人乳头状瘤病毒感染及其亚型与鼻内翻性乳头状瘤相关性探讨

目的 了解不同亚型的人乳头状瘤病毒(human papillomavirus,HPV)在鼻内翻性乳头状瘤(nasal inverted papilloma,NIP)中的分布,探讨其在NIP发病中的作用.方法 将78例NIP腊包埋组织标本分为单纯NIP组、伴不典型增生NIP组和NIP癌变组,同时选取40例健康体检者鼻腔粘膜组织作为健康对照组,采用聚合酶链反应(PCR)技术检测HPV6、11、16及18型感染情况.结果 78例NIP石蜡包埋组织标本HPV总阳性率为61.5％.单纯NIP组、伴不典型增生NIP组和NIP癌变组阳性率分别达59.5％、73.9％和46.2％.随着NIP临床分期级别的升高,HPV感染率也呈相应的上升趋势.单纯NIP组以低危型HPV6、11型感染为主,NIP癌变组则同时检出高危型HPV16型和HPV18型.结论 HPV感染在NIP发病中起着重要作用,其中高危型HPV感染能扩大NIP病变范围,而HPV16、18型可能与NIP恶变有关联.     

人乳头状瘤病毒16、18型变异及相关肿瘤

肿瘤的形成可由多种病毒引起[1],其一就是人类乳头状瘤病毒(Human papillomavirus,HPV).HPV是1949年从普通疣体浸出液中首次被观察到,1995年有研究证实HPV感染为宫颈癌的致病病原体.研究显示:HPV16、18能促使人类鳞状上皮的增生.目前HPV16、18变异体的致瘤性受到各国学者的广泛关注.     

伴重度异型增生的乳头状唾液腺瘤1例并文献复习

目的 探讨伴重度异型增生的乳头状唾液腺瘤(sialadenoma papilliferum,SP)的临床病理学特征及分子改变.方法 回顾性分析1例SP的临床病理特征、免疫表型及分子检测,并复习相关文献.结果 患者女性,61岁,发现磨牙后区肿物3年.镜下肿物呈双相生长模式,表面复层鳞状上皮呈乳头状增生,下方为大小不等的腺...     

胎盘型谷胱甘肽转移酶在喉肿瘤的表达及其意义

目的：了解胎盘型谷胱甘肽转移酶（ＧＳＴ－π）在喉息肉、鳞状上皮乳头状瘤、鳞状细胞癌的表达状况，探讨ＧＳＴ－π与上述病变之间的关系及意义。方法：常规病理诊断选择喉息肉１０例、乳头状瘤１０例、鳞状细胞癌２０例，用免疫组化ＬＳＡＢ法检测ＧＳＴ－π，统计学处理。结果：ＧＳＴ－π表达在喉息肉及癌旁正常鳞状上皮均为阴性，不典型增生鳞状上皮ＧＳＴ－π呈阳性表达。ＧＳＴ－π阳性率在喉乳头状瘤和喉鳞状细胞癌分别为２０％和８５％，两者之间差异具有显著性。结论：ＧＳＴ－π在喉良恶性肿瘤检测、判断病变进展及转归方面具有重要意义。     

原位核酸分子杂交技术检测宫颈鳞状上皮病变HPV感染

目的:观察宫颈鳞状上皮病变过程中HPV6/11、HPV16/18的表达,探讨其测定的临床意义.方法:选择病理诊断为宫颈慢性炎症50例、鳞状上皮乳头状瘤样增生30例、尖锐湿疣30例、上皮内瘤变89例、鳞癌50例共249例石蜡包埋标本,应用原位核酸分子杂交技术对其进行HPV6/11,HPV16/18检测.结果:慢性炎症组HPV6/11阳性表达4%,HPV16/18阳性表达0%;乳头状瘤样增生组HPV6/11阳性表达10%,HPV16/18阳性表达3.3%;尖锐湿疣组HPV6/11阳性表达93.3%,HPV16/18阳性表达23.3%;CIN组中Ⅰ级HPV6/11阳性表达48.9%,HPV16/18阳性表达42.2%;Ⅱ级HPV6/11阳性表达39.1%,HPV16/18阳性表达69.6%;Ⅲ级HPV6/11阳性表达9.5%,HPV16/18阳性表达66.7%;鳞癌组HPV6/11阳性表达6%,HPV16/18阳性表达82%.结论:应用原位核酸分子杂交技术检测宫颈鳞状上皮病变细胞的HPV6/11、HFV16/18,为临床早期诊断、鉴别诊断及评估预后提供可靠的理论依据.     

