嗜铬细胞瘤诊疗对策

目的:探讨和比较嗜铬细胞瘤包括不典型和复杂嗜铬细胞瘤的临床特点,总结诊断,鉴别诊断和治疗经验.方法:回顾性分析1982年1月～2002年12月221例嗜铬细胞瘤的临床表现,体征,实验室检查,影像学检查和病理检查资料.结果:本组病例男99例,女122例;平均年龄43.7岁.3例体检发现肿瘤,15例因消化道症状发现肿痛,3例于其他疾病随访中发现肿瘤.195例因血压增高发现肿瘤.176例为症状功能性嗜铬细胞瘤,21例为静止型嗜铬细胞瘤,15例为肾上腺外嗜铬细胞瘤(其中8例为多发性嗜铬细胞瘤),17例诊断为多发性嗜铬细胞瘤.13例为恶性嗜铬细胞瘤.结论:实验室捡查对症状功能性嗜铬细胞瘤的诊断意义较大.影像学检查有助于肾上腺偶发瘤中发现静止型嗜铬细胞瘤.肾上腺外嗜铬细胞瘤常常多发.肾上腺外多发、复发嗜铬细胞瘤有较高的恶变倾向,手术是治疗各种嗜铬细胞瘤的首选方法.     

腹部嗜铬细胞瘤的临床及螺旋CT多期扫描表现

目的 评价螺旋CT多期扫描在腹部嗜铬细胞瘤诊断和鉴别诊断中的价值.方法 回顾性分析70例患者的79个经病理证实为肾上腺嗜铬细胞瘤及腹内异位嗜铬细胞瘤的螺旋CT多期扫描表现.结果 70例患者中,有与嗜铬细胞瘤有关的内分泌症状者41例,隐匿型嗜铬细胞瘤15例,无功能嗜铬细胞瘤14例.单发63例,多发7例,共有79个病灶.肾上腺嗜铬细胞瘤60例,异位嗜铬细胞瘤8例,肾上腺嗜铬细胞瘤合并异位嗜铬细胞瘤2例.良性60例,恶性或术后复发10例.79个肿瘤病灶中,肿瘤均呈圆形或类圆形,长径2～15 cm,平均5.8 cm.6个长径≤4 cm的肿瘤病灶在扫描各时相均较均匀,25个肿瘤病灶有明显的血窦形成,48个肿瘤病灶有不同程度的出血、坏死和囊变灶,其中9个可见液-液平面.65个肿瘤为富血供,14个为中等血供.结论 约40%的腹部嗜铬细胞瘤无相关的内分泌症状,但腹部嗜铬细胞瘤多有较为特征性的CT表现:小的肿瘤较均匀而富血供;较大的肿瘤有不同程度的出血、坏死和囊变灶,为富血供或中等血供,约50%的病灶内可见血窦或液-液平面,有助于与其他疾病相鉴别.     

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。     

~(131)I-MIBG治疗恶性嗜铬细胞瘤

一、目的回顾性分析1例恶性嗜铬细胞瘤术后全身多发转移患者先后4次接受大剂量131I-MIBG治疗的经过,探讨131I-MIBG用于治疗手术难以切除或术后复发的嗜铬细胞瘤的价     

肾上腺外恶性嗜铬细胞瘤

临床上肾上腺外嗜铬细胞瘤少见,而恶性者罕见。肾上腺外嗜铬细胞瘤在人体多处均可发生,因此对于好发部位出现的临床上诊断不明确的肿块,均应警惕本病可能。通过B超、CT、MR扫描等影像学检查可对肿瘤进行定位诊断。手术治疗为首选。常规病理难以区别肿瘤的良恶性,应综合患者的临床表现、术中探查所见、术后病理及其他辅助诊断技术来综合判断。恶性患者术后可辅以环磷酰胺、长春新碱、氮烯咪胺等化学药物治疗或¹³¹I-MIBG、¹²³I-MIBG进行姑息性治疗。术后长期随访很重要。     

肾上腺嗜铬细胞瘤53例临床及病理分析

目的探讨肾上腺嗜铬细胞瘤组织形态、免疫组织化学及生物学行为特征.方法采用回顾性分析的方法,对53例肾上腺嗜铬细胞瘤进行临床、病理形态学分析及免疫组织化学检测CgA、Syn抗原标记物在肿瘤中的表达情况,并行临床资料分析及跟踪随访.结果46例有阵发性高血压,4例有持续性高血压,4例无自觉症状.50例细胞分化成熟,4例有周围组织浸润.免疫组化染色:CgA(+);Syn(-).结论CgA在嗜铬细胞瘤呈阳性表达,可用于鉴别肾上腺皮质腺瘤和嗜铬细胞瘤.嗜铬细胞瘤的良、恶性鉴别诊断主要依据是否有转移.     

