检测涎腺混合瘤细胞核AgNOR_S数目对临床的实用价值

 本文研究了30例涎腺混合瘤细胞核内银染核仁组成区蛋白（AgNORS）的数目。其结果显示在15例手术后二年有复发的病例中,其AgNORS数目为5～9个/核,平均7.02个/核。但在手术后二年没有复发的病例中,其AgNORS数目为2～5 3个/核,平均3.33个/核。二者之间有极显著差异。本文还研究了AgNORS数目与细胞分化程度及肿瘤成分的关系。这对于涎腺混合瘤术后是否需进一步治疗提供了有力的证据,具有较高的临床实用价值。     

肺原发性恶性涎腺混合瘤

本文报告１例经手术、病理证实的肺原发性恶性涎腺混合瘤，经检索３０年１９６５－１９９５来国外文献仅得１０例。本文结合文献上报导的１０例与我院的１例病人，对其组织发生，病理、免疫组化、临床分型特征、诊断、治疗及预后进行讨论，本病病理特点为肿瘤上皮细胞分散于粘液、软骨或玻璃样基质中与Ｓ－１００蛋白，胶南纤维酸性蛋白（ＧＦＡＰ）肌动蛋白，角蛋白及波纹蛋白胞浆免疫组化反应均阳性，给予临床分型，本病易误诊，首     

127例涎腺混合瘤临床病理分析

本文针对涎腺混合瘤组织学形态的多形性及手术后复发率高的临床特征，回顾性复习了术后随访五年以上的涎腺混合瘤１２７例临床病理资料，其中良性１１３例，恶性１４例。着重比较分析了原发肿瘤的发生特征、肿瘤的包膜特征以及肿瘤细胞成分和间质成分的构成特征等，并将其各自与肿瘤术后复发率之间的可能相关性进行了统计学处理，发现原发肿瘤为多结节者术后复发率明显高于单结节者，而肿瘤的包膜不完整或局部受侵、组织学形态以细胞成分构成优势或以粘液软骨样间质成分构成优势等均与肿瘤复发率无关。     

细胞学检查在诊断涎腺混合瘤临床应用中的体会

小针穿刺细胞学检查在肿瘤诊断及鉴别诊断中具有较高的应用价值 ,我们在 16例临床诊断为颌下及颈部淋巴结肿大的病例 ,经细胞学检查为涎腺混合瘤。病例来源与组成 :我科自 1987年 1月～ 2 0 0 0年 6月诊检 16例全部经手术后病理证实为混合瘤。其中男性 7例 ,女性 9例 ;患者年龄 2 3～ 5 7岁 ,平均年龄 40 .6岁 ,ｓ =9.14。颌下 11例(6 8.8% ) ,腮部 1例 (6 .2 % ) ,耳下 4例 (2 5 .0 % )。检查方法与染色 :用 5ｍｌ注射器对肿块进行多个方向的负压抽吸 ,穿出物涂片 ,瑞士染色检查。结果 :涂片中可见到片状 ,不规则形红染的粘液性物质及散在…     

针吸细胞学诊断涎腺混合瘤的标准探讨

混合瘤是涎腺肿瘤最常见的一种,其针吸细胞学诊断需与涎腺的其他肿瘤鉴别。１材料与方法１．１临床资料 １９８６年１２月～１９９８年１２月之间,经针吸细胞学检查且病理组织学证实的７５例患者,其中６８例组织学为涎腺混合瘤,３例粘液表皮样癌,２例肌上皮瘤,２例神经鞘瘤。１．２方法 用１０ｍｌ注射器和外径０．７ｍｍ的针头常规针吸,涂片立即以 ９５％酒精固定, ＨＥ染色后镜检。２结果 ６８例涎腺混合瘤观察到６种形态变化,与其他肿瘤比较见附表。３小结 涎腺混合瘤吸出物均为半粘稠血性物,涂片时有粘液感。涂片由腺上皮和肌…     

肺原发性恶性涎腺混合瘤(病例报告并文献复习)

