原发性皮肤B细胞性淋巴瘤3例报告

原发性皮肤淋巴瘤(primary cutaneouslymphoma,PCLs)是指临床上起源于皮肤的非霍奇金淋巴瘤(Non-HodgkinLymphoma,NHL),它原发并主要局限于皮肤,并在诊断后6个月内未发现皮肤以外肿瘤病变[1].皮肤淋巴瘤中,以T细胞性淋巴瘤(cutaneous Tlymphocyte lymphoma,CTCL)较多见,并易于辨认和诊断[2],但皮肤B细胞淋巴瘤(cutaneous B lym-phoctyelymphoma,CBCL)的发病率比人们认为的高[3].     

DNA甲基化与皮肤肿瘤的研究进展

DNA甲基化是表观遗传学的重要内容之一,该DNA修饰方式在不改变基因序列的前提下实现对基因表达的调控.多项研究证实,DNA甲基化异常与黑素瘤、皮肤基底细胞癌、皮肤鳞状细胞癌、皮肤T细胞淋巴瘤的发生密切相关,而DNA甲基化检测技术为检测DNA甲基化提供技术平台.通过甲基化检测技术分析基因异常甲基化已成为当前皮肤肿瘤早期诊断、治疗、预后评估等的方向.     

皮肤的结外鼻型NK/T细胞淋巴瘤1例

对1例皮肤的结外鼻型NK/T细胞淋巴瘤临床病理结合免疫组化染色、EB病毒原位杂交及T细胞受体基因重排进行分析.右胫后多发结节,组织病理特征为肿瘤组织在真皮及皮下组织内弥漫性浸润,肿瘤组织具有血管中心性及血管破坏性特点,肿瘤细胞具有异型性.瘤细胞表达CD2,CD56,颗粒酶B,EBER阳性,未检测到TCR克隆性基因重排.诊断为皮肤的结外鼻型NK/T细胞淋巴瘤.皮肤的结外鼻型NK/T细胞淋巴瘤恶性度高、预后差;诊断有赖于组织病理及免疫表型检测及EBER原位杂交技术.     

CTCL中树突状细胞和Th细胞及其与细胞凋亡的相关性研究

皮肤T细胞淋巴瘤是以皮肤辅助性T细胞的单克隆扩增为特征的皮肤肿瘤，近年来，其发病率和死亡率呈上升趋势，严重威胁人类健康。目前国内外在对该疾病进行的大量研究中发现，树突状细胞与皮肤T细胞淋巴瘤发生、发展关系密切。本文就皮肤T细胞淋巴瘤中树突状细胞与Th细胞及细胞凋亡的相关性作了综述。     

32例皮肤T细胞淋巴瘤外周血染色体分析

报告32例皮肤T细胞淋巴瘤(CTCL)患者外周血染色体分析。MF23例、非向表皮性T细胞琳巴瘤8例、Sézary综合征1例。其中26例外周血细胞有异常核型,受检细胞共320个,有异常核型为48个(15%)。结构畸变略多于数量畸变,前者主要表现为染色体缺失,后者主要表现为非整倍体。畸变率与CTCL之类型、病期及皮损范围无明显关联,但在MF肿瘤期畸变率显著升高,提示染色体崎变与病情、预后有一定关联。     

皮肤的结外鼻型NK/T细胞淋巴瘤1例及文献复习

目的报道1例皮肤结外鼻型NK/T细胞淋巴瘤,以引起临床和病理医师对此病的关注。方法通过临床病理分析结合免疫组化染色、EB病毒原位杂交及T细胞受体基因重排的PCR检测分析确诊。结果左膝内后方皮损初次活检诊断为结节性脂膜炎,1个月内再次活检示真皮和皮下脂肪内肿瘤大片坏死,瘤细胞异型性明显,血管中心性浸润和血管坏死。瘤细胞表达CD2,CD8,CD45RO,CD56,TIA-1,GranzymeB和LMP-1,EB病毒(+);未检测到TCR-γ的克隆性基因重排。诊断为皮肤的结外鼻型NK/T细胞淋巴瘤。结论皮肤的结外鼻型NK/T细胞淋巴瘤恶性度高、易误诊、预后差;诊断有赖于常规组织病理结合分子病理技术。     

