Multiple‐digit periungual Bowen's disease: a novel treatment approach with radiotherapy

Multiple periungual Bowen disease [BD; also known as squamous cell carcinoma (SCC) in situ] is rare. The pathogenesis of the disease is linked to human papilloma virus, and in some instances to chronic immunosuppression. The usual management of periungual BD is by local excision, Mohs micrographic surgery or distal phalanx amputation. Our patient was offered radiotherapy in the hope of maximizing residual function and minimizing morbidity from treatment. A good response was seen at 2 months post‐radiotherapy, but this was followed by relapses at 4 and 6 months post‐radiotherapy. Persistent anonychia resulted in improved access to the involved skin, making topical therapy possible. Radiotherapy can be a valuable management approach for periungual SCC/BD in locations where amputation could result in substantial disability.     

Periungual Bowen's Disease in a 12‐Year‐Old Boy Treated with Photodynamic Therapy

Bowen's disease (BD) usually occurs on sun‐exposed areas in elderly patients. BD rarely occurs in childhood and lesions of the nail unit and periungual area are likely associated with human papillomavirus infection. Herein, we report a case of BD presenting on the periungual area in a 12‐year‐old boy which was successfully treated with two sessions of photodynamic therapy.     

High‐risk human papillomavirus in a child with digital pigmented Bowen's disease: Case report and dermoscopic findings

Squamous cell carcinoma in situ, also known as Bowen's disease (BD), is a skin malignancy most commonly seen in middle‐aged and elderly adults. Pediatric BD is rare and can be a diagnostic challenge for physicians. Digital BD has largely been associated with human papilloma virus. We report an immunocompetent 11‐year‐old girl with periungual pigmented BD induced by high‐risk human papilloma virus.     

Matrix metalloproteinase‐7 activates heparin‐binding epidermal growth factor‐like growth factor in cutaneous squamous cell carcinoma

Background Tumour‐specific expression of matrix metalloproteinase (MMP)‐7 has been noted in cutaneous squamous cell carcinomas (SCCs) in patients with recessive dystrophic epidermolysis bullosa (RDEB). Objectives To examine the potential role of MMP‐7 in shedding of heparin‐binding epidermal growth factor‐like growth factor (HB‐EGF) in RDEB‐associated and sporadic SCCs. Methods Tissue microarrays of RDEB‐associated SCC (n = 20), non‐EB SCC (n = 60) and Bowen disease (n = 28) were immunostained for MMP‐7, CD44 variant 3 (CD44v3) and HB‐EGF. Shedding of HB‐EGF was studied in vitro using two cutaneous SCC cell lines. Results Immunohistochemical analysis showed that HB‐EGF was absent in tumour cells when MMP‐7 and CD44v3 colocalized, and that the absence of HB‐EGF was more pronounced in RDEB‐associated SCCs than in non‐EB SCCs. The loss of HB‐EGF in MMP‐7–CD44v3 double‐positive areas was interpreted to indicate shedding and activation of HB‐EGF; this was also detected in Bowen disease indicating its importance in the early phase of SCC development. Specific knockdown of MMP‐7 expression in human cutaneous SCC cells by small interfering RNA inhibited shedding of HB‐EGF and resulted in diminished activation of the EGF receptor (EGFR) and ERK1/2, and in reduced proliferation of SCC cells. Conclusions These findings provide evidence for the role of MMP‐7 in promoting the growth of cutaneous SCCs by shedding HB‐EGF, and identify EGFR signalling as a potential therapeutic target in RDEB‐associated SCC and unresectable sporadic cutaneous SCC.     

GLUT-1、Ki-67在皮肤肿瘤中的表达及意义

目的：探讨葡萄糖转运蛋白-1（GLUT-1）在脂溢性角化病（SK）、日光性角化病（AK）、Bowen病（BD）、鳞状细胞癌（SCC）中的表达及其与细胞增殖因子Ki-67之间的关系。方法：采用免疫组化法检测了95例不同皮肤肿瘤GLUT-1及Ki-67的表达。结果：GLUT-1及Ki-67在SK及正常皮肤都不表达,在AK、BD及SCC表达上调,并且二者的阳性表达强度间具有正相关性。结论：GLUT-1在恶性皮肤肿瘤中表达上调,与肿瘤的侵袭和转移有关。其表达强度可作为判断皮肤肿瘤恶性程度的检测指标,对诊断及鉴别诊断具有参考价值。     

