椎管内副神经节瘤临床病理学特征

目的探讨原发于椎管内副神经节瘤的组织起源、临床病理特点、鉴别诊断及生物学特征。方法对5例原发于椎管内副神经节瘤进行组织病理学及免疫组化观察,并复习临床资料及相关文献。结果椎管内副神经节瘤好发于中老年男性,临床表现大多无神经内分泌症状,常有局部神经压迫症状。组织学形态具有一般神经内分泌肿瘤的特征。免疫组化标记表达NSE、Syn和CgA,而CK、EMA、GFAP均阴性。随访:1例术后复发。结论副神经节瘤发生在椎管内极少见,诊断主要依靠组织学及免疫组化,其生物学行为应界定为潜在恶性或低度恶性。     

颈静脉球瘤1例及副神经节瘤文献复习

目的探讨颈静脉球瘤的临床病理特征和副神经节瘤的生物学行为。方法对1例颈静脉球瘤进行组织学观察和免疫组化标记,同时复习相关文献。结果颈静脉球瘤的组织学改变类似于其他部位的副神经节瘤,免疫组化标记:瘤细胞Syn、CgA和NSE均阳性,EMA、CK、HMB45、CD34和CD99均阴性。结论颈静脉球瘤是一种起源于副神经节的少见肿瘤,呈侵袭性生长,有低度恶性的生物学行为。根据肿瘤的组织学特征,结合CT或MR I影像学资料和免疫组化标记可以作出诊断。     

婴儿色素性神经外胚瘤1例报道并文献复习

目的 探讨婴儿色素性神经外胚瘤的临床病理特征、免疫组化、诊断和鉴别诊断要点。方法 对1例婴儿色素性神经外胚瘤进行组织学和免疫组化观察和文献复习。结果 婴儿色素性神经外胚瘤好发于1岁以内的婴儿,肿瘤多见于上颌骨和颅骨,表现为浸润性和溶骨性破坏。组织学上显示大的并含不等量色素颗粒的上皮样细胞和小的神经母细胞样细胞。免疫组化显示CK、HMB-45、S-100蛋白、NSE在上皮样细胞呈阳性表达,小圆形瘤细胞S-100蛋白、NSE阳性或部分阳性。肿瘤彻底切除,随访3年未发现转移和复发。结论 婴儿色素性神经外胚瘤是一种少见的起源于神经嵴细胞的肿瘤,具有特征性的临床病理改变,需要和神经母细胞瘤、恶性黑色素瘤及其它小圆细胞肿瘤鉴别,生物学行为属于潜在恶性或低度恶性肿瘤,彻底切除预后良好。     

混合性嗜铬细胞瘤-节细胞神经瘤临床病理特征并文献复习

目的探讨混合性嗜铬细胞瘤(composite pheochromocytoma,CP)-节细胞神经瘤的临床病理学特征、免疫表型、鉴别诊断及预后。方法对3例CP-节细胞神经瘤行免疫组化SP法染色,并复习相关文献。结果男性1例,女性2例,年龄37~64岁;其中例3为纵隔原发。镜下见瘤组织均由两种成分构成:一种为瘤细胞,核圆形或卵圆形,胞质细颗粒状,排列成器官样,核分裂象罕见;一种为束状排列的神经纤维瘤样背景下,散在及聚集分布的神经节细胞;结节边缘尚可见残留的肾上腺组织。免疫表型:嗜铬细胞瘤成分中CD56、CgA、Syn、vimentin均阳性,SMA、Melan-A、α-inhibin、NF均阴性,S-100支持细胞阳性,Ki-67增殖指数低;节细胞神经瘤成分中NF、S-100均阳性,Ki-67增殖指数低,其内神经节细胞中CgA、Syn弱阳性或阴性。结论CP是相对较罕见的肿瘤,而节细胞神经瘤为相对常见的一种混合成分,其在临床及放射学上无法与嗜铬细胞瘤区分,目前仅基于肿瘤的组织病理学特征进行诊断,需根据其内混合的不同成分(良性或恶性)来采取相应的临床治疗与随访。     