以皮肤斑块性浸润和肿瘤表现为主的B细胞淋巴瘤

1病例资料 病史:患者女,44岁。皮肤红斑、浸润性斑块2年,皮肤肿瘤半年。2000年8月开始在背部出现皮肤红斑,伴有发作性剧烈瘙痒。很快在红斑基础上发现浸润性红色斑块、结节。在当地医院治疗,用药不详。半年前发现面部及双腋前浸润性红色斑块的边缘上出现皮肤肿瘤,肿瘤生长迅速,半年内已长至鸡蛋大(图1A)。遂来笔者所在医院诊治,以“蕈样肉芽肿(肿瘤期)”收住院。既往史:患者无精尿病、心脏病、肝炎、结核等病史,无食物及药物过敏史。个人史:患者家族中无类似疾病患者,也无其他     

微小核糖核酸在皮肤肿瘤的研究进展

已有研究证实,miRNA参与恶性黑素瘤的发生,是诊断和治疗的新靶目标.近年研究发现,miRNA的调节异常已经成为基底细胞癌、皮肤鳞状细胞癌发病机制的一条重要途径;而且miRNA在其他皮肤肿瘤(蕈样肉芽肿、Merkel细胞癌)组织中的表达水平有不同程度的上调或下调,是这些肿瘤发生发展的影响因素.病毒编码的miRNA调节病毒基因的表达,参与病毒相关性皮肤肿瘤的发生.     

第四讲 皮肤淋巴瘤皮肤T细胞淋巴瘤向大细胞淋巴瘤转化

阐述皮肤T细胞淋巴瘤向大细胞淋巴瘤转化的临床表现、组织病理、免疫组织化学染色、分子生物学特征、诊断和鉴别诊断与治疗。     

皮肤淋巴瘤 第四讲 皮肤T细胞淋巴瘤向大细胞淋巴瘤转化

阐述皮肤T细胞淋巴瘤向大细胞淋巴瘤转化的临床表现、组织病理、免疫组织化学染色、分子生物学特征、诊断和鉴别诊断与治疗。     

Molecular cytogenetic analysis of Spitz nevi shows clear differences to melanoma

Spitz nevus is a benign neoplasm of melanocytes that can be difficult or impossible to distinguish from melanoma by clinical and histopathologic examination. We studied genomic DNA from 17 Spitz nevi by comparative genomic hybridization (CGH). Thirteen lesions showed no chromosomal aberrations, three cases had a gain involving the entire p-arm of chromosome 11, and one case showed a gain of chromosome 7q21-qter. Fluorescence in situ hybridization (FISH) on lesional tissue with a probe for the p-arm of chromosome 11 showed 6-10 p-arm signals per nucleus in those cases with a CGH-detected gain of chromosome 11p. One case with a normal CGH profile also showed increased copy number of 11p by FISH. Thus, the majority of Spitz nevi have a normal chromosomal complement at the level of CGH resolution; however some may contain gains, with 11p apparently being the most frequently involved location. These findings differ significantly from the previously reported changes in primary cutaneous melanoma, which show frequent deletions of chromosomes 9p (82%), 10q (63%), 6q (28%), and 8p (22%), as well as gains of chromosomes 7 (50%), 8 (34%), 6p (28%), 1q (25%) by CGH analysis. These clear differences in the location and frequencies of chromosomal aberrations in Spitz nevi and primary cutaneous melanomas could represent a basis for developing adjunctive techniques for refining accuracy in the difficult differential diagnosis of spitzoid melanocytic neoplasms.     

Molekulare Diagnostik bei melanozytären Tumoren

Melanoma therapy has undergone a paradigm shift. Classic chemotherapies with poor treatment responses have been replaced by modern immune checkpoint blockades and targeted therapies with excellent responses. The latter require precise diagnosis of mutations in the melanoma genome as molecular targets for the small molecules. The diagnosis of melanomas has also been supplemented by molecular techniques. Differential diagnosis of melanoma and melanoma simulators such as atypical Spitz nevi can be supported by fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH). Here we review the indications and methods for molecular diagnosis of melanocytic tumors.     