宫颈鳞状细胞癌和癌前病变中Skp2表达及其与HPV16/18感染的关系

目的 探讨skp2在宫颈鳞状细胞癌和癌前病变中的表达规律及其与人乳头状瘤病毒(HPV)感染之间的关系.方法 采用免疫组织化学(ABC法)和原位杂交检测Skp2蛋白和HPV16/18 DNA在30例正常宫颈鳞状上皮、29例宫颈低级别上皮内瘤变、31例高级别上皮内瘤变和31例宫颈鳞状细胞癌中的表达.结果 Skp2在正常宫颈鳞状上皮中呈阴性,与宫颈低级别上皮内瘤变(阳性表达率为13.8%,4/29)之间差异无统计学意义(P>0.05).随着上皮病变级别升高,表达也逐渐增强,在宫颈鳞状细胞癌中表达更强;HPV16/18 DNA在四组中的阳性表达率,除高级别上皮内瘤变和宫颈鳞状细胞癌两组间差异无统计学意义外(均为96.8%),其余各组之间差异均有统计学意义(P<0.01);在宫颈低级别上皮内瘤变中skp2蛋白表达和HPV感染相关无统计学意义,但在高级别上皮内瘤变和宫颈鳞状细胞癌两组中均呈正相关(γ高级别=0.373,γ癌 =0.416,P<0.05).结论 Skp2过表达主要在宫颈鳞状细胞癌形成的中晚期起作用,可作为一个早期诊断恶性的指标,且可能与HPV16/18感染有协同作用.E7-skp2-Rb可能是HPV感染诱导宫颈鳞状细胞癌形成的一条新致癌途径.     

TCT查验子宫颈涂片中HPV感染的研究

目的评价液基薄层细胞检测技术(TCT)检测宫颈涂片中人乳头状瘤病毒(human papilloma virus,HPV)感染的敏感性与准确性。方法对1030例外阴尖锐湿疣患者的子宫颈涂片,采用TCT检测技术进行细胞病理学诊断,其诊断标准依据The Bethesda System(TBS)分类法。同期行阴道镜指引下的子宫颈活组织检查和聚合酶链反应(PCR)技术检测宫颈拭子中的HPVDNA。结果应用PCR检测1030例宫颈拭子HPVDNA,阳性者37例(35.92%)。宫颈活组织学检查结果为ASCUS57例(5.53%);上皮内病变CIN11例,占总数的1%;占HPV( )百分率为29.73;占57例为非典型麟状细胞阳性的19.3。结论TCT作为一种细胞病理学检测技术,用于诊断宫颈HPV感染或亚临床感染,有临床应用价值。     

子宫颈癌中Hedgehog信号通路蛋白表达与人乳头状瘤病毒16型感染的关系

目的 探讨Hedgehog(Hh)信号通路蛋白在宫颈癌及其癌前病变中的临床病理学意义,并分析其与人乳头状瘤病毒(HPV)16型感染的关系.方法 32例正常宫颈上皮、71例宫颈上皮内瘤变(CIN;CIN Ⅰ 28例,CIN Ⅱ 18例,CIN Ⅲ25例)和80例宫颈鳞状细胞癌共183例选自延边大学医院、延边妇幼保健院和延边肿瘤医院病理科存档蜡块.应用PCR技术检测上述组织中HPV16型的感染情况,并应用Shh、Ihh、Ptch和Smo 4种Hh信号通路蛋白抗体、组织芯片和免疫组织化学EnVision法检测Hh信号通路蛋白在上述病变组织中的表达情况.结果 Shh、Ihh、Ptch和Smo在正常宫颈黏膜上皮中为弱阳性,而在宫颈癌和CIN Ⅲ中呈强阳性,其表达率均显著高于正常宫颈黏膜上皮(P均<0.05).80例官颈癌标本中HPV16阳性率是77.5%(62/80),而且Shh蛋白的强阳性率在HPV16型阳性的宫颈癌组织中显著高于HPV16阴性组(P<0.05).结论 Hh信号通路蛋白过表达可以作为宫颈癌及其癌前病变的早期辅助诊断指标并有望成为宫颈癌靶向治疗的新靶点,而且Shh蛋白的过表达与HPV16型感染密切相关.     

