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Cutaneous infections due to nontuberculous mycobacteria:: histopathological review of 28 cases.: Comparative study between lesions observed in immunosuppressed patients and normal hosts

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JOURNAL OF CUTANEOUS PATHOLOGY 2000年第3期27卷 124-129页

作者： Bartralot, R Pujol, RM García-Patos, V Sitjas, D Martín-Casabona, N Coll, P Alomar, A Castells, A Hosp Gen Valle Hebron Dept Dermatol Barcelona 08035 Spain Hosp Santa Creu & Sant Pau Dept Dermatol E-08025 Barcelona Spain Hosp Santa Creu & Sant Pau Dept Microbiol E-08025 Barcelona Spain

To evaluate the histopathological features observed in patients with cutaneous infections due to nontuberculous mycobacteria (NTM) and to compare the histopathological patterns observed in immunosuppressed patients and normal hosts. Twenty-eight biopsy specimens corresponding to 27 patients with cutaneous infections due to NTM were reviewed. Eighteen biopsies corresponded to normal hosts (14 Mycobacterium marinum, 2 Mycobacterium chelonae, 1 Mycobacterium terrae and Mycobacterium gordonae) and 10 biopsy specimens were obtained from 9 immunosuppressed patients (3 Mycobacterium chelonae, one of which had two biopsies, 1 Mycobacterium abscessus, 2 Mycobacterium kansasii, 1 Mycobacterium marinum, 1 Mycobacterium avium complex and 1 Mycobacterium simiae). A panel of histopathological features was evaluated by two independent observers in each biopsy specimen. Epidermal changes (acanthosis, pseudoepitheliomatous hyperplasia, exocytosis) were mainly observed in M. marinum infections. Tn immunosuppressed patients the infiltrate tended to be deeper, involving the subcutaneous tissue (100%) with a more diffuse distribution and constant abscess formation. A marked granulomatous inflammatory reaction was observed in 83% of immunocompetent and in 60% of immunosuppressed patients. In immunosuppressed patients a relationship between the chronic evolution of the disease and granuloma formation was demonstrated. A diffuse infiltrate of histiocytes with occasionally foamy appearance was noted in three biopsy specimens from thr ee patients with AIDS. Acute and chronic panniculitis was detected in 8 biopsy specimens. In one biopsy (M. chelonae) an acute suppurative folliculitis was observed. Different histopathological patterns can be noted in biopsy specimens from cutaneous nontuberculous mycobacterial infections. The evolution of the disease and the immunologic status of the host may explain this spectrum of morphological changes. Tuberculoid, palisading and sarcoid-like granulomas,

关键词：获得性免疫缺陷综合征/免疫学表皮/微生物学表皮/病理学肉芽肿/免疫学肉芽肿/微生物学肉芽肿/病理学免疫减弱宿主免疫抑制剂/治疗应用分枝杆菌非典型性/分离和提纯分枝杆菌非典型性/致病力分枝杆菌感染非典型性/并发症分枝杆菌感染非典型性/免疫学分枝杆菌感染非典型性/病理学脂膜炎/免疫学脂膜炎/微生物学脂膜炎/病理学回顾性研究皮肤疾病细菌性/病因学皮肤疾病细菌性/免疫学皮肤疾病细菌性/病理学青少年成年人老年人女(雌)性人类男(雄)性中年人

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Co-expression of p16^INK4A and laminin 5 γ2 by microinvasive and superficial squamous cell carcinomas in vivo and by migrating wound and senescent keratinocytes in culture

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AMERICAN JOURNAL OF PATHOLOGY 2003年第2期163卷 477-491页

作者： Natarajan, E Saeb, M Crum, CP Woo, SB McKee, PH Rheinwald, JG Harvard Univ Brigham & Womens Hosp Sch Med Dept Dermatol Boston MA 02115 USA Harvard Univ Brigham & Womens Hosp Sch Med Dept Pathol Boston MA 02115 USA Harvard Univ Sch Dent Med Dept Oral Med Infect & Immun Boston MA 02115 USA

