光线性角化病159例与皮肤鳞状细胞癌51例临床病理特征分析

目的了解滇东地区光线性角化病与鳞状细胞癌的疾病构成比、一般情况和临床病理特征。方法采用回顾性研究方法对曲靖市第一人民医院皮肤科2014年1月-2018年12月共5年行病理检查确诊的光线性角化病和皮肤鳞状细胞癌患者的临床和病理检查资料进行分析。结果159例光线性角化病(AK)与51例(SCC)鳞状细胞癌患者中女性多于男性,光线性角化病和鳞状细胞癌的发病平均年龄分别为(66.32±14.63)岁和(65.00±16.26)岁。光线性角化病和鳞状细胞癌患者皮损发生于曝光部位的分别占98.11%和78.43%。51例鳞状细胞癌患者中,有3例均是光线性角化病继发鳞状细胞癌,均为女性,年龄均>70岁,发病部位均为曝光部位。5年确诊光线性角化病患者占总病检患者的构成比相对稳定,其中鳞状细胞癌有所波动。AK病理分型分为肥厚型98例(61.64%)、萎缩型26例(16.35%)、棘层松解型12例(7.55%)、色素型9例(5.66%)、苔藓样型9例(5.66%)、鲍温样型5例(3.14%);SCC病理分级Ⅰ级39例(76.47%)、Ⅱ级11例(21.57%)、Ⅲ级1例(1.96%)、Ⅳ级0例。光线性角化病与鳞状细胞癌中临床诊断与病理诊断符合率分别为61.00%和56.86%,易被误诊为其他疾病。结论滇东地区光线性角化病与鳞状细胞癌以中老年女性为主,主要位于头面颈部等曝光部位,与紫外线关系密切,其中发生于曝光部位、皮损多样、病程长的老年女性光线性角化病患者易继发鳞状细胞癌,但临床病理诊断符合率较低,需引起重视。     

Utility of step sections: demonstration of additional pathological findings in biopsy samples initially diagnosed as actinic keratosis

OBJECTIVES: To discover additional diagnostic findings on step sections of biopsy samples showing features of actinic keratosis on the initial section and to correlate such findings with clinical and histological variables. DESIGN: Prospective study comparing initial histological findings with those noted on deeper tissue levels. SETTING: University-based dermatopathology practice. PATIENTS: Fifty-seven patients (36 men and 21 women) with biopsy samples from 69 skin lesions. MAIN OUTCOME MEASURES: Identification of additional pathological diagnoses in step sections and correlation with clinical diagnosis, size and location of lesion, history of skin cancer or immunosuppression, size and handling of specimen, and presence of ulceration on the initial level. RESULTS: Additional diagnostic findings were present on step sections in 23 specimens (33%), including 9 (13%) with squamous cell carcinoma in situ, 3 (4%) with basal cell carcinoma, and 2 (3%) with invasive squamous cell carcinoma. Three variables were significantly correlated with the discovery of cancer on step sections: (1) ulceration on the first level, (2) clinical diagnosis of skin cancer, and (3) history of skin cancer diagnosed by biopsy examination. The latter 2 variables were also correlated with the discovery of any additional finding, whether benign or malignant, on step sections. CONCLUSIONS: In biopsy samples initially diagnostic of actinic keratosis, examination of step sections contributes clinically important information. Step sections are particularly useful when a clinical diagnosis of skin cancer is present. The results of this study confirm the pathogenetic importance of actinic keratosis as a precursor to fully evolved malignant neoplasia and suggest that such lesions merit thorough histological study.     

