低分化滑膜肉瘤临床病理及分子遗传学研究

目的：研究低分化滑膜肉瘤的临床病理学特点及其分子遗传学表现。方法：收集低分化滑膜肉瘤标本121例，采用形态学观察和免疫组化染色，并用RT－PCR方法在石膜包埋组织中检测SYT－SSX融合mRNA表达。结果：12例低分化滑膜肉瘤中细胞型4例，大细胞型6例，高度恶性梭形细胞型2例。8例有随访资料其中4例死于肿瘤，平均生存时间18个月。免疫组化表现为CK和（或）EMA阳性，以EMA阳性率较高，同时vimentin阳性。S－100蛋白也有较高阳性率，多呈局灶或散在阳性。RT－PCR方法均可检测到SYT－SSXmRNA表达，对照组12例肿瘤包括恶性周围神经 鞘膜瘤、尤因肉瘤和恶性血管外皮瘤SYT－SSX检测全部阴性。结论：低分化滑膜肉瘤有其形态学及免疫表型特点，分子遗传学检测SYS－SSX融合mRNA有助于诊断和鉴别诊断。     

CD163在皮肤梭形细胞肿瘤中的诊断价值

皮肤恶性梭形细胞肿瘤种类较多,如非典型纤维黄色瘤(AFX)、梭形细胞鳞状细胞癌(SCC)、梭形细胞/促纤维增生性恶性黑色素瘤、皮肤隆突性纤维肉瘤(DFSP)和平滑肌肉瘤等,这些恶性梭形细胞肿瘤的形态学诊断有时比较困难.一般来说,AFX是一个排除性诊断,是根据免疫标记CK和S-100蛋白表达阴性,而组织细胞标记物CD68表达阳性而做出的诊断.     

前列腺特异性间质肉瘤2例报道并文献复习

目的 探讨前列腺特异性间质肉瘤(prostatic specialized stromal sarcoma,PSS)的临床病理学特点、免疫学表型、诊断和鉴别诊断要点.方法 通过常规HE染色及免疫组织化学标记,对2例PSS进行显微镜下组织学形态观察,并进行文献复习.结果 PSS细胞呈梭形及短梭形,呈束状、编织状、车辐状或弥漫性浸润生长,瘤细胞胞质丰富、嗜酸,细胞核主要呈卵圆形、短梭形,核仁不明显,可见较多增生且扩张的厚壁血管.免疫组化染色显示肿瘤细胞vimentin、CD34呈阳性表达,大部分病例PR阳性表达.结论 PSS是来源于前列腺激素依赖性特异性间质细胞的一种少见肉瘤.病理诊断主要依靠病理形态学和免疫组织化学标记,CD34和PR阳性是诊断该肿瘤的重要参考依据之一,鉴别诊断主要包括孤立性纤维性肿瘤/血管外皮细胞瘤、平滑肌肉瘤、横纹肌肉瘤、恶性外周神经鞘瘤等.     

滤泡树突状细胞肉瘤10例临床病理分析

目的探讨滤泡树突状细胞肉瘤(follicular dendritic cell sarcoma,FDCS)的临床病理学特征、鉴别诊断及D2-40的表达。方法收集10例FDCS及110例其他梭形细胞肿瘤,采用免疫组化法检测FDCS中D2-40的表达,并复习相关文献。结果 10例FDCS中男性6例,女性4例;年龄35～66岁。镜检:肿瘤细胞梭形或卵圆形,呈束状、席纹状、车辐状、片状排列或弥漫分布在炎症背景中。瘤细胞境界不清,胞质轻到中度嗜酸性;核呈卵圆形或梭形,可见单核和双核,甚至多核瘤巨细胞;核染色质稀疏,核仁小而清晰,核分裂象多少不等。80%的FDCS中D2-40显示胞膜或胞质强阳性,其他梭形细胞肿瘤中D2-40呈弱至中度阳性。随访2～51个月,5例手术后健在,1例转移,1例死亡,3例失访。结论由于FDCS病理学特征多样且少见,需与多种梭形细胞肿瘤鉴别,D2-40表达对鉴别诊断有帮助。     