The high frequency of mutation, deletion, and promoter silencing of the gene encoding p16(INK4A) (p16) in premalignant dysplasias and squamous cell carcinomas (SCC) of epidermis and oral epithelium classifies p16 as a tumor suppressor. However, the point during neoplastic progression at which this protein is expressed and presumably impedes formation of an SCC is unknown. induction of p16 has been found to be responsible for the senescence arrest of normal human keratinocytes in culture, suggesting the possibility that excessive or spatially abnormal cell growth in vivo triggers p16 expression. We examined 73 skin and oral mucosal biopsy specimens immunohistochemically to test this hypothesis. p16 was not detectable in benign hyperplastic lesions, but instead was expressed heterogeneously in some dysplastic and carcinoma in situ lesions and consistently at areas of microinvasion and at superficial margins of advanced SCCs. p16-positive cells in these regions coexpressed the gamma2 chain of laminin 5, identified previously as a marker of invasion in some carcinomas. Normal keratinocytes undergoing senescence arrest in culture proved to coordinately express p16 and gamma2 and this was frequently associated with increased directional motility. Keratinocytes at the edges of wounds made in confluent early passage cultures also coexpressed p16 and gamma2, accompanying migration to fill the wound. These results have identified the point during neoplastic progression in stratified squamous epithelial at which the tumor suppressor p16 is expressed and suggest that normal epithelia may use the same mechanism to generate non-dividing, motile cells for wound repair.

关键词：癌鳞状细胞/代谢癌鳞状细胞/病理学细胞黏附分子/代谢细胞运动细胞培养的周期素依赖激酶抑制剂p16/遗传学周期素依赖激酶抑制剂p16/代谢表皮/代谢表皮/病理学免疫组织化学角蛋白细胞/细胞学角蛋白细胞/代谢口腔黏膜/细胞学口腔黏膜/代谢口腔黏膜/病理学肿瘤侵润蛋白质亚单位/代谢皮肤肿瘤/代谢皮肤肿瘤/病理学伤口愈合动物人类小鼠

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The carcinoembryonic antigen (CEA) family (CD66) expressed in melanocytic naevi is not expressed in blue naevuscell naevi in dendritic type

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JOURNAL OF CUTANEOUS PATHOLOGY 2000年第7期27卷 351-358页

作者： Egawa, K Honda, Y Kuroki, M Ono, T Kumamoto Univ Sch Med Dept Dermatol Kumamoto 8600811 Japan Kumamoto Univ Sch Med Dept Pathol Kumamoto 860 Japan Fukuoka Univ Sch Med Dept Biochem 1 Fukuoka 81401 Japan

Background: Although sporadic reports have regarded the expression of the carcinoembryonic antigen (CEA) family in melanoma, there has been no information about the expression in precursor lesions of melanoma such as melanocytic naevi and blue naevi. Methods: The expression was immunohistochemically studied in frozen biopsy specimens of 45 acquired and 16 congenital melanocytic naevi and 20 blue naevi, using a panel of monoclonal and polyclonal antibodies that recognize different epitopes of CEA and related molecules. Results: Members of the CEA glycoprotein family were strongly expressed in all of the subtypes of melanocytic naevus. A reduced expression of the CEA glycoproteins with increased dermal depth or acquisition of a spindled morphology of naevus cells was apparent. The expression was not seen in the present blue naevi and normal epidermal melanocytes. Conclusions: Although the significance of the expression was not clarified, this report has clearly demonstrated that the CEA family is strongly expressed in melanocytic naevi and immunoreactivity is divergent between melanocytic naevi and blue naevi and between dermal naevus cell types, suggesting that the expression may be altered with architectual changes in the melanocyte-lineage cells.

关键词：抗体单克隆癌胚抗原/分析癌胚抗原/生物合成癌胚抗原/免疫学表皮/化学表皮/代谢表皮/病理学冷冻切片黑素细胞/化学黑素细胞/代谢黑素细胞/病理学痣蓝/化学痣蓝/代谢痣蓝/病理学痣色素/化学痣色素/代谢痣色素/病理学皮肤肿瘤/化学皮肤肿瘤/代谢皮肤肿瘤/病理学青少年成年人老年人女(雌)性人类男(雄)性中年人

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THE EFFECTS OF VINBLASTINE IN ASSESSMENT OF THE INFLUENCE OF AGE ON PROLIFERATIVE ACTIVITY OF MURINE PALATE AND FOOTPAD EPITHELIUM

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CELL PROLIFERATION 1994年第4期27卷 225-231页

作者： BERG, JH HILL, MW UNIV WESTERN AUSTRALIA SCH DENT179 WELLINGTON STPERTHWA 6000AUSTRALIA UNIV IOWA DOWS INST DENT RESIOWA CITYIA 52242

