A clinicopathological and immunohistochemical comparison of squamous cell carcinoma arising in scars versus nonscar SCC in Japanese patients

Squamous cell carcinoma (SCC) of the skin shows an indolent prognosis in general. However, the prognosis of SCC arising in a scar (scar carcinoma) is considered to be worse than that of SCC without any clinical history of injury (nonscar SCC). The aim of this study was to compare several indices, p53, Ki-67, E-cadherin, and beta-catenin, which are related to tumor behavior, between scar carcinoma and nonscar SCC clinicopathologically and immunohistochemically. The materials were from 10 cases of scar carcinoma and 10 cases of nonscar SCC. Clinicopathologically, the mean ages at diagnosis of scar carcinoma and nonscar SCC were 59.2 and 71.2, respectively. The most frequent anatomic site of scar carcinoma was the limbs. The most common cause of scars in our study was burns. The mean duration from the initial injury to the diagnosis of carcinoma was 30.5 years. Immunohistochemically, the mean labeling index (calculated as the percentage of positive cells) of p53 was 16.5 and 58.6 in scar carcinoma and nonscar SCC, respectively (P < 0.01, Welch test). The LI of Ki-67 was 19.1 in scar carcinoma and 52.1 in nonscar SCC (P < 0.01, Welch test). The rates of positivity of the other proteins, such as E-cadherin and beta-catenin, were similar between scar carcinoma and nonscar SCC. In this study, the follow-up time was short and the number of patients was small, and for these reasons it might not have been possible to obtain evidence that scar carcinoma is aggressive.     

Three cases of malignant melanoma arising on burn scars

It is well known that up to 2% of chronic burn scar lesions can transform into malignant tumors. Most of them are squamous cell carcinoma (SCC) and, more occasionally, basal cell carcinoma (BCC). The incidence of malignant melanoma (MM) is extremely low. To the best of our knowledge, there are only 23 such cases reported in the literature. We report here three cases of MM arising on burn scars and analyze the 23 cases reported previously. Case 1: a 74-year-old Japanese man sustained a burn injury on about 54% of his whole body surface when he was accidentally bathed in boiling oil at the age of 37 years old. Some small tumors developed on the burn scar on his right lumbar region. A wide excision of the tumor was performed. Case 2: a 51-year-old Japanese woman was injured on her right forearm and face by deep burns from a flame when she was 7 months old. She presented with a rapidly growing, painless black nodule on the dark skin lesion on her right forearm. She was treated with a wide excision followed by a full-thickness skin graft. Intravenous administration of one unit of OK-432 every week has been continued. Case 3: a 73-year-old Japanese woman was burned on her left leg and hand from a flame when she was 6 years old. A nodular lesion appeared within the ulcer two months previously and it was growing rapidly. This lesion was ulcerated on the top of its central area and was slightly reddish without any pigmentation. The patient was treated with a wide excision and a split-thickness skin graft. The 5-year survival rate of MM in an old burn scar is 53.6%. It is suggested that the prognosis of burn scar carcinoma is not worse than that of non-burn scar carcinoma.     

Where we stand with human hypertrophic and keloid scar models

We have yet to create a human scar model that demonstrates the complex nature of hypertrophic scar and keloid formation as well as ways to prevent them despite emerging advances in our understanding of the immune system, the inflammatory response, and proteomic and genomic changes after injury. Despite more complex in vitro models, we fail to explain the fundamental principles to scar formation, and the timeline of their development. The solution to developing the ideal in vitro scar model is one that mimics the heterogeneous cellular and molecular interactions, as well as the evolving structure and function of human skin.     

Epithelioid sarcoma and squamous cell carcinoma arising in a burn scar

Development of a malignant tumor is a well known complication of a chronic burn scar. Most of these tumors are squamous cell carcinomas and only 28 cases of burn scar sarcomas have been reported in literature. We report the first occurrence of the combination of squamous cell carcinoma and epithelioid sarcoma arising in a burn scar.     

