Deletion 20q12 is associated with histological transformation of nodal marginal zone lymphoma to diffuse large B-cell lymphoma.
缺失 20q12 与淋巴结边缘区淋巴瘤向弥漫大B细胞淋巴瘤的组织学转化相关。
- 作者列表："Qian L","Soderquist C","Schrank-Hacker A","Strauser H","Dupoux V","Tang CN","Smith JR","Sun A","Majumdar S","Nguyen T","Widura S","Landsburg DJ","Schuster SJ","Baxter RHG","Bogusz AM
:The genetic and molecular abnormalities underlying histological transformation (HT) of nodal marginal zone lymphoma (NMZL) to diffuse large B-cell lymphoma (DLBCL) are not well known. While del(20q12) is commonly deleted in myelodysplastic syndrome it has not previously been associated with DLBCL. We recently described a case of DLBCL harboring del(20q12) in a patient with a history of MZL involving lymph nodes and skin. Here we report eight matched cases of transformed MZL(tMZL): six from nodal MZL (tNMZL) and two from splenic MZL (tSMZL). We found >20% del(20q12) in 4/6 tNMZL, but not in tSMZL, nor in unmatched DLBCL, MZL with increased large cells (MZL-ILC), or MZL cases. To examine whether transformation is associated with a specific gene signature, the matched cases were analyzed for multiplexed gene expression using the Nanostring PanCancer Pathways panel. The differential gene expression signature revealed enrichment of inflammatory markers, as previously observed in MZL. Also, tMZL and de novo DLBCL were enriched for extracellular matrix proteins such as collagen and fibronectin, vascular development protein PDGFRβ, DNA repair protein RAD51, and oncogenic secrete protein Wnt11. A subset of genes is expressed differentially in del(20q12) tMZL cases vs non-del(20q12) tMZL cases. These results suggest a specific pathway is involved in the histological transformation of NMZL, which could serve as an indicator of aggressive clinical course in this otherwise indolent neoplasm.
: 淋巴结边缘区淋巴瘤 (NMZL) 向弥漫性大B细胞淋巴瘤 (DLBCL) 组织学转化 (HT) 的遗传和分子异常尚不清楚。虽然del(20q12) 在骨髓增生异常综合征中常见缺失，但以前与DLBCL无关。我们最近描述了一例DLBCL携带del(20q12) 的病例，患者有MZL累及淋巴结和皮肤的病史。这里我们报道了 8 例转化MZL(tMZL) 的匹配病例: 6 例来自淋巴结MZL (tNMZL)，2 例来自脾脏MZL (tSMZL)。我们在 20% tNMZL中发现> 4/6 del(20q12)，但在tSMZL中没有，在不匹配的DLBCL、大细胞增多的MZL (MZL-ILC) 或MZL病例中也没有发现。为了检查转化是否与特定的基因特征相关，使用Nanostring pancer Pathways panel分析匹配的病例的多重基因表达。差异基因表达标记揭示了炎症标志物的富集，如以前在MZL中观察到的。此外，tMZL和de novo DLBCL富含细胞外基质蛋白，如胶原和纤维连接蛋白、血管发育蛋白pdgfr β 、DNA修复蛋白RAD51 和致癌分泌蛋白wnt11。一个基因子集在del(20q12) tMZL病例与非del(20q12) tMZL病例中差异表达。这些结果表明一个特定的途径参与了NMZL的组织学转化，这可能作为这种惰性肿瘤侵袭性临床过程的指标。
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.
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.
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.