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        1. 【綜述】有特殊特征的黑素細胞痣:臨床皮膚鏡和反射式共聚焦顯微鏡表現(3)

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          靶樣含鐵血黃素沉積性痣


          臨床特征? 創傷性改變常發生于黑素細胞痣,尤其是隆起型或外生型痣(球狀痣)。由衣物、刮削或擦傷導致的機械性刺激(即使并不明顯)是最常見的外傷原因。靶樣含鐵血黃素沉積性痣(THN)患者常訴先前存在的痣色素突然改變,且常常無明確外傷。常見癥狀為壓痛和瘙癢。典型的臨床表現為突發的瘀斑、紫紅色暈,圍繞之前的中央隆起痣周圍形成靶樣外觀,無自覺癥狀。兒童和青少年多見,通常累及胸上部。Patrizi等人提出,THN之所以罕見是由于其自發性,以及快速消退性。主要與靶樣含鐵血黃素沉積性血管瘤(THH)相鑒別,THH臨床表現為軀干或四肢單個小型環狀靶樣皮損,青年多見。其他鑒別診斷包括黑素瘤、創傷性血管角化瘤、含鐵血黃素沉積性皮膚纖維瘤和徽章痣。


          組織病理學,可見纖維蛋白沉積,紅細胞外滲,伴有鞋釘樣內皮細胞的擴張血管數量增加,且與痣細胞融合。邊緣暈的特點為出血和含鐵血黃素沉積,同時伴有不規則的薄壁裂隙狀血管通道(分離真皮乳頭層的膠原束)??梢娨允人嵝粤<毎麨橹鞯难仔约毎p度浸潤。濕疹樣改變消失后,可見真皮乳頭層及中間網狀真皮層僅少量含鐵血黃素沉積,纖維化和少數收縮血管腔。


          皮膚鏡? 靶樣含鐵血黃素沉積性痣顯示為球狀黑素細胞痣的典型特征:在痣上及其周圍(尤其是不規則大小和形狀的墨黑色區域)有血管出血性改變,為紅色至紫色(或黑色),通??梢姸狐c狀血管。靶樣暈顯示,淺色且邊界不清的內區周圍繞以伴有鋸齒狀邊緣的均質性紅色區域。在發展過程中,中央痣持續存在,瘀斑暈最終消失,無復發傾向。皮膚鏡對區分黑色素沉著中的血液是非常有幫助的,并且有助于鑒別THH與TNH。


          反射式共聚焦顯微鏡 ?尚無描述THN反射式共聚焦顯微鏡特征的文獻。本文報道了1例(RCM能顯示復合痣的特征)外圍有環狀圖案,且伴有密集和稀疏細胞巢的病例。真皮淺層內,痣細胞和黑素細胞巢與溢出的紅細胞和炎性細胞融合。


          處理? 推薦局部抗炎藥或類肝素乳膏治療1-2周,從而幫助癥狀消退。若在一個月內色素痣不能恢復典型外觀,則可采取手術切除。



          Figure 9 Targetoidhaemosiderotic nevus. Clinical (a), and dermoscopy (b) image taken at baseline,showing the presence of a ill-de?ned inner area surrounded by a homogeneousreddish zone with peripheral-jagged margins. Dermoscpy (c) of the same lesionafter 15 days of topical steroid cream. The central nevus persists and the ecchymotichalo had disappeared. (d) RCM mosaic image at the level of the DEJ taken atthe baseline visit, showing the presence of a ringed pattern at the periphery(white arrows). (e) Nevus cells and melanocytic nests (circle)amalgamated with extravasated erythrocytes and in?ammatory cells (red arrows).

          圖9. 靶樣含鐵血黃素沉積性痣?;€處的臨床圖片(a),和皮膚鏡圖像(b)顯示邊界不清的內區周圍繞以伴有鋸齒狀邊緣的均質性紅色區域。外用類固醇乳膏治療15天后,同一皮損的皮膚鏡(c)圖像。中央痣持續存在,瘀斑暈消失。(d)表皮真皮交界處基線的RCM拼接圖像顯示,外圍存在環狀圖案(白色箭頭)。(e)痣細胞與黑素細胞巢(圓圈內)與溢出的紅細胞和炎性細胞融合(紅色箭頭)。