Caspase-3在皮肤鳞状细胞癌及光线性角化病中的表达

目的：检测Caspase-3在皮肤鳞状细胞癌及光线性角化病组织中的表达。方法： 应用免疫组化法检测16例皮肤鳞状细胞癌皮损、27例光线性角化病皮损及24例正常皮肤组织中Caspase-3蛋白的表达。结果：Caspase-3在皮肤鳞状细胞癌、光线性角化病及正常皮肤组织的表达率分别为37.50%,51.85%,79.17%,其表达含量在皮肤鳞状细胞癌、光线性角化病、正常皮肤组织逐渐增加。结论：Caspase-3蛋白表达下调可能参与皮肤鳞状细胞癌及光线性角化病的发病过程。     

Thermal keratoses and squamous cell carcinoma in situ associated with erythema ab igne

A 60-year-old black woman had a large hyperkeratotic lesion and multiple smaller hyperkeratotic papules and plaques on the lower part of her legs in areas of erythema ab igne. Histologic examination of the largest lesion showed hyperplastic carcinoma in situ and the multiple smaller lesions showed varying degrees of squamous cell atypia and dermal elastosis. Histologically, these lesions were identical to solar-induced atypia, indicating that squamous cell carcinoma arising in erythema ab igne may be biologically similar to actinic carcinoma. Discussed here are clinical and histologic features of the thermal-induced lesions and other types of thermal-induced carcinomas.     

Treatment of cutaneous squamous cell carcinomas by intralesional interferon alfa-2b therapy.

BACKGROUND AND DESIGN--Intralesional recombinant interferon alfa-2b has been shown to be effective in the treatment of actinic keratoses and basal cell carcinomas. This open-label study was designed to evaluate the effectiveness and cosmetic result of this therapy on actinically induced, primary cutaneous squamous cell carcinomas. Thirty-six squamous cell carcinomas (28 invasive lesions and 8 in situ lesions) ranging in size from 0.5 to 2.0 cm in the longest dimension were treated with interferon alfa-2b 1.5 million units injected intralesionally three times per week for 3 weeks. Eighteen weeks following therapy, the treatment sites were excised and examined for histologic evidence of remaining tumor. RESULTS--Thirty-three (97.1%) of 34 evaluable lesions revealed an absence of squamous cell carcinoma histologically after therapy, although three biopsy specimens (8.8%) obtained after treatment showed actinic keratoses, for an overall complete response rate of 88.2%. The lesion not eliminated after treatment was an invasive squamous cell carcinoma. The investigators and patients independently judged 93.9% of cases to have a very good or excellent cosmetic result. Adverse reactions were limited to those influenzalike symptoms well recognized to occur with interferon therapy and these were well tolerated. Only one patient discontinued therapy due to side effects. CONCLUSIONS--This trial demonstrates that intralesional interferon is effective in the treatment of small sun-induced squamous cell carcinomas with well-tolerated side effects and a highly acceptable cosmetic result.     

Actinic keratoses

Actinic keratoses are defined as proliferation of cytologically atypical keratinocytes in the zone of epidermal-dermal junction in photodamaged skin. In the northern hemisphere the prevalence of actinic keratoses ranges depending on different epidemiological studies from 11% to 25% for people aged 40 or older. The main cause of actinic keratoses is exposure to UVB radiation in sunlight UVB radiation induces mutations in the telomerase gene and in the tumor suppressor gene P53, which can also be detected in invasive squamous cell carcinoma. The only histological parameter to distinguish between actinic keratoses and SCC is the level of invasiveness. The risk for actinic keratoses to develop into SCC is about 16% over lo years. For this reason and because of the high prevalence of actinic keratoses, it has been suggested to replace the term,, actinic keratosis K with intraepidermal squamous cell carcinoma' to better characterize the lesion. In the following review recent aspects of pathogenesis and therapy of actinic keratoses are discussed.     

