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Diagnosing Cutaneous Melanocytic Tumors in the Molecular Era: Updates and Review of Literature. 分子时代的皮肤黑色素细胞肿瘤诊断:最新进展和文献综述。
IF 1.6 Q3 DERMATOLOGY Pub Date : 2024-01-18 DOI: 10.3390/dermatopathology11010005
Chelsea Huang, Tiffany Wing-See Lau, Bruce R Smoller

Over the past decade, molecular and genomic discoveries have experienced unprecedented growth, fundamentally reshaping our comprehension of melanocytic tumors. This review comprises three main sections. The first part gives an overview of the current genomic landscape of cutaneous melanocytic tumors. The second part provides an update on the associated molecular tests and immunohistochemical stains that are helpful for diagnostic purposes. The third section briefly outlines the diverse molecular pathways now utilized for the classification of cutaneous melanomas. The primary goal of this review is to provide a succinct overview of the molecular pathways involved in melanocytic tumors and demonstrate their practical integration into the realm of diagnostic aids. As the molecular and genomic knowledge base continues to expand, this review hopes to serve as a valuable resource for healthcare professionals, offering insight into the evolving molecular landscape of cutaneous melanocytic tumors and its implications for patient care.

在过去的十年中,分子和基因组学的发现经历了前所未有的发展,从根本上重塑了我们对黑色素细胞肿瘤的认识。本综述包括三个主要部分。第一部分概述了当前皮肤黑色素细胞肿瘤的基因组概况。第二部分介绍有助于诊断的相关分子检测和免疫组化染色的最新进展。第三部分简要概述了目前用于皮肤黑色素瘤分类的各种分子途径。本综述的主要目的是简明扼要地概述黑色素细胞肿瘤所涉及的分子通路,并展示它们与诊断辅助工具的实际结合。随着分子和基因组知识库的不断扩大,本综述希望能成为医护专业人员的宝贵资源,让他们深入了解皮肤黑色素细胞肿瘤不断发展的分子情况及其对患者护理的影响。
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引用次数: 0
Giant Folliculosebaceous Cystic Hamartoma of the Face 面部巨型毛囊囊性脂肪瘤
IF 1.9 Q3 DERMATOLOGY Pub Date : 2023-12-31 DOI: 10.3390/dermatopathology11010004
Ramona Tasar, Melanie Peckruhn, Jörg Tittelbach
Folliculosebaceous cystic hamartoma (FSCH) is a rare and benign form of cutaneous hamartomas. These skin lesions often lead to clinical and histopathological misdiagnosis due to their similarities to cutaneous lesions with overproduction of clustered sebaceous glands. Clinically, the lesions often present as solitary, skin-colored, pedunculated warts to cauliflower-like, exophytic papules and nodules, usually with a diameter ranging 0.5–1.5 cm that rarely exceed 2 cm in size. Only a small number of giant variants are reported in the literature with a diameter in the range of 5–23 cm. The vast majority of the lesions appear in the central face and show a striking predilection for the nose, ears, and scalp, but also emerge on the nipples, extremities, and genitals. Histologically, the epithelial components of folliculosebaceous cystic hamartoma comprise dilated infundibular cystic proliferation with surrounding mesenchymal components, which commonly include fibroplasia and vascular and adipose tissue proliferation. These histological characteristics were coined by Kimura and colleagues (1991). To the best of our knowledge, our case represents the biggest variant of giant folliculosebaceous cystic hamartoma.
