically degrades heparan sulfate proteoglycans, a chief component of the ECM. Previous studies have demonstrated HPR expression in various malignancies and that there is differential HPR expression between benign and malignant tumors. Currently, there is no technique that can reliably predict the malignant behavior of some pheochromocytomas. This study tests whether HPR is differentially expressed in malignant and benign pheochromocytomas. METHODS: Paraffin-embedded specimens from 29 pheochromocytomas were evaluated. The tissues were collected from surgical specimens over a 10-year period from 26 patients (8 males, 18 females) with a mean age of 47 years (range 19-78 years, median 47 years). One female patient underwent 3 separate operations for malignant pheochromocytoma and thus provided 3 specimens. Another female patient had both the primary tumor and a liver metastasis processed, and therefore provided 2 specimens. Patient charts and pathology reports were reviewed to classify the pheochromocytomas as either benign or malignant. Based on clinical behavior and/or pathological evidence of metastasis or invasion into surrounding tissues, 10 specimens were malignant and 19 had benign behavior. As a control, normal adrenal tissue from 3 nephrectomy specimens was included in the study, as was tissue from 1 adrenocortical adenoma. All 33 specimens were tested for HPR gene expression by in situ hybridization (ISH) with an antisense RNA probe and immunohistochemistry (IHC) with an anti-HPR antibody. Statistical analysis was done using the chi(2) test of proportions to determine if HPR expression correlated with malignancy using ISH, IHC, or both tests together. RESULTS: Using ISH, the percentage of HPR expression in the malignant pheochromocytomas was 50% while HPR expression in the benign tumors was 21% (P = 0.11). Using IHC, the percentage of HPR expression in the malignant pheochromocytomas was 80% while HPR expression in the benign tumors was 32% (P = 0.01). Considering both tests cumulatively, all 10 malignant pheochromocytomas stained positive for HPR by ISH and IHC, while only 37% of the benign tumors were positive for HPR expression (P = 0.001). The one adrenal adenoma and the 3 normal adrenal glands processed stained negative for HPR expression by both ISH and IHC. CONCLUSIONS: HPR expression is higher in malignant pheochromocytomas than in benign pheochromocytomas or normal tissue. HPR may contribute to the invasive characteristics of malignant pheochromocytomas and might be used as a marker to distinguish malignant from benign pheochromocytomas. HPR expression might also be used as a prognostic tool in guiding long-term patient follow-up.     

嗜铬细胞瘤诊疗:单中心142例报告

目的 提高嗜铬细胞瘤的诊疗水平.方法 回顾性分析2002年8月至2010年2月手术治疗的142例患者145例次病理确诊嗜铬细胞瘤临床资料,并对术后近期高血压恢复情况及远期肿瘤复发情况进行随访.肿瘤直径1.3～18.0 cm,平均5.9 cm,位于肾上腺内的单发肿瘤117例,双侧肿瘤10例,异位肿瘤10例,肾上腺及肾上腺外同时存在肿瘤5例.有典型儿茶酚胺症状者98例(69.0%),隐匿型嗜铬细胞瘤44例(31.0%).术前给予酚苄明或甲磺酸多沙唑嗪准备l周以上.142例患者行手术145例次,开放手术91例次,腹腔镜54例次. 结果 142例术后病理均为嗜铬细胞瘤,其中良性83例、恶性23例、可疑恶性36例.术中血压骤增与术前血儿茶酚胺水平相关,与术前血压、术前应用a受体阻滞剂时间长短及肿瘤大小无关.术后高血压症状缓解87例,11例仍需药物控制血压.围手术期死亡1例.术后91例随访3～96个月,中位时间46个月,复发转移10例,其中5年内死于肿瘤复发转移6例. 结论嗜铬细胞瘤确诊主要依据临床表现、生化定性检查及影像学定位检查,手术切除肿瘤是嗜铬细胞瘤的根治方法,对于术前血儿茶酚胺水平明显升高的患者更应警惕术中血压变化,术前应给予更充分的准备.

