混合性嗜铬细胞瘤临床病理学特征分析

目的探讨混合性嗜铬细胞瘤(composite pheochromocytoma, CP)临床病理特征、免疫表型、诊断及鉴别诊断。方法收集2011年1月至2019年1月浙江省人民医院收治的5例CP, 对5例CP的临床、影像学、组织学、免疫组织化学特征及预后进行观察, 探讨其临床病理特征及鉴别诊断。结果 CP患者中男性4例, 女性1例, 男女发病比例为4∶1, 发病年龄52～68岁(平均年龄59岁, 中位年龄54岁), 肿瘤最大径3～4 cm(平均最大径3.6 cm, 中位最大径3.5 cm);临床表现多为无明显症状的肾上腺肿块;典型的形态为两种成分组成, 一种为瘤细胞呈不规则巢状排列, 瘤细胞胞质细颗粒状、嗜碱性或双嗜性, 核分裂象罕见;另一种为由不规则交叉束状排列的施万细胞及散在分布的神经节细胞组成;免疫组织化学示嗜铬细胞瘤弥漫表达PHOX2B(5/5)、突触素(5/5)、嗜铬粒素A(CgA, 5/5), 支持细胞S-100蛋白阳性(5/5), 节细胞神经瘤弥漫表达S-100蛋白(5/5)、神经丝蛋白(5/5), 其内神经节细胞PHOX2B、突触素、CgA弱阳性;5例均接受手术切除, ...     

混合性嗜铬细胞瘤六例临床病理学特征

目的探讨混合性嗜铬细胞瘤的临床病理特点、免疫表型、鉴别诊断及预后。方法回顾性分析解放军总医院第一医学中心病理科2013至2019年确诊的6例混合性嗜铬细胞瘤, 总结其临床特点、影像学表现及病理特征。结果患者年龄37～68岁, 中位年龄48岁。男女比为5∶1。肿瘤最大径3～9 cm, 平均直径4.6 cm。CT及MRI显示肿瘤呈实性或囊实性, 2例考虑为嗜铬细胞瘤, 3例考虑为皮质腺瘤, 1例考虑为皮质腺瘤或嗜铬细胞瘤。镜下观察1例表现为嗜铬细胞瘤与节细胞神经母细胞瘤(混杂型)混合, 5例表现为嗜铬细胞瘤与节细胞神经瘤混合。免疫组织化学示本组病例嗜铬细胞瘤成分表达突触素、嗜铬粒素A、神经细胞黏附分子(CD56), 不同程度表达S-100蛋白, Ki-67阳性指数均小于3%;节细胞神经瘤成分中神经节细胞表达神经元特异性烯醇化酶(NSE)、神经丝蛋白(NF)、突触素, 间质表达S-100蛋白, Ki-67阳性指数小于3%;节细胞神经母细胞瘤中神经母细胞瘤成分表达NSE、NF、突触素, 弱阳性表达CD99, Ki-67阳性指数小于3%。6例均获得随访资料, 患者均健在, 无复发转移, 术后生存...     

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。     

膀胱嗜铬细胞瘤14例临床病理分析

目的：探讨膀胱嗜铬细胞瘤的临床病理学特征、病理诊断以及鉴别诊断。方法：搜集14例膀胱嗜铬细胞瘤患者的临床病理资料,回顾性总结膀胱嗜铬细胞瘤的临床及病理学特征,复习相关文献。结果：14例患者中男性8例、女性6例;年龄14~63岁,平均年龄46.7岁。肿瘤最大径从0.2~8 cm不等,平均最大径2.5 cm。以排尿后头痛、心悸、血压升高为临床主要症状。镜下可见较一致的多边形或圆形上皮样肿瘤细胞,排列成条索、巢团及片状结构,形成典型的zellballen细胞巢,无包膜,在膀胱壁中浸润性生长;肿瘤间质富含薄壁血管,大部分血管呈血窦状、无显著扩张;大部分细胞较一致,散在少数胞体形状不规则、核大深染的瘤细胞,部分胞浆略嗜碱性,核分裂罕见,瘤巢周边见散在梭形细胞。免疫组织化学显示肿瘤细胞CgA、Syn阳性,增殖指数Ki-67阳性1%~10%不等,瘤巢周边梭形细胞S-100阳性;瘤细胞AE1/AE3阴性。9例采用经尿道膀胱肿物切除,其中4例复发。5例采用膀胱部分切除术,其中2例复发。结论：膀胱嗜铬细胞瘤是发生于膀胱的罕见肿瘤,需要依赖组织形态与免疫组织化学特点与其它膀胱肿瘤进行鉴别诊断;单纯肿瘤切除容易局部复发,引起转移的恶性病例少见。     

