1. What is the most likely infectious etiology of this lesion?
Download 18.75 Kb.
|
|
Case1 Case 1 A 42-year-old woman presents to the physician's office for a routine gynecologic examination.She is feeling well and has no specific complaints at this visit.While reviewing your records,you see that she has not come in for a Papanicolaou (Pap)smear in approximately 5 years.She admits that she has not come in because she has been feeling fine and did not think it was really necessary.She has a history of 3 pregnancies resulting in three full-term vaginal deliveries of healthy children.She was treated at 22 years of age for Chlamydia infection.She has never had an abnormal Pap smear.Her social history is notable for a 1-pack per day smoking history for the past 25 years.She is divorced from her first husband and is sexually active with a live-in boyfriend for the past 3 years.She has had 7 sexual partners in her lifetime.Her examination today is normal.You perform a Pap smear as part of the examination.The report arrives 10 days later with the diagnosis of high-grade squamous intraepithelial lesion. 1.What is the most likely infectious etiology of this lesion? 2.What specific virus types confer a high risk of cervical neoplasia? 3. Where on a cellular level does this organism tend to replicate in benign diseases?In malignancies? CLINICAL CORRELATION DISCUSSION Characteristics of the causative agent Diagnosis Treatment and prevention COMPREHENSION QUESTIONS 1 A second-year medical student is researching the role of HPV in causing cancer.Which of the following types of cancer is HPV most commonly associated with? A.Anogenital B.Breast C.Lung D.Oral E.Prostate 2 A 40-year-old woman is diagnosed with cervical intraepithelial disease.Biopsy is suspicious for HPV related disease.What histological features support the role of HPV? A.Central,basophilic intranuclear cellular inclusions B.Cowdry type A intranuclear cellular inclusions C.Enlarged multinucleated cells D.Cytoplasmic vacuolization and nuclear enlargement of cells E.Numerous atypical lymphocytes 3 Which of the following viral families is known to be causally associated with tumor formation in healthy appearing human adults? A.Flavivirus B.Papovavirus C.Paramyxovirus D.Polyoma virus 网址链接：https://ininet.org/case-1-introduction.html?page=15 Case30 Human Papillomavirus Most likely infectious etiology of this lesion: human papillomavirus (HPV)-related infection. Specific virus types confer a high risk of cervical neoplasia: HPV types 16 and 18 are most commonly associated with anogenital neoplasias. Location of replication in benign diseases and malignancies: The site of replication in benign HPV infections occurs in the host neoplasm where the viral DNA remains extrachromosomal. However, in HPV-related malignancies the viral DNA is integrated into the host genome. Summary: A 42-year-old woman has high-grade squamous intraepithelial neoplasia on a Pap smear. CLINICAL CORRELATION Introduction Human papillomavirus (HPV) preferentially infects the squamous epithelium of skin and mucous membranes causing epithelial proliferation and the development of cutaneous warts and genital, oral, and conjunctival papillomas. Although most HPV infections are benign, and most warts or lesions regress spontaneously with time, some HPV viral types have been shown to be linked to cervical and anogenital carcinomas (Table 30-1). Approach to Suspected HPV Infection Definitions Koilocytes: Enlarged keratinocytes with shrunken nuclei. Poikilocytosis: Presence of perinuclear cytoplasmic vacuolization and nuclear enlargement of epithelial cells. Papillomas: An epithelial neoplasm producing finger-like projections from the epithelial surface. Condylomas: Epithelial neoplasm and hyperplasia of the skin, resulting in the formation of a large cauliflower-like mass. Discussion Characteristics of HPV that Impact Transmission Human papillomavirus (HPV) is a member of the papovavirus family. Over 100 distinct types of HPV have been identified based on DNA sequence studies. It