β-catenin在纤维瘤病诊断及鉴别诊断中的作用

目的 探讨β-catenin在纤维瘤病诊断及鉴别诊断中的作用.方法 对54例纤维瘤病及形态学相似的梭形细胞肿瘤23例存档病例进行临床病理学特征分析,采用免疫组化EnVision两步法检测β-catenin及CD34的表达水平.结果 46例纤维瘤病发生于四肢,4例发生于腹壁及肠系膜,4例发生于颈部.其中男性16例,女性38例.发病年龄8～70岁,平均29.6岁.肿瘤最大直径1～23 cm.肿瘤细胞常呈束状排列,部分区域细胞丰富,部分区域细胞稀疏,间质中常可见胶原纤维,部分区域可见玻璃样变,局灶可见出血囊性变.细胞轻度异型,未见明确核分裂象及坏死.免疫组化结果 示纤维瘤病β-catenin的阳性率为96.3%,其中轻度和中-重度阳性分别占18.5%和77.8%;肿瘤细胞CD34均呈阴性.其它23例梭形细胞肿瘤中,β-catenin的阳性率为17.4%,明显低于纤维瘤病(P<0.05).阳性肿瘤主要包括孤立性纤维性肿瘤,呈细胞核阳性;皮肤隆突性纤维肉瘤,呈弥漫胞质阳性.结论 β-catenin在纤维瘤病中阳性率比较高,主要为核阳性,也可表达于其它梭形细胞肿瘤,细胞核和细胞质均可阳性.联合检测β-catenin和CD34可辅助诊断纤维瘤病.     

类似胃肠间质瘤的胃梭形细胞间叶源性肿瘤31例临床病理分析

目的比较发生于胃的类似胃肠间质瘤(gastrointestinal stromal tumor, GIST)的梭形细胞间叶源性肿瘤,探讨其临床病理特征的关系。方法采用HE和免疫组化EnVision两步法检测31例与GIST类似的胃梭形细胞肿瘤,分析各类肿瘤的组织病理学特点、免疫表型及分子病理学特征。结果 31例类似GIST的胃梭形细胞间叶源性肿瘤,分别为平滑肌瘤14例,炎性纤维性息肉9例,神经鞘瘤5例,钙化性纤维性肿瘤1例,炎性肌纤维母细胞瘤1例,恶性周围神经鞘膜瘤1例。31例与GIST类似的梭形细胞肿瘤免疫组化均表达vimentin,不表达CD117和Dog-1;14例平滑肌瘤弥漫表达α-SMA和desmin;9例炎性纤维性息肉弥漫表达CD34;5例神经鞘瘤弥漫表达S-100,局部表达EMA;1例炎性肌纤维母细胞瘤表达α-SMA,局部表达CD34和actin;1例恶性周围神经鞘膜瘤弥漫表达NSE和SOX10,不表达S-100、CD99、CD34、EMA等。31例与GIST类似的梭形细胞肿瘤除1例恶性周围神经鞘膜瘤Ki-67增殖指数约20%,其余Ki-67增殖指数均10%。结论诊断类似GIST的胃梭形细胞间叶源性肿瘤,应综合考虑肿瘤的临床病理特点、免疫表型以及分子病理学特征,避免误诊。     