47例软组织颗粒细胞瘤临床病理分析

目的回顾性分析47例软组织颗粒细胞瘤(GCT)的临床病理特征并行增殖活性检测。方法收集1975至2008年武汉大学附属医院病理科GCT存档资料47例,分析其临床及组织病理学特征并随访,应用免疫组化方法行S-100、CD68、NSE及Ki-67染色。结果 GCT好发于舌部,女性多见。镜下观察所有肿瘤由多边形瘤细胞组成,胞质中有丰富的嗜酸性颗粒,且S-100、CD68及NSE染色均为阳性。24例良性GCT呈膨胀性生长,其余20例良性及3例细胞不典型性病例均为侵袭性生长。少数肿瘤细胞Ki-67染色阳性。随访的30例中1例肿瘤细胞明显呈不典型性者复发并死亡,1例细胞典型性者复发后组织学呈不典型性,1例细胞典型性者复发两次后组织学呈恶性,27例无复发。结论大多数软组织GCT为良性,少数具有潜在恶性,应注意随访。少数肿瘤细胞Ki-67阳性提示该肿瘤具有较低的增殖活。     

原发性肾上腺非霍奇金淋巴瘤3例并文献复习

目的探讨原发性肾上腺恶性淋巴瘤的临床病理特征。方法对3例原发性肾上腺恶性淋巴瘤进行临床、病理组织学和免疫组织化学观察,并结合文献探讨其临床表现、病理形态及鉴别诊断。结果本病临床上无特异性,组织学上瘤细胞呈弥漫片状分布,细胞体积较大,多呈圆形或卵圆形,核仁明显,核深染,异型性明显,核分裂象易见。免疫表型：瘤细胞CD45、CD20、CD79α阳性,CD3、CK、S-100蛋白、CEA、Syn及CgA阴性。结论原发性肾上腺恶性淋巴瘤是一种罕见的恶性度较高的肿瘤,预后差。病理诊断上应与继发性肾上腺恶性淋巴瘤鉴别。     

泌尿系统神经内分泌肿瘤16例临床病理分析

目的探讨泌尿系统神经内分泌肿瘤(neuroendocrine tumors,NETs)的临床病理学特征、诊断及鉴别诊断、治疗及预后。方法回顾性分析16例泌尿系统NETs(膀胱11例、输尿管1例、肾脏4例)的临床病理特点、免疫表型、诊断及鉴别诊断、治疗及预后,并复习相关文献。结果 16例NETs中男性11例,女性5例;年龄48～84岁,平龄65岁;小细胞癌10例,副神经节瘤4例,类癌及不典型类癌各1例;12例患者有随访资料,其中6例死亡,均为小细胞癌(3～21个月),6例存活,包括4例膀胱副神经节瘤(7～88个月)、1例肾类癌(14个月)和1例膀胱小细胞癌合并尿路上皮癌(42个月)。结论 NETS发生在泌尿系统中较为罕见,主要为小细胞癌、副神经节瘤及类癌。根据其典型组织形态及神经内分泌免疫组化标志物(Syn、CgA、CD56)阳性鉴别,需谨慎排除转移可能。副神经节瘤及类癌预后较好,小细胞癌侵袭性高,预后差。     

眼眶原发性副神经节瘤的临床病理与发生学探讨

目的探讨眶部原发性副神经节瘤的临床病理特征及其与伴随的睫状神经和副神经节样组织的关系。方法复习病史及有关文献。采用HE、PAS、网状纤维(W ilder法)和免疫组化染色,观察肿瘤和邻近的副神经节样组织的形态和免疫表型特征。结果患儿女性,6岁。因左眼眼球突出,在某医院第一次行肿瘤切除后症状复发,于2000年8月住入安徽医科大学第一附属医院眼科,分别在8月和9月进行第二、三次手术。第三次剜出物为眶内容,3.5 cm×3.5 cm×2 cm,其中见一灰白色病灶,2.5 cm×1.0 cm。镜检:肿瘤有薄层纤维性包膜;包膜外结缔组织内有粗大的神经纤维分支及一团副神经节样组织;肿瘤实质由上皮样主细胞及短梭形支持细胞组成,间质为丰富的血窦样小血管,后者将实质细胞分隔成大小不一的实性细胞巢(细胞球)。PAS染色主细胞胞质内未见菱形或矩形或针状结晶。免疫组化显示:主细胞弥漫表达CgA、NSE、NF(中等阳性)和Syn(弱阳性),不表达CK、EMA、S-100蛋白、GFAP、HMB45、desm in及CD34,极少数vim entin阳性;支持细胞普遍表达vim entin,极少数表达S-100蛋白;瘤旁神经纤维强表达S-100蛋白、NF及NSE;副神经节样组织内大细胞强表达CgA、NSE和NF。病理学诊断副神经节瘤。术后随访2年,无复发,后失访。结论眶内原发性副神经节瘤极罕见。临床表现为眶内占位常引起的症状,无特异性,临床难以确诊。病理检查必须借助免疫组化和(或)电镜检查才能确诊。治疗以手术为主,可加用或单独选用放射治疗。40%病例可有复发,但无转移报道。本例瘤旁有睫状神经及一团副神经节(样)组织,提示此瘤与能分化为睫状副神经节之干细胞的异常分化有关。     

