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C-C chemokine receptor 4 expression in CD8+ cutaneous T-cell lymphomas and lymphoproliferative disorders, and its implications for diagnosis and treatment.

C-C c hemokine重新c ep t或 4 表达C D8 + c u t aneous T-c ell淋巴瘤和lymphoprolifera t我紊乱,并且i t s impli c a t离子用于诊断和t rea t men t。

  • 影响因子:2.67
  • DOI:10.1111/his.13960
  • 作者列表:"Geller S","Hollmann TJ","Horwitz SM","Myskowski PL","Pulitzer M
  • 发表时间:2020-01-01

AIMS:Patients with aggressive CD8+ cutaneous T-cell lymphomas (CTCLs) progress rapidly and respond poorly to therapy. Confounding treatment planning, there is clinicopathological overlap between aggressive CD8+ CTCLs and other lymphoproliferative disorders (LPDs). Hence, improved diagnostic methods and therapeutic options are needed. The aim of this study was to examine C-C chemokine receptor 4 (CCR4) expression as a diagnostic and therapeutic biomarker in CD8+ CTCLs/LPDs. METHODS AND RESULTS:Forty-nine cases (41 patients) with CD8+ CTCLs/LPDs were examined, including CD8+ mycosis fungoides (MF) (n = 14), aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma (AETCL) (n = 8), subcutaneous panniculitis-like T-cell lymphoma (SPTCL) (n = 7), CD30+ LPDs (n = 6), primary cutaneous γδ T-cell lymphoma (GDTCL) (n = 6), and others (n = 8). Immunohistochemical tissue staining was performed with a CCR4 monoclonal antibody on formalin-fixed paraffin-embedded tissue sections. CCR4 immunostaining was graded as percentage infiltrate, i.e. high (>25%) and low (≤25%), and the results were correlated with clinicopathological diagnoses. CCR4 expression was seen in 69% of the studied cases. Any CCR4 positivity was seen in all CD8+ MF cases, in 83% of CD30+ LPD cases, in 75% of AETCL cases, in 33% of GDTCL cases, and in none of the SPTCL cases. High CCR4 expression was seen in 79% of CD8+ MF cases versus 33% of CD30+ LPD cases, in 17% of GDTCL cases, and in 12.5% of AETCL cases. Patients with more advanced MF stage had higher CCR4 expression. CONCLUSIONS:CCR4 immunohistochemistry may be an adjunct in distinguishing advanced CD8+ MF from other CD8+ CTCLs/LPDs. Although CCR4 expression may justify therapeutic targeting of this receptor in CD8+ MF, the role of such therapies in other CD8+ CTCLs/LPDs is not yet clear.


目的: Pa t ien t s wi t h积极CD8 + cu t aneous T细胞淋巴瘤 (C T CLs) 进展迅速反应不佳t o t herapy.混杂治疗计划,侵袭性CD8 + CTCLs与其他淋巴增殖性疾病 (LPDs) 之间存在临床病理重叠。因此,需要改进诊断方法和治疗选择。本研究的目的是检查C-C的c血红素c受体 4 (C C R 4) 表达作为diagnosti c和治疗ti c生物标志物在C D8 + C T C Ls/LPDs中。 ME T HODS和RESUL T S: 对t y-9 例 (41 pa t ien t s) wi t h CD8 + C T CLs/LPDs进行检查,包括CD8 + 蕈样肉芽肿 (MF) (n = 14) 、侵袭性表皮t (ropic) CD8 + cy t o t oxic T细胞淋巴瘤 (AE T CL) (n = 8) 、subcu t panniculi t是样T细胞淋巴瘤 (SP T CL) (n = 7),CD30 + LPDs (n = 6),原发性cu t同期 γ δ T细胞淋巴瘤 (GD T CL) (n = 6),o t hers (n = 8)。用CCR4 单克隆抗体在福尔马林固定石蜡包埋的组织切片上进行免疫组织化学染色。CCR4 免疫染色分级为百分比浸润,即高 (>25%) 和低 (≤ 25%),结果与临床病理诊断相关。69% 的研究病例可见CCR4 表达。在所有CD8 + MF病例中,在 83% 的CD30 + LPD病例中,在 75% 的AETCL病例中,在 33% 的GDTCL病例中,在没有SPTCL病例中观察到任何CCR4 阳性。高CCR4 表达见于 79% 的CD8 + MF病例与 33% 的CD30 + LPD病例、 17% 的GDTCL病例和 12.5% 的AETCL病例。MF分期越晚期的患者CCR4 表达越高。 结论: CCR4 免疫组化可能是区分晚期CD8 + MF和其他CD8 + CTCLs/LPDs的辅助手段。虽然CCR4 的表达可能证明该受体在CD8 + MF中的治疗靶向是合理的,但这种治疗在其他CD8 + CTCLs/LPDs中的作用尚不清楚。