Abstract：

Objective To review the experience in diagnosis and treatment of pheochromocytoma in a single center. Methods A total number of 142/145 pheochromocytoma cases treated surgically in our institute from August 2002 to February 2010 were retrospectively reviewed. The mean diameter of tumor was 5.9 cm (1.3- 18. 0 cm). The majority of the tumors (92.9%) were adrenal pheochromocytomas. Ninety-eight patients (69.0 % ) presented initially with hypertension, whereas 44 patients (31%)presented with adrenal incidentaloma. A specific anti-hypertensive pre-surgery preparation with phenoxybenzamine or doxazosine mesylate was started over 1 week before the operation.Of the 142 patients, 91 accepted open surgery, 54 accepted laparoscopic surgery, of which, 5 converted from laparoscopic surgery to open surgery. Results Histopathological results showed that all the cases were pheochromocytoma, while 83 cases were benign, 23 cases were malignant and 37 cases were suspected malignant. Sudden rising of blood pressure during operation was related to the preoperative serum level of catecholamine. Eighty-seven of 98 patients with preoperative hypertension had normal postoperative blood pressure; the remaining 11 patients reduced the dosage of anti-hypertension medication postoperatively. During the follow-up of 3-96 months (median 46 months), 10 of 91patients had a recurrence or metastasis. Six patients died of recurrences or metastasis within 5 years.Conclusions The procedures of qualitative and locative diagnosis of phechromocytoma include clinical manifestations, biochemical tests and imaging investigation. Surgical excision is the fundamental treatment for cure. Patients with high serum level of catecholamine tend to have a sudden rising of blood pressure during operation. Preoperative management is extremely important for the safety of the patient. Intensive follow up is necessary.     

The effect of tumor necrosis factor-alpha on human malignant glial cells.

The influence of human recombinant tumor necrosis factor-alpha has been assessed on a cell line (U-251) derived from a human malignant glial tumor. The results of this study demonstrate that tumor necrosis factor-alpha at doses of 50 and 100 ng/ml: 1) did not have cytotoxic or cytostatic effects on the U-251 cell line; 2) significantly increased the intracellular activity of manganese superoxide dismutase but had no effect on copper and zinc superoxide dismutase, catalase, or glutathione peroxidase activity; and 3) did not significantly alter the intracellular or extracellular general protease and collagenase type IV activity of these cells. The resistance of the U-251 cell line to tumor necrosis factor-alpha cytotoxicity may be related in part to the high intrinsic manganese superoxide dismutase activity present in this cell line combined with the ability of this cell line to induce substantial amounts of protective manganese superoxide dismutase activity in response to tumor necrosis factor-alpha.     

CoX-2在恶性嗜铬细胞瘤中的表达及与VEGF、MVD的关系

目的：探讨CoX2能否成为一种预判恶性嗜铬细胞瘤的指标．并阐明其与VEGF、MVD间的关系。方法：选取经手术治疗且具有完整的临床、病理和随访资料的嗜铬细胞瘤患者存档石蜡标本38例,其中良性组21例,恶性组17例。另取20例正常肾上腺组织作为对照组。采用免疫组织化学技术,检测良、恶性嗜铬细胞瘤及正常肾上腺髓质组织中CoX2、VEGF的表达情况及MVD表达情况。结果：①CoX2在恶性组中表达最高,良性组中表达较低,对照组中无表达．恶性组与良性组及恶性组与对照组之间CoX2的表达差异有统计学意义（P〈0．05）。②VEGF在恶性组中呈高表达．VEGF在恶性组中的表达与在良性组和对照组中的表达差异有统计学意义（P-〈0．05）,在良性组和对照组中的表达差异没有统计学意义（P〉0．05）。③MVI）在恶性组中表达最高,良性组次之,对照组最少,两两之间的表达差异有统计学意义（P〈0．05）。①在嗜铬细胞瘤中CoX2与VEGF的表达呈正相关,CoX-2的表达与MVD呈正相关．VEGF的表达与MVD呈正相关。结论：CoX2和VEGF有望成为预判恶性嗜铬细胞瘤的一种指标。     