肺透明细胞瘤8例临床病理特征

目的探讨肺透明细胞瘤的临床病理学特征、诊断及鉴别诊断。方法采用免疫组化EnVision法染色检测Melan A、CD34、SMA、desmin、S-100、CKpan、TTF-1、Syn、CgA等表达,分析其临床病理学特征,并复习相关文献。结果 8例患者发病年龄29～60岁,平均为(50±2)岁,无临床症状或仅有轻微咳嗽,多为体检时发现,CT示肿瘤为肺外周孤立性结节。瘤体最大径0.8～3 cm,呈结节状、界清无包膜,瘤体切面灰白或灰红色,质地中等;镜下见肿瘤细胞呈圆形或卵圆形,部分呈梭形,胞质透明,无异型,未见核分裂象,瘤细胞围绕血管周围呈巢状或器官样排列。免疫表型:Melan A(7/8)、CD34(7/8)均阳性,SMA(4/8)局灶阳性,Ki-67增殖指数1%; desmin、S-100、CKpan、TTF-1、Syn、CgA均阴性。结论肺透明细胞瘤属于良性肺血管周上皮样细胞肿瘤,需与肺原发或转移性透明细胞癌、肌上皮瘤、副神经节瘤、类癌、转移性恶性黑色素瘤等鉴别,结合组织学形态及免疫组化检测可资鉴别。     

INSM1在嗜铬细胞瘤/副神经节瘤和肾上腺皮质腺瘤中的表达和病理诊断价值

目的 探讨胰岛素瘤相关蛋白1(insulinoma-associated protein 1, INSM1)在嗜铬细胞瘤/副神经节瘤和肾上腺皮质腺瘤中的表达及其在鉴别诊断中的意义。方法 采用免疫组化EnVision两步法检测INSM1在嗜铬细胞瘤/副神经节瘤和肾上腺皮质腺瘤中的表达。结果 32例嗜铬细胞瘤中31例INSM1阳性(31/32,96.88%),其中高表达20例(20/32,62.50%)。9例肾上腺外副神经节瘤INSM1均阳性,其中高表达8例(8/9,88.89%)。33例肾上腺皮质腺瘤中INSM1均阴性。INSM1在嗜铬细胞瘤/副神经节瘤中的表达显著高于肾上腺皮质腺瘤(P<0.001)。INSM1高表达的嗜铬细胞瘤/副神经节瘤具有更高的Ki67增殖指数(P=0.016),但与患者性别(P=0.190)、年龄(P=0.439)、肿瘤TNM分期(P=0.793)、生长模式(P=0.495)、凝固性坏死(P=0.790)和脉管/包膜侵犯(P=0.790)均无显著相关性。INSM1鉴别嗜铬细胞瘤/副神经节瘤与肾上腺皮质腺瘤的敏感性为97.6%,特异性为100%,ROC曲线下...     

Update on Adrenal Tumours in 2017 World Health Organization (WHO) of Endocrine Tumours