74例胃肠道间质瘤临床病理与生物学行为评价

目的　探讨在胃肠道间质瘤(GIST)的病理诊断和预后分析上采用一种简单实用且重复性好的病理学“标准”,以利于GIST的日常病理诊断和生物学行为评价及指导治疗,并对Fletcher等推荐的GIST生物学行为评价表进行评估。方法　85例消化道间叶组织肿瘤,复习其病理形态学并应用CD117、CD34、平滑肌肌动蛋白(SMA)、结蛋白、S 100等进行免疫组织化学标记,结合 31例随访资料进行分析。结果　85例消化道间叶组织肿瘤中,GIST74例,平滑肌瘤和交界性平滑肌瘤 8例(食管),平滑肌肉瘤 1例(直肠 ),神经鞘瘤 1例 (胃 ),恶性纤维组织细胞瘤 1例 (肠系膜 )。74例GIST中,发生在胃和小肠的分别为 34例和 30例,占 86. 5%,食管 3例,胃肠道外(肠系膜、网膜、后腹膜)7例。年龄 23~80岁,平均 52 5岁, 40岁以上者占 85%,男性 45例,女性 29例。镜下观察:梭型细胞型 48例,上皮样细胞型 10例,混合细胞型 16例。瘤细胞呈长、短梭形和圆形,胞质丰富弱嗜酸性,排列呈旋涡状、栅栏状或弥漫巢状。免疫组织化学: 85例消化道间叶组织肿瘤波形蛋白均阳性,其中 74例表达CD117,诊断为GIST,表达形式有弥漫胞膜 /胞质强阳性、散在阳性、胞质点状着色等,其中 54例同时表达CD34 (阳性率 72. 9% ), 25例表达SMA, 5例表达结蛋白, 5例表达S 100蛋白。在 85例     

胃肠道上皮样血管肉瘤四例临床病理学观察

目的探讨胃肠道血管肉瘤的临床病理特征、免疫表型、诊断及鉴别诊断。方法分析4例胃肠道血管肉瘤的临床病理资料,荧光原位杂交(FISH)检测C-MYC基因是否扩增。结果2例发生在胃,1例在十二指肠与空肠交汇处,1例位于回肠。4例均为中老年人,女1例,男3例。年龄51~62岁。镜下,肿瘤在黏膜层与肌层浸润性生长;见大片血湖及含铁血黄素沉积,形成假裂隙样或腺样结构;瘤细胞呈梭形或上皮样。免疫组织化学4例均弥漫强阳性表达CD31、ERG、Fli-1;3例弥漫强阳性表达CD34;3例不同程度的表达细胞角蛋白和上皮细胞膜抗原;3例FISH检测C-MYC均为阴性。结论胃肠道血管肉瘤是一种罕见的起源于血管内皮细胞的恶性肉瘤,活检标本极易被误诊为低分化腺癌。     

女性生殖系统恶性Müllerian混合瘤临床病理分析

目的探讨女性生殖系统恶性Müllerian混合瘤的发生、免疫表型和鉴别诊断.方法对16例子宫、输卵管和卵巢恶性Müllerian混合瘤进行临床病理和免疫组织化学观察.结果 16例患者中,恶性Müllerian混合瘤发生于子宫颈2例,子宫体11例,输卵管1例,卵巢2例.同源性9例(56%),异源性7例(44%).癌转移7例(44%),其中异源性转移5例(71%),以肉瘤成分转移为主.免疫表型在14例中所有癌成分CK和所有肉瘤成分Vim呈阳性表达,43%病例的肉瘤成分呈CK和Vim双相表达,Des 9例阳性(64%),MG 4例阳性(29%),CD68 5例阳性(36%).结论女性生殖系统恶性Müllrian混合瘤可能来源于中胚层,多发生于子宫,其异源性肿瘤恶性度高,转移快.肿瘤的全面检查和免疫表型可作为鉴别诊断的重要参考依据.     