原发性浅表食管小细胞神经内分泌癌15例的临床病理学特征

目的 分析原发性浅表食管小细胞神经内分泌癌的临床病理学及免疫组织化学特征,以寻找浅表食管小细胞神经内分泌癌合适的诊断标志物及治疗方法.方法 回顾性分析15例原发性浅表食管小细胞神经内分泌癌的临床病理学特征,并采用免疫组织化学MaxVision方法检测嗜铬粒素A(CgA)、神经元特异性烯醇化酶(NSE)、突触素、CD56、甲状腺转录因子-1(TTF-1)、细胞角蛋白AE1/AE3、CK34βE12及CK10/13在食管小细胞神经内分泌癌中的表达.结果 原发性浅表食管小细胞神经内分泌癌的发病率占同期浅表食管癌的4.8％(15/312).患者中位生存时间19个月,平均生存时间23.7个月.1、2和5年生存的分别有10、5和1例.免疫组织化学标志物NSE、突触素、AE1/AE3均为阳性,CD56阳性14例,TTF-1阳性9例,CgA阳性8例,CK34βE12阳性1例,CK10/13均为阴性.结论 原发性浅表食管小细胞神经内分泌癌恶性度高,进展快速,预后很差.建立在放化疗联合外科切除基础上的系统性治疗或许有助于延长患者的生存期.NSE、突触素、AE1/AE3、CD56、TTF-1、CgA在食管小细胞神经内分泌癌中的高表达对其诊断及鉴别诊断具有一定应用价值.     

节细胞性副神经节瘤临床病理学观察北大核心CSCD

目的探讨节细胞性副神经节瘤(gangliocytiCparaganglioma,GP)临床病理特征。方法收集郑州大学第一附属医院2011年1月至2017年12月诊断的4例GP患者资料。通过病历查询获得患者临床资料及病理诊断,采用HE染色及RocheBenchMarkXT全自动免疫组织化学检测仪检测广谱细胞角蛋白(CKpan)、突触素、嗜铬粒素A(CgA)、CD56、神经元特异性烯醇化酶(NSE)及神经丝蛋白(NF)等标志物。通过电话随访收集患者预后资料。结果4例患者中男性2例,女性2例,均以间断性腹痛、腹胀入院。发病年龄47~73岁,中位年龄56岁。术前均行CT检查显示十二指肠降段肠壁局限性增厚,并于增强后轻度强化;3例超声内镜检查示肿物为位于十二指肠降段黏膜或黏膜下层的低回声影。瘤体最大径0.6~1.8cm,平均1.2cm。镜下,肿瘤均由上皮样细胞、梭形细胞和节细胞样细胞构成,三者比例不一。上皮样细胞表达CKpan、突触素、CgA和CD56;梭形细胞表达S-100蛋白、SOX-10;节细胞样细胞表达NF、突触素、CgA和CD56;3种细胞均表达NSE。4例患者术后随访3~30个月,均未复发或转移。结论GP是一种好发于十二指肠的具有良性生物学特性的肿瘤,多可采用内镜下完整切除,预后极好。尽管其发生率极低,但对于发生在十二指肠,尤其是第二段位于黏膜及黏膜下层的病变,在鉴别诊断时应尽量考虑到GP的可能。     

