Methylaminolaevulinate-based photodynamic therapy of Bowen's disease and squamous cell carcinoma

Background  Photodynamic therapy (PDT) with methylaminolaevulinate (MAL) is an approved noninvasive treatment option for actinic keratosis and Bowen's disease (BD), two precursors of invasive squamous cell carcinoma (SCC).
Objectives  To assess efficacy, prognostic features, tolerability and cosmetic outcome of MAL-PDT for the treatment of BD and SCC.
Methods  In total, 112 biopsy-proven lesions of BD and SCC in 55 subjects were treated in an outpatient setting. MAL cream (160 mg g⁻¹) was applied for 3 h prior to illumination with a light-emitting diode source (wavelength range 635 ± 18 nm; light dose 37 J cm⁻²). A second MAL-PDT session was given 7 days later. Complete response rate at 3 months after the last treatment, recurrence rate at the 24-month follow-up, and cosmetic outcome were recorded.
Results  The overall complete response rates were 73·2% at 3 months and 53·6% at 2 years. Clinical thickness, atypia and lesion depth were significant predictors of the response at 3 months when using a univariate analysis ( P  <   0·001). A multivariate logistic regression model, with robust variance estimation, showed that cell atypia was the only statistically significant independent predictor of the treatment outcome at 3 months.
Conclusions  MAL-PDT may represent a valuable, effective and well tolerated treatment option with good cosmetic outcome for superficial, well-differentiated (Broders' scores I and II) BD and microinvasive SCC. In contrast, its use for superficial SCCs with a microinvasive histological pattern and for nodular, invasive lesions, particularly if poorly differentiated keratinocytes are present (Broders' scores III and IV), should be avoided.     

E-钙黏素在鳞癌、Bowen病和脂溢性角化病中的表达

目的: 检测E-钙黏素(E-cadherin)在皮肤鳞状细胞癌(SCC)、Bowen病(BD)、脂溢性角化病(SK)中的表达.方法: 用免疫组化染色方法检测10例正常皮肤,20例SCC、20例BD、20例SK中E-钙黏素的表达.结果: E-钙黏素在SK表皮中的表达与正常表皮相似,在SCC中表达显著减弱或完全无表达,而在Bowen病表皮正常区域表达正常或下调.结论: E-钙黏素在恶性皮肤癌中表达异常,可能与表皮肿瘤的侵袭和转移有关.     

Spindle cell squamous cell carcinoma arising in Bowen's disease: Case report and review of the published work

A 79‐year‐old Japanese woman presented with an ulcerated, brown‐red nodule in the center of a sharply demarcated, tan‐brown plaque situated on the left side of her right breast. Histologically, the plaque demonstrated an acanthosis with an intraepidermal epithelioma of Borst‐Jadassohn. Small oval nests of bland‐appearing basophilic cells in the periphery gradually enlarged into nests of various sizes and irregular shapes, composed of densely cohesive, atypical basophilic cells above the central nodule. The atypical keratinocytes shifted to atypical spindle cells beneath the acanthotic epidermis, penetrating deep into the subcutaneous tissue. In addition to vimentin and p63, the spindle cells were positive for several cytokeratin (CK) markers, including AE1/AE3, 34βE12 and CK5/6, which showed more intense signals closer to the epidermis. Basophilic cells in the clonal nests were positive for p63, AE1/AE3, 34βE12 and CK5/6. The MIB‐1 index was estimated at approximately 40–50% in both the bland‐appearing and the atypical basophilic cells. We describe the first case of spindle cell squamous cell carcinoma arising in an intraepidermal epithelioma expressed by clonal Bowen's disease, which was difficult to differentiate from clonal seborrheic keratosis.     

Invasive squamous cell carcinoma arising in refractory perianal Bowen's disease in a HIV-positive individual

A 54-year-old HIV-positive homosexual man presented with erythematous and pigmented plaques on background erythema in the perianal region, histologically consistent with Bowen's disease. Perianal Bowen's disease represents high-grade anal intraepithelial neoplasia, which is considered a precursor lesion of invasive anal squamous cell carcinoma. This patient's anal intraepithelial neoplasia was unresponsive to multiple treatment modalities including cryotherapy, serial curettage and cautery, topical 5-fluorouracil and 5-aminolaevulinic acid photodynamic therapy. He progressed to develop a poorly differentiated squamous cell carcinoma of the anus three and a half years after the Bowen's disease was diagnosed. The squamous cell carcinoma was treated with combined chemoradiation. A recurrence of high-grade anal intraepithelial neoplasia was noted 6 months after completion of chemoradiation.     

Treatment of multiple lesions of Bowen's disease and squamous cell carcinoma with topical imiquimod

We observed complete clinical and histopathologic remission of papules, plaques and nodules in two patients with multiple lesions of Bowen's disease and squamous cell carcinoma. Our findings indicate that topical imiquimod is a potentially promising therapeutic approach for the local treatment of early forms of cutaneous neoplasia, such as Bowen's disease and squamous cell carcinoma because it is a non-invasive therapy with a good cosmetic outcome. It may therefore be worthy of consideration in a subgroup of patients who cannot have or do not wish to have surgery.     