The fourth edition of the World Health Organization (WHO) classification of endocrine tumours contains substantial new findings for the adrenal tumours. The tumours are presented in two chapters labelled as “Tumours of the adrenal cortex” and “Tumours of the adrenal medulla and extra-adrenal paraganglia.” Tumours of the adrenal cortex are classified as cortical carcinoma, cortical adenoma, sex cord stromal tumours, adenomatoid tumour, mesenchymal and stromal tumours (myelolipoma and schwannoma), haematological tumours, and secondary tumours. Amongst them, schwannoma and haematological tumours are newly documented. The major updates in adrenal cortical lesions are noted in the genetics of the cortical carcinoma and cortical adenoma based on the data from The Cancer Genome Atlas (TCGA). Also, a system for differentiation of oncocytoma from oncocytic cortical carcinoma is adopted. Tumours of the adrenal medulla and extra-adrenal paraganglia comprise pheochromocytoma, paraganglioma (head and neck paraganglioma and sympathetic paraganglioma), neuroblastic tumours (neuroblastoma, nodular ganglioneuroblastoma, intermixed ganglioneuroblastoma, and ganglioneuroma), composite pheochromocytoma, and composite paraganglioma. In this group, neuroblastic tumours are newly included in the classification. The clinical features, histology, associated pathologies, genetics, and predictive factors of pheochromocytoma and paraganglioma are the main changes introduced in this chapter of WHO classification of endocrine tumours. The term “metastatic pheochromocytoma/paraganglioma” is used to replace “malignant pheochromocytoma/paraganglioma.” Also, composite pheochromocytoma and composite paraganglioma are now documented in separate sections instead of one. Overall, the new classification incorporated new data on pathology, clinical behaviour, and genetics of the adrenal tumours that are important for current management of patients with these tumours.     

Immunocytochemistry of paragangliomas—value of staining for S-100 protein and glial fibrillary acid protein in diagnosis and prognosis

Surgical specimens of 65 adrenal and 27 extra-adrenal paragangliomas, the latter comprising 11 carotid body, five jugulotympanic, one aorticopulmonary, eight aorticosympathetic and two visceral autonomic tumours, were examined immunocytochemically for the presence of glial fibrillary acid protein (GFAP) and S-100 protein. Six adrenal and four extra-adrenal (one parasympathetic and three sympathetic) neoplasms pursued a malignant clinical course. S-100 staining of sustentacular (type 2) cells was seen in both adrenal (48/65) and extra-adrenal (23/27) lesions, the 10 malignant tumours being entirely devoid of S-100 protein positive cells. GFAP positivity of type 2 cells was seen in only 16 of the extra-adrenal tumours, all of these lesions belonging to the group of benign parasympathetic paragangliomas. The presence of S-100 positive type 2 cells may thus help to exclude malignancy in individual paraganglioma cases, while GFAP positivity of such cells renders possible the correct typing of benign parasympathetic paragangliomas.     

Carney''s triad: gastric leiomyosarcoma, pulmonary chondroma and extra-adrenal paraganglioma in young females

The case of a 13-year-old girl with a gastric leiomyosarcoma and a pulmonary osteochondroma is presented. The association of these two tumours and extra-adrenal paraganglioma has been described as a triad by Carney. The patient is free of recurrence of the gastric tumour with no evidence of paraganglioma 10 months after the operation. To our knowledge this is the first case of the triad reported in the UK.     

Multiple primary malignant paragangliomas of the bladder and retroperitoneal space

An observation of the primarily multiple malignant paraganglioma of the urinary bladder and retroperitoneal space in combination with multiple uterine fibromyomas in a woman of 46 is described. Duration of the hypertension was 30 years. Hypertension crisis (up to 300/180 mm Hg) were usually associated with the urine discharge. Surgical removal of tumours was followed by a severe hypertension due to the catecholamine release into the circulation. Grimelius method confirmed the presence of endocrine granules in the cytoplasm of tumour cells. The role of chronic endocrine pathology in the evolution of extra-adrenal chromaffinomas and some questions of morphogenesis are discussed.     

Dual CD117 expression in gastrointestinal stromal tumor (GIST) and paraganglioma of Carney triad: a case report

Carney triad is a rare syndrome, with only 20 complete cases reported. We report a 36-year-old white woman with complete Carney triad, including metastatic gastric stromal tumor (GIST), pulmonary chondroma, and nonfunctioning extra-adrenal paraganglioma. Immunohistochemistry was positive for CD34 and CD117 (c-kit) in the GIST, and positive for chromogranin and CD117 in the paraganglioma. Ultrastructural studies demonstrated skeinoid fibers in the GIST. To our knowledge, this is the 21st complete Carney triad case reported and the first report of dual expression CD117 in both GIST and paraganglioma, a finding with intriguing pathogenetic implications related to the organization of the autonomic nervous system.     