恶性外周神经鞘瘤52例临床病理分析

目的观察恶性外周神经鞘瘤的临床病理学特征、诊断及鉴别诊断。方法回顾性分析52例恶性外周神经鞘瘤的临床病理学及免疫表型特征并复习相关文献。结果 52例患者中,男女发病率为1∶1,年龄4~71岁,头颈部18例(35%),四肢12例(23%),躯干9例(17%),深部组织8例(15%),椎管内4例(8%),生殖道1例(2%)。镜下肿瘤组织呈束状或漩涡状排列,瘤细胞短纺锤形、卵圆形、梭形,核分裂象易见。免疫表型:瘤细胞局灶表达S-100蛋白,Ki-67增殖指数10%~70%。结论恶性外周神经鞘瘤罕见,侵袭性高,预后差,其组织形态复杂多样,需与滑膜肉瘤、纤维肉瘤、血管外皮瘤、富于细胞性神经鞘瘤、纤维型脑膜瘤以及平滑肌肉瘤等鉴别。     

Immunostaining for SYT protein discriminates synovial sarcoma from other soft tissue tumors: analysis of 146 cases.

Synovial sarcoma in its classic biphasic form can be distinguished readily from other soft tissue lesions; however, monophasic and poorly differentiated forms are diagnostically more problematic. For this reason, we assessed the efficacy of immunostaining for SYT and SSX1 proteins, the gene products resulting from unique synovial sarcoma translocation, to distinguish synovial sarcoma from other soft tissue lesions. A total number of 146 cases were analyzed, including 47 synovial sarcoma cases (all of which were verified by FISH to have t(X; 18) translocation and SYT-SSX fusion gene) and 99 soft tissue tumors of various types. A polyclonal IgG antibody against SYT was used to stain formalin-fixed paraffin embedded tissues. Forty-one out of 47 (87%) synovial sarcoma displayed strong positive nuclear staining (ranging from 80 to 90% of the tumor cells) for SYT antibody. Nineteen of 99 (19%) non-synovial sarcoma cases showed variable nuclear and cytoplasmic staining with SYT, which ranged from 20 to 60% of tumor nuclei, and included malignant peripheral nerve sheath tumor (5/25), solitary fibrous tumor (2/14), Ewing sarcoma (2/6), low grade fibromyxoid tumor (2/4), extraskeletal mesenchymal chondrosarcoma (2/6), gastrointestinal tumor (4/17), epithelioid sarcoma (2/2). The remaining non-synovial sarcomas were negative. This is the first study demonstrating SYT protein expression in tissue sections of synovial sarcoma. This method could provide an easy, rapid and widely applicable means of assisting in the diagnosis of synovial sarcoma, particularly when material and/or resources are unavailable for PCR or FISH-based testing. However, as variable weak staining for SYT may be encountered in a small percentage of non-synovial sarcoma sarcomas, a positive interpretation should be made only when the staining is strong, nuclear and present in the majority of cells.     

Cytokeratin expression in malignant Triton tumor.

A malignant Triton tumor in a 9-year-old boy is described. The first biopsy which was taken from the thenar prominence was diagnosed as a monophasic fibrous synovial sarcoma based on the finding of a spindle cell neoplasm with plump nuclei and cytokeratin expression. The true nature of the tumor became apparent when a second biopsy was investigated. In this specimen a rhabdomyosarcomatous component was found in association with a spindle cell sarcoma fulfilling the criteria of a malignant schwannoma. Immunohistochemical staining using antibodies against vimentin, desmin, muscle-specific actin, cytokeratin, glial fibrillary acidic protein, protein S-100, Leu 7 and myoglobin served to distinguish the two tumor components and documented the possible reactivity of malignant Triton tumor for cytokeratins.     

Infrequent SMARCB1/INI1 gene alteration in epithelioid sarcoma: a useful tool in distinguishing epithelioid sarcoma from malignant rhabdoid tumor