Oral S‐1 in advanced cutaneous squamous cell carcinoma

Squamous cell carcinoma (SCC) is the second most common type of skin cancer in Japan, and its incidence has been increasing in recent years. Early diagnosis and complete excision can provide a high cure rate. However, advanced cases of SCC showing local invasion, regional lymph node metastasis or distant metastasis are not curative and are difficult to treat with surgery alone. Some chemotherapy regimens have been used for treating advanced cutaneous SCC. However, almost all these regimens require intravenous administration and result in serious toxicities in elderly people. We gave S‐1, a novel oral chemotherapeutic agent, for six patients with advanced cutaneous SCC. Three patients achieved complete response and one achieved partial response. Two patients showed stable disease. The overall response rate was 66.7% (four of six patients), and the disease control rate was 100%. Two of six patients developed grade 3 anaemia. Oral S‐1 treatment is safe and effective for treating advanced cutaneous SCC. However, a prospective trial is necessary to confirm the effectiveness of oral S‐1 for advanced cutaneous SCC.     

蛋白激酶D1及其磷酸化位点在皮肤鳞状细胞癌、Bowen病及光线性角化病组织中的表达

目的 探讨蛋白激酶DI(PKD1)及其磷酸化位点pPKD1-tyr463和pPKD1-ser916在鳞状细胞癌(SCC)、Bowen病和光线性角化病(AK)中的表达及意义.方法 收集新鲜SCC、Bowen病、AK及正常皮肤组织各10份,RT-PCR法检测各组样本中PKD1在基因水平的表达,Western印迹法检测各组样本中PKD1及其磷酸化位点在蛋白水平的表达.另收集蜡块组织SCC 50份、Bowen病20份、AK 20份及正常表皮组织10份,免疫组化检测PKD1、pPKD1-tyr463及pPKD1-ser916的表达情况.结果 正常皮肤组织、SCC、Bowen病和AK组织中PRKD1 mRNA的表达量分别为0.64±0.09、5.37±1.06、2.69±0.72和2.43±0.46,4组间差异有统计学意义(F=21.37,P＜0.05),且SCC、Bowen病和AK组织的表达水平均显著高于正常组织(P＜0.05),SCC组织又显著高于AK和Bowen病组织(均P＜ 0.05),而Bowen病与AK组织的表达量差异无统计学意义(P＞0.05).PKD1总蛋白及pPKD1-tyr463在SCC和Bowen病组织中主要表达在棘层细胞及异形细胞的细胞质和细胞膜,且阳性表达率均显著高于正常皮肤组和AK组(均P＜0.01);pPKD1-ser916仅在部分高分化SCC癌巢中少量表达,而低分化鳞癌、AK、Bowen病及正常皮肤组织中均未见表达;SCC组中PKD1阳性表达率随鳞癌病理分级的提高而增加,且PKD1与pPKD1-tyr463的表达呈正相关(rcc=0.479,P＜0.05).Western印迹检测结果与免疫组化检测结果大致相符.结论 PKD1及其磷酸化位点Tyr463可能参与复层鳞状上皮来源的皮肤肿瘤的形成和进一步发展分化,在皮肤SCC形成进程中PKD1可能通过Tyr463位点活化而发挥促进作用.     

Prognostic variables in high‐risk cutaneous squamous cell carcinoma: a review

Cutaneous squamous cell carcinoma (SCC) is a growing public health problem in the United States. A subset of high‐risk SCC exhibits a more aggressive clinical trajectory including increased local recurrence and lymph node metastasis. However, there are no universally accepted criteria to help define and manage these patients. This review provides an overview of the high‐risk features of cutaneous SCC, prognostic stratification of various staging systems and treatment options. It further examines the prognostic factors influencing the staging of cutaneous head and neck SCC.     

Porocarcinoma coexisting at a site of Bowen disease in a 63‐year‐old woman

Porocarcinoma is an unusual, locally aggressive and potentially fatal neoplasm. Several cutaneous malignancies have been described in association with porocarcinoma, including squamous cell carcinoma, basal cell carcinoma and tricholemmal carcinoma. Previous reports have indicated that the occurrence of malignant tumours in combination with porocarcinoma is extremely rare, in particular with regard to Bowen disease (BD). We report an uncommon case of porocarcinoma occurring synchronously in a single BD lesion in a 63‐year‐old woman with multiple BD lesions. The clinical and histological findings confirmed this diagnosis.     