Topical and light-based treatments for actinic keratoses

Actinic keratosis is currently believed to be an early stage in the evolution of squamous cell carcinoma. Active and intensive treatment of actinic keratosis may prevent the formation of invasive squamous cell carcinoma and potential metastases. While destructive methods of treatment of actinic keratosis remain the gold standard for the eradication of visible and palpable actinic keratoses, new medical therapies may accomplish this goal more comfortably and reliably for the patient. Newer topical medications, light therapy and photodynamic therapy are generating promising results that presage more widespread use in the future. These novel therapies for the early treatment of actinic keratosis may be administered in combination or serially, with the locus of treatment at any given time possibly restricted to a region of affected skin. Treatment of incipient or subclinical lesions may mitigate the risk of future squamous cell carcinomas lesions. Widespread actinic keratosis constitutes a persistent medical problem that requires long-term management. The role of traditional and novel treatments in the routine treatment of actinic keratosis will be determined by the efficacy, limitations and the practicality of each of these methods in individual patients. As the first stage of squamous cell carcinoma, actinic keratosis is worthy of prompt evaluation and active treatment.     

Actinic cheilitis: histologic study of the entire vermilion and comparison with previous biopsy

BACKGROUND: Actinic cheilitis (AC), is the very superficial, incipient form of actinically induced squamous cell carcinoma of the lower lip. Few studies of actinic cheilitis analyzed the entire lip vermilion searching for microscopic areas of progressing carcinoma. METHODS: Twenty patients with biopsy proved actinic cheilitis presenting with diffuse clinical changes were submitted to vermilionectomy of lower lip. Surgical specimens were sectioned every 3 mm, studied histopathologically and findings were compared with the biopsy. Histological findings were classified as 'AC', carcinoma in situ (CIS), superficially invasive squamous cell carcinoma (SISCC), and invasive squamous cell carcinoma (ISCC). RESULTS: Comparison between biopsies and most severe changes on vermilionectomies revealed coincidental changes in 10 cases (50%), more severe changes on biopsy occurred in two cases (10%) and in eight cases (40%) the changes on vermilionectomy were more severe. SISCC was diagnosed in nine cases (45%): of these, two had been detected on biopsy, six had shown a milder aspect on biopsy, and in one biopsy had shown ISCC. Foci of discontinuous areas of SISCC were detected in four cases (20%). CONCLUSIONS: These findings suggest that cases of AC presenting with poorly demarcated lesions may bear severe histopathological changes irregularly distributed along the vermilion.     

Ulcerative pigmented squamous cell carcinoma in a 101-year-old Japanese woman

Pigmented squamous cell carcinoma is a rare variant of squamous cell carcinoma. We report a case of pigmented squamous cell carcinoma with dermoscopic examination probably arisen from actinic keratosis in a 101-year-old woman who was surgically treated under general anesthesia. In addition, we discuss indications of general anesthesia in elderly patients with skin cancer, differential diagnosis and dermoscopic features of pigmented squamous cell carcinoma.     

P27 and mib1 expression in actinic keratosis, Bowen disease, and squamous cell carcinoma

The histologic boundary between actinic keratosis, Bowen disease, and invasive squamous cell carcinoma is not clear in many cases. We determined nuclear expression of p27 (a protein associated with cellular quiescence) and Ki-67 (a marker of proliferation) immunohistochemically in actinic keratosis, Bowen disease, and squamous cell carcinoma to see if differential patterns of expression for p27 exist and how these might correlate with Ki-67 expression. We determined a labeling index for p27-stained nuclei and assessed the pattern of Ki-67 expression. The student's t test was used to evaluate the p27 labeling index. The p27 labeling index was decreased in invasive aggregates of squamous cell carcinoma (76.9+/- 1.1%) when compared with those of normal epidermis (97.2+/- 2.4%), actinic keratosis (95.3 +/- 1.4%), and Bowen disease (98.0+/- 0.5%). Ki-67 was expressed in a scattered to confluent linear pattern in the basal/parabasal cell layer of normal epidermis and actinic keratosis. Keratinocytes in squamous cell carcinoma exhibited Ki-67 in the peripheral layers of the neoplasm and frequently within the tumor aggregates. Ki-67 was observed in nuclei throughout the full thickness of the epidermis in Bowen disease. The staining pattern of Ki-67 in Bowen disease separated this entity from others under study. The combination pattern of p27 and Ki-67 staining can be used to support differentiation of actinic keratosis, Bowen disease, and squamous cell carcinoma.     