has circular, double-stranded DNA genome contained within a small, nonenveloped capsid. HPV has a predilection for infecting the squamous epithelium of skin and mucous membranes. HPV is transmitted from person to person by direct contact, sexual intercourse, or via delivery through an infected birth canal. As a nonenveloped virus, HPV is more environmentally resistant to acids, detergents, and desiccation, which allows for transmission via contaminated fomites. HPV gains entry through breaks in the skin and replicates in the basal cell layer of the epithelium. HPV DNA is replicated, and the viral particles are assembled in the nucleus of epithelial cells with late viral gene expression occurring in the upper layers of differentiated keratinocytes. In benign lesions, such as common skin warts, the viral DNA remains extrachromosomal in the nucleus of the infected epithelial cell. However, more commonly in carcinomas or high-grade intraepithelial lesions viral DNA becomes integrated into the host genome. The viral genome encodes transforming genes, which have been shown to cause the inactivation of proteins that inhibit cellular growth, making infected cells more susceptible to mutation or other factors that may lead to the development of dysplasia and cancer. HPV DNA, primarily types 16 and 18, has been shown to be present in more than 95 percent of cervical carcinoma specimens. Because of their high occurrence in cervical cancers, these HPV types are considered to be high-risk, whereas HPV types 6 and 11 are considered low-risk and many other HPV types are considered benign. Yet, because many HPV-related infections (even those with types 16 and 18) are benign with lesions that can regress spontaneously, the utility of characterizing specific HPV types in clinical specimens remains to be determined. Diagnosis HPV infection presents clinically with the growth of a variety of cutaneous warts and papillomas. Warts result from HPV replication stimulating excessive growth of the epidermal layers above the basal layer (Figure 30-1). Different types of warts (flat, plantar, or common), genital condylomas, and laryngeal papillomas can develop depending on the infecting viral type and the site of infection. Laryngeal papillomas can occur in infants born to mothers with active HPV genital lesions. While rare, these papillomas often require repeated surgical removal. Anogenital warts occur on the squamous epithelium of the external genitalia and anorectum and are most commonly caused by HPV types 6 or 11, however, these lesions rarely undergo malignant transformation. HPV types 16 and 18 are responsible for most cases of cervical intraepithelial neoplasia and cancer. Cervical cancer usually develops after a progression of cellular changes from cellular atypia to low-grade intraepithelial lesion, high-grade intraepithelial lesion and subsequently to carcinoma. Although the mechanisms of host defenses against HPV are not well understood, the immune system, especially cellular immunity, are important in the control of HPV infections. HPV diseases occur more frequently and tend to be more severe in immunocompromised hosts. Treatment and Prevention Although many HPV infections are benign with the resulting warts or lesions regressing spontaneously with time, because of the strong association of HPV with cervical carcinomas and transmission via vaginal delivery, physical treatment and removal of lesions is often performed. Physical treatment of warts and other lesions involves local cellular destruction by means of cryotherapy, acid application or electrocautery. Alternatively, immune stimulant therapy is used to promote immunologic clearance of the abnormal cells using either the injection of interferon or topical applications of imiquimod. Cervical cancer usually develops after a progression of cellular changes from cellular atypia to low-grade intraepithelial lesion, high-grade intraepithelial lesion, and subsequently to carcinoma. The introduction of routine screening of women for cervical cancer