          結締組織增生性痣


          臨床特征? 結締組織增生性痣(硬化性)是一種鮮少報道且無明顯特征的良性黑素細胞增生,目前僅有數篇病例分析報告發表。臨床上,DN通常為小型(直徑可達1cm)肉色、紅色或輕度色沉的丘疹或結節,常見于中青年(平均年齡30歲)的四肢,女性略為多見。組織病理學上,DN以梭形或上皮樣黑素細胞為特征,且伴有容易嵌入纖維間質的假核。DN屬于伴有促結締組織成分的皮膚增生性疾病病譜(包括皮膚纖維瘤、硬化性藍痣、促結締組織增生性SN、DN以及結締組織增生性黑素瘤組成)。它們的差異有時可能會給臨床醫師和組織病理學家的診斷帶來困難。


          皮膚鏡? 目前僅報道3例患者的皮膚鏡特征:粉紅色的紅斑上覆細小的淺棕色網狀物。DN在顏色和結構通常對稱,并且缺乏黑素瘤特征性表現。皮膚纖維瘤和DN的共有特征為:皮損位于四肢,其大小介于幾mm至1或2cm之間。從臨床上來說,兩者的皮損都表現為堅硬的丘疹或結節,有時可能會引起如疼痛或瘙癢之類的臨床癥狀。然而,臨床上出現凹陷征(皮膚纖維瘤體征)和皮膚鏡發現周圍繞以微小著色網絡的中央白色斑塊是皮膚纖維瘤的特征性表現,但在DN患者中均未見到(圖10)。


          反射式共聚焦顯微鏡 ?暫無結締組織增生性痣的反射式共聚焦顯微鏡特征的描述。本文報道了1例患者在皮膚淺層顯示有規則的蜂巢狀圖案,無非典型細胞和paget樣擴散。在真皮表皮交界處可見邊緣形狀規則的乳突。共焦顯微鏡無法觀測到皮下增生的特征。



          Figure 10 Desmoplastic nevus.(a) Clinical view and close up (b) of a small pigmented papule arising on theupper arm of middle aged woman with multiple nevi (arrow). (c) Dermoscopy,exhibiting a tiny light brown network lying on a brownish erythematous background.Scattered, small, brown globules are also visible. (d) RCM mosaic image at thelevel of the DEJ. Regularly shaped edged papillae are visualized. An area ofepidermal achantosis is present at one sideof the lesion (white square), visible at areas with enlarged interpapillaryspaces. See the corresponding dermoscopic image (b, white square). No featuresof the underling dermal proliferation were detectable because of the limits indepth penetration of the tool.

          圖10 結締組織增生性痣。1例多發性痣中年女性患者上臂出現的小型色素性丘疹(箭頭)的(a)臨床圖片和(b)特寫。(c)皮膚鏡顯示褐色紅斑上覆細小的淺棕色網狀物??梢娚⒃诘淖厣∏?。(d)真皮表皮交界處RCM的拼接圖像,可見邊緣形狀規則的乳突。在皮損的一側,表皮棘層增厚(白色方框),可見乳突間距增大。見相應的皮膚鏡圖像(b,白色方框)。由于工具貫穿深度的限制,因此無法檢測到皮下增生的特征。


          處理? 基于DN的發展進程及其罕見的皮膚鏡特征,因此大多數患者需切除DN。主要與結締組織增生性黑素瘤(常見于老年患者的日光暴露部位)鑒別診斷。


          白色發育異常痣


          臨床特征? 目前僅介紹了5例白色發育異常黑素細胞痣(DMN)患者。這些痣臨床表現為白色至淺紅色斑疹且皮膚紋理加深,側光照下觀察可見銀色“光亮”外觀。白色DMN的臨床鑒別診斷包括特發性點狀白斑、扁平疣、黑色素減退斑、皮膚松垂、白色糠疹、色素減退性蕈樣肉芽腫、白癜風、炎癥后色素減退、硬化性萎縮性苔蘚、淺表性局限性硬皮病以及麻風病。切向光照下所見到的銀色光亮為白色DMN臨床診斷的線索。在上述5例DMN患者中有4例黑素瘤患者,其中2例患有2種原發性無黑素性黑素瘤。因此白色DMA與多發性原發性無黑素性黑素瘤有明顯關聯,但系列病例分析提示占所有黑素瘤發生率<2%。在此,本文介紹另外1例69歲且伴有黑素瘤的白色DMN女性患者,其背部有一個淺表擴散型黑素瘤(厚度為0.5mm)。原發性黑素瘤附近可見銀色光亮的圓形斑疹,組織病理學診斷為發育不良痣。組織病理學顯示濃染和多形性細胞核的非典型黑素細胞數量增加,成巢并且以獨立的個體排列,主要位于真皮表皮交界處和真皮乳頭層(圖11.)。