本文报告1例经手术、病理证实的肺原发性恶性涎腺混合瘤,经检索30年(1965～1995)来国外文献仅得10例。本文结合文献上报导的10例与我院的1例病人,对其组织发生、病理、免疫组化、临床分型及特征、诊断、治疗及预后进行讨论。认为本病病理特点为肿瘤上皮细胞分散于粘液、软骨或玻璃样基质中与S—100蛋白,胶质纤维酸性蛋白(GFAP),肌动蛋白,角蛋白及波纹蛋白胞浆免疫组化反应均阳性。给予临床分型。本病易误诊。首选治疗为手术。预后差。     

复发性涎腺多形性腺瘤的处理

复发性多形性腺瘤多见于腮腺和颌下腺,小涎腺则极少见。腮腺多形性腺瘤采取简单摘除的剜出术（ｅｎｕｃｌｅａｔｉｏ）,复发率高达２０％～４５％。采取保存面神经的腮腺腺叶及肿瘤切除术,复发率为０％～３％。因此,这一术式被认为是治疗腮腺肿瘤的标准术式。尽管如此,但复发性涎腺多形性腺瘤临床时有所见。１复发原因１．１瘤体的“裸露区域（ｂａｒｅａｒｅａ）”一般认为多形性腺瘤都有包膜,但其厚薄不一,有的部分较厚,有的仅在镜下看到几束胶原纤维,而瘤体紧贴正常腺组织而呈“裸露”状态。包膜内可见瘤组织浸润,或呈指样突起…     

涎腺肿瘤细胞核DNA定量分析初步研究

作者应用流式细胞术对91例涎腺肿瘤进行胞核DNA定量分析,探讨核DAN倍体水平和细胞分裂增殖活动与病理类型和恶性度的关系。发现核DNA倍体水平与病理类型无关。异倍体更多地出现于恶性肿瘤中,异倍体肿瘤细胞DNA合成旺盛、分裂增殖更为活跃。DNA倍体水平和细胞增殖活动随肿瘤恶性度增加而增加。作者还分析计算出依据核DNA含量定性诊断的境界值。     

涎腺肿物120例临床分析

涎腺肿物是颌面部常见疾病,其病理类型十分复杂。不同类型的肿物其病理特点及生物学行为均不同。故其治疗和预后也不相同。临床资料我科自１９９０年至１９９８年间共收治涎腺肿物１２０例,其中男６１例,女５９例。年龄从１０岁到８０岁。其中腮腺肿物８５例,占７０．...     

涎腺多形性腺瘤106例诊治体会

目的 探讨涎腺多形性腺瘤的临床特点、诊断方法及治疗原则。方法 对我科近14年来收治的106例涎腺多形性腺瘤的临床资料进行回顾性分析。结果 106例涎腺多形性腺瘤中，以腮腺最为常见，占52％，颌下腺、腭部、上唇次之，分别为36．8％、8．5％、2．7％。本组共复发4例。结论 细针抽吸细胞学活检可作为涎腺多形性腺瘤的常规术前检查，治疗的成功与否关键在于第一次的手术方式。     

大涎腺肿瘤108例临床分析

目的　对大涎腺肿瘤的临床特点和病理学特点进行分析 ,探索大涎腺肿瘤的发生发展规律并讨论诊断和治疗中存在的一些问题。方法　对 1990～ 1998年间收治的经组织学确诊的 10 8例大涎腺肿瘤的临床和病理特点进行回顾性综合分析 ,对诊断和治疗中存在的问题提出见解。结果　 10 8例大涎腺肿瘤中 ,良性肿瘤 81例占 75 % ,恶性肿瘤2 7例占 2 5 %。良性肿瘤中又以多形性腺瘤和囊肿为多见 ,分别占良性肿瘤的 72 .84%和 2 7.16%。舌下腺囊肿占舌下腺肿瘤的 75 % ,腮腺多形性腺瘤占腮腺肿瘤的 5 9.46%。结论　大涎腺肿瘤的发生发展有一定的规律可循。术前穿刺细胞学检查和涎腺X -线造影对诊断和治疗方案有指导意义。摘除舌下腺是根治舌下腺囊肿的最有效的办法 ,肿瘤摘除加腺体的部分或全部切除是防止多形性腺瘤复发的关键因素     

