Adenocarcinoma with signet ring cells of the axilla: two case reports and review of the literature.

Adenocarcinoma with signet ring cells (ASRC) is a rare skin neoplasm whose histology shows a solid tumor intermingled with signet ring cells in variable numbers. There have been only ten reported cases. All were elderly males affected on the eyelids except for a single case in the axilla. Two new patients with ASRC of the axilla are described. In both of them, immunohistochemical studies revealed neoplastic cells that had differentiated toward apocrine glands. These are the second and third reported cases of ASRC in the axilla, one of them is the first ASRC case in a female. It seemed that the apocrine sweat gland or aberrant breast tissue in the axilla were possible origins of these tumors.     

Primary signet‐ring cell carcinoma of the axilla

Primary cutaneous histiocytoid or signet‐ring cell carcinoma represents an extremely rare adnexal neoplasm that most frequently presents on the eyelid but more rarely may present in the axilla. As this tumor can resemble metastatic carcinoma with signet‐ring cells, especially lobular carcinoma of the breast, it can often present a diagnostic challenge. We present a case of cutaneous signet‐ring cell carcinoma presenting in the axilla and outline the challenges of diagnosing this rare malignancy.     

Invasive head and neck cutaneous squamous cell carcinoma: clinical and histopathological characteristics,frequency of local recurrence and metastasis

BACKGROUND

squamous cell carcinoma is the second most common type of skin malignancy and may evolve to regional lymph node and distant metastases.

OBJECTIVE

The objective of this study was to evaluate patients with head and neck cutaneous squamous cell carcinoma to identify its clinical and histopathological characteristics, as well as the frequency of local recurrence and metastasis.

METHODS

A retrospective cohort of patients with head and neck cutaneous squamous cell carcinoma. Inclusion criteria: histopathological confirmation, follow-up for longer than one year after diagnosis. Exclusion criteria: immunosuppression; lip and oral cavity squamous cell carcinoma; and non-surgical resection of the lesion. We evaluated demographic, clinical and anatomopathologic findings and explored their associations.

RESULTS

Sixty-one patients with 79 tumors and followed by 4.8±3.0 years were selected. The average age was 67.1 years, and 63% of tumors had up to two centimeters. Seven tumors (8.9%) recurred and two of them had positive margins. Recurrence was associated with higher Broders'' grade (p<0.01). Two patients (3.3%) had regional lymph node metastases. There were no distant metastases. Seventy tumors were considered to be usual tumors (89.7%), and 68 (87.2%) were classified as Broders'' grade 1 and 2. Additionally, 64.1% of tumors had a depth of invasion below four millimeters. Thirteen tumors (16.7%) had positive histological margins.

CONCLUSIONS

Most patients had good prognosis in the first year of follow-up, confirming that head and neck cutaneous squamous cell carcinoma has a better prognosis than squamous cell carcinoma of other regions such as mucosa, oral cavity, and internal organs.     

Signet‐ring cell/histiocytoid carcinoma in the axilla: A case report with genetic analysis using next‐generation sequencing

Signet‐ring cell/histiocytoid carcinoma (SRCHC) is a very rare skin appendage cancer, with an extremely rare occurrence in the axilla. This study describes the 11th case of SRCHC occurring in the axilla and reports the first gene alteration analysis performed for SRCHC. An 85‐year‐old Japanese male presented with a tumor in the left axilla. Biopsy of the axilla nodule demonstrated diffuse proliferation of histiocytoid neoplastic cells and signet‐ring cells in the dermis and subcutis. Immunohistochemistry revealed loss of E‐cadherin expression in these neoplastic cells. Accordingly, SRCHC of the axilla was diagnosed. Genetic analysis using next‐generation sequencing demonstrated missense mutation of PIK3CA (c1633G>A, pGlu545Lys) and no CDH1 gene mutation.SRCHC of the axilla is considered equivalent to a histiocytoid variant of invasive lobular breast carcinoma. The present SRCHC case demonstrated a pathogenic PIK3CA mutation, which is observed in invasive lobular carcinoma. Additional large case studies are required to clarify the clinicopathological features and gene alterations in SRCHC of the axilla.     