毛囊性皮脂囊肿(FSCH)是一种罕见的良性皮肤血管瘤。由于这些皮肤病变与皮脂腺过度分泌的皮肤病变相似,因此常常导致临床和组织病理学误诊。临床上,这些病变通常表现为单发、皮肤色、有蒂的疣到菜花样、外生性丘疹和结节,直径通常在 0.5-1.5 厘米之间,大小很少超过 2 厘米。文献中只报道了少数直径在 5-23 厘米之间的巨大变体。绝大多数病变出现在面部中央,并明显偏爱鼻子、耳朵和头皮,但也会出现在乳头、四肢和生殖器。从组织学角度看,毛囊囊肿的上皮成分包括扩张的内膜囊性增生和周围的间质成分,间质成分通常包括纤维增生、血管和脂肪组织增生。这些组织学特征由 Kimura 及其同事(1991 年)提出。据我们所知,我们的病例是巨型毛囊囊肿的最大变异。
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引用次数: 0
A Case of Pleomorphic Dermal Sarcoma: Giant Exophytic Tumor of the Medial Canthus 一例多形性真皮肉瘤:内侧鱼尾纹巨型外生瘤
IF 1.9 Q3 DERMATOLOGY Pub Date : 2023-12-29 DOI: 10.3390/dermatopathology11010003
Rylee Moody, Kavita Darji, Tricia A Missall, Peter Chow, R. Behshad
We present the case of a 99-year-old Caucasian female who was referred for treatment of a painless, 8.0 cm × 7.8 cm exophytic, pedunculated, ulcerated tumor of the left medial canthus. Pathology showed spindled, oval, and polygonal cells with pleomorphic nuclei. Many multinuclear giant cells and mitotic figures were also noted. The tumor was highlighted with CD10, showed focal positivity with actin, desmin, and CD68, and had increased Ki67 immunohistochemical staining. The tumor was negative for pancytokeratin, CK5/6, p63, MART-1/MelanA, S100, Sox10, p40, CD34, and CD23. Based on clinicopathologic correlation, the diagnosis of pleomorphic dermal sarcoma (PDS) was made. Pleomorphic dermal sarcoma (PDS) refers to a deep, histologically high-grade tumor that often resembles other tumors clinically and histologically. As PDS is frequently aggressive and related to adverse outcomes, it is important to recognize its distinguishing features in comparison to other similar entities, including atypical fibroxanthoma (AFX) and pleomorphic leiomyosarcoma (PLMS). To our knowledge, there is only one other reported case in the literature of PDS occurring on the eye. By reviewing and understanding characteristic etiologies, locations of presentation, histopathological features, and management techniques, pathologists can make a more accurate diagnosis and dermatologists can provide more effective patient care in a timely manner.
本病例是一名 99 岁高加索女性的病例,她因左侧内眦长出一个 8.0 厘米 × 7.8 厘米的无痛、外生性、有蒂、溃疡性肿瘤而转诊治疗。病理结果显示,肿瘤细胞呈纺锤形、椭圆形和多角形,细胞核多形性。此外,还发现许多多核巨细胞和有丝分裂。肿瘤突出显示 CD10,肌动蛋白、desmin 和 CD68 呈局灶阳性,免疫组化染色显示 Ki67 增高。肿瘤的泛影角蛋白、CK5/6、p63、MART-1/MelanA、S100、Sox10、p40、CD34 和 CD23 均为阴性。根据临床病理相关性,诊断为多形性真皮肉瘤(PDS)。多形性真皮肉瘤(PDS)是指一种组织学上等级较高的深部肿瘤,在临床和组织学上通常与其他肿瘤相似。由于多形性真皮肉瘤常具有侵袭性,且与不良预后有关,因此必须认识到它与其他类似实体(包括非典型纤维黄瘤(AFX)和多形性细肌瘤(PLMS))的不同之处。据我们所知,文献中仅报道过一例发生在眼部的 PDS。通过回顾和了解特征性病因、发病部位、组织病理学特征和处理技术,病理学家可以做出更准确的诊断,皮肤科医生也可以及时为患者提供更有效的治疗。
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引用次数: 0
Perforating Fibrous Histiocytoma Mimicking Keratoacanthoma: A Case Report 模仿角化棘皮瘤的穿孔性纤维组织细胞瘤:病例报告
IF 1.9 Q3 DERMATOLOGY Pub Date : 2023-12-25 DOI: 10.3390/dermatopathology11010002
Alina Lungu, Aurélie Hsieh, Gürkan Kaya, S. Menzinger