Vulval intraepithelial neoplasia and periungual Bowen's disease concordant for mucosal (HPV-34) and epidermodysplasia verruciformis (HPV-21) human papillomavirus types

Human papillomavirus (HPV) infection is associated with genital malignancy and specific cutaneous malignancies. We report a case of an HPV-associated concurrent vulval intraepithelial neoplasia and periungual Bowen's disease in a young immunocompetent Afro-Caribbean woman with no known risk factors for either disease. HPV genotyping studies detected multiple alpha and beta papillomaviruses with concordance for HPV-34 [a high-risk (HR) mucosal type], and HPV-21 [an epidermodyslasia verruciformis (EV) type] in both vulval and finger tissue. Although the HR-mucosal viruses detected are likely to have a pathogenic role in vulval intraepithelial neoplasia, this is the first report of concordance for EV HPV types in both genital and nongenital skin premalignancies. This case, in the context of accumulating epidemiological and experimental data in cutaneous SCC, raises the question of whether EV HPV may contribute to vulval malignancy, and further study is merited.     

Pseudocarcinomatous hyperplasia mimicking squamous cell carcinoma in a case of CD56‐positive cytotoxic T‐cell lymphoma

We present the case of an 84‐year‐old patient with a cutaneous CD56 positive cytotoxic T‐cell lymphoma associated with substantial pseudocarcinomatous hyperplasia mimicking squamous cell carcinoma (SCC). The patient presented with a 7‐month history of several progressive, ulcerated plaques on his right forearm. An initial biopsy showed changes consistent with a diagnosis of SCC for which the patient underwent surgical treatment. Several months later, the patient developed recurrent ulcerated plaques on the right forearm of which several biopsies were performed. The biopsies repeatedly showed marked pseudocarcinomatous hyperplasia resembling SCC. Deeper punch biopsies, however, showed a dense superficial and deep infiltrate of markedly atypical lymphocytes. Immunohistochemical analysis revealed strong positive staining for CD3, CD8, CD56 with negative stains for CD30 and Epstein‐Barr virus‐encoded small non‐polyadenylated RNAs (EBER). Staining for beta F1 and gamma‐delta T‐cell receptor (γδ TCR) were both negative. This constellation was most consistent with a diagnosis of cutaneous peripheral T‐cell lymphoma, unspecified in association with marked pseudocarcinomatous hyperplasia. Our case adds cutaneous peripheral T‐cell lymphoma, unspecified to the list of conditions associated with pseudocarcinomatous hyperplasia (PCH) and illustrates once again the potential pitfalls of distinguishing marked pseudocarcinomatous hyperplasia from SCC.     

Subungual keratoacanthoma: analysis of cell proliferation and copy number variation of oncogenes compared with periungual squamous cell carcinoma

Background. Subungual keratoacanthoma (SUKA) is a rare cutaneous tumour with several features distinct from ordinary KA. SUKA may not show spontaneous regression and sometimes grows progressively, resulting in phalangeal bone destruction. This makes its distinction from digital squamous cell carcinoma (SCC) difficult. Aim. To investigate differences in molecular expression between SUKA and digital SCC. Methods. In addition to immunohistochemical analysis of Ki‐67, one of the markers differentiating KA from SCC, we investigated the copy numbers of various oncogenes by multiplex ligation‐dependent probe amplification (MLPA) using two cases of SUKA and three cases of periungual SCC. Results. Ki‐67 was moderately or strongly positive in SCC but negative in SUKA. The MLPA analysis showed that the nuclear factor (NF)κB1 and cortactin (CTTN; formerly known as EMS1) genes are amplified in SUKA but not in digital SCC. This increase in NFκB1 was confirmed by immunohistochemical analysis. Conclusion. NFκB1 could be a novel marker to differentiate between SUKA and SCC. Although this study was performed on limited numbers of patients with SUKA, MLPA analysis could be applied to differentiate other benign tumours from their malignant counterparts.     

Cyclin A and beta-catenin expression in actinic keratosis, Bowen's disease and invasive squamous cell carcinoma of the skin