小涎腺肿瘤60例临床分析

目的　探讨小涎腺肿瘤的发病情况 ,临床特点及诊断治疗。方法　对 1 980～ 1 995年间收治的经病理确诊的 60例小涎腺肿瘤的年龄、性别、好发部位、诊断、治疗等进行了回顾性综合分析。结果　 60例口腔小涎腺肿瘤 ,良性肿瘤 2 6例占 43 .33 % ,恶性肿瘤 34例占 56 .67% ,良性肿瘤中的混合瘤多见占良性肿瘤的 69.2 3 % ,恶性肿瘤中以黏液表皮样癌为多 ,1 4例占恶性肿瘤的 41 .1 8% ,手术 +放疗者占恶性肿瘤的 38.2 4 % ,5年生存率为 68.97%。结论　小涎腺肿瘤中恶性肿瘤多于良性肿瘤。术前X线检查和术中冰冻病理检查对诊断和治疗方案有指导意义。首次手术彻底性是防止复发的关键。术后辅助放疗可降低恶性肿瘤复发率     

Genomic landscape of salivary gland tumors

Effective treatment options for advanced salivary gland tumors are lacking. To better understand these tumors, we report their genomic landscape. We studied the molecular aberrations in 117 patients with salivary gland tumors that were, on physician request, tested in a Clinical Laboratory Improvement Amendments (CLIA) laboratory (Foundation Medicine, Cambridge, MA) using next-generation sequencing (182 or 236 genes), and analyzed by N-of-One, Inc. (Lexington, MA). There were 354 total aberrations, with 240 distinct aberrations identified in this patient population. Only 10 individuals (8.5%) had a molecular portfolio that was identical to any other patient (with four different portfolios amongst the ten patients).The most common abnormalities involved the TP53 gene (36/117 [30.8% of patients]), cyclin pathway (CCND1, CDK4/6 or CDKN2A/B) (31/117 [26.5%]) and PI3K pathway (PIK3CA, PIK3R1, PTEN or AKT1/3) (28/117 [23.9%]). In multivariate analysis, statistically significant co-existing aberrations were observed as follows: TP53 and ERBB2 (p = 0.01), cyclin pathway and MDM2 (p = 0.03), and PI3K pathway and HRAS (p = 0.0001). We were able to identify possible cognate targeted therapies in most of the patients (107/117 [91.5%]), including FDA-approved drugs in 80/117 [68.4%]. In conclusion, salivary gland tumors were characterized by multiple distinct aberrations that mostly differed from patient to patient. Significant associations between aberrations in TP53 and ERBB2, the cyclin pathway and MDM2, and HRAS and the PI3K pathway were identified. Most patients had actionable alterations. These results provide a framework for tailored combinations of matched therapies.     

The evolving landscape of salivary gland tumors

Salivary gland cancers are a rare, histologically diverse group of tumors. They range from indolent to aggressive and can cause significant morbidity and mortality. Surgical resection remains the mainstay of treatment, but radiation and systemic therapy are also critical parts of the care paradigm. Given the rarity and heterogeneity of these cancers, they are best managed in a multidisciplinary program. In this review, the authors highlight standards of care as well as exciting new research for salivary gland cancers that will strive for better patient outcomes.     

The role of immune surveillance in malignant transformation of benign salivary gland tumors

Pleomorphic adenoma (PA), the most common salivary gland tumor, is a benign tumor that carries a risk of malignant transformation to various histologies of carcinoma ex pleomorphic adenoma (CA exPA). Recently, genomic analyses have provided deeper insights into the molecular biology of salivary gland cancers. However, the molecular processes that underlie the progression from PA to CA exPA are largely unknown. In this study, we used RNAseq data from CA ex PA of myoepithelial (n = 24) or salivary duct histology (n = 6), de novo myoepithelial carcinoma (n = 16) and de novo salivary duct carcinoma (n = 10), and compared their constituent immune tumor microenvironments. We found that increasing levels of immune infiltration and activation were associated with a generally lower probability of cancer developing ex-PA, suggesting that immune surveillance may constrain the malignant transformation of benign salivary tumors. More immunologically infiltrated tumors were more likely to have developed de novo. Taken together, these data suggest a role for tumor escape from immune surveillance in the development of CA exPA. The immune-cold microenvironments of CA ex PA tumors may in part explain their more aggressive clinical behavior.     