Ki67在瘢痕癌中的表达及其临床意义

目的探讨Ki67在瘢痕癌组织中的表达及与患者临床特征的关系。方法应用免疫组化SP法检测Ki67在27例患者瘢痕癌组织中的表达,并结合瘢痕癌患者的临床特征进行分析。结果 27例患者瘢痕癌组织的Ki67检出率为100%。根据Ki67阳性细胞百分率将患者分为3组,≤10%组10例,11%~40%组10例,≥41%组7例。进一步分析发现各组的Ki67阳性细胞百分率与瘢痕溃疡持续时间长短、浸润深度和手术后复发相关,Ki67阳性细胞百分率越高,溃疡持续时间越短(P0.05)、浸润越深(P0.01)、手术后越易复发(P0.05);而与瘢痕病程、溃疡面积无关(P0.05)。结论 Ki67的表达在瘢痕癌浸润深度和术后复发的临床评估中具有重要的指导意义。     

Malignant melanoma arising in the scar of lupus vulgaris and response to treatment with topical azelaic acid

A patient with in situ malignant melanoma and squamous cell carcinoma arising in the scar of lupus vulgaris is described. Although the development of squamous cell carcinoma is a well recognized complication this is the first report of melanoma arising within the scar of inactive lupus vulgaris. Treatment with topical azelaic acid resulted in considerable histological improvement of the melanoma.     

皮肤病理性瘢痕及瘢痕癌组织中Cx32 mRNA和蛋白检测及基因突变分析

目的探讨Cx32mRNA及其基因突变在皮肤病理性瘢痕及瘢痕癌中的表达Cx32蛋白的分布。方法以病理性瘢痕、瘢痕癌组织为研究对象,正常皮肤组织为对照。采用免疫组织化学(SP)法分别检测Cx32蛋白水平,采用核酸分子原位杂交法检测Cx32mRNA,结合图像分析,分别观测3组被检组织中所检各项指标的强度(阳性面积与平均光密度)。从14例病理性瘢痕和14例瘢痕癌石蜡包埋组织中提取DNA,运用PCR扩增及扩增目的片段直接测序的方法,进行突变检查。结果 Cx32蛋白和Cx32mRNA在瘢痕癌中呈弱阳性或阴性,在病理性瘢痕上皮中呈阳性或强阳性,两者相比差异有统计学意义(P<0.01),但在病理性瘢痕上皮组和正常皮肤组相比差异无统计学意义(P>0.05)。28例样本经PCR反应后,6例扩增出目的条带(4例病理性瘢痕、2例瘢痕癌),经测序分析均未发现致病性与非致病性突变位点。结论瘢痕癌中Cx32的低表达,可能与瘢痕癌的发生发展有相关性,Cx32基因突变在瘢痕癌发生发展过程中的意义有待进一步探讨。     

Basal Cell Carcinoma Presenting Late in a Shotgun Scar

The development of a basal cell carcinoma (BCC) as a late complication of a shotgun injury is a rare clinical entity. We report the case of a 68-year-old Caucasian man who developed a BCC at the site of a scar from a shotgun pellet entry wound that was sustained 14 years previously. We emphasize the importance of excluding malignancy in a non-healing lesion and discuss the possible etiologic factors in the development of a BCC at the site of previous trauma.     

Dermatofibrosarcoma Protuberans Arising from a Burn Scar

Malignant neoplasms arising in burn scars are well known. In previous literature, 25 cases of burn scar sarcomas were reported. However, dermatofibrosarcoma protuberans is very rare and only two cases have been reported. A 43-year-old Korean man presented with multiple erythematous clustered plaques and nodules and a skin-colored subcutaneous mass on the chest after a severe burn injury at the age of 8 years. A biopsy specimen revealed dermatofibrosarcoma protuberans. The tumor was excised widely to include the surrounding burn scar. Herein, we report this third case of dermatofibrosarcoma protuberans arising from a burn scar.     

皮肤病理性瘢痕上皮中Cx43和C-myc的表达及意义

目的探讨皮肤病理性瘢痕上皮中Cx43和C-myc表达及意义。方法检测正常皮肤、病理性瘢痕和瘢痕癌组织中4种癌基因、4种抑癌基因和1种凋亡抑制基因蛋白水平和分子水平的表达;采用免疫组织化学SP法和核酸分子原位杂交技术,结合图像分析,对两两比较有统计学意义的Cx43和C-myc进行分析。结果 Cx43蛋白和mRNA在正常皮肤表皮为强阳性表达,在皮肤瘢痕上皮为阳性表达,在皮肤瘢痕癌组织为阴性或弱阳性表达,其表达水平和表达强度逐渐降低,两两比较差异有统计学意义(P<0.05);C-myc蛋白在正常皮肤表皮、皮肤瘢痕上皮和瘢痕癌组织中的表达分别为弱阳性、阳性和强阳性,其表达水平和表达强度逐渐增强,两两比较差异有统计学意义(P<0.05)。结论皮肤病理性瘢痕上皮中Cx43的表达降低、C-myc的表达升高,可能与瘢痕上皮癌变有相关性。     