BACKGROUND: Actinic keratosis (AK) has been defined as a precancerous lesion or an early phase in the evolution of squamous cell carcinoma (SCC) and histological changes seen in the individual cells of an AK are indistinguishable from those seen in SCC, which invade the dermis. Cyclin A is an increasingly utilized proliferation marker that has functions in both S phase (DNA replication) and initiation of mitosis, whereas alterations of beta-catenin, the molecule involved in cell-cell adhesion and in signalling transduction, could promote invasive and proliferative capacities of malignant tumours. OBJECTIVES: To determine cyclin A and beta-catenin expression pattern in cutaneous SCC and in in situ lesions classified as keratinocytic intraepidermal neoplasia (KIN) and, using traditional terms, as AK and Bowen's disease (BD), and to analyse it in relation to SCC differentiation, diameter and thickness. METHODS: Immunohistochemical staining was performed on 110 formalin-fixed paraffin-embedded tissue samples with the streptavidin-biotin technique using antibodies to cyclin A and beta-catenin. On histological examination, 53 lesions were diagnosed as AK, 16 as BD and 41 as SCC-11 well differentiated (WD), 16 moderately differentiated (MD) and 14 poorly differentiated (PD). Using KIN classification, 22 lesions were KIN1, 23 were KIN2 and 24 were KIN3. For cyclin A, distribution and labelling index (LI), and for beta-catenin, level of membranous staining and presence of aberrant (nuclear/cytoplasmic) localization were examined. RESULTS: Diffuse cyclin A presence was observed more frequently in BD than in AK (P < 0.0001) or SCC (P = 0.0002), and in SCC-PD compared with SCC-WD (P < 0.0001) or SCC-MD (P = 0.0003). Differences between KIN3 and KIN2, as well as KIN3 and KIN1 lesions, were statistically significant (P < 0.0001), and the same result appeared when KIN1 and KIN2 cases were grouped and compared with those of KIN3 (P < 0.0001). Cyclin A LI was significantly lower (P < 0.05) in AK than in BD or SCC, but no difference between BD and SCC was found, and LI in BD was even higher than in SCC-WD or SCC-MD, while analysis regarding SCC differentiation and KIN classification revealed the same correlation as for the cyclin A distribution. Reduced or absent beta-catenin membranous staining was found in 90 cases (81.8%), more often in SCC than in AK (P = 0.03) or in AK and BD grouped together (P = 0.02). There was no statistical difference between SCCs of various level of differentiation, or between different KIN grades. Diffuse loss of membranous beta-catenin staining showed 36 lesions (32.7%), more frequently SCC than AK (P = 0.003) or AK and BD grouped (P = 0.006), as well as SCC-PD compared with SCC-WD (P = 0.01) and SCC-MD (P = 0.03), whereas all KIN comparisons remained nonsignificant. Aberrant beta-catenin cellular localization demonstrated 28 lesions (25.5%), most often in the basal or peripheral parts and in the lesions with diffuse beta-catenin loss (P = 0.009), but revealed no correlation with the histological type, SCC level of differentiation or KIN grades. Diffuse loss of membranous beta-catenin staining was found to be significantly more frequent in SCC thicker than 4 mm (P = 0.03), while all other comparisons between cyclin A or beta-catenin with the tumour size remained nonsignificant. Cyclin A LI was higher in cases with diffuse loss of membranous staining (P = 0.001) or with aberrant cellular localization of beta-catenin (P = 0.002). CONCLUSIONS: Cyclin A LI showed greater difference between AK and BD than between BD and SCC, suggesting that increased proliferation (measured by cyclin A LI) characterizes progression of in situ lesions from AK to BD, whereas reduced beta-catenin expression separates more clearly SCC from the in situ lesions. Diffuse pattern of loss of membranous beta-catenin staining correlated better with the type of lesion, SCC differentiation and tumour size than reduced expression in general or aberrant cellular localization of beta-catenin. KIN classification does not seem to be supported by our findings, except when KIN1 and KIN2 lesions (in situ, partial thickness) are grouped.     

Therapeutic and immune effects of 5‐aminolevulinic acid photodynamic therapy on UVB‐induced squamous cell carcinomas in hairless mice

The therapeutic effects of 5‐aminolevulinic acid (ALA)‐mediated photodynamic therapy (PDT) on cutaneous squamous cell carcinoma (SCC) are not fully understood, and the usefulness of topical PDT in the treatment of SCC is still debatable. The most interesting aspect in SCC PDT is perhaps its potential in inducing antitumor immune responses. In this study, cutaneous SCCs were established by UVB irradiation of hairless mice and treated with multiple ALA PDT. Immunohistochemistry assays showed that ALA PDT could induce quick apoptosis, overexpression of TNFα and marked increases in DCs, CD4⁺ and CD8⁺ cells in tumor interstitium and subcutaneous connective tissues. However, a complete response was only achieved for small SCCs. The clinical value of ALA PDT‐induced specific antitumor immune responses in long‐term control of SCCs deserves further study.     