A 31-year-old male presented with a firm, well-demarcated, erythematous, crateriform, and ulcerated nodule in the left lumbar region, which persisted for 3 months. Clinically, a keratoacanthoma was suspected. The histological analysis was consistent with perforating fibrous histiocytoma, a rare histopathologic variant of fibrous histiocytoma. To our knowledge, this is the third case reported in the literature.
一名 31 岁的男性左腰部出现一个坚硬、分界清楚、红斑、火山口状和溃疡的结节,持续了 3 个月。临床上怀疑是角化棘皮瘤。组织学分析结果与穿孔性纤维组织细胞瘤一致,这是纤维组织细胞瘤的一种罕见组织病理学变异。据我们所知,这是文献中报道的第三个病例。
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引用次数: 0
Claudin-4 Upregulation in Acantholytic and Autoimmune-Mediated Bullous Disorders 角质溶解症和自身免疫性红斑狼疮中 Claudin-4 的上调
IF 1.9 Q3 DERMATOLOGY Pub Date : 2023-12-21 DOI: 10.3390/dermatopathology11010001
Chau M. Bui, H. Vuong, Minh-Khang Le, Kristin J Rybski, Hatice B Zengin, Haiming Tang, Bruce R. Smoller
Claudin-4 is a key component of tight junctions, which play an important role in the formation of the epidermal barrier by forming a circumferential network in the granular layer that serves as a gatekeeper of the paracellular pathway. The aim of this study is to illustrate claudin-4 immunohistochemical staining patterns of different blistering disorders. We collected 35 cases, including two Hailey–Hailey disease, one Darier disease, three Grover disease, one acantholytic acanthoma, two warty dyskeratoma, 11 pemphigus vulgaris (PV) including six mucosal PV, and two pemphigus foliaceus. For comparison, we included five cases of normal skin, five eczema, and three bullous pemphigoid cases. Claudin-4 demonstrated weak-to-moderate expression in keratinocytes located in the stratum granulosum, keratinocytes surrounding hair follicles, and adnexal glands. Further, claudin-4 exhibited moderate-to-strong membranous staining in disrupted keratinocytes surrounding and within the acantholytic and bullous areas in 16/22 of the acantholytic cases (not seen in the six cases of mucosal PV) and all three bullous pemphigoids. This finding suggests that claudin-4 is upregulated in these conditions, which may be a compensatory response to the disrupted barrier function. This finding could shed light on the molecular mechanisms underlying disrupted barrier function in blistering disorders, independent of the specific underlying disease mechanism.
Claudin-4是紧密连接的一个关键组成部分,紧密连接在颗粒层形成一个环形网络,作为细胞旁通路的守门员,在表皮屏障的形成过程中发挥着重要作用。本研究旨在说明不同水疱病的 claudin-4 免疫组化染色模式。我们收集了 35 例病例,包括 2 例海利-海利病、1 例达里尔病、3 例格罗弗病、1 例棘皮溶解性棘皮瘤、2 例疣状角化不良瘤、11 例寻常天疱疮(PV)(包括 6 例粘膜天疱疮)和 2 例叶状天疱疮。为了进行比较,我们还纳入了五例正常皮肤病例、五例湿疹病例和三例大疱性类天疱疮病例。Claudin-4在位于颗粒层的角质细胞、毛囊周围的角质细胞和附属腺体中表现为弱至中度表达。此外,在 16/22 例棘皮溶解病例(未见于 6 例粘膜 PV)和所有 3 例大疱性丘疹病例中,Claudin-4 在棘皮溶解区和大疱区周围和内部的中断角质细胞中显示出中等至强的膜染色。这一发现表明,在这些情况下,claudin-4 上调,这可能是对屏障功能紊乱的一种代偿反应。这一发现可以揭示水疱性疾病中屏障功能紊乱的分子机制,而与具体的潜在疾病机制无关。
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引用次数: 0
Dermatomyositis with Eosinophils. 伴有嗜酸性粒细胞的皮肌炎
IF 1.9 Q3 DERMATOLOGY Pub Date : 2023-11-21 DOI: 10.3390/dermatopathology10040039
Isabella I Sanchez, Henry O Herrera, Ashley Elsensohn, Bonnie A Lee, Christina N Kraus