Squamous cell carcinoma arising on a skin graft 64 years after primary injury

Malignant degeneration of a chronic wound is often described by the term, Marjolin's ulcer. We present a case of a squamous cell carcinoma that developed in a patient 64 years after the initial injury during World War II. Tissue contusion and detachment required repeated surgery and full skin grafting in several hospitals. The patient had a persistent ulcer in the right popliteal region for the last 3 years. Excisional biopsy in our department showed a bifocal low-grade invasive squamous cell carcinoma of the skin. Because of extensive inflammation and previous scar formation it was difficult to determine the status of the surgical margins. Therefore, we proceeded with amputation at the right thigh. Some 6 months after surgery the general condition of the patient remains excellent.     

Human hypertrophic and keloid scar models: principles,limitations and future challenges from a tissue engineering perspective

Most cutaneous wounds heal with scar formation. Ideally, an inconspicuous normotrophic scar is formed, but an abnormal scar (hypertrophic scar or keloid) can also develop. A major challenge to scientists and physicians is to prevent adverse scar formation after severe trauma (e.g. burn injury) and understand why some individuals will form adverse scars even after relatively minor injury. Currently, many different models exist to study scar formation, ranging from simple monolayer cell culture to 3D tissue‐engineered models even to humanized mouse models. Currently, these high‐/medium‐throughput test models avoid the main questions referring to why an adverse scar forms instead of a normotrophic scar and what causes a hypertrophic scar to form rather than a keloid scar and also, how is the genetic predisposition of the individual and the immune system involved. This information is essential if we are to identify new drug targets and develop optimal strategies in the future to prevent adverse scar formation. This viewpoint review summarizes the progress on in vitro and animal scar models, stresses the limitations in the current models and identifies the future challenges if scar‐free healing is to be achieved in the future.     

细胞周期蛋白A,p21~(WAF1)及C-myc在皮肤瘢痕及瘢痕癌中的表达及意义

目的探讨细胞周期蛋白A(CyclinA),p21WAF1和C-myc在病理性皮肤瘢痕和瘢痕癌中的表达及意义。方法采用免疫组化(SP)法分别检测正常皮肤、皮肤瘢痕和瘢痕癌中CyclinA,p21WAF1和C-myc蛋白的表达,采用原位杂交技术分别检测CyclinA mRNA,p21WAF1 mRNA的表达,并对数据进行统计学分析。结果 CyclinA,p21WAF1及其mRNA在瘢痕癌组织中呈强阳性表达,与正常皮肤组及皮肤瘢痕组比较,差异均有统计学意义(P<0.01);但其在正常皮肤组与瘢痕组比较,差异无统计学意义(P>0.05);C-myc蛋白在正常皮肤、皮肤瘢痕和瘢痕癌组织中的表达分别为弱阳性、阳性和强阳性,差异均有统计学意义(P<0.01)。瘢痕癌中CyclinA与CyclinA mRNA;Cy-clinA与p21WAF1,C-myc;CyclinA mRNA与p21WAF1 mRNA的表达均呈正相关。结论 CyclinA,C-myc的高表达与皮肤瘢痕癌的发生有相关性,这两种因子在瘢痕癌的发生中发挥协同作用;C-myc蛋白的表达可作为皮肤瘢痕癌变早期诊断的一个指标。p21WAF1在瘢痕癌中高表达的意义尚有待于进一步论证。     

Verrucous Carcinoma of Skin

Five different cases of verrucous proliferative lesions of skin are described and discussed. One of each developed in a chronic ulcer on a heel, in a scar on a lower leg, and on the penis, and two appeared in the region of the buttock in relation to chronic inflammatory sinuses. All these lesions showed morphological and clinical features of verrucous carcinoma which are described. It has been concluded that the variously named verrucous lesions in the literature (epithelioma cuniculatum, florid papillomatosis, giant cutaneous papilloma and papillomatosis cutis carcinoides), as well as our five cases represent a verrucous carcinoma which is a particular type of squamous cell carcinoma. This tumor develops typically in moist areas which are frequently sites of chronic inflammation. Despite the favorable prognosis, it is a potentially invasive tumor.     