表达突触素的胃血管球瘤临床病理及免疫标记分析北大核心CSCD

目的 分析表达突触素的胃血管球瘤的临床病理特征及其与胃神经内分泌肿瘤的鉴别.方法 收集温州医科大学附属台州医院病理科2010年1月至2016年6月连续诊断的6例胃血管球瘤,8例其他部位的血管球瘤,7例胃神经内分泌肿瘤,分析其临床病理特征及免疫组织化学标记.结果 胃血管球瘤大多发生在胃窦部的固有肌层,弥漫强表达突触素（5/6）,而在其他部位的血管球瘤无突触素表达.胃神经内分泌肿瘤大多发生在胃底、胃体部的黏膜层和黏膜下层,除弥漫强表达突触素（7/7）外,还高表达嗜铬粒素A（6/7）、CD56（5/7）,不表达平滑肌肌动蛋白（0/7）.结论胃血管球瘤与神经内分泌肿瘤的形态学有些相似性,且均可以强表达突触素,但其好发部位及免疫标记有显著不同可资鉴别.     

卵巢未分化癌1例报道及文献复习

目的:探讨卵巢未分化癌临床病理学特征、诊断和鉴别诊断.方法:对1例卵巢未分化癌行HE染色和免疫组织化学染色,同时进行文献复习.结果:肿瘤主要由实性瘤细胞巢组成,部分呈条索状,细胞圆形或多角形,胞质嗜酸或透亮,异型性明显,部分瘤细胞呈梭形,梭形细胞区可见腺样结构.细胞核圆形,核分裂象多见.肿瘤坏死明显,存活瘤细胞围绕血管分布类似于卵巢移行细胞癌.圆形的肿瘤细胞弥漫性表达广谱细胞角蛋白(pancytokeratin,CKpan)、上皮膜抗原(epithelial membranous antigen,EMA) CD99,而嗜铬素A(chromogranin A,CgA)、突触素(syanptophysin,Syn)、白细胞共同抗原(leueocyte common antigen,LCA)、抑制素-α和α-甲胎蛋白(α-fetoprotein,AFP)表达阴性;梭形肿瘤细胞CKpan、波形蛋白表达阳性,而平滑肌肌动蛋白(smooth muscle actin,SMA)、肌形成蛋白(myogenin Dl,MyoDl)、S-100蛋白表达阴性 结论:卵巢未分化癌是一种少见的未分化或仅有小灶性分化的高度恶性的卵巢肿瘤,诊断时须与小细胞癌、粒层细胞瘤、低分化腺癌、高级别浆液性癌、移行细胞癌和恶性中胚叶混合瘤鉴别.     

膀胱副神经节瘤23例临床病理学分析

目的探讨膀胱副神经节瘤(PUB)的临床病理特点、诊断、鉴别诊断及免疫特征。方法收集福建医科大学附属第二医院(7例)、福建省立医院(8例)、福建医科大学附属协和医院(6例)及福建医科大学附属第一医院(2例)2010年5月至2018年11月手术切除的23例PUB临床及病理资料, 采用免疫组织化学EliVision法检测细胞角蛋白(CK)、GATA3、CD56、突触素、嗜铬粒素A(CgA)、S-100蛋白、HMB45、SDHB、OCT3/4及Ki-67, 并复习文献综合分析。结果患者中女性14例, 男性9例, 年龄21～73岁(平均年龄51岁), 临床上出现反复头痛、头晕及心悸, 排尿性晕厥, 血压升高, 视力模糊, 肉眼血尿, 阵发性面色苍白等症状。肿物最大径0.9～6.0 cm(平均最大径约2.5 cm)。大体观察:大部分肿物凸向腔内, 边界尚清, 位于黏膜固有层或固有肌层, 切面呈结节样, 灰黄、灰褐色, 质地中等。镜下观察:低倍镜下肿瘤细胞在黏膜固有层及固有肌层间膨胀性生长或穿插浸润性生长, 肿瘤细胞呈巢状(Zellballen)、器官样排列, 少部分病例肿瘤细胞排列成菊形团样结构;...     