Loss of SMARCB1/INI1 protein expression is considered useful for confirming a histologic diagnosis of malignant rhabdoid tumor. However, loss of SMARCB1/INI1 protein expression has recently been reported in other tumors as well, including a few cases of epithelioid sarcoma. In addition, the histopathologic differences between proximal-type epithelioid sarcoma and malignant rhabdoid tumor have not been conclusively defined. We analyzed SMARCB1/INI1 protein expression in 54 epithelioid sarcoma (proximal-type, 25; distal-type, 29) and examined alterations of the SMARCB1/INI1 gene in the cases lacking protein expression. We found that 19 (76.0%) proximal-type epithelioid sarcoma and 27 (93.1%) distal-type epithelioid sarcoma showed loss of SMARCB1/INI1 protein expression. Analysis of 39 cases with loss of protein expression revealed 4 cases (10.3%) with SMARCB1/INI1 gene alterations at the DNA level (homozygous deletion, 2; 1- or 2-bp deletion, 2) that could have induced the loss of gene products, and all 4 of these were proximal-type epithelioid sarcoma. Epithelioid sarcoma was thus associated with a high frequency of loss of SMARCB1/INI1 protein expression similar to that in malignant rhabdoid tumor. However, the frequency of SMARCB1/INI1 gene alteration at the DNA level in proximal-type epithelioid sarcoma was significantly lower than that in malignant rhabdoid tumor. In addition, the prognosis of patients with malignant rhabdoid tumor is significantly worse than that of patients with proximal-type epithelioid sarcoma (P = .001). Therefore, proximal-type epithelioid sarcoma and malignant rhabdoid tumor are suggested to be distinctive tumors with respect to the mechanism of the loss of SMARCB1/INI1 protein expression. Analysis of alterations in the SMARCB1/INI1 gene may thus be a useful diagnostic tool to distinguish proximal-type epithelioid sarcoma from malignant rhabdoid tumor.     

骨的恶性巨细胞瘤临床病理观察

目的 探讨骨的恶性巨细胞瘤临床病理学特征及其诊断和鉴别诊断.方法 对13例恶性巨细胞瘤的临床及病理学资料进行回顾性分析.结果 13例恶性巨细胞瘤中原发性恶性巨细胞瘤6例,发病年龄21-71岁,平均年龄39.5岁.复发后继发性恶性巨细胞瘤7例,发病年龄27-52岁,平均年龄36.7岁.6例原发性恶性巨细胞瘤除可见到骨巨细胞瘤区域外,还可见到高度恶性的梭形细胞肉瘤区域,7例继发性恶性巨细胞瘤其原发性肿瘤均为骨巨细胞瘤,而复发性肿瘤则呈恶性纤维组织细胞瘤/未分化肉瘤形态.结论 诊断恶性巨细胞瘤时需将临床、影像及病理结合,并除外其他肉瘤如富含巨细胞的骨肉瘤、富含巨细胞的恶性纤维组织细胞瘤等.     

Epithelial-type and neural-type cadherin expression in malignant noncarcinomatous neoplasms with epithelioid features that involve the soft tissues