          Figure 11 White dysplasticnevus. (a) Atypical pigmented lesion on the upper back of a 69-year-old woman.(b) Close up showing the pigmented lesion, histologically diagnosed assuper?cial spreading melanoma (0.5 mm thickness). Adjacent to the melanoma,note the presence of a silvery shine lesion (arrow). (c) Histopathology. At lowpower histological examination, the epidermis shows lentiginous hyperplasia andfocalbridging of the papillae. (d) At higher magni?cation, singlemelanocytes are irregularly distributed at the junction showing random cytologicalatypia.

          圖11 白色發育不良痣。(a)1例69歲女性患者上背部的非典型色素性皮損(b)色素性皮損特寫,組織學診斷為淺表性擴散型黑素瘤(厚度為0.5mm)。黑素瘤附近發現有銀色光亮的皮損(箭頭)。(c)組織病理學。低倍率組織學檢查發現,表皮有雀斑樣增生和乳突局部橋連。(d)高倍率鏡下,可見單個黑素細胞不規則散布在交界處,并見細胞異型。


          皮膚鏡? 由于色素沉著完全缺失,因此沒有這些皮損的皮膚鏡特征報告。


          反射式共聚焦顯微鏡? 目前尚無白色發育不良痣的RCM描述。


          處理? 為排除白色DMN,應對出現白色至淺紅色斑疹且皮膚紋理加深,但不能明確分類的患者進行活組織檢查。此外,應特別留意白色DMN和黑素瘤之間可能存在的聯系。


          氣球樣細胞痣(BCN)


          臨床特征? 氣球樣細胞痣是公認的組織學診斷,其臨床表現與其他色素痣類似。病理組織學上,BCN是以明顯或完整的大型水泡性的透明細胞(稱為氣球狀細胞)為特點。氣球細胞是伴有淺染色且胞質呈空泡狀(通常是黑素體形成存在缺陷)的黑素細胞。


          皮損常見于頭部和頸部,其次為軀干和四肢。男女比例幾乎為1:1。BCN多發生于30歲以下青年,無自覺癥狀,通常為棕色,可能表現為平滑的丘疹或息肉。


          皮膚鏡 ?Stolz 等人先前在彩色圖譜中已介紹BCN的皮膚鏡特征。近期,Jaimes等人報道有大量聚集的白色球狀結構,其與氣球樣細胞痣巢相對應(圖12)。


          反射式共聚焦顯微鏡? 尚無氣球樣細胞痣的RCM描述。在本文介紹的1例患者中,其白色球狀結構對應黑素細胞巢。巢內的黑素細胞以胞質呈空泡狀為特點,見環繞暗色核的光亮區域(圖12)。



          Figure 12 Balloon cell nevus.(a) Dermoscopy, displaying numerous aggregated white globular structures that correspondto nests of ballon cells. A light brown, regular network is visible at the periphery.(b) RCM at the level of the super?cial dermis showing aggregates of densenests. (c) Close up of a melanocytic nest, melanocytes within the nest are characterizedby the presence of a vacuolized cytoplasm, visible as shiny areas (whitearrows) surrounding a dark nucleus (red arrow).

          圖12 氣球樣細胞痣。(a)皮膚鏡,顯示大量聚集的白色球狀結構,與氣球樣細胞巢對應。外圍可見淺棕色規則網絡。(b)真皮淺層的RCM顯示密集的細胞巢聚集。(c)黑素細胞巢特寫,巢內的黑素細胞以胞質呈空泡狀為特點,見環繞暗色核(紅色箭頭)的光亮區域(白色箭頭)。


          處理? 氣球樣細胞痣被認為是良性病變,應保守治療。




          黑素細胞痣可能會表現出與特征明顯的交界痣、復合痣或真皮痣相對立的特征。特有的組織病理學亞型或創傷、炎癥或免疫驅動現象可能導致普通痣出現異常的臨床表現。對這些痣的臨床、皮膚鏡以及RCM特征(可用時)的認知可能有助于提高在日常臨床實踐中診斷的準確性。