Multiplexed single-cell analysis of FNA allows accurate diagnosis of salivary gland tumors

Diagnosing salivary gland tumors (SGTs) through fine-needle aspiration (FNA) biopsies is challenging due to the overlapping cytomorphologic features between benign and malignant tumors. The authors developed an innovative, multiplexed cycling technology for the rapid analyses of single cells obtained from FNA that can facilitate the molecular analyses and diagnosis of SGTs. Antibodies against 29 protein markers associated with 7 SGT subtypes were validated and chemically modified via custom linker–bio-orthogonal probes (FAST). Single-cell homogenates and FNA samples were profiled by FAST cyclic imaging and computational analysis. A prediction model was generated using a training set of 151,926 cells from primary SGTs (N = 26) and validated on a separate cohort (N = 30). Companion biomarker testing, such as neurotrophic tyrosine receptor kinase (NTRK), was also assessed with the FAST technology. The FAST molecular diagnostic assay was able to distinguish between benign and malignant SGTs with an accuracy of 0.86 for single-cell homogenate samples and 0.88 for FNA samples. Profiling of multiple markers as compared to a single marker increased the diagnostic accuracy (0.82 as compared to 0.65-0.74, respectively), independent of the cell number sampled. NTRK expression was also assessed by the FAST assay, highlighting the potential therapeutic application of this technology. Application of the novel multiplexed single-cell technology facilitates rapid biomarker testing from FNA samples at low cost. The customizable and modular FAST-FNA approach has relevance to multiple pathologies and organ systems where cytologic samples are often scarce and/or indeterminate resulting in improved diagnostic workflows and timely therapeutic clinical decision-making.     

PCNA和Ki-67在涎腺良、恶性多形性腺瘤中的表达及意义

目的：研究涎腺良、恶性多形性腺瘤的临床病理特点,生物学行为及细胞增殖活性,为其临床诊断及预后评估提供依据。方法：对114例涎腺良、恶性多形性腺瘤进行回顾性分析,对其中20例多形性腺瘤、9例多形性腺瘤生长活跃型及9例恶性多形性腺瘤采用SABC和LSAB免疫组化法观察增殖细胞核抗原（PCNA）和增殖细胞核相关抗原（Ki-67）的表达和分布。结果：恶性多形性腺瘤的PCNA及Ki-67表达水平显著高于多形性腺瘤及多形性腺瘤生长活跃型,其PI值较后二者差异有显著性（P〈0．01）;良性多形性腺瘤的复发组PCNA和Ki-67的表达明显高于原发组,二者之间有显著性差异（P〈0．01）。结论：PCNA和Ki-67检测在判断多形性腺瘤恶性增殖方面有重要意义,对良性多形性腺瘤复发预测有重要的参考价值。     