环氧化酶-2在表皮肿瘤中的表达

目的 探讨环氧化酶-2在不同表皮肿瘤中的表达及意义。方法 选择鳞状细胞癌8例、基底细胞上皮瘤10例、Bowen病8例和脂溢性角化病12例,运用免疫组化方法观察肿瘤细胞中环氧化酶-2的表达。结果 与正常表皮相比,环氧化酶-2在鳞状细胞癌、Bowen病、基底细胞上皮瘤中的表达明显上调,尤其以鳞状细胞癌中的表达最强。而环氧化酶-2在脂溢性角化病中的表达与正常人皮肤的表达近似。结论 环氧化酶-2表达的上调可能在表皮肿瘤的发生发展中发挥一定作用。     

Notch1基因对裸鼠皮肤鳞状细胞癌移植瘤细胞增殖和凋亡的影响

目的 探讨Notch1基因在人皮肤鳞状细胞癌SCL-1细胞裸鼠移植瘤中的作用。方法 于裸鼠腋下接种0.2 ml 1 × 108/ml的SCL-1细胞悬液,建立人皮肤鳞状细胞癌裸鼠移植瘤模型,将其分为三组：未处理组（接种PBS悬浮的未转染细胞）,空载体转染组（接种空载体转染的细胞）和Notch1转染组（接种Notch1转染的细胞）。连续2周观察转染荷瘤裸鼠的生长情况,采用TdT介导的dUTP缺口末端标记技术（TUNEL）研究肿瘤组织中的细胞凋亡,利用RT-PCR和Western印迹研究肿瘤组织中Notch1、bcl-2和bax mRNA和蛋白的表达。结果 Notch1转染组中肿瘤的生长明显受到抑制,其肿瘤的重量为（0.574 ± 0.219） g,显著低于未处理组（2.642 ± 0.404） g和空载体转染组（2.606 ± 0.512） g（F = 26.642,P 值均 < 0.01）。TUNEL结果表明,Notch1转染组每500个细胞中凋亡的细胞数为87 ± 9,明显高于未处理组（8 ± 2）和空载体转染组（10 ± 3）中细胞凋亡的数目（P < 0.05）;此外,RT-PCR和Western印迹结果表明Notch1转染组中裸鼠肿瘤组织Notch1和bax mRNA和蛋白表达均显著上升,而bcl-2的表达显著下调,三组间比较差异具有统计学意义（P值均 ＜ 0.05）。结论 Notch1基因能抑制人皮肤鳞状细胞癌细胞SCL-1裸鼠皮下移植瘤的生长,诱导SCL-1细胞凋亡,后者可能与bax表达的上升和bcl-2表达的下调相关。     

黄芩素对A431细胞埃兹蛋白表达及侵袭力的影响

目的 探讨黄芩素是否通过抑制埃兹蛋白来实现抑制A431细胞增殖、细胞周期进程及伪足的形成。方法 采用细胞划痕、微孔滤膜法（Transwell）检测黄芩素对A431细胞爬行的影响;RT－PCR检测黄芩素对A431细胞埃兹蛋白mRNA表达量的影响;Western印迹检测黄芩素及siRNA对A431细胞埃兹蛋白表达及其磷酸化的影响;扫描电镜观察黄芩素及siRNA对A431细胞伪足形成的影响。结果 细胞划痕实验显示,培养24 h时,黄芩素 5、10、20 μmol/L组细胞闭合宽度占原宽度的比例分别为13.3% ± 1.7%、7.6% ± 1.6%和5.9% ± 1.3%,黄芩素呈浓度依赖性抑制A431细胞爬行运动,黄芩素各组与阴性对照组（16.3% ± 2.3%）比较,差异均有统计学意义。Transwell实验证实,5、10、20 μmol/L黄芩素处理A431细胞48 h后,穿过人工基底膜的细胞数量分别为（46.5 ± 3.8）、（34.3 ± 3.4）和（25.3 ± 2.3）个/Hp,各处理组与阴性对照组（56.3 ± 3.8个/Hp）经方差分析,P < 0.01;而与siRNA组（28.3 ± 2.1个/Hp）比较,P > 0.05。Western印迹及RT－PCR检测显示,0、5、10、20、40 μmol/L黄芩素处理A431细胞48 h后,黄芩素呈浓度依赖性地抑制A431细胞埃兹蛋白/磷酸化埃兹蛋白及埃兹蛋白mRNA表达,埃兹蛋白mRNA与β-肌动蛋白mRNA灰度值之比值与阴性对照组比较,P值均 < 0.01;而与siRNA组比较,P > 0.05;埃兹蛋白、磷酸化埃兹蛋白在A431细胞中的表达量（与β-肌动蛋白灰度值之比）与阴性对照组比较,P值均 < 0.01;而40 μmol/L黄芩素处理组与siRNA处理组比较,P > 0.05。扫描电镜显示,48 h后20 μmol/L黄芩素组A431细胞伪足数量为（5.3 ± 1.9）个,长度明显缩短,与阴性对照组（22.6 ± 2.8个）比较,P < 0.01;siRNA组为（4.5 ± 2.8）个,与阴性对照组比较,P > 0.05。结论 黄芩素可能通过直接或间接抑制埃兹蛋白表达及其磷酸化而抑制A431细胞的增殖、爬行,从而达到抗肿瘤增殖及浸润转移的目的。     