Data concerning changes in the rate of cell proliferation of stratified epithelia with increasing age are conflicting. In the present study young (3-month-old) and old (22-month-old) C57Bl/6NNia male mice were injected intraperitoneally with 2, 3, 4 or 8 mg vinblastine sulfate/kg body weight and killed after 1.5, 3,4.5 or 6 h. The number of arrested metaphase figures per 1000 basal cells was counted in histological sections. Data were analysed using a multivariate analysis of variance. There was a significant difference between the accumulation of mitotic figures in footpad epidermis and palate epithelium and both tissues contained an increased number of mitotic figures with increasing periods of accumulation at all dose levels. In the footpad epidermis neither the age of the animal nor the dose of vinblastine had a significant effect on the number of mitotic figures. In contrast, for palate epithelium the accumulation of mitotic figures was significantly less in the old mice compared with the young mice and at a dose of vinblastine of 2 mg/kg compared with the higher doses. There was a statistically significant interaction between the dose of vinblastine and its period of action. It was concluded that the different tissues manifest a differential sensitivity to vinblastine and that only palate epithelium showed a significant reduction in proliferative activity with age.

关键词：衰老/生理学抗肿瘤药植物/药理学细胞分裂/药物作用细胞分裂/生理学剂量效应关系药物表皮/病理学上皮细胞/病理学后肢/病理学小鼠近交C57BL 有丝分裂/药物作用有丝分裂/生理学腭/细胞学长春碱/药理学动物男(雄)性小鼠

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Impaired hair follicle morphogenesis and cycling with abnormal epidermal differentiation in nackt mice, a cathepsin L-deficient mutation

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AMERICAN JOURNAL OF PATHOLOGY 2002年第2期161卷 693-703页

作者： Benavides, F Starost, MF Flores, M Gimenez-Conti, IB Guénet, JL Conti, CJ Univ Texas MD Anderson Canc Ctr Sci Pk Res Div Smithville TX 78957 USA Sci Pk Dept Vet Sci Bastrop TX USA Inst Pasteur Unite Genet Mammiferes Paris France

We previously described an autosomal-recessive mutation named nackt (nkt) exhibiting partial alopecia associated with CD4(+) T-cell deficiency. Also, we recently reported that nkt (now CtSl(nkt)) comprises a deletion in the cathepsin L (Ctsl) gene. Another recent study reported that Ctsl knockout mice have CD4(+) T-cell deficiency and periodic shedding of hair, which recapitulate the nkt mutation and the old furless (fs) mutation. The current study focuses on the dermatological aspects of the nkt mutation. Careful histological analysis of skin development of homozygous nkt mice revealed a delayed hair follicle morphogenesis and late onset of the first catagen stage. The skin of Ctsl(nkt)/Ctsl(nkt) mice showed mild epidermal hyperplasia and hyperkeratosis, severe hyperplasia, of the sebaceous glands, and structural alterations of hair follicles. Epidermal differentiation seems to be affected in nkt skin, with overexpression of involucrin and profilaggrin/filaggrin along with focal areas of keratin 6 expression in the interfollicular epidermis. Severe epidermal hyperplasia, acanthosis, orthokeratosis, and hyperkeratosis were only observed in mice maintained in nonpathogen-free environments. The analysis of Rag2(-/-) Ctsl(nkt)/Ctsl(nkt) double-mutant mice indicates that the skin defect remains under the absence of T and B cells. This animal model provides in vivo evidence that cysteine protease cathepsin L plays a critical role in hair follicle morphogenesis and cycling, as well as epidermal differentiation.

关键词：秃发/遗传学秃发/病理学组织蛋白酶L 组织蛋白酶类/遗传学细胞分化/遗传学半胱氨酸内肽酶类表皮/病理学毛囊/胚胎学毛囊/代谢毛囊/病理学免疫组织化学小鼠突变型形态发生/遗传学突变动物女(雌)性男(雄)性小鼠

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Update on inherited bullous dermatoses

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DERMATOLOGIC CLINICS 1999年第3期17卷 473-+页

作者： Marinkovich, MP Stanford Univ Sch Med Stanford CA 94305 USA

Bullous diseases are becoming increasingly better understood owing to the active research which has taken place in this field over the past decade. Advances in understanding of bullous disease pathophysiology is translating into clinical applications for diagnosis and therapy that will greatly enhance the quality of care bullous disease patients may receive now and in the future. This review focuses on the progress which has been achieved in inherited bullous dermatoses.