鼻腔及副鼻窦内翻性乳头状瘤p53、Ki-67和CD44v6表达

鼻腔及副鼻窦内翻性乳头状瘤(inverted papilloma，IP)是少见的良性肿瘤，以具有潜在的复发和癌变倾向为特征。现将温州医学院附属一院1984～1999年共47例报道如下，观察其临床特点、病理形态及免疫表型，探讨其临床病理与生物学行为及预后的关系。     

非浸润性内翻性尿路上皮肿瘤临床病理分析

目的探讨非浸润性内翻性尿路上皮肿瘤的病理类型及其生物学行为。方法收集尿路上皮内翻性乳头状瘤及非典型内翻性乳头状瘤共69例,严格按照2004年WHO诊断内翻性乳头状瘤的标准并参照外生性肿瘤的分类标准重新诊断,进行分类,并追踪患者预后。结果经重新诊断,69例分为内翻性乳头状瘤28例,无复发;非浸润性内翻性尿路上皮癌13例,2例复发;乳头状瘤或低度恶性潜能的乳头状尿路上皮肿瘤11例,无复发;有争议的17例,争议集中在诊断为内翻性乳头状瘤还是低级别的非浸润性内翻性尿路上皮癌,1例复发。结论非浸润性内翻性尿路上皮肿瘤的病理类型,可分为良性的内翻性乳头状瘤,镜下表现为内生性的成熟的尿路上皮;异型增生的非浸润性内翻性尿路上皮癌,镜下表现为内生性的异型增生的尿路上皮,局灶可伴外生性成分;交界性的低度恶性潜能的内翻性尿路上皮肿瘤,镜下表现介于内翻性乳头状瘤与低级别非浸润性内翻性尿路上皮癌之间,即无法明确诊断为内翻性乳头状瘤或非浸润性内翻性尿路上皮癌。这样的分类更利于病理医生对内生性的尿路上皮肿瘤的认识及诊断,进而指导临床医生对内生性的尿路上皮肿瘤进行恰当治疗。     

The predictive value of human papilloma virus (HPV) typing in the prognosis of bronchial squamous cell papillomas

Five solitary squamous papillomas of bronchus with variable degrees of dysplasia, one combined with a laryngeal papilloma and with a neuroendocrine carcinoma in the contralateral lung, and five papillomas combined with invasive squamous cell carcinomas were investigated for their expression of human papilloma virus DNA by in situ hybridization. Benign squamous cell papillomas showed an association with papilloma virus type 11 and rarely type 6, whereas types 16 or 18, sometimes in combination with types 31/33/35 were found in papillomas associated with carcinomas. In one patient a benign papilloma containing human papilloma virus type 18 and 31/33/35-positive preceded a recurrence combined with carcinoma by 2 years; this recurrent papilloma and the carcinoma were also positive for human papilloma virus 18 DNA. We suggest that human papilloma virus typing should be performed in every squamous cell papilloma of bronchus. Patients with papillomas exhibiting human papilloma virus 16 or 18 positivity are at high risk for the development of squamous cell carcinoma. Furthermore, virus typing may be of prognostic importance in relation to the development of squamous carcinoma.     

Image analysis in the discrimination of verrucous carcinoma and squamous papilloma.