with Papanicolaou (Pap) smears has resulted in finding more abnormalities in earlier, more treatable stages, and a marked reduction in the death rate from cervical cancer. Most deaths from cervical cancer now occur in women who have not had adequate Pap smear screening. Research on HPV-vaccine development is ongoing. A prospective study of an HPV-16 virus-like particle vaccine has indicated the potential for prevention of persistent infection with the HPV type 16. Infection with HPV can be prevented by avoiding direct contact with infected skin lesions. Sexual transmission of HPV can be prevented by safe sex practices. ANSWERS
[30.2] D. HPV produces characteristic cytoplasmic vacuolization and nuclear enlargement of squamous epithelial cells, referred to as koilocytosis; answers A, B, C, and E are incorrect: Both Cowdry type A intranuclear inclusions and enlarged multinucleated cells can be seen with herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections; central, basophilic intranuclear inclusion bodies are seen in CMV infections, whereas the presence of atypical lymphocytes is seen specifically in Epstein-Barr virus (EBV) infections. [30.3] B. HPV is a member of the Papovavirus family and is causally associated with cervical cancer in otherwise healthy individuals; answers A, C, D, and E are incorrect: Hepatitis C virus is a member of the Flaviviruses family and causes chronic hepatitis and in severe cases is a factor in liver cancer development; Paramyxoviruses include agents such as respiratory syncytial virus and measles virus and are not associated with carcinomas; human polyoma viruses include BK and JC viruses, which have been associated with immunocompromised patients, and their role in formation of human tumors is still under investigation. 翻译（有道+医学词库）： 人类乳头状瘤病毒 该病变最有可能的感染性病因:人乳头瘤病毒(HPV)相关感染。 特定的病毒类型导致宫颈瘤变的高风险:HPV 16型和18型最常与肛门生殖器瘤变相关。 良性疾病和恶性肿瘤中的复制部位:良性HPV感染的复制部位发生在宿主肿瘤中，其中病毒DNA仍位于染色体外。然而，在hpv相关的恶性肿瘤中，病毒DNA被整合到宿主基因组中。 摘要:一名42岁女性在巴氏涂片上有高级别鳞状上皮内瘤变。 临床相关性 介绍 人乳头瘤病毒(HPV)优先感染皮肤和黏膜的鳞状上皮，导致上皮增殖，以及皮肤疣和生殖器、口腔和结膜乳头瘤的发展。虽然大多数HPV感染是良性的，并且大多数疣或病变随着时间的推移会自发消退，但一些HPV病毒类型已被证明与宫颈癌和肛门生殖器癌相关(表30-1)。 疑似HPV感染的处理方法 定义 空泡细胞:增大的角质形成细胞，核皱缩。 细胞异位:核周细胞质空泡化，上皮细胞核增大。 乳头状瘤:一种从上皮表面产生指状突起的上皮肿瘤。 尖锐湿疣:皮肤上皮性肿瘤和增生，导致形成大菜花状肿块。 讨论 影响传播的HPV特征 人乳头瘤病毒(Human papillomavirus, HPV)是papovavirus家族的一员。根据DNA序列研究，已确定了100多种不同类型的HPV。它具有包含在一个小的无包膜衣壳内的环状双链DNA基因组。HPV好发于皮肤黏膜的鳞状上皮。人乳头瘤病毒通过直接接触、性交或通过受感染的产道分娩在人与人之间传播。作为一种无包膜病毒，HPV对酸、洗涤剂和干燥具有更强的环境抗性，从而允许通过受污染的污染物传播。 HPV通过皮肤的裂口进入皮肤，并在上皮基底层细胞中复制。HPV DNA被复制，病毒颗粒在上皮细胞的细胞核中组装，晚期病毒基因表达发生在分化的角质形成细胞的上层。在良性病变(如常见的皮肤疣)中，病毒DNA仍然存在于被感染的上皮细胞的细胞核内的染色体外。然而，在癌症或高级别上皮内病变中更常见的情况是病毒DNA整合到宿主基因组中。病毒基因组编码转化基因，这些基因已被证明会导致抑制细胞生长的蛋白质失活，使受感染的细胞更容易发生突变或其他可能导致不典型增生和癌症发展的因素。 HPV DNA，主要是16和18型，已经被证明存在于超过95%的宫颈癌样本中。由于它们在宫颈癌中的高发病率，因此这些HPV型别被认为是高危型，而HPV 6型和11型被认为是低危型，许多其他HPV型别被认为是良性的。然而，由于许多HPV相关感染(即使是16型和18型感染)是良性的，病变可以自发消退，因此在临床标本中确定特定HPV型别的效用仍有待确定。 诊断 HPV感染在临床上表现为多种皮肤疣和乳头状瘤的生长。疣是由于HPV复制刺激基底层以上表皮层过度生长所致(图30-1)。不同类型的疣(扁平疣、足底疣或普通疣)、生殖器湿疣和喉乳头状瘤的发展取决于感染病毒的类型和感染部位。喉乳头状瘤可发生于有活动性HPV生殖器病变的母亲所生的婴儿。虽然罕见，这些乳头状瘤往往需要反复手术切除。肛门生殖器疣发生在外生殖器和肛门直肠的鳞状上皮上，最常由HPV 6型或11型引起，但这些病变很少发生恶变。HPV 16型和18型是大多数官颈上皮内瘤样病变和癌症的病因。宫颈癌通常发生在从细胞异型性到低级别上皮内病变、高级别上皮内病变以及随后癌变的细胞变化过程中。虽然宿主对HPV的防御机制尚不完全清楚，但免疫系统，尤其是细胞免疫，在控制HPV感染中至关重要。在免疫功能低下的宿主中，HPV疾病的发生频率更高，且往往更严重。 治疗和预防 虽然许多HPV感染是良性的，所导致的疣或病变会随着时间的推移自发消退，但由于HPV与宫颈癌和经阴道分娩传播、物理治疗的强相关性 通常切除病变。疣和其他病变的物理治疗包括通过冷冻疗法、酸敷或电灼等方法破坏局部细胞。或者，免疫刺激疗法通过注射干扰素或局部应用咪喹莫特来促进异常细胞的免疫清除。宫颈癌通常发生在细胞变化从细胞异型性发展到低级别上皮内病变、高级别上皮内病变，然后发展为癌的过程中。采用巴氏涂片对妇女进行宫颈癌常规筛查，结果在更早期、更可治疗的阶段发现更多的异常，宫颈癌死亡率显著降低。目前，大多数死于宫颈癌的妇女没有进行充分的巴氏涂片筛查。关于hpv疫苗开发的研究正在进行中。对HPV-16病毒样颗粒疫苗进行的一项前瞻性研究表明，该疫苗有可能预防HPV 16型的持续感染。避免直接接触感染的皮损可预防HPV感染。人乳头瘤病毒的性传播可通过安全性行为加以预防。 答案 [30.1] A.在列出的癌症类型中，HPV最常与肛门生殖器癌相关，其中包括宫颈癌。 [30.2] D. HPV使鳞状上皮细胞产生特征性的细胞质空泡化和细胞核增大，称为空泡细胞增多症;在单纯疱疹病毒(HSV)和水痘-带状疱疹病毒(VZV)感染中，可以看到Cowdry A型核内包涵体和增大的多核细胞;中枢嗜碱性核内包涵体见于CMV感染，而非典型淋巴细胞的存在则特异性见于eb病毒(EBV)感染。 [30.3] B. HPV是Papovavirus家族的一员，与其他健康个体的宫颈癌有因果关系;丙型肝炎病毒是黄病毒家族的一员，可引起慢性肝炎，在重症病例中是发生肝癌的一个因素;副粘病毒包括呼吸道合胞体病毒和麻疹病毒等病原体，与癌症无关;人类多瘤病毒包括与免疫功能低下患者相关的BK和JC病毒，它们在人类肿瘤形成中的作用仍在研究中。 Download 18.75 Kb. Share with your friends:
|