恶性嗜铬细胞瘤的诊断与治疗

目的 提高对恶性嗜铬细胞瘤的诊断水平。方法 对７例肾上腺恶性嗜铬细胞瘤进行回顾性分析。结果 本组患者肾上腺嗜铬细胞直径均大于７．０ｃｍ,内部结构为不均质,囊实相间;有血儿茶酚胺、尿香草基扁桃酸异常增高而无高血压的分离现象,并伴有进行性消瘦、血沉加快等。结论 部分病例组织病理学与临床过程不一致,术后应长期随访。恶性嗜铬细胞瘤复发及转移率高,术后应进行瘤床放疗和全身化疗。     

Catecholamine metabolism in pheochromocytoma and normal adrenal medullae

The tissue contents of catecholamine, its precursor and its major metabolites were determined in 8 human pheochromocytomas and 26 normal adrenal glands. Pheochromocytomas contained significantly larger amounts of norepinephrine, dopamine, dihydroxyphenylalanine, tyrosine hydroxylase activity, metanephrine, normetanephrine and vanillylmandelic acid than did normal adrenal medullae. The content ratio of epinephrine/norepinephrine in normal adrenal medullae was significantly higher than that in pheochromocytomas but there were considerable individual variations in the metanephrine/normetanephrine and vanillylmandelic acid/3-methoxy-4-hydroxyphenylethylglycol ratios in pheochromocytomas. In normal adrenal medullae the tissue content of tyrosine hydroxylase activity correlated inversely with the tissue contents of epinephrine (r equals -0.78, p less than 0.001), norepinephrine (r equals -0.78, p less than 0.001) and total catecholamines (r equals -0.87, p less than 0.001), respectively but no significant relation was found between both parameters in pheochromocytomas. These results indicate the possible presence of a negative feedback mechanism of catecholamine via tyrosine hydroxylase in normal adrenal medullae but none in pheochromocytomas. In addition, the increased degradation catecholamine pathway in pheochromocytomas appears to be unstable compared to that in normal adrenal medullae.     

Dopamine-secreting Pheochromocytomas: In Search of a Syndrome

Pheochromocytomas rarely produce dopamine as the only catecholamine. Two cases are reported here, and a review of the literature was conducted. Unlike norepinephrine-and epinephrine-secreting tumors, dopamine-secreting pheochromocytomas lack a classic clinical presentation and are often asymptomatic. Urinary and serum metabolites cannot be relied on to make the diagnosis, and serum or urine dopamine levels (or both) must be measured when dealing with a potential pheochromocytoma. Dopamine-secreting tumors are less likely to enhance with metaiodobenzylguanidine (MIBG) scanning and may benefit from the use of positron emission tomography. Treatment is en bloc surgical excision; but unlike other pheochromocytomas, α-blockade is not indicated as it may lead to hypotension and cardiovascular collapse. Metyrosine is a medication that can be useful for preoperative control of symptoms from these tumors. The function of metyrosine is to block dopamine synthesis; it has no α-blocking effect. This medication is an option for controlling symptoms but should not be used routinely in these patients. The prognosis for patients with these tumors is worse than for those with an epinephrine- and norepinephrine-secreting tumor. Because of their asymptomatic nature, dopamine-secreting pheochromocytomas tend to be detected later and are more likely to be malignant at the time of diagnosis.     

