Compound Clear Cell Sarcoma of the Skin-A Potential Diagnostic Pitfall: Report of a Series of 4 New Cases and a Review of the Literature.
皮肤复合透明细胞肉瘤 -- 潜在的诊断陷阱: 4 例新发病例系列报告及文献综述。
- 作者列表："Luzar B","Billings SD","de la Fouchardiere A","Pissaloux D","Alberti L","Calonje E
:The proliferation of cells with melanocytic lineage and a nested pattern has traditionally been regarded as a characteristic feature of a wide range of benign and malignant melanocytic proliferations. Herein, we report a series of 4 clear cell sarcomas, including 3 primary cutaneous and 1 metastatic to the skin, associated with a clear-cut intraepidermal proliferation of tumor cells representing a serious potential diagnostic pitfall. All patients were male individuals, aged from 17 to 71 years (mean: 42 y). The size of the tumors ranged from 8 to 55 mm (mean: 22.2 mm, median: 13 mm). Two tumors arose on a lower extremity and 1 each on the scalp and chest. Cutaneous metastasis developed on the limb proximal to the amputation site. Histologically, all tumors were variably circumscribed nodular or multinodular proliferations within the dermis, focally extending into the subcutis. They were composed of nests and fascicles of pale spindled and epithelioid cells with finely granular or pale cytoplasm, elongated nuclei with a single prominent nucleolus, featuring mild nuclear pleomorphism, and surrounded by delicate fibrous septa. Scattered wreath-like giant cells were present in all cases. Mitotic activity was low (mean and median: 3.5 mitoses/mm). The intraepidermal component consisted in all 4 cases of nests of tumor cells localized at the dermal-epidermal junction. Nests were well-defined and composed of spindled or epithelioid cells with irregular hyperchromatic nuclei, prominent nucleoli, and scant to moderately abundant eosinophilic to pale cytoplasm. Lentiginous proliferation of epithelioid tumor cells was coupled with focal upward migration of isolated tumor cells in a single case. By immunohistochemistry, all tumors were S100 protein, melan A, and HMB45 positive. By fluorescence in situ hybridization analysis, 3 tumors displayed rearrangements in the EWSR1 gene, whereas reverse transcriptase polymerase chain reaction confirmed EWSR1(e8)/ATF1(e4) translocation in the remaining case. In conclusion, an epidermal component in primary cutaneous clear cell sarcomas, or cutaneous metastasis of the tumor, is exceptional and represents a potential diagnostic pitfall. Careful attention to the salient morphologic features in the dermal component of the tumor, as well as confirmation of EWSR1 gene rearrangement by fluorescence in situ hybridization or reverse transcriptase polymerase chain reaction, is necessary for correct recognition of the tumor and to avoid erroneous diagnosis of a benign or malignant melanocytic proliferation.
: 具有黑素细胞谱系和嵌套模式的细胞增殖传统上被认为是广泛的良恶性黑素细胞增殖的特征。在此，我们报告了一系列 4 个透明细胞肉瘤，包括 3 个原发性皮肤和 1 个转移至皮肤，与明确的肿瘤细胞表皮内增殖相关，代表一个严重的潜在诊断陷阱。所有患者均为男性，年龄 17 ~ 71 岁，平均 42 岁。肿瘤大小 8 ~ 55mm (平均 22.2mm，中位数 13mm)。下肢出现两个肿瘤，头皮和胸部各 1 个。截肢部位近端肢体发生皮肤转移。组织学上，所有肿瘤在真皮内呈不同程度的局限性结节状或多结节状增生，灶状延伸至皮肤下炎。它们由苍白纺锤状和上皮样细胞的巢和束组成，胞浆细颗粒或苍白，核细长，核仁单一突出，核多形性轻微，周围有纤细的纤维间隔。所有病例均存在散在的花环样巨细胞。有丝分裂活性低 (平均值和中位数: 3.5 核分裂/mm)。表皮内成分包括位于真皮-表皮连接处的所有 4 例肿瘤细胞巢。巢界限清楚，由纺锤状或上皮样细胞组成，细胞核不规则深染，核仁突出，胞浆嗜酸性至苍白稀少至中等丰富。上皮样肿瘤细胞的缓慢增殖与单个病例中分离的肿瘤细胞的局灶性向上迁移相偶联。经免疫组织化学检测，所有肿瘤均为S100 蛋白、melan A和HMB45 阳性。通过荧光原位杂交分析，3 例肿瘤显示EWSR1 基因重排，而逆转录聚合酶链反应证实EWSR1(e8)/ATF1(e4) 易位。总之，原发性皮肤透明细胞肉瘤或肿瘤皮肤转移中的表皮成分是特殊的，代表了潜在的诊断陷阱。仔细注意肿瘤真皮成分的显著形态学特征，以及通过荧光原位杂交或逆转录聚合酶链反应确认EWSR1 基因重排，对于正确识别肿瘤和避免良性或恶性黑素细胞增殖的错误诊断是必要的。
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.