膀胱嗜铬细胞瘤的诊断及治疗

目的 探讨膀胱嗜铬细胞瘤的临床诊断及治疗方法.方法 回顾性分析了1995至2004年6例膀胱嗜铬细胞瘤患者的临床资料及随访结果,并复习相关文献.结果 6例术后病理均为嗜铬细胞瘤.4例术前未发现转移的膀胱嗜铬细胞瘤患者术后临床症状消失,随访至今未见复发.2例有淋巴结转移的病例中,1例行转移淋巴结切除术,术后行化疗,随访至今未见复发;另1例因转移的淋巴结与髂血管关系紧密,未能切除.术中放置银夹,术后行放疗,效果不佳.转移的淋巴结未见明显缩小,临床症状及体征也未见好转,2年后因全身多发转移死亡.结论 膀胱嗜铬细胞瘤典型的临床症状是排尿时头痛、头晕、心悸、出汗,血尿和高血压等,可用B超、CT、膀胱镜行定位诊断,血尿儿茶酚胺(catechol amine,CA)测定行定性诊断.手术治疗为主要的治疗方法.膀胱恶性嗜铬细胞瘤最常转移的部位为髂血管旁淋巴结.早期发现,早期手术,术后辅以化疗能取得较好的疗效.术后监测临床症状及血尿儿茶酚胺,可以了解有无转移或复发.     

1例恶性嗜铬细胞瘤多发转移的多学科协作诊疗

恶性嗜铬细胞瘤是起源于嗜铬组织的罕见恶性肿瘤,是否发生转移是判断其良恶性的标准。本例患者以多发肝、肺、骨转移就诊,查多项肿瘤标志物、胃镜、胸腹强化CT、PET-CT均难以确诊,行肝转移瘤穿刺活检,病理示:（肝右叶）恶性神经内分泌肿瘤,结合右侧肾上腺嗜铬细胞瘤切除术病史及免疫组织化学结果,考虑为恶性嗜铬细胞瘤肝、肺、骨转移。目前恶性嗜铬细胞瘤尚无标准治疗,文献报道使用CVD方案（环磷酰胺、长春新碱、达卡巴嗪）和靶向药物舒尼替尼能取得一定治疗效果。本例患者接受2个周期CVD化疗及1个疗程索坦治疗后,疾病仍缓慢进展。通过多学科讨论,认为131I-MIBG（131I-间位碘苄胍）可以作为该患者下一步治疗的选择。      

嗜铬素A和突触素在肾上腺肿瘤中的表达及其临床意义

目的探讨嗜铬素A（CgA）和突触素（Syn）在各型肾上腺肿瘤中的表达及其临床意义。方法对69例肾上腺肿瘤和4例正常肾上腺组织运用免疫组化方法进行组织染色,研究C外和Syn的表达,并采用x^2检验进行统计学分析。结果在正常肾上腺组织,CgA和Syn主要表达于髓质。CgA在全部25例嗜铬细胞瘤中均呈阳性表达,而在肾上腺皮质肿瘤中极少表达;Syn在肾上腺皮质腺瘤、皮质癌、嗜铬细胞瘤及肾上腺转移癌的阳性表达率分别为96．4％（27／28）、87．5％（7／8）、96．0％（24／25）和75．0％（6／8）。结论CgA在肾上腺皮质与髓质肿瘤间、嗜铬细胞瘤与恶性嗜铬细胞瘤间的表达率差异有统计学意义。CgA、Syn可作为标志物对各型肾上腺肿瘤进行鉴别诊断。     

肾上腺外嗜铬细胞瘤二例报告

嗜铬细胞瘤是一种少见的肿瘤,约有10～30%发生于肾上腺外的交感神经节或副交感神经节之嗜铬组织中。我科收治腹主动脉旁恶性嗜铬细胞瘤及膀胱壁嗜铬细胞瘤各一例,现报告如下。病例介绍例1,女,60岁,左上腹包块8年,入院前一年来感左上腹发胀,食欲减退,低热,以腹块待查人     

Clinical characteristics of pheochromocytoma patients with germline mutations in SDHD.