关键词：表皮/病理学大疱性表皮松解/诊断大疱性表皮松解/遗传学大疱性表皮松解/治疗预后皮肤疾病水疱大疱性/诊断皮肤疾病水疱大疱性/遗传学皮肤疾病水疱大疱性/治疗女(雌)性人类男(雄)性

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Immunohistochemical localization of ornithine decarboxylase in skin tumors

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JOURNAL OF CUTANEOUS PATHOLOGY 2000年第7期27卷 338-343页

作者： Kagoura, M Toyoda, M Matsui, C Morohashi, M Toyama Med & Pharmaceut Univ Fac Med Dept Dermatol Toyama 9300194 Japan

Background: Ornithine decarboxylase (ODC) plays an important role in the biosynthesis of polyamines. Induction of ODC and polyamine synthesis has been demonstrated in neoplastic tumors and is thought to be related to the degree of malignancy. Methods: In this study, we investigated a series of basal cell epitheliomas (BCE), Bowen's disease, squamous cell carcinomas (SCC), and metastatic tumors of the skin using an antibody against ODC for immunohistochemistry. Results: Eight of 12 cases of BCE failed to show a positive reaction for ODC. In Bowen's disease, 5 of 13 cases diffusely showed positive reaction for ODC. Fourteen of 15 cases of SCC showed ODC expression, the intensity of which was decreased in the peripheral layer. At higher magnification, the distribution of ODC in the positive SCC cases showed granular and heterogenous patterns. Ten of 14 cases of metastatic skin tumors exhibited positive reactions, and well-differentiated adenocarcinomas tended to show more strongly positive than poorly-differentiated ones. Conclusions: These results support the conclusion that the intensity and the incidence of positive immunohistochemical staining for ODC correlate with the degree of cellular differentiation, and furthermore, that heterogenous distribution of ODC staining may be associated with heterogeneity of tumor cells.

关键词： Bowen病/酶学 Bowen病/病理学癌基底细胞/酶学癌基底细胞/病理学癌鳞状细胞/酶学癌鳞状细胞/病理学细胞分化表皮/酶学表皮/病理学免疫组织化学鸟氨酸脱羧酶/分析皮肤肿瘤/酶学皮肤肿瘤/病理学人类

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Transgenic expression of cyclin-dependent kinase 4 results in epidermal hyperplasia, hypertrophy, and severe dermal fibrosis

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AMERICAN JOURNAL OF PATHOLOGY 2001年第1期159卷 369-379页

作者： de Marval, PLM Gimenez-Conti, IB LaCava, M Martinez, LA Conti, CJ Rodriguez-Puebla, ML Univ Texas MD Anderson Hosp & Tumor Inst Sci Pk Res Div Smithville TX 78957 USA Univ Texas MD Anderson Hosp & Tumor Inst Dept Carcinogenesis Smithville TX 78957 USA

In a previous report we have described the effects of expression of D-type cyclins in epithelial tissues of transgenic mice. To study the involvement of the D-type cyclin partner cyclin-dependent kinase 4 (CDK4) In epithelial growth and differentiation, transgenic mice were generated carrying the CDK4 gene under the control of a keratin 5 promoter. As expected, transgenic mice showed expression of CDK4 in the epidermal basal-cell layer. Epidermal proliferation increased dramatically and basal cell hyperplasia and hypertrophy were observed. The hyperproliferative phenotype of these transgenic mice was independent of D-type cyclin expression because no overexpression of these proteins was detected. CDK4 and CDK2 kinase activities increased in transgenic animals and were associated with elevated binding of p27(Kip1) to CDK4. Expression of CDK4 in the epidermis results in an increased spinous layer compared with normal epidermis, and a mild hyperkeratosis in the cornified layer. In addition to epidermal changes, severe dermal fibrosis was observed and part of the subcutaneous adipose tissue was replaced by connective tissue. Also, abnormal expression of keratin 6 associated with the hyperproliferative phenotype was observed in transgenic epidermis. This model provides in vivo evidence for the rot of CDK4 as a mediator of proliferation in epithelial cells independent of D-type cyclin expression.