Wide area digital dermoscopy applied to basal cell carcinoma

In situations in when a dermoscopic record of a large lesion is desirable, the resulting images are usually restricted to a small field of view due to the limited diameter of dermatoscope lenses. This limitation often produces several photographs separately, thus losing the possibility of a single-image global evaluation. In these case reports, we show examples of a recently published image montage technique called Wide Area Digital Dermoscopy, in this case, applied to basal cell carcinomas.     

CXCR7在常见皮肤恶性肿瘤及其细胞株中的表达及意义

目的 探讨趋化因子受体CXCR7在皮肤鳞状细胞癌、基底细胞癌、侵袭性皮肤黑素瘤及其细胞株中的表达及其意义。方法 收集30例皮肤鳞状细胞癌、25例基底细胞癌、30例皮肤黑素瘤的癌组织,采用免疫组织化学方法,检测CXCR7蛋白表达水平。采用RT-PCR、细胞免疫组化方法检测CXCR7在A375、M14、A431、HaCaT细胞株中mRNA及蛋白水平。结果 CXCR7在侵袭性皮肤黑素瘤中表达明显,高表达率为80%（24/30）,皮肤鳞状细胞癌及基底细胞癌分别为26.67%（8/30）、8%（2/25）;皮肤黑素瘤CXCR7高表达率与鳞状细胞癌、基底细胞癌比较,差异均有统计学意义（χ2值分别为17.16和28.36,P值均 < 0.05）。CXCR7 mRNA在A375、M14、A431细胞株中均可检出,其中A375表达最强,而HaCaT细胞不表达;细胞免疫组化显示,仅在A375细胞见棕黄色颗粒着色。结论 皮肤黑素瘤及其细胞株A375高表达CXCR7,其可能参与了其恶性侵袭与转移。     

皮肤恶性肿瘤microRNA的研究进展

MicroRNA(miRNA)分子广泛参与调控机体细胞的增生、分化、代谢、凋亡等生理病理活动,通过各种复杂的机制调控肿瘤的发生和发展。近来研究发现,皮肤肿瘤中存在miRNA的异常表达,提示miRNA亦参与皮肤肿瘤的发生和发展过程,同时人们对二者的关系及其具体机制进行了研究。该文对基底细胞癌(basal cell carcinoma,BCC)、鳞状细胞癌(squamous cell carcinoma,SCC)、恶性黑素瘤(malignant melanoma,MM)miRNA研究进展作一概述。     

基底细胞癌中肿瘤相关信号通路研究进展

肿瘤的发生、发展、浸润以及转移中均伴随着相关信号通路的信号失调.基底细胞癌是一种最为常见的皮肤恶性肿瘤.大量的研究发现,以Hedgehog信号通路为核心包括wnt、表皮生长因子受体、Notch、转化生长因子β/骨形态发生蛋白、FasL-Fas、P13K-AKT、促分裂原活化蛋白激酶和核因子-κB等多种信号通路的失调在其肿瘤生物学行为中发挥着重要的作用.更为重要的是,基底细胞癌中Hedgehog信号通路在信号传导途径中与包括wnt、表皮生长因子受体、转化生长因子β/骨形态发生蛋白和Notch等信号通路存在着交联机制.这些信号通路的研究对于更加深入地揭示基底细胞癌的肿瘤发生发展机制及寻找更加准确的药物治疗靶点具有重要的意义.