PURPOSE: We examined the value of SDHD mutation screening in patients presenting with apparently sporadic and familial pheochromocytoma for the identification of SDHD-related pheochromocytomas. PATIENTS AND METHODS: This retrospective study involved 126 patients with adrenal or extra-adrenal pheochromocytomas, including 24 patients with a family history of multiple endocrine neoplasia 2, von Hippel-Lindau disease, neurofibromatosis type 1, or paraganglioma (PGL). Conformation-dependent gel electrophoresis and sequence determination analysis of germline and tumor DNA were used to identify SDHD alterations. The clinical and molecular characteristics of sporadic and hereditary tumors were compared. We reviewed the literature and compared our results with those from previously published studies. RESULTS: Pathogenic germline SDHD mutations were identified in three patients: two (2.0%) of the 102 apparently sporadic pheochromocytoma patients and one patient with a family history of PGL. These patients presented with multifocal disease (two of three multifocal patients) or with a single adrenal tumor (one of 82 patients). In the literature, mutations are mostly found in patients 相似文献   

Neuropeptide Y expression distinguishes malignant from benign pheochromocytoma

No reliable gross or microscopic features distinguish benign from malignant pheochromocytomas. The diagnosis of malignant pheochromocytoma is based solely on the presence of regional or distant metastases. This study evaluated the expression of neuropeptide Y messenger RNA (mRNA) in nine benign and 11 malignant pheochromocytomas and has found that neuropeptide Y mRNA was expressed in all nine benign tumors but in only four of 11 malignant tumors (P = .0084). These data suggest that the determination of neuropeptide Y expression in the evaluation of patients with pheochromocytoma may have prognostic significance.     

Pheochromocytoma

Opinion statement Pheochromocytoma is a rare tumor, but it represents a potentially curable form of hypertension. In patients with inherited pheochromocytoma, benign and bilateral tumors are more common. The diagnosis of pheochromocytoma rests in biochemical confirmation of catecholamine excess. Plasma-free metanephrine levels are arguably the most sensitive and specific test for the biochemical diagnosis of pheochromocytoma in high-risk patient populations. A timed 24-hour urine collection for total catecholamines and metabolic products (eg, vanillylmandelic acid and metanephrines) is the favored confirmatory test. Localization is most commonly accomplished with high-resolution computed tomography imaging, but magnetic resonance imaging can also be used. If both of these imaging modalities are nonlocalizing or equivocal, then radiolabeled meta-iodobenzylguanidine or somatostatin can be used to identify an adrenal or extra-adrenal tumor (paraganglioma). These imaging modalities can be used in the evaluation of patients with suspected or confirmed recurrent or metastatic disease. Systemic therapies for the treatment of patients with recurrent or metastatic disease have been disappointing. Radiation therapy is best applied for palliative relief of pain associated with bony metastases. In the absence of radiographic evidence for local tumor invasion, laparoscopic resection of small-to medium-sized (< 6 cm) pheochromocytomas is indicated. Abundant evidence indicates that this approach is safe and well tolerated and results in more rapid recovery and less long-term wound morbidity compared to open anterior or posterior adrenalectomy. Open anterior adrenalectomy is appropriate for patients with large or recurrent tumors, suspected or documented locoregional invasion, or for those patients in whom a laparoscopic approach is technically contraindicated. For selected patients with pheochromocytoma in the von Hipple-Lindau syndrome or multiple endocrine neoplasia type 2 setting in which the cumulative incidence of clinical bilateral tumors is high, a corticalsparing approach may minimize the risk of Addisonian complications.     

Predicting metastasis of pheochromocytomas using DNA flow cytometry and immunohistochemical markers of cell proliferation: A positive correlation between MIB-1 staining and malignant tumor behavior.

BACKGROUND: In the absence of metastases, there are no reliable microscopic features that distinguish malignant from benign pheochromocytomas. Because a common feature of malignancy is the loss of cell cycle regulation and normal growth arrest, the authors hypothesized that analysis of the cell cycle could be used to aid in the diagnosis of malignant pheochromocytoma. METHODS: Cell cycle analysis of archival samples of 51 pheochromocytomas (40 sporadic, 11 familial) from 45 patients, including 6 malignant and 45 benign tumors, was conducted. Flow cytometry data and immunohistochemistry for markers of cell proliferation (proliferating cell nuclear antigen [PCNA] and MIB-1 [Ki-67]) were correlated with the authors' clinical data base records, with a mean follow-up of 66 months. RESULTS: No correlation of DNA ploidy, S-phase fraction by flow cytometry, or PCNA with malignancy was observed. Staining for the MIB-1 nuclear proliferation marker was positive in 3 of 6 (50%) of the malignant pheochromocytomas and negative in all 45 benign tumors (P< 0.01). CONCLUSIONS: Contrary to some previous reports, a diploid DNA pattern does not necessarily predict benign behavior of pheochromocytoma. In this study, cell cycle analysis and, in particular, assessment of the MIB-1 nuclear proliferation marker was useful in the histologic evaluation of pheochromocytoma, as MIB-1 was expressed only in malignant tumors.     