Malignant giant pheochromocytoma: a case report and review of the literature

Malignant pheochromocytoma is a rare disease and surgical resection is the only curative treatment. There are no definitive histological or cytological criteria of malignancy, as it is impossible to determine this condition in the absence of advanced locoregional disease or metastases. We report a case of a patient with a giant retroperitoneal tumour, the second largest to be published, which was diagnosed as a malignant pheochromocytoma; it was treated with surgery. The literature is reviewed to evaluate tumour features and criteria to distinguish between benign and malignant pheochromocytomas.     

Pheochromocytoma associated with neurofibromatosis 1: a report of two cases

Pheochromocytomas may occur as either sporadic or familial tumors. Clinical features of pheochromocytomas in neurofibromatosis 1 (NF1) patients are similar to those in patients with sporadic pheochromocytomas, unlike pheochromocytomas associated with other hereditary syndromes. Here we report two cases of pheochromocytoma associated with NF1. Case 1: A 29-year-old man with previously undiagnosed NF1, was admitted to our hospital for hypertension and a right adrenal tumor. On physical examination, café-au-lait spots and neurofibromas were observed on his body. Serum and urine catecholamine levels were markedly elevated. Case 2: The patient was a 46-year-old man with NF1. The tumor was incidentally detected by ultrasonography. Serum and urine catecholamine levels were similarly elevated. 131I-MIBG scintigraphy showed an abnormal accumulation in the right adrenal gland. After this diagnosis of pheochromocytoma associated with NF1, open adrenalectomy was performed. No evidence of malignancy was seen in either case.     

Pheochromocytoma of the Adrenal gland Scaled Score (PASS) to separate benign from malignant neoplasms: a clinicopathologic and immunophenotypic study of 100 cases

No comprehensive series has evaluated the histologic features of pheochromocytoma to separate benign from malignant pheochromocytoma by histomorphologic parameters only. Fifty histologically malignant and 50 histologically benign pheochromocytomas of the adrenal gland were retrieved from the files of the Armed Forces Institute of Pathology. The patients included 43 females and 57 males, with an age range of 3-81 years (mean 46.7 years). Patients usually experienced hypertension (n = 79 patients). The mean tumor size was 7.2 cm (weight was 222 g). Histologically, the cases of malignant pheochromocytomas of the adrenal gland more frequently demonstrated invasion (vascular [score = 1], capsular [score = 1], periadrenal adipose tissue [score = 2]), large nests or diffuse growth (score = 2), focal or confluent necrosis (score = 2), high cellularity (score = 2), tumor cell spindling (score = 2), cellular monotony (score = 2), increased mitotic figures (>3/10 high power fields; score = 2), atypical mitotic figures (score = 2), profound nuclear pleomorphism (score = 1), and hyperchromasia (score = 1) than the benign tumors. A Pheochromocytoma of the Adrenal gland Scaled Score (PASS) weighted for these specific histologic features can be used to separate tumors with a potential for a biologically aggressive behavior (PASS > or =4) from tumors that behave in a benign fashion (PASS <4). The pathologic features that are incorporated into the PASS correctly identified tumors with a more aggressive biologic behavior. Application of these criteria to a large cohort of cases will help to elucidate the accuracy of this grading system in clinical practice.     

不同临床表现类型的嗜铬细胞瘤

目的　提高对嗜铬细胞瘤的诊断和治疗水平。　方法　总结 1987年 6月～ 1998年 8月诊治的嗜铬细胞瘤 90例。　结果　本组 90例中 3 6例 5 1例次表现为 :肾上腺外者 14例 ,无症状性5例 ,复发性 8例 ,恶性或恶变者 15例 ,双侧或多发性 4例 ,家族性及多发性内分泌腺瘤 5例。 3 6例嗜铬细胞瘤随访 6个月～ 10年 ,8例复发 ,恶变 3例。　结论　手术切除肿瘤是嗜铬细胞瘤有效的治疗方法。复发性嗜铬细胞瘤并不都是恶性肿瘤 ,但因恶性倾向较大 ,需密切随诊。家族性嗜铬细胞瘤常为双侧或多发性。