Verrucous carcinoma is a differentiated variant of squamous cell carcinoma and may present diagnostic difficulties as it may be erroneously diagnosed as squamous papilloma. In this study, the sizes of the intermediate cells in these two conditions were measured by means of morphometric analysis. Biopsies from 28 patients with verrucous carcinoma, 25 patients with squamous papilloma, and ten squamous cell carcinomas were analysed. A significant difference was shown (P less than 0.001) by an uncorrelated t-test between verrucous carcinoma and squamous papilloma. The former had a mean cell area of 373 microns 2 and the latter 184 microns 2. Squamous cell carcinomas differed from the other two neoplasms by their large range of cell areas both within and between cases. Thus, image analysis can be of diagnostic help in cases where no firm initial histopathological diagnosis can be obtained. The diagnosis should be made on morphological grounds, but a mean cell area greater than 300 microns 2 supports a diagnosis of verrucous carcinoma whereas an area less than 250 microns 2 supports a diagnosis of squamous papilloma.     

Metachronous squamous cell carcinomas evolving from independent oropharyngeal and pulmonary squamous papillomas: association with human papillomavirus 11 and lack of aberrant p53, Rb, and p16 protein expression

Squamous cell carcinoma evolving from squamous papilloma in both the upper and lower respiratory tract in the same patient is uncommon. The molecular mechanisms underlying the progression have not been well investigated. We herein describe a case of squamous cell carcinoma arising from respiratory papilloma in two independent occasions. The patient initially had oropharyngeal squamous cell carcinoma arising in a squamous papilloma at the age of 25 years. He subsequently developed squamous cell carcinoma in the left lower lobe of the lung, which was also associated with squamous papilloma, 8 years after the complete excision of the oropharyngeal lesion. Polymerase chain reaction-based broad-spectrum human papillomavirus DNA amplification and typing showed the presence of human papillomavirus type 11 DNA in both oropharyngeal and pulmonary tumors. Immunohistochemical studies showed that the expression status of p53, Rb, and p16 proteins was unaltered during tumor progression. These observations indicate that human papillomavirus 11-associated neoplastic transformation and tumor progression in the respiratory tract may not involve aberrant regulation of the p53 and Rb signaling pathways.     

Papilloma of lip associated with human papilloma viruses-32 infection in a child

Squamous papilloma is the most common benign oral epithelial lesion, and it is well known to be associated with human papilloma virus 6 and 11. Here, we report a case of squamous papilloma associated with human papilloma viruses (HPV)-32 in a 4-year-old boy who presented with a verrucous lesion on the lower lip. HPV-32 is often associated with a rare benign condition focal epithelial hyperplasia (FEH). A limited number of lesions and the absence of characteristic histology ruled out FEH in our patient. To the best of our knowledge, the association of oral squamous papilloma with HPV-32 is hitherto unreported.     

Cytological findings of mixed squamous cell and glandular papilloma in the lung

Pulmonary mixed squamous cell and glandular papilloma is an extremely rare neoplasm. This is the first cytological report of such a rare neoplasm. A 59‐year‐old Japanese man was admitted to the hospital complaining of a persistent cough and bloody sputum. A bronchial endoscopic examination revealed an endobronchial polypoid tumor. Upon bronchial brush cytology by Papanicolaou stain, squamous dysplasia showing mild atypia was suspected. The smears showed moderate cellularity with singly scattered cells or loose clusters of cells, consisting of squamous cells and a few columnar cells. Nuclei of the squamous cells showed mild atypia, but there was no nuclear atypia of the columnar cells. Upon intraoperative pathological examination by frozen section, pulmonary mixed squamous cell and glandular papilloma was suspected. Intraoperative imprint cytology by Ultrafast Papanicolaou stain showed a few differences in comparison with bronchial brush cytology, which were thought to be due to differences in obtaining cytological specimens or the steps prior to the staining. The patient underwent a segmentectomy of the left lung. Histopathological diagnosis confirmed a mixed squamous cell and glandular papilloma. The postoperative course has been uneventful for 5 years after surgery. It was thought that cytology was diagnostically inadequate on its own in the present case. However, mixed squamous cell and glandular papilloma must be considered as another type of pulmonary tumor in cytological preparations, especially in a case showing endobronchial papillary growth by bronchoscopy. Diagn. Cytopathol. 2010;38:913–917. © 2010 Wiley‐Liss, Inc.     