乳腺复发性叶状肿瘤临床病理分析

目的:探讨乳腺复发性叶状肿瘤临床及病理特征。方法:收集2011年01月至2019年12月在我院进行手术治疗的叶状肿瘤病例,并找出其中复发的病例,分析复发病例的临床及病理组织学特征。结果:叶状肿瘤137例,共有10例为复发病例,其中9例为单次复发,1例复发两次,复发病例中良性叶状肿瘤7例,交界性叶状肿瘤2例,恶性叶状肿瘤1例。所有的肿物均为局部复发,良性、交界及恶性叶状肿瘤复发率分别为5.9%、15.4%、20%。其中3例（30%）出现组织学升级,1例良性叶状肿瘤复发为交界性叶状肿瘤,1例交界性叶状肿瘤复发为恶性叶状肿瘤,1例良性叶状肿瘤第一次复发为交界性叶状肿瘤,第二次复发为恶性叶状肿瘤。免疫组化标记CD117、CD34、CD10、p53、p16在原发及复发肿瘤中表达无差异。Ki67增殖指数在复发病例中均升高,并且核分裂数也增多。结论:良性、交界性、恶性叶状肿瘤均可复发,其中恶性叶状肿瘤复发率最高,肿瘤多为局部复发,部分肿瘤复发后出现组织学升级,复发后肿瘤细胞增殖活性增强。     

Pheochromocytoma and functional paraganglioma syndrome: no longer the 10% tumor

Pheochromocytomas and abdominal paragangliomas are catecholamine-producing tumors of the sympathetic nervous system, while head and neck paragangliomas are non-secreting tumors of parasympathetic origin. Recent developments in clinical and molecular research on these tumor forms have significantly clarified their genetic backgrounds and challenged the view of "pheochromocytoma as the 10% rule tumor." Firstly, a larger proportion of these tumors are today discovered in normotensive patients during imaging carried out for other reasons than suspicion of pheochromocytoma. Secondly, although the differential diagnosis between malignant and benign tumors remains a challenge, the risk of malignancy well exceeds the classical 10% in patients with extra-adrenal disease, and/or carriers of germ-line SDHB mutations. Finally, up to a third of patients carry a germ-line mutation in a gene predisposing to pheochromocytoma and/or paraganglioma. Identification of a constitutional mutation in RET, VHL, SDHD, or SDHB has implications for clinical screening and follow-up for both the patient and for relatives at risk who can be identified by screening for the same mutation. Genetic testing in apparently sporadic cases is therefore regarded as beneficial, especially in patients diagnosed before 50 years of age, and in patients with bilateral, multifocal, malignant and/or extra-adrenal disease.     

Somatic and occult germ-line mutations in SDHD, a mitochondrial complex II gene, in nonfamilial pheochromocytoma

Most pheochromocytomas are sporadic but about 10% are though to be hereditary. Although the etiology of most inherited pheochromocytoma is well known, little is known about the etiology of the more common sporadic tumor. Recently, germ-line mutations of SDHD, a mitochondria complex II gene, were found in patients with hereditary paraganglioma. We sought to determine whether SDHD plays a role in the development of sporadic pheochromocytomas and performed a mutation and deletion analysis of SDHD. Among 18 samples, we identified 4 heterozygous sequence variants (3 germ-line, 1 somatic). One germ-line SDHD mutation IVS1+2T>G (absent among 78 control alleles) is predicted to cause aberrant splicing. On reinvestigation, this patient was found to have a tumor of the carotid body, which was likely a paraganglioma. Another patient with malignant, extra-adrenal pheochromocytoma was found to have germ-line c.34G> A (G12S). However, this sequence variant was also found in 1 of 78 control alleles. The third, germ-line nonsense mutation R38X was found in a patient with extra-adrenal pheochromocytoma. The only somatic heterozygous mutation, c.242C>T (P81L), has been found in the germ line of two families with hereditary paraganglioma and is conserved among four eukaryotic multicellular organisms. Hence, this mutation is most likely of functional significance too. Overall, loss of heterozygosity in at least one of the two markers flanking SDHD was found in 13 tumors (72%). All of the tumors that already harbored intragenic SDHD mutations, whether germ-line or somatic, also had loss of heterozygosity. Our results indicate that SDHD plays a role in the pathogenesis of pheochromocytoma. Given the minimum estimated germline SDHD mutation frequency of 11% (maximum estimate up to 17%) in this set of apparently sporadic pheochromocytoma cases and if these data can be replicated in other populations, our observations might suggest that all such patients be considered for SDHD mutation analysis.