Carney Triad in an Adult with Aggressive Behavior: The First Case in Korea

Carney triad is a rare syndrome of unknown etiology characterized by having at least two out of three following neoplasms: gastrointestinal stromal tumor, pulmonary chondroma and extra-adrenal paraganglioma. About 100 cases have been reported worldwide. We report a case of Carney triad in a 42-year-old woman presented with a gastrointestinal stromal tumor in the stomach and a malignant functioning paraganglioma in the retroperitoneum that was fatal five years after diagnosis. The gastrointestinal stromal tumor was diagnosed as intermediate-risk of aggressive behavior and diffusely positive for c-kit whereas the retroperitoneal paraganglioma was negative for c-kit. Genetic analyses showed no mutations of KIT, PDGFRA, SDHB, SDHC, and SDHD genes in both tumors. To our best knowledge, this is the first case of Carney triad in Korea.     

Paraganglioma of the tongue

Paragangliomas are neuroendocrine tumors arising from extra-adrenal autonomic ganglia. We present what is to our knowledge the first immunohistochemically documented case of a paraganglioma of the tongue, a 2.5-cm benign tumor growing in the position of the foramen cecum. The patient was an elderly woman who presented with throat irritation. The histologic profile and ultrastructural appearance of this lesion were classic for paraganglioma, and cells stained strongly for neurosecretory granules by immunohistochemistry. Carcinoid, ectopic thyroid neoplasm, and other tumors that mimic paraganglioma were ruled out on immunohistochemical grounds. To our knowledge, paraganglia have not been previously documented in the tongue; this tumor may have arisen from a branch of cranial nerve VII or IX, or from an embryologic remnant of the thyroid or thyroid capsule.     

Mesenteric paraganglioma: a case report and review of the literature

Approximately 5% to 10% of paragangliomas occur in extra-adrenal sites, which can extend from the upper cervical region to the pelvis, parallel to the autonomic nervous system. This distribution corresponds to the embryologic development of the paraganglia from neural crest cells. Rarely, extra-adrenal paragangliomas can also occur aberrantly outside this distribution. We report such a case of extra-adrenal paraganglioma occurring in the anterior mesentery in a 76-year-old man. Two case reports exist in the literature describing extra-adrenal paragangliomas in the posterior mesentery. Normal paraganglionic tissue has been described at the roots of the superior and inferior mesenteric arteries, theoretically explaining the origin of the posterior mesenteric paragangliomas. Our case can best be attributed to the ventral migration of paraganglionic tissue through these vessels to reach the anterior mesentery, where they could potentially give rise to paragangliomas in this site.     

Primary paraganglioma of the lung

There are few reported cases of primary pulmonary paraganglioma in the pathology literature. Given the historical confusion surrounding bronchial tumors, widespread use of the term "chemodectoma" and classification of these lesions as paraganglioma in an outdated World Health Organization classification of lung tumors, the recognition of tumors arising from paraganglia within the lung has not been accepted by leading authorities. We present a well-documented case of a primary pulmonary paraganglioma with typical morphologic features and a supporting immunohistochemical profile. The 0.9 cm endobronchial tumor was submucosal and composed of nests of ovoid cells with abundant eosinophilic cytoplasm, cytoplasmic vacuoles, round to oval nuclei with speckled chromatin, and occasional conspicuous nucleoli. The nests of cells were surrounded by thin-walled vascular channels and stellate spindle cells. The ovoid cells showed strong diffuse staining for chromogranin A, synaptophysin, and faint staining for S-100; they were negative for cytokeratin AE1/AE3, Cam 5.2, and epithelial membrane antigen. The stellate spindle cells stained intensely positive for S-100 protein. A critical review of reported cases of pulmonary chemodectomas and paragangliomas in the English literature features few, if any, well-documented examples. While this exceedingly rare tumor should be discerned from carcinoid tumor, it remains unknown if primary pulmonary paragangliomas behave aggressively like intra-abdominal extra-adrenal paragangliomas, or in a more indolent manner observed with extra-adrenal paragangliomas in other locations.     

良恶性嗜铬细胞瘤鉴别诊断的分子生物化学研究进展

恶性嗜铬细胞瘤大约占嗜铬细胞瘤的10%,副神经节瘤中恶性比例更高些.由于从临床表现、组织病理上进行嗜铬细胞瘤的良恶性诊断均存在一定的局限性,近几年来不同国家的研究组运用分子生物学的手段对嗜铬细胞瘤的良恶性鉴别进行了研究,并取得了一定的进展:SDHB突变可能与恶性嗜铬细胞瘤关系较大,其他一些基因与分子标记物的联合应用也可能成为判断嗜铬细胞瘤潜在恶性的标志.本文就近几年在分子生物学方面对于良恶性嗜铬细胞瘤进行鉴别诊断所取得的进展作一综述.