          下附英文原文


          Targetoid haemosiderotic nevus


          Clinical features? The occurrence of traumatic changes is frequent in melanocytic nevi, particularly in those that are elevated or exophytic (globular nevi). Mechanical irritation, even not apparent, by clothing, shaving or scratching is most common causes of injury.Targetoid haemosiderotic nevus (THN) is reported by patients as a sudden change in pigmentation in a previously known nevus, and it is very frequent that they do not recognize the injury. Tenderness and itching are common symptoms. The typical clinical appearance is the sudden development of an asymptomatic ecchymotic, violaceous halo causing a target-like phenomenon around a long-lasting central elevated nevus. It presents more often in children and young adults, usually localized on the upper part of the thorax. Patrizi et al. propose that the rarity of THN is due to its spontaneous and rapid regression. The major differential diagnosis is with targetoid haemosiderotic haemangioma (THH) that clinically presents as a single, small, annular target-like lesion on the trunk or an extremity of young adults. Other differential diagnoses include melanoma, traumatized angiokeratoma, haemosiderotic dermato?broma and cockade nevus.


          Regarding histopathology, ?brin deposits, extravasates of erythrocytes and an increased number of ectatic blood vessels with hobnail endothelial cells are seen, amalgamated with nevus cells. Peripheral halo is characterized by extensive haemorrhage and haemosiderin deposits in concert with irregular, thin-walled, slit-shaped vascular channels that dissect between collagen bundles of the papillary dermis. A mild in?ammatory in?ltrate mainly composed by eosinophils is observed. After the eczema disappears, only scant haemosiderin deposits, ?brosis and few collapsed vascular lumina in the papillary and mid-reticular dermis are seen.


          Dermoscopy? Targetoid haemosiderotic nevus shows the typical features of globularmelanocytic nevus with vascular haemorrhagic (red to purple or black) changes superimposed on the nevus and particularly surrounding it: especially irregularly sized and shaped, jet-black areas and often comma-shaped vessels can be seen. The targetoid halo demonstrates a pale, ill-de?ned inner area surrounded by a homogeneous reddish zone with peripheral-jagged margins. In the evolution, the central nevus persists and the ecchymotic halo ultimately disappears, with no tendency to recur. Dermoscopy is very helpful to differentiate blood from melanin pigmentation, and helps to differentiate THN fromTHH (Fig. 9).


          Re?ectance confocal microscopy? There is no description in the literature of a THN, up to date. Herein we report on a case, where RCM was able to show the features of a compound nevus, with presence of a ringed pattern at the periphery and dense and sparse nests. In the super?cial dermis nevus cells and melanocytic nests were amalgamated with extravasated erythrocytes and in?ammatory cells (Fig. 9).


          Management??One or two weeks of treatment with local anti-in?ammatories or a heparinoid cream is recommended to facilitate the regression of the phenomenon. If the nevi do not recover a typical appearance within a month, surgical excision should be performed.


          Uncommon variants


          Desmoplastic nevus


          Clinical features? Desmoplastic (sclerotic) nevus is an infrequently reported, poorly characterized, benign melanocytic proliferation, with only few case series published to date. Clinically, DN is usually a small (up to 1 cm in diameter), ?esh-coloured, erythematous, or slightly pigmented papule or nodule often occurring on the extremities of young adults (average age, 30 years), with a slight female predominance. Histopathologically, DN are characterized by spindle-shaped or epithelioid melanocytes, with readily appreciable pseudonucleoli embedded within a ?brotic stroma. DN is included in the spectrum of dermal proliferations with a desmoplastic component composed by dermato?broma, sclerotic blue nevus, desmoplastic SN, DN and desmoplastic melanoma. Their differentiation can sometimes represent a diagnostic dilemma for both clinicians and histopathologists.


          Dermoscopy??Dermoscopically, only three cases have been described up to now, exhibiting a tiny light brown network lying on a pinkish erythematous background. DN is usually symmetric in colour and structure and devoid of any melanoma-speci?c criteria. Features shared by dermato?broma and DN include their location on the extremities and their size ranging between few millimetres and 1 or 2 cm. Clinically, both lesions appear as ?rm papules or nodules that may sometimes cause clinical symptoms such as pain or itch. However, clinical dimpling sign and the dermoscopic central white patch surrounded by a delicate pigment network are speci?c features of dermato?broma that were not seen in our cases of DN (Fig. 10).