梅花针叩刺增强氨基酮戊酸光动力治疗光线性角化病、基底细胞癌、鳞状细胞癌的研究

目的 探讨梅花针叩刺预处理对氨基酮戊酸光动力（ALA-PDT）治疗光线性角化病、基底细胞癌、鳞状细胞癌的疗效影响,以及梅花针叩刺预处理的安全性。 方法 通过病例对照研究,对6例光线性角化病,3例结节型基底细胞癌,3例原位鳞状细胞癌进行梅花针叩刺 ＋ ALA-PDT治疗,同时选取皮损类型及分期类似的患者仅单纯ALA-PDT治疗作为对照组。 结果 梅花针叩刺 ＋ ALA-PDT治疗组单次治疗对光线性角化病的完全缓解率明显高于单纯ALA-PDT组［1级皮损12/12比10/14,2级皮损79.5%（31/39）比57.9%（22/38）,3级皮损36.6%（15/41）比17.0%（7/41）,均P ＜ 0.05］。梅花针叩刺 ＋ ALA-PDT治疗组中光线性角化病获得完全缓解所需的治疗次数有所减少,3级皮损平均治疗1.9次获得完全缓解;单纯ALA-PDT组3级皮损平均2.6次获得完全缓解。梅花针叩刺 ＋ ALA-PDT治疗原位皮肤鳞状细胞癌（皮损厚度超过0.3 mm）,获得完全缓解治疗次数少于单纯ALA-PDT组。结节型基底细胞癌在增加梅花针叩刺后治疗效果亦增强。梅花针叩刺患者疼痛无明显增加。 结论 梅花针叩刺可增强ALA-PDT治疗光线性角化病,基底细胞癌,鳞状细胞癌的疗效,而不增加不良反应。     

抗增殖蛋白2在皮肤鳞状细胞癌中的表达及其对A431细胞增殖的影响

目的：观察抗增殖蛋白2在皮肤鳞状细胞癌、鲍温病、日光性角化病组织中的表达情况及其对A431细胞增殖作用的影响。方法：采用免疫组织化学方法检测抗增殖蛋白2在40例皮肤鳞状细胞癌、18例鲍温病、17例日光性角化病组织以及9例正常皮肤组织中的表达水平。采用CRISPR-Cas9法构建两组靶向敲除抗增殖蛋白2的皮肤鳞状细胞癌A431细胞模型（KO299组及KO320组）,使用Western印迹法证实其敲除效果,通过CCK8法及细胞克隆形成实验分析其对细胞增殖的影响。使用Western印迹法对AKT蛋白表达及其ser473位点磷酸化产物水平进行分析。 结果：抗增殖蛋白2在皮肤鳞状细胞癌(90.00％)、鲍温病(66.70％)、日光性角化病(41.18％)的表达高于正常组织(0.00％)（均P<0.05）,皮肤鳞状细胞癌抗增殖蛋白2表达高于日光性角化病(P<0.05)。在不同性别、年龄、部位、病程、肿瘤直径、浸润深度、分化、Broder分级的皮肤鳞状细胞癌组织中抗增殖蛋白2的表达差异无统计学意义（均P>0.05）。两组抗增殖蛋白2敲除组A431细胞的蛋白表达水平、细胞活力、克隆形成数显著低于对照组 (均P<0.05)。p-AKT表达随抗增殖蛋白2表达水平的降低而显著下调（均P<0.01）。结论：抗增殖蛋白2的表达可能促进了皮肤鳞状细胞癌的发生,并且其机制可能与促癌基因AKT蛋白活化相关。     

Muir-torre syndrome with intriguing squamous lesions: a case report and review of the literature