Sarcoidosis cicatrizal

—Skin involvement in the form of scar sarcoidosis represents one of the most unusual forms of skin sarcoidosis. We present the case of a 56-year-old woman with changes in old scars as the onset of systemic sarcoidosis. The patient presented violaceous infiltration in some of her old, previously stable scars. Through a histopathological study, epithelioid-cell granulomas were observed in the superficial dermis and part of the reticular dermis. The lesions progressed, involving healthy skin as well, coinciding with the development of bilateral anterior uveitis. The symptoms were controlled with topical ophthalmic corticosteroids and chloroquine. The pathogenesis of scar sarcoidosis seems to be attributable to a hypersensitivity reaction in which the macrophage previously stimulated by an inert substance contaminating the injury is reactivated by sarcoidosis, thus infiltrating these old scars.     

改良菱形皮瓣在面部基底细胞癌手术缺损修复中的应用

目的：分析改良菱形皮瓣在面部基底细胞癌手术缺损修复中的应用。方法：选取2012年2月至2016年5月在我院就诊的面部基底细胞癌患者为研究对象，采用常规肿瘤切除术及改良菱形皮瓣修复术对患者进行治疗，对患者的术后不良反应、瘢痕恢复情况等进行总结分析。结果：本研究共纳入41例患者，术后所有患者皮瓣均I期成活，创面平整，未见皮下血肿及感染，周围器官未发生明显位移或畸形；其中2例患者眼部略有牵拉变形，随访1年后变形情况逐渐改善，双眼基本对称；术后瘢痕评估结果显示，患者瘢痕颜色评分为0.61±0.08、平整度评分为0.40±0.06、弹性评分为0.72±0.15、宽度评分为0.86±0.10。结论：改良菱形皮瓣在面部基底细胞癌手术缺损的修复中有较好的疗效。     

Lymphoepithelioma-like carcinoma arising in the scar from a previously excised basal cell carcinoma

We report a case of a primary lymphoepithelioma-like carcinoma of the skin (LELCS) associated with scar from a previous excision of basal cell carcinoma. The patient was a 68-year-old female with a 3.0 mm skin-colored pearly papule on her forehead that developed over 2–3 months. The patient had a history of a basal cell carcinoma in the same location, which was completely excised 1 year earlier. A biopsy and subsequent excision of the tumor were performed. The tumor consisted of small islands of large pleomorphic mitotically active epithelioid cells surrounded by a very dense lymphoplasmacytic infiltrate. The tumor was associated with dermal scar. There was no connection of tumor with the unremarkable epidermis. Immunohistochemical examination showed that the epithelioid tumor cells were positive for pan-cytokeratin and epithelial membrane antigen, supporting the morphologic impression of LELCS. The lesion was negative for Epstein-Barr virus. Retrospective review of the original excision specimen confirmed the diagnosis of an ordinary basal cell carcinoma. Forty-five cases of LELCS have been reported to date. We report the first case of LELCS to arise in the scar from an excision of a cutaneous malignancy     

Recurrent keratoacanthoma with vascular invasion: A diagnostic and management dilemma

A 71-year-old man with chronic renal failure and on peritoneal dialysis presented with recurrence of multiple keratotic nodules along a surgical scar. This was 6 months after the excision of a recurrent keratotic nodule reported as squamous cell carcinoma from the same site. The lesions were initially reported as squamous cell carcinomas, but on review of histology were consistent with keratoacanthomas. One of the keratoacanthomas showed vascular invasion. These responded well to low-dose acitretin at 10 mg three times per week and the patient stayed in remission after 18 months of follow up.     

Maligne Hauttumoren in beruflich verursachten Narben

Background

The occurrence of neoplasms in injury scars ?C as consequence of occupational accidents ?C may lead to compensation according to the statutory accident insurance regulations. According to newer regulatory attempts in occupational dermatology, certain criteria have to be met before the diagnosis of a neoplasm induced by a scar is accepted and compensation is due.

Material and methods

Based on a retrospective analysis of 217 dermatological claim files between 2007 and 2009 of the IPA (including 22 follow-ups), medical opinions on neoplasms developing in possible occupational scars were re-evaluated using criteria of the German social accident insurance and the Bamberg medical bulletin, part II (Bamberger Merkblatt, BM II) to see how well they qualified for recognition as an occupational or accident-related disorder.

Results

Three cases were identified where a neoplasm was suspected of having developed in an occupationally-related scar. One of the insured events entitled for compensation. Following the guidelines of the BM II, this case was approved as an occupational disease secondary to injuries with resultant reduction in earning capacity, whereas the others did not meet the requirements.

Conclusions

Two problems in evaluating malignant tumors in occupational scars are the long latency period and the documentation of a scar. The tumor excision specimen should be histologically re-examined to document the presence of an associated scar.