Dermatomyositis is an idiopathic inflammatory myopathy that often presents with symmetric proximal skeletal muscle weakness and characteristic skin findings. Typical skin biopsy findings include vacuolar changes of the basal layer, increased dermal mucin, and a predominantly lymphocytic infiltrate. We report a case of dermatomyositis presenting as intensely pruritic papules and plaques, with initial histopathology being atypical of dermatomyositis due to the presence of eosinophils. The initial biopsy demonstrated a superficial dermatitis with eosinophils, initially thought to represent a drug eruption. A second biopsy of the same cutaneous manifestation was performed at a later time given high clinical suspicion for dermatomyositis and demonstrated a more classic vacuolar interface dermatitis with increased mucin and an absence of eosinophils. Notably, increased pruritus was specifically associated with the lesion that demonstrated tissue eosinophilia. The case illustrates the importance of considering tissue eosinophilia in the histologic presentation of dermatomyositis.

皮肌炎是一种特发性炎症性肌病,通常表现为对称性近端骨骼肌无力和特征性皮肤症状。典型的皮肤活检结果包括基底层空泡样改变、真皮粘蛋白增加以及主要的淋巴细胞浸润。我们报告了一例皮肌炎病例,患者表现为剧烈瘙痒的丘疹和斑块,由于嗜酸性粒细胞的存在,最初的组织病理学结果并不典型。最初的活组织检查显示,患者患有嗜酸性粒细胞的表皮皮炎,最初被认为是药物疹。由于临床上高度怀疑该患者患有皮肌炎,因此稍后又对同一皮肤表现进行了第二次活组织检查,结果显示该患者患有更典型的空泡性界面皮炎,粘蛋白增加,但没有嗜酸性粒细胞。值得注意的是,瘙痒加重与显示组织嗜酸性粒细胞增多的皮损特别相关。该病例说明了在皮肌炎的组织学表现中考虑组织嗜酸性粒细胞的重要性。
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引用次数: 0
Folliculotropic Mycosis Fungoides Is Associated with Decreased PD1 Staining Compared with Classic Mycosis Fungoides. 与经典型蕈样肉芽肿相比,毛囊萎缩型蕈状肉芽肿与PD1染色减少有关。
IF 1.9 Q3 DERMATOLOGY Pub Date : 2023-10-23 DOI: 10.3390/dermatopathology10040038
Haiming Tang, Kristin J Rybski, Yi Luan, Bruce R Smoller

Programmed cell death protein 1 (PD-1) plays a pivotal role in immune system regulation, with its expression levels linked to malignancy prognosis. However, existing reports on PD-1 staining in mycosis fungoides (MF) present conflicting findings, and little attention has been given to PD-1 staining in different MF variants. To address this, we conducted a retrospective study, employing immunohistochemistry to examine PD-1 expression in cases of folliculotropic MF and non-folliculotropic MF. We analyzed 24 cases of folliculotropic MF and 18 cases of non-folliculotropic MF, and recorded both the percentage of PD-1-labeled tumor cells and the intensity score (negative, weak, medium, or strong). Our results revealed significant disparity in PD-1 labeling between patch/plaque MF and folliculotropic MF (p = 0.028). Non-folliculotropic MF exhibited higher PD-1 labeling in tumor cells (58.3%) compared to folliculotropic MF (40.2%). Notably, there was no significant difference in PD-1 staining between folliculotropic MF and non-folliculotropic MF when both were in the early stage/indolent disease category. However, when considering the tumor stage, folliculotropic MF exhibited PD-1 staining in tumor cells at a rate of 21.1%, while non-folliculotropic MF showed PD-1 staining in tumor cells at a rate of 46.6% (p = 0.005). Additionally, among folliculotropic MF cases, 13 out of 24 cases displayed differing PD-1 expression patterns between epidermal and dermal components, with preserved PD-1 staining in the epidermal component and loss of staining in the dermal component. Furthermore, consistent with the prior literature, tumor cells with large cell transformations exhibited significantly lower PD-1 labeling (p = 0.017). Our findings showcase the unique PD-1 staining patterns in MF.

程序性细胞死亡蛋白1(PD-1)在免疫系统调节中发挥着关键作用,其表达水平与恶性肿瘤预后有关。然而,关于蕈样肉芽肿(MF)中PD-1染色的现有报道提出了相互矛盾的发现,并且很少关注不同MF变体中的PD-1染色。为了解决这一问题,我们进行了一项回顾性研究,采用免疫组织化学方法检测了PD-1在促卵泡性MF和非促卵泡性MF.我们分析了24例促卵泡性MF和18例非促卵泡型MF,并记录了PD-1标记的肿瘤细胞的百分比和强度评分(阴性、弱、中等或强)。我们的结果显示,贴剂/斑块MF和促卵泡MF之间的PD-1标记存在显著差异(p=0.028)。与促卵泡MF(40.2%)相比,非促卵泡MF在肿瘤细胞中表现出更高的PD-1标签(58.3%)。值得注意的是,当促卵泡MF和非促卵泡MF都属于早期/惰性疾病类别时,它们的PD-1染色没有显著差异。然而,当考虑到肿瘤分期时,促卵泡性MF在肿瘤细胞中表现出PD-1染色的比率为21.1%,而非促卵泡性MF在肿瘤细胞显示出PD-1阳性的比率为46.6%(p=0.005)。此外,在促卵泡性mfc病例中,24例中有13例在表皮和真皮成分之间表现出不同的PD-1表达模式,在表皮成分中保留了PD-1染色,而在真皮成分中失去了染色。此外,与先前的文献一致,具有大细胞转化的肿瘤细胞表现出显著较低的PD-1标记(p=0.017)。我们的发现展示了MF中独特的PD-1染色模式。
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引用次数: 0
The Effect of Bacillus coagulans Induced Interactions among Intestinal Bacteria, Metabolites, and Inflammatory Molecules in Improving Natural Skin Aging. 凝结芽孢杆菌诱导肠道细菌、代谢产物和炎症分子之间的相互作用在改善自然皮肤衰老中的作用。
IF 1.9 Q3 DERMATOLOGY Pub Date : 2023-09-28 DOI: 10.3390/dermatopathology10040037
Keiichi Hiramoto, Sayaka Kubo, Keiko Tsuji, Daijiro Sugiyama, Yasutaka Iizuka, Hideo Hamano

Background: Lactic acid bacteria consumption serves several health benefits to humans. However, their effect on natural skin aging is still unclear.