Clinical Features of Cutaneous Premalignant Lesions in Busan City and the Eastern Gyeongnam Province,Korea: A Retrospective Review of 1,292 Cases over 19 Years (1995~2013)

BackgroundThe global prevalence of premalignant lesions has been continuously increasing in recent years, but there has been little research regarding the distribution and incidence of cutaneous premalignant lesions in Korean populations.ObjectiveWe conducted this retrospective study to analyze recent trends in the incidence and clinical patterns of cutaneous premalignant lesions in the Korean population.MethodsWe reviewed 1,292 cases (3,651 lesions) of patients with cutaneous premalignant lesions, including actinic keratosis (AK) and Bowen''s disease (BD), from the Department of Dermatology at Dong-A University Hospital (January 1995 to December 2013).ResultsThe average cutaneous premalignant lesion annual incidence was 1.82%, and the incidence continuously increased from 0.70% to 4.25% over the study period. The most common cutaneous premalignant lesion was AK (75.85%), followed by BD (24.15%). The mean age of onset was 68.76 years (men, 70.89 years; women, 65.56 years), and the male:female ratio of patients was 1:1.52. Major skin cancers, including squamous cell carcinoma (SCC, 8.90%), basal cell carcinoma (BCC, 6.42%), and malignant melanoma (MM, 0.70%), were detected in 15.79% of patients with cutaneous premalignant lesions. Three patients (0.23%) were previously diagnosed with both SCC and BCC. In addition, 59.13% of patients had a single lesion, while 40.87% had multiple lesions. Patient age, history of previous skin cancers, and occupation-related exposure to ultraviolet radiation were more common in patients with multiple lesions.ConclusionCutaneous premalignant lesion incidence has gradually increased in the Korean population.     

Livin和Smac在鲍恩病及皮肤鳞状细胞癌中的表达

目的：确定Livin和Smac在鲍恩病（BD）及皮肤鳞状细胞癌（SCC）中的表达和意义.方法：应用免疫组化SP法检测35例BD和32例SCC中Livin和Smac的表达,分析二者表达的相关性.结果：Livin表达：BD组高于BD癌旁组织（P〈0.001）;BD癌旁组织高于正常对照组（P〈0.05）.SCC组高于SCC癌旁组织（P〈0.001）;SCC癌旁组织高于正常对照组（P〈0.05）.SCC组高于BD组（P〈0.05）.Smac表达：BD组低于BD癌旁组织（P〈0.01）;BD癌旁组织低于正常对照组（P〈0.05）;SCC组低于SCC癌旁组织（P〈0.001）;SCC癌旁组织低于正常对照组（P〈0.05）;SCC组低于BD组（P〈0.05）.Livin和Smac在BD中表达无相关性（P〉0.05）,在SCC中表达呈负相关（P〈0.05）.结论：Livin的过表达和Smac的低表达可能在BD和SCC的发生、发展中起一定作用.     

Cutaneous lip tumours treated with Mohs micrographic surgery: clinical features and surgical outcome

BACKGROUND: The Australian Mohs micrographic surgery (MMS) database was initiated in 1993 by the Skin and Cancer Foundation Australia (SCFA) with the aim of collecting prospective data, and involved all Mohs surgeons in the country. OBJECTIVES: To present a large series of patients with cutaneous lip tumours treated with MMS in Australia between 1993 and 2002. METHODS: This prospective multicentre case series included all patients with cutaneous lip tumours who were monitored by the SCFA. The main outcome measures were patient demographics, reason for referral, duration of tumour, site, preoperative tumour size and postoperative defect size, recurrences prior to MMS, histological subtypes, perineural invasion and 5-year recurrence after MMS. RESULTS: There were 581 patients (66.1% women and 33.9% men, P < 0.0001) with a mean +/- SD age of 58 +/- 15 years. The upper lip was the most common site involved (81.1%). Basal cell carcinoma (BCC) was diagnosed in 82.3%, squamous cell carcinoma (SCC) in 16.5%, Bowen's disease (BD) in 0.7% and microcystic adnexal carcinoma (MAC) in 0.5% of cases. BCC was more common on the upper lip and in women, whereas SCC was more common on the lower lip and in men (P < 0.0001). Most upper lip tumours occurred in women (75.4%), whereas most lower lip tumours occurred in men (73.6%). SCC was associated with a larger tumour and postoperative defect size compared with the other tumours. The 5-year recurrence for BCC was 3.0%, and there were no cases of recurrence for SCC, BD or MAC. CONCLUSIONS: BCC was the most common cutaneous lip tumour managed by MMS, and was significantly more common on the upper lip and in women. The low 5-year recurrence rate emphasizes the importance of margin-controlled excision.