Herpes oncolytic therapy of salivary gland carcinomas

Bcl-xL functions as a dominant regulator of apoptotic cell death and is implicated in chemotherapeutic resistance of malignant pleural mesothelioma (MPM). Mesothelioma cell lines demonstrate increasing levels of Bcl-xL as resistant clones are selected in vitro. Moreover, upon introduction of antisense oligonucleotides specific to Bcl-xL mRNA, MPM cells are sensitized to chemotherapeutic agents. Here we describe the therapeutic effects of a novel combination therapy, Bcl-xL antisense oligonucleotide (ASO 15999) and cisplatin, on mesothelioma cell lines in vitro and in vivo; in addition, efficacy of ASO 15999 in decreasing tumor load as well as its effect on survival in an animal model. Finally, we initiated preliminary toxicity studies involved with intraperitoneal (IP) injections of ASO 15999 into mice. This novel combination, with doses of cisplatin four times below established IC(50) levels, significantly decreased viability of MPM cell lines after 48 hr. The growth of established mouse flank human tumor xenografts was reduced with intra-tumor administration of ASO 15999. Local spread and development of IP xenografts was reduced with treatments of ASO alone, and survival of mice afflicted with these xenografts was prolonged after administration of ASO alone and ASO 15999 + cisplatin combination therapy. These findings suggest that ASO 15999 sensitizes MPM cell lines to the toxic effects of cisplatin. ASO 15999 induced reduction of Bcl-xL is effective in slowing the progression of human mesothelioma cell lines both in vitro and in vivo. More notably, the combination of Bcl-xL ASO and cisplatin extends survival in an orthotopic tumor xenograft model.     

ALDH/CD44 identifies uniquely tumorigenic cancer stem cells in salivary gland mucoepidermoid carcinomas

A small sub-population of cells characterized by increased tumorigenic potential, ability to self-renew and to differentiate into cells that make up the tumor bulk, has been characterized in some (but not all) tumor types. These unique cells, namedcancer stem cells, are considered drivers of tumor progression in these tumors. The purpose of this work is to understand if cancer stem cells play a functional role in the tumorigenesis of salivary gland mucoepidermoid carcinomas. Here, we investigated the expression of putative cancer stem cell markers (ALDH, CD10, CD24, CD44) in primary human mucoepidermoid carcinomas by immunofluorescence, in vitro salisphere assays, and in vivo tumorigenicity assays in immunodeficient mice. Human mucoepidermoid carcinoma cells (UM-HMC-1, UM-HMC-3A, UM-HMC-3B) sorted for high levels of ALDH activity and CD44 expression (ALDH^highCD44^high) consistently formed primary and secondary salispheres in vitro, and showed enhanced tumorigenic potential in vivo (defined as time to tumor palpability, tumor growth after palpability), when compared to ALDH^lowCD44^low cells. Cells sorted for CD10/CD24, and CD10/CD44 showed varying trends of salisphere formation, but consistently low in vivo tumorigenic potential. And finally, cells sorted for CD44/CD24 showed inconsistent results in salisphere formation and tumorigenic potential assays when different cell lines were evaluated. Collectively, these data demonstrate that salivary gland mucoepidermoid carcinomas contain a small population of cancer stem cells with enhanced tumorigenic potential and that are characterized by high ALDH activity and CD44 expression. These results suggest that patients with mucoepidermoid carcinoma might benefit from therapies that ablate these highly tumorigenic cells.     

Predictors of nodal metastasis in salivary gland cancer

OBJECTIVES: This study was conducted to determine clinical and histologic factors that would predict nodal metastasis in patients with major salivary gland cancer. METHODS: A retrospective study of 40 patients who underwent surgery, including neck dissection, for major salivary gland cancer between 1975 and 1997 was performed. Patient charts were reviewed, and clinical and pathologic data were extracted along with outcome. Predictive factors were identified and survival curves were obtained. RESULTS: Neck dissections were performed in 40 patients, which revealed histologic evidence of tumor in lymph nodes in 15 cases. Histologically proven metastasis was found in 16% of specimens from elective and 73% of specimens from therapeutic neck dissection. Five-year overall and locoregional disease-free survival rates for histologically positive and negative groups were 40% versus 63% (P < 0.05) and 67% versus 69% (P = 0.59), respectively. Univariate analysis of the factors revealed that clinical evidence of nodal metastasis (P < 0.001) and high-grade cancer (P < 0.033) predicted histologic nodal involvement. Multivariate analysis revealed that only a positive neck examination was a significant predictive factor (OR = 31, 95%CI = 2.99-312). CONCLUSIONS: Our results suggest that clinical neck examination is a reliable predictor of regional metastasis in patients with major salivary gland cancer. In view of the low frequency of occult metastases, routine elective treatment of the neck is not recommended.