关键词：细胞周期蛋白依赖激酶4 细胞周期蛋白质依赖激酶类/遗传学细胞周期蛋白质依赖激酶类/代谢细胞周期蛋白质依赖激酶类/生理学细胞周期蛋白类/代谢表皮/代谢表皮/病理学表皮/生理学纤维化增生肥大角蛋白质类/代谢小鼠转基因/遗传学原癌基因蛋白质类视网膜母细胞瘤蛋白质/代谢皮肤/代谢皮肤/病理学动物人类小鼠

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Expression of MK6a dominant-negative and C-terminal mutant transgenes in mice has distinct phenotypic consequences in the epidermis and hair follicle

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DIFFERENTIATION 1999年第2期65卷 97-112页

作者： Wojcik, SM Imakado, S Seki, T Longley, MA Petherbridge, L Bundman, DS Bickenbach, JR Rothnagel, JA Roop, DR Baylor Coll Med Dept Cell Biol Houston TX 77030 USA Baylor Coll Med Dept Dermatol Houston TX 77030 USA Univ Queensland Dept Biochem Brisbane Qld 4072 Australia Univ Iowa Dept Anat & Cell Biol Iowa City IA 52242 USA

Mouse keratin 6a (MK6a) is constitutively expressed in a single cell layer of the outer root sheath (ORS) of hair follicles, but its synthesis can be induced in interfollicular epidermis including the basal cell layer in response to perturbing stimuli. A basally inducible human K6 (HK6) isoform has not been described, and it is not clear which of the known HK6 isoforms is expressed in the ORS. In this study we show that expression of a dominant-negative MK6a construct (Delta 2B-P) in the interfollicular epidermis caused severe blistering and neonatal lethality, suggesting that mutations in a yet to be identified basally expressed HK6 isoform might result in a severe blistering phenotype. Surviving Delta 2B-P animals showed transgene expression only in isolated epidermal cells and not in all cells of the ORS, but nevertheless developed severe alopecia. Expression of two different C-terminal mutant transgenes also caused alopecia while a third C-terminal mutant had no phenotypic consequences. Electron microscopy revealed that Delta 2B-P expression resulted in the collapse of keratin filaments, while destruction of hair follicles in the two phenotypic C-terminal mutant lines occurred in the absence of filament abnormalities. The latter finding indicates that the innermost ORS cells are uniquely sensitive to expression of even slightly altered K6 proteins, suggesting that mutations affecting an HK6 isoform expressed in this cell layer could result in alopecia in humans as well.

关键词：发病年龄秃发/遗传学氨基酸序列动物新生表皮/代谢表皮/病理学表皮/超微结构基因表达基因显性毛囊/代谢毛囊/病理学毛囊/超微结构角蛋白质类/生物合成角蛋白质类/遗传学角蛋白质类/超微结构小鼠近交BALBC 小鼠转基因显微镜检查电子分子序列数据诱变定点表型蛋白质亚型/生物合成蛋白质亚型/遗传学皮肤疾病/遗传学皮肤疾病/病理学时间因素转基因动物小鼠

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Lichenoid, erosive and ulcerated dermatofibromas. Three additional clinico-pathologic variants

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JOURNAL OF CUTANEOUS PATHOLOGY 2000年第3期27卷 112-117页

作者： Yus, ES Soria, L de Eusebio, E Requena, L Hosp Clin San Carlos Dept Dermatol Fac Med Madrid 28040 Spain Fdn Jimenez Diaz Dept Dermatol E-28040 Madrid Spain Univ Complutense Dept Dermatol E-28040 Madrid Spain Univ Autonoma Madrid Fac Med Madrid Spain

On the occasion of a case of dermatofibroma with histological lichenoid features, we reviewed from our files all the cases in which the epidermis, usually hyperplastic in dermatofibroma, was, in some was, partially or completely destroyed. Among a total of 484 dermatofibromas, we found three lichenoid, six erosive and two ulcerated cases. In the three lichenoid cases, the columnar epidermal basal cells were lacking (squamotization of the basal layer) and in two of them there was a cleft between the epidermis and the dermatofibroma. Three of the six eroded cases were large pedunculated dermatofibromas with inflammatory phenomena of variable intensity. One case was in the center of a plaque of lichen simplex chronicus with some eroded area. In the other two cases, as well as in the two ulcerated lesions, neither inflammation nor epidermal changes usually attributed to rubbing or scratching were seen. Only in three of the eleven cases dermatofibroma was proposed (with question mark) as a clinical diagnosis. Both followup and histopathology supported the benign nature of these cases. We may conclude that: i) Lichenoid, erosive and ulcerated changes in dermato fibroma are infrequent phenomena which may make a clinical diagnosis difficult;and ii) in the presence of an otherwise histopathologically typical dermatofibroma, erosion and ulceration should not be considered as suspicious of malignancy.

关键词：表皮/病理学组织细胞瘤良性纤维性/分类组织细胞瘤良性纤维性/病理学苔癣样疹/病理学皮肤肿瘤/分类皮肤肿瘤/病理学皮肤溃疡/病理学成年人老年人老年人 80以上女(雌)性人类男(雄)性中年人

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