Abstract：

Deregulation of signaling pathways is commonly accompanied with the initiation, development,infiltration and metastasis of many kinds of tumors.Basal cell carcinoma(BCC)is a most common form of skin malignancy.Numerous studies have shown that many signaling pathways including Wnt, epidermal growth factor receptor(EGFR), Notch, transforming growth factor(TGF)β/bone morphogenetic protein(BMP), FasL-Fas, PI3K-AKT, mitogen-activated protein kinase(MAPK), nuclear factor kappa B, etc, play an essential role in the biological behaviors of BCC.Of these signaling pathways, Hedgehog is the core pathway.Most importantly, there are some cross-talks between Hedgehog pathway and Wnt, EGFR, TGFβ/BMP, Notch pathway in the signal transduction in BCC.Researches on these signaling pathways in BCC may contribute to the illumination of pathogenesis of BCC and searches for accurate therapeutic targets.     

Jagged1蛋白在银屑病、基底细胞癌及皮肤鳞状细胞癌中的表达

目的探讨Jagged1蛋白在银屑病、基底细胞癌及皮肤鳞状细胞癌中的表达及意义。方法采用免疫组化Envision法检测Jagged1蛋白在银屑病、基底细胞癌及皮肤鳞状细胞癌皮损中的表达。结果 Jagged1蛋白在寻常性银屑病患者皮损中呈阴性表达,在基底细胞癌及皮肤鳞状细胞癌中的表达较正常人皮肤增强,差异有统计学意义(P<0.01);Jagged1蛋白在基底细胞癌及皮肤鳞状细胞癌中的表达较银屑病增强,差异有统计学意义(P<0.05)。结论 Jagged1蛋白在银屑病发病机制中与角质形成细胞异常增生及真皮乳头血管增生等组织病理变化可能不相关,提示此蛋白可能与皮肤恶性肿瘤的异常增生有关。     

Contribution to characterization of skin field cancerization activity: morphometric,chromatin texture,proliferation, and apoptosis aspects

BackgroundA skin field cancerization is a cutaneous area with subclinical changes resultant from chronic sun exposure, with a higher predisposition to development of pre-neoplastic and neoplastic lesions. So far, there are no well-defined objective parameters that can indicate their degree of activity.ObjectivesTo describe and compare morphometric aspects and expression of factors related to apoptosis and cell proliferation in actinic keratosis (AK), in both photoexposed and photoprotected epidermis.MethodsA cross-sectional study of patients with actinic keratosis in the forearms, biopsied at two points: the actinic keratosis and the axillary region. The biopsies of the actinic keratosis, perilesional area, and axilla were evaluated through keratinocyte intraepithelial neoplasia (KIN), and immunohistochemistry of p53, survivin, and Ki67. Nuclear morphometry of basal layer cells was performed through digital image analysis: entropy, area, perimeter, Ra, fractal dimension, circularity, color intensity, and largest diameter.ResultsThere were 13 patients included and 38 actinic keratosis biopsied. In morphometry, 1039 nuclei were analyzed, of which 228 represented axillary skin, 396 demonstrated actinic keratosis, and 415 represented the perilesional area to the actinic keratosis. There was a significant difference (p < 0.05) in all variables tested for the topographies evaluated. A significant correlation was identified between nucellar morphometric elements, KIN, proliferation markers, and apoptosis. Joint patterns of p53, Ki67, and KIN discriminated the topographies sampled.Study limitationsThis was a cross-sectional study with a small number of patients.ConclusionsThere are patterns of proliferation, resistance to apoptosis, and different cellular morphometrics between photoprotected skin and photoexposed skin. The joint expression of p53, Ki67, and KIN can characterize skin field cancerization activity.     