Muir-Torre syndrome (MTS) is an autosomal, dominantly inherited disorder characterized by sebaceous neoplasms and visceral malignancies. We report a 56-year-old woman who underwent resections of extraocular sebaceous carcinoma, sebaceous epithelioma, actinic keratosis, and keratoacanthoma (KA)-like squamous cell carcinoma (SCC) with venous invasion metachronously over a 9-year period. Because of the mixed, unusual features of the skin lesions, and her history of endometrial and colorectal cancers that had been resected 12 years and 1 year, respectively, before the present event, a possible diagnosis of Muir-Torre syndrome was suggested. Immunohistochemical studies revealed loss of hMSH2 expression in all the cutaneous lesions including the actinic keratosis, and also in the endometrial and colorectal cancers. This patient presented with intriguing squamous lesions including keratoacanthoma-like squamous cell carcinoma that showed venous invasion and actinic keratosis, and associated loss of hMSH2 expression, in addition to the sebaceous neoplasms typical of Muir-Torre syndrome.     

Die aktinische Keratose

Actinic keratoses are defined as proliferation of cytologically atypical keratinocytes in the zone of epidermal-dermal junction in photodamaged skin. In the northern hemisphere the prevalence of actinic keratoses ranges depending on different epidemiological studies from 11% to 25% for people aged 40 or older. The main cause of actinic keratoses is exposure to UVB radiation in sunlight. UVB radiation induces mutations in the telomerase gene and in the tumor suppressor gene p53, which can also be detected in invasive squamous cell carcinoma. The only histological parameter to distinguish between actinic keratoses and SCC is the level of invasiveness. The risk for actinic keratoses to develop into SCC is about 16% over 10 years. For this reason and because of the high prevalence of actinic keratoses, it has been suggested to replace the term "actinic keratosis" with "intraepidermal squamous cell carcinoma" to better characterize the lesion. In the following review recent aspects of pathogenesis and therapy of actinic keratoses are discussed.     

Case-based experience in the use of 5-fluorouracil cream 0.5% as monotherapy and in conjunction with glycolic acid peels for the treatment of actinic keratosis

Abstract

Actinic keratosis, commonly indicative of photodamage, requires treatment secondary to the risk of progression to squamous cell carcinoma. A number of effective treatments for actinic keratosis are available, including topical and lesion-directed therapies. While lesion-directed therapies such as cryotherapy are appropriate for isolated lesions, topical 5-fluorouracil is an effective modality for the treatment of multiple facial actinic keratoses. 5-Fluorouracil, available in a number of formulations, offers patients the benefit of treating subclinical lesions and may help to improve the overall appearance of the skin. In many cases, combination therapy is a better treatment option than monotherapy. The cases presented here demonstrate the use of topical 5-fluorouracil cream 0.5% as monotherapy and in conjunction with glycolic acid peels to treat facial actinic keratoses in two patients with extensive histories of prior actinic keratosis and skin cancer.     

Carcinoma spinocellulare and cutaneous T-cell lymphomas

Two cases of squamous cell carcinoma in patients with cutaneous T cell lymphoma are presented, together with a survey of the rather sparse literature on this subject. The cases presented showed considerable differences in their course. The mutagenic effects of the therapies used against the lymphoma are claimed to be responsible for the development of squamous cell carcinoma in almost all the published reports. However, we think the disturbances of the immune system caused either by the lymphoma itself or by the therapy might be a decisive factor in the development of secondary tumors. This possibility is supported by a comparison of immunosuppressed renal transplant recipients, who frequently develop squamous cell carcinomas of the skin. Frequent clinical follow-up examination of patients with cutaneous T cell lymphomas and early biopsy of suggestive lesions seem mandatory for differentiation between squamous cell carcinomas and tumorous infiltrations of the primary lymphoma. Radical surgical excision, which allows histological examination of the tumor margins, is the therapy of choice for these frequently very aggressive squamous cell carcinomas.     