          Re?ectance confocal microscopy ?Re?ectance confocal microscopy features of desmoplastic nevus have not been yet described. Here, we present one case, showing a regular honeycombed pattern in the super?cial layers, with no atypical cells nor pagetoid spread. At the level of DEJ regularly shaped edged papillae were visualized. No features of the underling dermal proliferation were detectable by means of confocal microscopy (Fig 10).


          Management? In most of the cases, DN are removed because a history of changes and because of their unusual dermatoscopic features. Main differential diagnosis is with desmoplastic melanoma, which is more frequently seen in old patients on sunexposed areas.


          White dysplastic nevus


          Clinical features??Up to date, ?ve patients with white dysplastic melanocytic nevi (DMN) have been described. These nevi appear clinically as white to pale red macules with accentuated skin markings and a silvery ‘shining’ appearance when observed with tangential light. Clinical differential diagnosis of these white DMN include idiopathic guttate, ?at warts, hypomelanosis, anetoderma, pityriasis alba, hypopigmented mycosis fungoides, vitiligo, post-in?ammatory hypopigmentation, lichen sclerosus et atrophicus, super?cial morphea and leprosy. The silvery shine seen under tangential light is a clue for clinical diagnosis of white DMN. Notably, of the ?ve patients with white DMN, four patients had a melanoma with two of them presenting with two primary amelanotic melanomas. The association of white DMN with multiple primary amelanotic melanoma is signi?cant given that primary amelanotic melanoma is rare, with the largest series suggesting an incidence of <2% of all melanomas. Herein, we present an additional case of white DMN associated with melanoma in a 69-year-old women, who presented with a super?cial spreading melanoma (0.5 mm thickness) on the back. Close to the primary melanoma, a silvery shining roundish macule was seen, which has been histopathologically diagnosed a dysplastic nevus. Histologically, this lesion showed an increased number of atypical melanocytes with hyperchromatic and pleomorphic nuclei, arranged as solitary units and in nests, mainly at the DEJ and the papillary dermis (Fig. 11).


          Dermoscopy? There are no reports of the dermoscopy of these lesions due to complete absence of pigmentation.


          Re?ectance confocal microscopy? There is no description on white dysplastic nevi up to know.


          Management ?To rule out white DMN, biopsy should be taken from patients who present with white to pale-red macules with accentuated skin markings, which cannot be clearly classi?ed. In addition, special attention should be paid to the possible association of white DMN with melanoma.


          Balloon cell nevus (BCN)


          Clinical features? Balloon cell nevus is a well-recognized histological entity, having a clinical presentation that is not distinctive. Histologically, BCN is characterized by a predominance or complete occurrence of large, vesicular, clear cells, called balloon cells. Balloon cells are de?ned as melanocytes with pale-staining and vacuolated cytoplasms, which often have a defect in melanosome formation.


          The most common site of the lesion appears to be the head and neck area, followed by the trunk and extremities. Male to female ratio is almost 1: 1 similar. BCN presents mainly in the ?rst three decades of life and it is usually asymptomatic, generally brown and may appear as a smooth papule or may be polipoid.


          Dermoscopy? Dermoscopy of BCN have been described previously only in the colour atlas by Stolz et al. and in recent report by Jaimes et al., revealing numerous aggregated white globular structures that correspond to ballon cell nevi nests (Fig. 12).


          Re?ectance confocal microscopy? Balloon cell nevus have never been described in RCM. Here, we describe one case in which white globular structures correspond to melanocytic nests. Melanocytes within the nests are characterized by the presence of a vacuolized cytoplasm, visible as shiny areas surrounding a dark nucleus (Fig. 12).


          Management??Balloon cell nevus is considered a benign lesion and management should be conservative.


          Conclusion


          Melanocytic nevi may sometimes display features deviating from well-characterized aspect of junctional, compound or dermal nevi. Peculiar histopathological subtypes or traumatic, in?ammatory or immunodriven phenomena may result in unusual clinical presentations of common nevi. Recognition of clinical, dermoscopic and when available, RCM features of these nevi may be helpful in everyday clinical practice to improve diagnostic accuracy.


          由MediCool醫庫軟件涂秀麗 吳茵蕓編譯,上海市皮膚病醫院陳裕充博士審核

          原文來自:JEADV 2014, 28, 833–845




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