CONTEXT: Transmembrane adhesion molecules, epithelial-type cadherin (ECAD) and neural-type cadherin (NCAD), help in regulating transformations between epithelial and mesenchymal cells in the developing embryo and in maintaining the epithelioid phenotype. Consequently, the presence of epithelioid cells in certain malignant noncarcinomatous neoplasms raises speculation that the expression of ECAD and NCAD in these neoplasms may have diagnostic significance. OBJECTIVE: To investigate the utility of ECAD and NCAD immunoexpression in distinguishing malignant (noncarcinomatous) neoplasms with epithelioid features that involve the soft tissues. DESIGN: Membranous immunoreactivity of anti-ECAD and anti-NCAD was evaluated on archived cases selected from the files of the Armed Forces Institute of Pathology. RESULTS: Epithelial-type cadherin was found in biphasic synovial sarcoma (35 of 35 cases), malignant melanoma (13/21), monophasic fibrous synovial sarcoma (13/26), clear cell sarcoma (4/9), poorly differentiated synovial sarcoma (3/13), diffuse mesothelioma (4/20), malignant epithelioid peripheral nerve sheath tumor (1/6), and epithelioid sarcoma (5/62). Neural-type cadherin was observed in chordoma (11/11), biphasic synovial sarcoma (30/35), diffuse mesothelioma (14/20), malignant melanoma (14/25), epithelioid sarcoma (24/63), epithelioid angiosarcoma (1/4), poorly differentiated synovial sarcoma (2/13), clear cell sarcoma (1/10), and monophasic fibrous synovial sarcoma (1/26). Eighteen cases of primary cutaneous squamous cell carcinomas all tested positive for ECAD, whereas NCAD was focally observed in 5 cases. No expression of either molecule was observed in cases of epithelioid hemangioendothelioma (n = 9), alveolar soft part sarcoma (n = 8), and extraskeletal myxoid chondrosarcoma (n = 7). CONCLUSIONS: Epithelial-type and neural-type cadherins are found in a variety of noncarcinomatous neoplasms with epithelioid features that involve the soft tissues and can be utilized, in association with other immunomarkers, in distinguishing chordoma (100% NCAD) from extraskeletal myxoid chondrosarcoma and conventional chondrosarcoma of bone (0% NCAD), squamous cell carcinoma (100% ECAD) from epithelioid sarcoma (8% ECAD), and biphasic synovial sarcoma (100% ECAD) from diffuse mesothelioma (20% ECAD).     

Pericardial synovial sarcoma, a potential for misdiagnosis: clinicopathologic and molecular cytogenetic analysis of three cases with literature review

Synovial sarcomas arising in unexpected locations may lead to diagnostic challenges. In this report, we describe 3 cases of synovial sarcoma that manifested clinically as primary pericardial lesions. All 3 cases occurred in men in their fourth decade. Fever, cough, chest pain, and chest distress were the most common symptoms. Histologically, 2 of the tumors were spindle cell monophasic, and 1 tumor was biphasic. By immunohistochemical studies, the tumor cells were positive for cytokeratins and epithelial membrane antigen. In addition, the tumor cells displayed focal immunoreactivity for calretinin, cytokeratin 5/6, and HBME-1, resulting in the initial interpretations of malignant mesotheliomas. None of the 3 cases were diagnosed correctly until subsequent molecular cytogenetic assays demonstrated the presence of SYT gene rearrangements. As there are overlapping morphologic features between pericardial synovial sarcoma and mesothelioma, molecular analysis is essential for differential diagnoses.     

The correlation between morphology and the expression of TGF-β signaling pathway proteins and epithelial-mesenchymal transition-related proteins in synovial sarcomas

Synovial sarcoma (SS) is a malignant tumor of soft tissue and is noted for late local recurrence and metastasis. Aberrant epithelial-mesenchymal transition (EMT) has been implicated in the pathogenesis of diverse human malignancies. Immunohistochemical techniques were used to assess EMT-related proteins (E-cadherin, N-cadherin, β-catenin, Snail, and Slug) and the TGF-β1 pathway (TGF-β1 and Smad2/3) proteins expression in different histological subtypes and epithelial mesenchymal compositions of SS. The expression of cell-surface (E-cadherin) and cytoskeletal proteins (β-catenin) were higher significantly in biphasic SSs (BSSs) (70.4%, 51.9%) than MFSSs (both for 10%). Among monophasic fibrous SSs (MFSSs) samples, E-cadherin protein expression was negatively correlated with expression Snail, Slug, TGF-β1, and Smad2/3. The expression levels of Snail and Smad2/3 were correlated with the pTNM stage (I-II vs. III-IV; P=0.047, P=0.021) and TGF-β1 exhibited a tendency toward a positive correlation with pTNM stage (I-II vs. III-IV; P=0.052), but did not correlate with the histological grade (p>0.05). Interestingly, our data showed that expression of E-cadherin protein correlated with greater survival in SS patients. Overexpression of Snail, and TGF-β1 is associated with suppressed expression of E-cadherin in MFSSs, which supports the hypothesis that the MFSS subtype may have developed via neoplastic EMT.