作者列表:["Zhang B","Li L","Zhang N","Zhao M","Liu Y","Wei L","Ma L","Xu Z"]

METHODS::Blue rubber bleb naevus syndrome (BRBNS) is an extremely rare venous malformation that often manifests as multiple haemangioma-like lesions in the skin and gastrointestinal tract. The drug sirolimus plays a key role in the signalling pathway of angiogenesis and subsequent development of BRBNS and its use has been described in several case reports. We present a case series of four patients with BRBNS who exhibited good treatment response to sirolimus. All four patients were administered oral sirolimus at doses of 1.0-1.5 mg/m2 /day with a target drug level of 5-10 ng/mL and median treatment duration of 20 months. All patients had a reduction in the size of the lesions and a normalization of coagulopathy with tolerable drug adverse reactions at follow-up. Sirolimus may be effective and safe in paediatric patients with BRBNS. Further prospective studies are suggested to evaluate the long-term effectiveness of this drug.

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作者列表:["Pham CT","Juhasz M","Sung CT","Mesinkovska NA"]

METHODS:BACKGROUND:Human papillomavirus (HPV) infections are associated with common dermatologic and nondermatologic diseases. Although HPV vaccines are well established as preventive measures for genital warts and cervical neoplasia, their use as therapeutic agents deserves greater attention. OBJECTIVE:To evaluate the use of HPV vaccine(s) as a treatment modality for cutaneous and/or mucosal disease. METHODS:A primary literature search using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted in January 2019 by using the PubMed and Cochrane databases. RESULTS:A total of 63 articles with 4439 patients were included. The majority of patients with cutaneous warts, recurrent respiratory papillomatosis, and squamous and basal cell carcinomas were successfully treated with HPV vaccination. Preliminary data on patients with pre-existing anogenital warts, cervical intraepithelial neoplasia, anal intraepithelial neoplasia, and vulvar intraepithelial neoplasia is promising. LIMITATIONS:This review was limited by the lack of controls, patients' previous HPV vaccination status, and publication bias. CONCLUSION:The commercially available three-dose, quadrivalent HPV vaccine is a potential therapeutic option for the treatment of cutaneous warts, recurrent respiratory papillomatosis, and squamous and basal cell carcinomas. Noncommercially available HPV vaccines demonstrate therapeutic response for treating anogenital warts, cervical intraepithelial neoplasia, anal intraepithelial neoplasia, and vulvar intraepithelial neoplasia. The vaccine's efficacy as an adjunct therapy for HPV-associated cutaneous and/or mucosal disease warrants further exploration.

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作者列表:["Lang UE","Love NR","Cheung C","McCalmont TH","Kim J"]

METHODS::Our understanding of melanoma precursors and progression to melanoma has developed as a result of advances in the field of molecular diagnostics. We now better understand the potential for genetic heterogeneity within a single lesion. Combined tumors can pose a diagnostic challenge when deciding the line between benign and malignant, which in turn has direct implications for patient management. Primary cilia (PC) are ubiquitous sensory organelles that have essential functions in cellular proliferation, differentiation, and development. The ciliation index (percentage of ciliated melanocytes) has been shown to reliably differentiate melanoma, which fail to ciliate, from melanocytic nevi, which retain PC. We therefore analyzed the potential for using the ciliation index to differentiate benign and malignant components in combined melanocytic lesions. We collected patient samples (n = 10) of unequivocal combined lesions with both melanoma and associated nevus components. Melanocytes were highlighted with SOX10 and costained with gamma-Tubulin and acetylated alpha-Tubulin to highlight the basal body and cilium, respectively. The number of melanocytes retaining cilia under high-power microscopy was examined. The melanoma component had average of 4% ciliation (SD: 7%), whereas the associated nevus component was significantly higher with 59% ciliation (SD: 17%). These data show that PC may be a reliable means of distinguishing benign from malignant components within a single tumor. The ciliation index may be a helpful tool in distinguishing challenging cases of combined lesions of melanoma in situ with a dermal nevus component from invasive melanoma, thus promoting improved staging and clinical management.

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