Epidermal growth factor receptor overexpression and genetic aberrations in metastatic squamous-cell carcinoma of the skin

BACKGROUND: Cutaneous squamous-cell carcinoma (SCC) sometimes causes lymph node metastasis and results in poor prognosis. However, little is known about cytogenetic alterations underlying tumor progression or metastasis. The aim of the present study was to investigate the genetic aberrations and expression of epidermal growth factor receptor (EGFR) in metastatic SCC of the skin. METHODS: We undertook comparative genomic hybridization (CGH) analysis of 4 specimens which were obtained from a case of cutaneous SCC, including the primary lesion and 3 lymph nodes of the metastatic lesion. RESULTS: Only one amplified locus (7p12-13) was detected in any metastatic lymph node, in which the EGFR gene is located. Therefore, we applied immunohistochemistry for EGFR to 5 cases of metastatic SCC including the case analyzed using CGH and 4 other cases (5 primary and 5 metastatic lesions). EGFR was expressed in 4 of 5 cases (both primary and metastatic lesions, including the case analyzed using CGH), and the staining patterns of primary and metastatic lesions were different. The primary tumors were focally weakly positive for immunostaining (+), whereas the 4 metastases were diffusely and strongly positive (+++). CONCLUSIONS: Our findings suggest that the clone with EGFR expression might selectively metastasize in some cutaneous SCCs. The existence of an EGFR-negative case reveals that EGFR expression is not always required for skin carcinogenesis, but expression of EGFR might confer metastatic potential of cutaneous SCCs.     

原发皮肤结外NK/T细胞淋巴瘤一例并文献复习

报道1例原发皮肤结外NK/T细胞淋巴瘤,并复习文献。患者,女,42岁。全身皮肤瘀斑、皮下结节20余天,发热4 d。右股内侧皮损组织病理示:大量淋巴细胞及浆细胞呈弥漫性浸润。免疫组化结果:CD3、CD43、CD56、颗粒酶B(Granzyme B,GгB)、细胞毒性蛋白(TIA)-1均(+)、Ki-67 LI约60%阳性;原位杂交EBER(+)。本病恶性程度高,需尽早进行组织病理检查及免疫组化染色以帮助诊断。     

Nodular lesions arising in a large congenital melanocytic naevus in a newborn with eruptive disseminated Spitz naevi

Congenital malignant melanoma within a pre‐existing large congenital melanocytic naevus (CMN) is exceedingly rare. Its incidence is difficult to determine due to the small number of reported cases and because of problems associated with diagnosis. Some benign nodular proliferations (called proliferative nodules) arising in CMN, while rare, are significantly more common and can mimic malignant melanoma clinically or histologically. There are no reported cases of congenital melanoma or benign proliferative nodules in CMN in patients who also had eruptive disseminated Spitz naevi. We describe a girl who was noted to have a dark‐brown plaque with several large erythematous nodules affecting the scalp at delivery, in addition to multiple erythematous dome‐shaped papules that developed in a disseminated manner over several months, beginning at 10 days of age. It was difficult, not only clinically but also histologically, to determine the benign or malignant nature of all of these lesions. As primary cutaneous melanoma, atypical proliferative nodules in CMN, bland CMN or CMN with foci of increased cellularity and Spitz naevi show clear differences in the genetic aberration patterns, comparative genomic hybridization (CGH) could be a diagnostic help in ambiguous cases such as this. CGH performed on this patient showed multiple DNA copy number changes in the most atypical nodule, but such alterations could not be found in the remainder of the lesions. CGH showed differences between the nodular lesions that occurred in the CMN and helped us in supporting the diagnosis of this unique case of benign proliferative nodules and a possible congenital melanoma arising in a large CMN, associated with multiple widespread eruptive Spitz naevi.     