Cytologic-histologic correlations in the diagnosis of inverted sinonasal papilloma

We present cytologic data from multiple samples from two cases of inverted sinonasal papilloma (ISP). These samples displayed the entire spectrum of squamous cell changes, including benign squamous papilloma, variable degrees of dysplasia, and invasive squamous cell carcinoma. In all instances, the cytologic impression coincided with the final diagnosis based on frozen and/or permanent histologic sections from the same samples. We suggest that cytologic examination be viewed as a useful initial approach in the diagnosis of ISP, and in the differential diagnosis of other tumors that occur in the same sites.     

Mixed squamous cell and glandular papilloma of the lung: a case study and literature review

Mixed squamous cell and glandular papilloma (mixed papilloma) of the lung is an extremely rare neoplasm, with only 10 cases reported so far in the English literature. We present a case study of endobronchial mixed papilloma with immunohistochemical and etiological investigations. A 49-year-old male with a smoking history complained of hemoptysis, presented with a lung mass closely adjacent to large vessels in the computed tomography findings, and underwent lobectomy. The 3.0-cm sized polypoid tumor was histologically diagnosed as endobronchial mixed papilloma. Immunohistochemically, intracellular mucin was positive for MUC5AC, which is expressed in tracheobronchial goblet cells. CAM5.2 and CK19 were diffusely positive, indicating that the tumor originated from the columnar epithelium by squamous metaplasia. CEA and CA19-9 were focally positive. A human papillomavirus (HPV) investigation with in situ hybridization using a wide spectrum probe and a newly-developed PCR system did not detect any HPV infection. Including this case with a detailed HPV investigation, all of the reported cases of mixed papilloma were HPV-negative, and a literature review including newly-reported cases indicated a high frequency of smoking in such cases. Endobronchial mixed papillomas might have a smoking-related etiology.     

Inverted ductal papilloma of minor salivary gland: case report with immunohistochemical study and literature review

Inverted ductal papilloma (IDP) is a type of ductal papilloma arising in ducts of minor salivary glands. Very few cases, and no cases in Japan, have been reported. Reported herein is a case of IDP with a review of the literature. The patient was a 49-year-old man presenting with a lump in the right buccal mucosa of the premolar area of the mandible. The tumor was excised en bloc after a biopsy diagnosis of IDP. On the surface of the covering epithelium, an opening was seen to be filled with mucinous material. On cut surface the opening led to the tumor cavity. The major portion of the tumor parenchyma was made up of papillary proliferation of basaloid squamous cells. Some crypts, microcysts, and mucous cells were seen. There were no findings suggestive of a malignant tumor. The patient's postoperative course was uneventful and there has been no recurrence after 1 year's follow up. Immunohistochemical analysis of the present case supports the hypothesis that IDP originates from squamous metaplasia and proliferation of minor salivary gland duct cells.     

Solitary peripheral pulmonary papilloma evaluation on frozen section: A potential pitfall for the pathologist

Endobronchial papilloma is a rare entity that is in the differential for solitary pulmonary nodule. It almost always follows a benign course, with only rare malignant transformation being reported in the squamous variant. No malignant transformation of the glandular variant has been reported to the best of our knowledge, and therefore endobronchial papilloma must be distinguished from more aggressive neoplasms. This distinction is particularly important when one encounters this neoplasm in a peripheral location at frozen section. We report a case of a 65-year-old female with an incidentally discovered solitary peripheral pulmonary nodule identified during a commercial whole-body screening computed tomography (CT) scan. Interval scans revealed a concerning doubling time, and she presented to the surgical service for removal of the mass. Intraoperative frozen section evaluation revealed histologic characteristics favoring a benign neoplasm. Permanent histologic section revealed a glandular papilloma. Over 7 years of follow-up revealed a benign clinical course.