Methods: This study examined the effects of skin naturalization (particularly skin drying) by administering a spore-bearing lactic acid bacteria (Bacillus coagulans) in mice for 2 years.

Results: B. coagulans administration improved the natural skin of mice and significantly increased proportions of the genera Bacteroides and Muribaculum, among other intestinal bacteria. As metabolites, increases in nicotinic acid, putrescin, and pantothenic acid levels and a decrease in choline levels were observed. Increased hyaluronic acid, interleukin-10, and M2 macrophage levels indicate aging-related molecules in the skin. Intestinal permeability was also suppressed. Thus, these changes together improved natural skin aging.

Conclusions: This study revealed that B. coagulans administration improved the natural skin aging in mice. This enhancement might be induced by the interaction of alterations in intestinal flora, metabolites, or inflammatory substances.

背景:食用乳酸菌对人类健康有益。然而,它们对皮肤自然衰老的影响尚不清楚。方法:本研究通过在小鼠体内施用带有孢子的乳酸菌(凝结芽孢杆菌)2年来检测皮肤自然化(特别是皮肤干燥)的影响。结果:凝结芽孢杆菌给药改善了小鼠的自然皮肤,并显著增加了拟杆菌属和Muribaculum属以及其他肠道细菌的比例。作为代谢产物,观察到烟酸、腐胺和泛酸水平增加,胆碱水平下降。透明质酸、白细胞介素-10和M2巨噬细胞水平的升高表明皮肤中存在与衰老相关的分子。肠道通透性也受到抑制。因此,这些变化共同改善了皮肤的自然老化。结论:本研究表明,给予凝结芽孢杆菌可以改善小鼠的自然皮肤老化。这种增强可能是由肠道菌群、代谢产物或炎症物质的相互作用引起的。
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引用次数: 0
Dermatopathology 皮肤病理学
IF 1.9 Q3 DERMATOLOGY Pub Date : 2022-10-01 DOI: 10.1007/978-3-030-82820-2
Werner Kempf, Markus Hantschke, H. Kutzner
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引用次数: 0
Drug-Induced vs. Viral Maculopapular Exanthem—Resolving the Dilemma 药物致黄斑丘疹vs.病毒性黄斑丘疹:解决困境
IF 1.9 Q3 DERMATOLOGY Pub Date : 2022-05-07 DOI: 10.3390/dermatopathology9020021
S. Khandpur, R. Ahuja
Maculopapular exanthem is a commonly encountered presentation in routine clinical practice, and differentiation between its two most common etiologies, i.e., viral- and drug-induced, often poses a diagnostic dilemma. Clinical, hematological and biochemical investigations are seldom reliable in distinguishing between a drug reaction and a viral exanthem. Certain key histopathological features such as the presence of a moderate degree of spongiosis, extensive basal cell damage with multiple necrotic keratinocytes and dermal infiltrate rich in eosinophils or lymphocytes and histiocytes may favor a drug exanthem, while distinctive epidermal cytopathic changes and lymphocytic vasculitis point towards a viral etiology. Similarly, notable immunohistochemical markers such as IL-5, eotaxin and FAS ligand may support a diagnosis of a drug-induced maculopapular eruption. Histopathological and immunohistochemical evaluations may help in distinguishing between the two etiologies when faced with a clinical overlap, especially in patients on multiple essential drugs when drug withdrawal and rechallenge is not feasible.
黄斑丘疹是一种常见的临床表现,其两种最常见的病因,即病毒和药物引起的区分,往往造成诊断困境。临床、血液学和生化检查在区分药物反应和病毒检查方面很少可靠。某些关键的组织病理学特征,如存在中度海绵状病,广泛的基底细胞损伤伴多个坏死角质形成细胞和真皮浸润丰富的嗜酸性细胞或淋巴细胞和组织细胞,可能有利于药物检查,而明显的表皮细胞病变和淋巴细胞血管炎则指向病毒病因。同样,显著的免疫组织化学标志物如IL-5、eotaxin和FAS配体可能支持药物性黄斑丘疹的诊断。当面临临床重叠时,组织病理学和免疫组织化学评估可能有助于区分两种病因,特别是在需要多种基本药物且无法停药和重新挑战的患者中。
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引用次数: 2
期刊
Dermatopathology
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