嗜铬细胞瘤组织芯片免疫组化标记的诊断价值分析

目的 探讨肾上腺嗜铬细胞瘤组织芯片免疫组化标记的诊断价值。方法 制备肾上腺组织芯片，含样本163例，其中正常肾上腺15例，肾上腺皮质增生2例，嗜铬细胞瘤41例，肾上腺皮质腺瘤72例，肾上腺皮质癌22例，肾上腺转移癌11例。用免疫组织化学EnVision法检测多种免疫标记的表达情况。结果 肾上腺髓质素(adrenomedullin，ADM)阳性率分别为：正常肾上腺髓质100％(5／5)，嗜铬细胞瘤60．5％(23／38)，肾上腺皮质肿瘤及转移癌呈阴性；CgA：嗜铬细胞瘤阳性率86．8％(33／38)；Syn：嗜铬细胞瘤阳性率73．7％(28／38)，肾上腺皮质癌阳性率28．6％(6／21)，肾上腺皮质腺瘤及转移癌呈阴性；S-100蛋白：嗜铬细胞瘤支持细胞阳性率47.4％(18／38)；MelanA(A103)和inhibin α在嗜铬细胞瘤呈阴性，但肾上腺皮质及皮质肿瘤高表达。结论 在嗜铬细胞瘤的诊断和鉴别诊断中，必须联合应用ADM、CgA、S-100蛋白等多种标记。组织芯片技术为快速原位检测提供了有效的手段。     

间叶性软骨肉瘤23例临床病理和免疫表型分析

目的 探讨间叶性软骨肉瘤的临床病理和免疫表型特点.方法 复习23例骨及软组织间叶性软骨肉瘤的临床和病理学资料,对其中14例进行免疫组织化学(EnVision法)染色.结果男性14例,女性9例,年龄范围12～47岁,其中原发于骨的病变13例,原发于软组织5例,早期症状以局部肿块和疼痛为主.镜下组织学特点为含有原始间叶性小细胞和分化良好的软骨成分,二者有移行过渡,可见"骺板样软骨".原始间叶性小细胞免疫组织化学染色阳性表达Sox9(14/14)、CD99(12/14)、波形蛋白(6/14)、CD56(4/14)、CD57(4/14)、神经元特异性烯醇化酶(3/14)、结蛋白(1/14);Ⅱ型胶原、S-100蛋白、上皮细胞膜抗原、PCK、突触素、嗜铬粒素A、CD34、c-erbB2均阴性.结论间叶性软骨肉瘤少见,结合组织病理形态特征及免疫组织化学染色对病理鉴别诊断有较大帮助.

Abstract：

Objective To study the clinicopathologic and immunohistochemical features of mesenchymal chondrosarcoma. Methods The clinical and histologic features of 23 cases of mesenchymal chondrosarcoma were analyzed. Immunohistochemical study was also performed in 14 of the cases. ResultsThe age of patients ranged from 12 to 47 years. Fourteen of them occurred in males. Thirteen cases involved the bony skeleton and 5 cases affected the soft tissue. The patients presented with pain and/or swelling. Histologically, the tumor consisted of a mixture of undifferentiated small round cells and hyaline cartilage. Transition between the two components was demonstrated and growth plate-like cartilage was observed. Immunohistochemical study showed that the small round cells were positive for Sox9 (14/14), CD99(12/14), vimentin (6/14), CD56 (4/14), CD57(4/14), neuron-specific enolase (3/14) and desmin(1/14). They were negative for Coll-Ⅱ, S-100 protein, epithelial membrane antigen, pan-cytokeratin, synaptophysin, chromogranin A, CD34 and c-erbB2. Conclusions Mesenchymal chondrosarcoma is a rare malignant tumor. Thorough histologic examination, when coupled with immunohistochemical findings, is helpful in arriving at a correct diagnosis.     

Extra-adrenal pheochromocytoma-ganglioneuroma. A case report.