肿瘤相关基因NET-1在皮肤鳞状细胞癌中的表达

目的 研究NET-1蛋白在皮肤鳞状细胞癌(SSCC)中表达的临床与病理意义.方法 通过基因生物工程技术制备针对NET-1蛋白大部分细胞外区的多克隆抗体,应用免疫组化SP法检测NET-1基因蛋白在56例SSCC组织、50例皮肤上皮内瘤变(SINⅠ～Ⅲ级)及10例正常人皮肤(NS)组织中的表达.结果 ①NET-1蛋白阳性表达定位清晰,为细胞膜和/或胞质,组织背景非特异性反应弱或无;②NET-1仅表达在SINⅢ中上皮全层,阳性率为93.75%,在SSCC中表达阳性率为96.43%.NET-1在SSCC和SINⅢ中的阳性率显著高于SINⅠ～Ⅱ级,其阳性率为44.22%.③SSCC细胞不同Ki67表达强度、浸润深度和皮肤肿瘤TNM分期中NET-1表达除有显著筹异外,还与NET-1阳性表达呈显著正相关.在不同SSCC组织类型中,疣状鳞癌与梭形细胞鳞癌和经典鳞癌之间NET-1表达有显著差异.结论 本文设计合成的NET-1抗体在SSCC石蜡标本中定位良好,可能是一个新的诊断SSCC的辅助组织学标记.     

外阴硬化萎缩性苔藓与外阴鳞状细胞癌的基因研究

外阴硬化萎缩性苔藓是较为常见的一种慢性皮肤黏膜病变，部分患者可能发展为外阴鳞状细胞癌。近年来的研究发现，外阴硬化萎缩性苔藓可能与多种癌基因、抑癌基因突变及其表达异常存在着密切联系。综述与外阴硬化萎缩性苔藓和外阴鳞状细胞癌相关的十余种癌基因与抑癌基因，分析从外阴硬化萎缩性苔藓发展到外阴鳞状细胞癌的因素。     

皮肤基底细胞癌T钙黏蛋白的表达及其DNA异常甲基化分析

目的 检测皮肤基底细胞癌(BCC)中T钙黏蛋白的表达以及异常甲基化.方法 采用免疫组化法和CpG岛甲基化特异性PCR方法,对29例BCC和19例正常人暴光部位皮肤的组织标本进行T钙黏蛋白的表达及甲基化检测.结果 正常皮肤皆表达T钙黏蛋白,29例BCC中8例(27.59%)检测到T钙黏蛋白表达(P<0.05),9例BCC(31.03%)和19例正常皮肤中的1例(5.26%)检测到T钙黏蛋白启动子区域的异常甲基化(P<0.05).结论 T钙黏蛋白表达降低与皮肤基底细胞癌的发病机制相关,T钙黏蛋白启动子区域的异常甲基化与蛋白低表达可能相关.     

埃兹蛋白在皮肤鳞状细胞癌、基底细胞上皮瘤、脂溢性角化病中的表达及临床意义

目的 探讨埃兹蛋白（ezrin）在脂溢性角化病、基底细胞上皮瘤、皮肤鳞状细胞癌中的表达及其与临床病理参数之间的相关性。方法 采用免疫组化法（SP法）检测36例皮肤鳞状细胞癌、27例基底细胞上皮瘤和20例脂溢性角化病、10例正常人皮肤中埃兹蛋白表达水平。结果 埃兹蛋白在正常人皮肤、脂溢性角化病、基底细胞上皮瘤、皮肤鳞状细胞癌中的阳性率分别为20.0%,25.0%,66.7％和91.3%,除脂溢性角化病组外,各肿瘤组与正常人对照组比较,阳性率差异均有统计学意义（H = 40.061,P < 0.01）。埃兹蛋白表达水平与皮肤肿瘤良恶性、与皮肤鳞状细胞癌的病理分级及肿瘤有无淋巴结转移均呈正相关（r分别为0.87,0.80,0.89）。COX回归显示,埃兹蛋白表达水平是皮肤鳞状细胞癌预后的独立影响因素之一。结论 脂溢性角化病、基底细胞上皮瘤、皮肤鳞状细胞癌组织中埃兹蛋白阳性表达水平与皮肤肿瘤的良恶性、皮肤鳞状细胞癌病理分级及有无淋巴结转移有关。