Analysis of cytogenetic abnormalities in squamous cell carcinoma by array comparative genomic hybridization

IntroductionFew conventional cytogenetic studies of squamous cell carcinoma (SCC) have been performed to date. The introduction of cytogenetic techniques such as comparative genomic hybridization (CGH) has resolved some of the problems associated with conventional cytogenetics. The aim of this study was to analyze the presence of genetic abnormalities in a series of patients with SCC using the technique of array CGH.Material and methodsThe study included 8 patients (7 men and 1 woman; mean age, 75 years) diagnosed with primary SCC. DNA was extracted from frozen tissue and analyzed by array CGH.ResultsAll cases had genetic alterations, with gains more frequent than losses. The chromosomal regions with gains, in descending order of frequency, were as follows: 5p15.2, 9q31.3-q33.2, 13q, 18q22, 1p21-p22, 1q24-q25, 3p13, 4q33-q34 (HMGB2, SAP30), 20p12.2 (JAG1), 21q21.1, and Xq21.33. The region 9p13.1-p13.3 was the only one to display recurrent loss. No correlation was observed between the presence of gains or losses and the clinical and pathological characteristics of the tumors.ConclusionsThis is the first study to use the technique of array CGH to analyze genetic alterations in SCC. The finding of certain previously described aberrations (gain of 5p) suggests the existence of recurrent abnormalities. Likewise, the observation of alterations in small regions of chromosome 1 highlights the sensitivity of the technique to detect small changes. Application of the technique to a larger series of cases will provide greater insight into the genetic abnormalities implicated in the process of tumorigenesis in SCC.     

GLUT-1、Ki-67在皮肤肿瘤中的表达及意义

目的：探讨葡萄糖转运蛋白-1（GLUT-1）在脂溢性角化病（SK）、日光性角化病（AK）、Bowen病（BD）、鳞状细胞癌（SCC）中的表达及其与细胞增殖因子Ki-67之间的关系。方法：采用免疫组化法检测了95例不同皮肤肿瘤GLUT-1及Ki-67的表达。结果：GLUT-1及Ki-67在SK及正常皮肤都不表达,在AK、BD及SCC表达上调,并且二者的阳性表达强度间具有正相关性。结论：GLUT-1在恶性皮肤肿瘤中表达上调,与肿瘤的侵袭和转移有关。其表达强度可作为判断皮肤肿瘤恶性程度的检测指标,对诊断及鉴别诊断具有参考价值。     

儿童皮肤淋巴瘤的治疗进展

儿童皮肤淋巴瘤是指原发于皮肤的有明显异质性的一组淋巴增殖性疾病,分类主要依据WHO-EORTC和WHO系统.最常见类型为皮肤成熟T细胞淋巴瘤与皮肤成熟B细胞淋巴瘤.儿童皮肤淋巴瘤罕见,因临床表现与成人有差异及临床试验少、用药更慎重等原因,治疗方法主要基于个案报道.治疗包括局部外用药、光疗、放化疗、手术、干细胞移植及新型药物治疗等.各类型皮肤淋巴瘤的治疗方法与疗效差异大,保守治疗在大多数儿童期蕈样肉芽肿以及其他惰性生物学特征的皮肤淋巴瘤中有效,具有侵袭性生物学特征的皮肤淋巴瘤仍需化疗、靶向治疗等.侵袭性皮肤淋巴瘤在儿童较成人比例高,需重视系统评估与随访观察.     

The role of molecular genetics in dermatologic diagnosis

Modern molecular techniques have tremendously expanded our knowledge about the biologic processes in healthy individuals as well as our understanding about the pathologic events in an increasing number of dermatological diseases. These technologies initially came from basic molecular biology and genetic research but have become firmly anchored in clinical diagnosis approaches. Included in this group are immunohistochemistry (IHC), polymerase chain reaction (PCR), fluorescence in situ hybridization (FISH), chromogen in situ hybridization (CISH), comparative genomic hybridization (CGH), and microarray technology. IHC and PCR already belong to the armamentarium for routine daily diagnostics due to their high degree of standardization and reproducibility, ease of use and relatively low costs. Others like FISH and CISH are currently employed for specific indications in a growing number of larger laboratories, whereas CGH and microarray technology still remain in the hands of a few highly specialized laboratories. These new ancillary methods will help to improve diagnostic accuracy particularly in cases in which conventional histopathology is ambiguous. In addition, they will provide new and important information concerning the prognosis, progression and response rate to therapies in several particular malignant diseases.