A case of rare extra-adrenal tumor composed of pheochromocytoma-ganglioneuroma which developed in a 48-year-old Japanese male is reported. Histologically, the tumor contained equal proportion of two distinct patterns, pheochromocytoma and ganglioneuroma. Immunohistochemical examination revealed that pheochromocytoma cells were positive for Leu-7 and ganglion cells in ganglioneuroma were positive for vasoactive intestinal peptide (VIP), respectively. Neuron specific enolase (NSE) was positive in the neoplastic cells of both components, and S-100 protein was also positive in fibers around ganglion cells. Ultrastructural examination revealed that neurosecretory granules were present in the neoplastic cells.     

Prediction of malignant behavior of pheochromocytomas and paragangliomas using immunohistochemical techniques

Pheochromocytomas and paragangliomas arise from the adrenal glands and extraadrenal paraganglia, respectively. Malignant behavior of these tumors is uncommon and is, in part, dependent on their sites of origin, such as extraadrenal location. Morphologic criteria for malignancy of pheochromocytoma and paragangliomas have not been clearly defined. In this study, to clarify the histologic features that distinguish the benign from malignant pheochromocytomas and paragangliomas, we examined metastatic and nonmetastatic tumors using immunohistochemical techniques. A total of eight cases, five pheochromocytomas from the adrenal glands (four benign and one malignant tumor) and three paragangliomas with invasion or metastasis, were studied. The markers used in this study were chromogranin A, synaptophysin, NCAM (CD56), SNAP25, neuron-specific enolase, S-100 protein, and MIB-1. Our results suggest that MIB-1 immunostaining is a useful adjunct marker to predict malignant behavior in these tumors.     

鼻腔鼻窦畸胎癌肉瘤的病理特征及其诊断

目的探讨鼻腔鼻窦畸胎癌肉瘤的临床病理学特征及诊断和鉴别诊断。方法对5例经病理证实的鼻腔鼻窦畸胎癌肉瘤的临床、放射影像学和病理学资料作回顾性分析,对标本行免疫组织化学染色（EnVision法）,并对所有病例进行了随访。结果患者5例,均为男性,年龄34—43岁,平均39岁。临床表现主要为单侧鼻腔堵塞、涕中带血和头痛,检查发现鼻腔充满新生物,表面光滑,有蒂,触之易出血;放射影像学均为局部占位,密度均匀,未见明显的囊性变、钙质沉着和骨化。病理检查：肿瘤多为碎组织,质地中等偏嫩,镜下观察肿瘤常由3个胚层的组织构成,外胚层的鳞状上皮团、中胚层瘤样增生的平滑肌纤维、软骨和骨组织及内胚层的富有黏液细胞的纤毛柱状上皮及排列成腺管样结构的消化道、呼吸道上皮,其中未成熟的神经上皮细胞、胞质透明的鳞状细胞团、梭形细胞肉瘤和腺癌成分最具诊断价值。免疫组织化学染色,不同胚层的组织对应相应的免疫标记,细胞角蛋白、上皮细胞膜抗原标记外胚层的复层鳞状上皮、内胚层的消化道和呼吸道上皮,波形蛋白、平滑肌肌动蛋白等标记梭形细胞肉瘤区域和平滑肌等组织,S-100蛋白、神经元特异性烯醇化酶、突触素等标记未成熟的神经上皮组织,且nestin阳性,CD99标记较为原始小细胞。5例患者首次病理诊断分别为毛细血管瘤、嗅神经上皮瘤、嗅神经母细胞瘤、颅咽管瘤及恶性混合瘤。随访结果：2例复发,1例颈部转移。结论鼻腔鼻窦畸胎癌肉瘤是一种由3胚层组成,具有畸胎瘤和癌肉瘤特征的罕见恶性肿瘤,具有特征性的组织病理学和免疫组织化学染色特点,应多取材多切片,以免误诊和漏诊。     