Suspected skin malignancy: a comparison of diagnoses of family practitioners and dermatologists in 493 patients

BACKGROUND: In the Irish health system, dermatology patients present to their family practitioner for diagnosis and treatment, and are referred to a dermatologist for a second opinion where diagnosis is in doubt or when there has been therapeutic failure. The level of expertise in dermatology amongst family practitioners varies considerably. AIM: To compare the diagnoses of general practitioners and dermatologists over a selected period in patients with a possible diagnosis of skin cancer. METHODS: Four hundred and ninety-three patients were seen by one of two dermatologists over a 1-year period at a rapid referral clinic for patients suspected by their family practitioners of having unstable or possibly malignant skin lesions; 213 of these patients had a diagnosis made on clinical examination by the dermatologist, while 264 had diagnostic or therapeutic biopsies performed; 16 patients defaulted on surgery. RESULTS: The diagnoses of the family practitioners agreed with the diagnoses of the dermatologists on patients diagnosed clinically in 54% of cases. Thirty-eight patients had histologically proven skin malignancy. These were diagnosed accurately by the referring family practitioner in 22% of patients, while the dermatologists made the correct diagnosis prior to biopsy in 87%. CONCLUSIONS: In over 50% of cases diagnosed clinically, the dermatologist and family practitioner agreed. Histologically proven skin cancers were diagnosed accurately in only 22% of cases by family practitioners, compared to 87% of cases by dermatologists. Specific areas of diagnostic difficulty for family practitioners include benign pigmented actinic and seborrheic keratoses, squamous cell carcinoma, and melanoma. Postgraduate education for family practitioners should be directed towards these areas of deficiency. Dermatologists had difficulty distinguishing pigmented actinic keratoses from melanoma.     

Ber EP4与EMA染色在皮肤基底细胞上皮瘤和鳞状细胞癌诊断中的意义

目的 观察BerEP4和EMA染色在皮肤基底细胞上皮瘤和鳞状细胞癌诊断中的意义.方法 用免疫组化SP法检测BerEP4和EMA在皮肤基底细胞上皮瘤、鳞状细胞癌、光线性角化病、Bowen病、脂溢性角化病、寻常疣和基底鳞状细胞癌皮损肿瘤成分及周围组织、皮肤附属腺体中的表达.结果 所有基底细胞上皮瘤和基底鳞状细胞癌肿瘤细胞呈BerEP4阳性,而鳞状细胞癌、光线性角化病、Bowen病、脂溢性角化病和寻常疣呈BerEP4阴性;多数鳞状细胞癌、Bowen病和部分光线性角化病肿瘤细胞及病变区域呈EMA阳性,而基底细胞上皮瘤、基底鳞状细胞癌、脂溢性角化病和寻常疣呈EMA阴性.结论 联合使用BerEP4和EMA能很好地协助诊断皮肤基底细胞上皮瘤、基底鳞状细胞癌、癌前病变及一些良性增生性皮肤病.     

Las células claras en el carcinoma espinocelular cutáneo

IntroductionAlthough few cases of squamous cell carcinoma (SCC) with clear cells have been published, we believe that these cells are often present in SCC.Material and methodsWe studied 249 SCCs, analyzing a number of clinical and histological variables. Various immunohistochemical techniques (immunoperoxidase method) were used to determine whether adnexal differentiation was present.ResultsThere were 96 SCCs with a proportion of clear cells of over 25 %. Advanced or established SCCs and SCCs associated with Bowen disease contained a larger proportion of clear cells. We defined 2 histological patterns: a) clear cells around the keratin pearls of SCCs arising from pre-existing actinic keratosis and with indirect signs of human papilloma virus infection in hair follicles; and b) clear cells that simulate adnexal differentiation in lesions arising on pre-existing Bowen disease lesions. There were also 19 carcinomas with true adnexal differentiation.DiscussionClear cells are frequently observed in SCC, though large numbers of clear cells are present only in certain SCCs. The appearance of clear cells in SCCs is progressive and they are only present in more advanced SCC. The presence of clear cells is suggestive of adnexal differentiation; however, in the majority of cases, their presence is due to infiltration of normal adnexal structures by the cells of pagetoid Bowen disease. True adnexal differentiation exists only in a small percentage of cases (7.6 % in our study). The histological pattern described as clear cells around keratin pearls practically rules out this differentiation.