Immunohistochemical features of the human retina and retinoblastoma

The immunohistochemical features of 24 retinoblastoma specimens from 22 patients, 15 with unilateral and 7 with bilateral disease, were examined by the labelled streptavidin biotin (LSAB) method and compared with those of specimens from the remaining morphologically normal retina. In the normal retina, S-100 protein, glial fibrillary acidic protein (GFAP) and vimentin were detected in astrocytes and/or Müller cells. Neurofilament protein was seen in axons of the ganglion cells, synaptophysin was present in both plexiform layers, bcl-2 oncoprotein was seen in ganglion cells and bipolar cells, and neuron-specific enolase (NSE) was detected in ganglion cells, bipolar cells and photoreceptor cells and in their cell processes. While retinoblastoma (Rb) protein expression was noted in ganglion cells, bipolar cells, and some photoreceptor cells, p53 protein was not expressed at all. In all retinoblastomas, strong NSE expression and weak bcl-2 expression was observed in almost all tumour cells and synaptophysin was localized in rosette-forming cells, while tumour cells were devoid of S-100, GFAP, vimentin and neurofilament protein. These findings support the view that retinoblastomas are composed of neuron-committed cells. In addition, no Rb protein expression was detected in retinoblastomas, whereas p53 expression was found in 18 cases (75%).     

十二指肠神经节细胞副神经节瘤临床病理观察

收集1例42岁十二指肠神经节细胞副神经节瘤(ganglioeytic paraganglioma,GP)男性患者的临床资料,对手术标本采用HE染色及免疫组织化学染色进行病理学观察,并复习国内外文献报道的相关病例进行临床及病理学特征分析.光镜下可见3种细胞成分:神经内分泌细胞、伴神经鞘细胞分化的梭形细胞(梭形细胞)和神经节细胞.神经内分泌细胞呈假腺管样结构排列,细胞胞质嗜酸性,核卵圆形,大小一致,无核分裂象;梭形细胞形成小的束状结构,包绕神经内分泌细胞;节细胞散在分布.3种细胞均无明显的细胞异型性.在该病例中还可见到小束状的平滑肌成分.免疫组织化学:神经内分泌细胞CgA,Syn,CD56和CK阳性,梭形细胞S-100和vimentin阳性,节细胞S-100和NF阳性.十二指肠GP是一种罕见的肿瘤,十二指肠各个部位均可发生,依据其特征性的镜下表现并结合免疫组织化学可做出正确诊断.     

胸部原始神经外胚层瘤5例临床病理分析

目的 探讨胸部原始神经外胚层瘤(PNET)的临床病理特征、免疫学表型及其鉴别诊断。方法 对5例发生于胸部的PNET进行光镜观察和免疫组化研究。结果 5例PNET中4例为女性,1例男性,年龄12～52岁,平均27．0岁。肿瘤体积较大,平均直径11．4cm,无包膜或包膜不完整。镜下：肿瘤由小圆细胞构成,细胞胞质少,部分区域肿瘤细胞胞质透亮,可见Homer-Wwright菊形团和假菊形团。免疫表型：5例CD99(MIC2)、NSE阳性,4例synaptophysin阳性,3例vimentin阳性,2例S-100蛋白阳性。结论 胸部PNET是较少见的高度恶性软组织肿瘤,其诊断主要依据病理形态学特征及免疫组化标记。     

Pheochromocytomas and ganglioneuromas in the aging rats: morphological and immunohistochemical characterization

We investigated, morphologically and immunohistochemically, 74 medullary adrenal tumors, including 64 pheochromocytomas (14 malignant and 50 benign), 9 ganglioneuromas, and 1 malignant schwannoma. The tumors were detected in 2-year-old Wistar and Sprague-Dawley rats from carcinogenicity studies. Morphologically, benign pheochromocytomas were characterized by monomorphic, small, basophilic cells with almost absence of mitoses. Malignant pheochromocytomas presented a low grade of pleomorphism, higher rate of mitoses, necrosis, infiltrative growth and in 1 case metastases in the lung. Ganglioneuromas were characterized by ganglion and neuron-like cells embedded in an eosinophilic matrix containing neurites, Schwann cells, and scant fibrovascular elements. All pheochromocytomas were strongly immunoreactive for tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis. Subpopulations of chromaffin cells expressed chromogranin A (CGA) positivity. Matrix and Schwann cells were positive for S-100 and for glial fibrillary acidic protein (GFAP). In focal areas of the tumors, ganglion cells and axons were positive for neurofilament proteins (NFP) and synaptophysin. Ganglion cells exhibited peripherin and beta-tubulin. Proliferative activity of the tumors was assessed by immunostaining the endogenous cell proliferation associated-antigen Ki-67 and the proliferating cell nuclear antigen (PCNA). As expected, cell proliferation indices were much higher in malignant pheochromocytomas than in benign, yet ganglioneuromas remained immunonegative. Considering that Ki-67 antigen is more specific for cell proliferation, it should be regarded as marker of choice for supporting the differential diagnosis between benign and malignant pheochromocytomas.     

Pigmented Pheochromocytoma: an Unusual Variant of a Common Tumor

Pheochromocytoma is a neuroendocrine tumor arising from the adrenal medulla. A number of variants of pheochromocytoma are known; however, pigmented pheochromocytoma is extremely rare, with only few cases reported in literature. We report the cases of two patients with pigmented pheochromocytoma. Case 1 was a 28-year-old female who presented with complaints of breathlessness, palpitations, and anxiety for 5 years, which had worsened over the last 8 months. Computed tomography (CT) abdomen showed a right suprarenal mass. Case 2 was that of an 18-year-old girl who presented with similar complaints and was diagnosed with hypertension. CT abdomen showed bilateral adrenal masses. Urinary vanillyl mandelic acid was raised in both patients. Sections examined from all three tumors showed cells arranged in Zellballen pattern, separated by thin fibrovascular septae. Tumor cells showed moderate to marked nuclear pleomorphism in case 1. Mitoses were, however, not seen. There was no evidence of capsular or vascular invasion. Many of the tumor cells showed intracytoplasmic black pigment, which was positive for Fontana–Masson and was bleach-labile, confirming it as melanin. Hemosiderin deposition was also identified. Large areas of hemorrhagic necrosis were seen in case 1. Tumor cells were immunopositive for chromogranin and synaptophysin, while they were negative for HMB-45. Electron microscopy was performed. A final diagnosis of pigmented pheochromocytoma was rendered in both cases. Pigmented pheochromocytoma is a very rare tumor, which needs to be differentiated from other pigmented tumors like malignant melanoma of adrenal gland and pigmented adrenal adenoma. Histochemistry and immunohistochemistry help in making this distinction.     

Malignant pheochromocytoma in a young adult forming the structure simulating Homer Wright rosette: differentiation from neuroblastoma on repeating fluorescence in situ hybridization

A peculiar adrenal tumor was analyzed using immunohistochemistry, electron microscopy, and fluorescence in situ hybridization (FISH) with multiple bacterial artificial chromosome (BAC) probes. The patient was a 34-year-old woman with a mass above the left kidney and multiple metastases. Her serum and urine dopamine level were elevated, and a diagnosis of malignant pheochromocytoma was made. The patient died approximately 3 years after her first visit. On post-mortem an adrenal tumor composed of small round cells forming Homer Wright rosette-like structures, a feature rarely observed in pheochromocytoma, was found. Immunohistochemistry was positive for chromogranin A and synaptophysin, and negative for cytokeratin, vimentin and neurofilaments. Because these results did not rule out a diagnosis of neuroblastoma, the tumor was further characterized on FISH with multiple BAC probes for loci known to be altered in neuroblastoma or pheochromocytoma, according to information in the literature that was for the most part obtained using comparative genomic hybridization. FISH demonstrated loss of heterozygosity at 11p, and gains at 16p, 19p, and 19q, a profile that favored a diagnosis of malignant pheochromocytoma over neuroblastoma. This case demonstrates that repeating FISH is useful for differential diagnosis.