银屑病素在光线性角化病、Bowen病及皮肤鳞状细胞癌组织中的表达及意义

目的 研究银屑病素在光线性角化病、Bowen病及皮肤鳞状细胞癌(鳞癌)中的表达.方法 用免疫组化的方法检测18例正常皮肤组织、20例光线性角化病、25例Bowen病、21例高分化皮肤鳞癌及16例低分化鳞癌皮损中银屑病素的表达.结果 银屑病素在正常皮肤组织中表达阳性率为11.1％.在光线性角化病中19例银屑病素表达于角质层至棘层上1～3层,胞质着色,阳性率为95.0％.在Bowen病中22例银屑病素表达于表皮全层角质形成细胞,胞质着色,空泡状细胞包膜及胞质着色,阳性率为88％.在高分化鳞癌中20例银屑病素表达于角质层至棘层全层,角化珠及角化不良细胞着色,阳性率为95.2％;在低分化鳞癌中13例银屑病素表达于角质层至棘层上1～5层,低分化的鳞状细胞不着色,阳性率为92.3％.与正常皮肤组相比,银屑病素在光线性角化病、Bowen病、高分化鳞癌和低分化鳞癌中的表达差异均有统计学意义(P＜0.01).银屑病素在光线性角化病、Bowen病、高分化鳞癌中表达强度逐渐升高,而在低分化鳞癌中表达强度降低,但仍高于正常皮肤组织(P＜0.05).结论 银屑病素在鳞状细胞分化异常的皮肤病中表达异常.     

p27及skp2在皮肤鳞状细胞癌和Bowen病中的表达

p27是新发现的细胞周期调控因子,S相激酶相关蛋白(skp2)参与p27的降解,我们采用免疫组化方法对皮肤鳞状细胞癌和Bowen病组织中的p27和skp2的表达进行检测.     

A case of epidermodysplasia verruciformis associated with squamous cell carcinoma and Bowen's disease: a therapeutic challenge

Epidermodysplasia verruciformis (EV) is a very rare and chronic disease characterized by a susceptibility to cutaneous infections by a group of phylogenetically related human papillomavirus (HPV) types. We present here a 52-year-old man previously diagnosed and treated as squamous cell carcinoma but also found to have epidermodysplasia verruciformis lesions in association with Bowen's disease. The patient was effectively treated with a combination of interferon therapy (6 million units, twice a week) and topical imiquimod for Bowen's disease (five times a week). We conclude that topical imiquimod is very effective in the treatment of Bowen's disease and may be combined with systemic interferon therapy in rare cases with multiple vivid presentations of HPV infections.     

Immunohistochemical characterization of cellular infiltrates in squamous cell carcinoma and Bowen's disease occurring in one patient.

We investigated populations of the infiltrating cells in Bowen's disease (BD) and squamous cell carcinoma (SCC), both of which arose in the same patient, using the Avidin-Biotin-peroxidase complex method with eight monoclonal antibodies. T lymphocytes were most predominant among infiltrating cells; NK cells, B cells, and monocytes were rarely seen in either BD or SCC. Analysis of subsets of the infiltrating T lymphocytes revealed that the number of suppressor/cytotoxic (s/c) T cells was twice that of helper/inducer (h/i) T cells in BD, while the number of s/c T cells was lower than that of h/i T cells in SCC. The immunohistochemical results in the present case differed from those of predominant infiltration of h/i T cells and of s/c T cells in three other reports of BD and SCC. These results suggest that the population of the cellular infiltrates may be modulated by the nature of tumors and by the immuno-competent state of the hosts.     

Raptor、Rictor和磷酸化Akt在日光性角化病、Bowen病及鳞状细胞癌中的表达

目的:检测Raptor、Rictor和磷酸化Akt(p-Akt)在日光性角化病、Bowen病和鳞状细胞癌中的表达。方法:采用免疫组化法检测Raptor、Rictor及p-Akt(Ser473)在20例正常皮肤、20例日光性角化病、20例Bowen病及40例鳞状细胞癌中的表达。结果:Raptor在鳞状细胞癌、Bowen病和日光性角化病中的阳性表达率分别为87.50%、70.00%和60.00%,均高于正常皮肤的25.00%(均P0.05);其中低分化鳞状细胞癌中Raptor的阳性表达率为100%,高于高分化鳞状细胞癌的阳性表达率75%(P0.05)。Rictor在鳞状细胞癌、Bowen病和日光性角化病中的阳性表达率分别为80.00%、70.00%及55.00%,均高于正常皮肤阳性表达率的20%(均P0.05);p-Akt(Ser473)在鳞状细胞癌、Bowen病和日光性角化病中的阳性表达率分别为77.50%、65.00%及50.00%,而正常皮肤阳性表达率为0。鳞状细胞癌、Bowen病和日光性角化病中Rictor的阳性表达水平和p-Akt(Ser473)的阳性表达水平均呈正相关(均P0.05)。结论:Raptor、Rictor和p-Akt(Ser473)的高表达可能与日光性角化病、Bowen病和鳞状细胞癌的发生发展有关。     

Altered distribution of 1-2B7B antigen in basal cell carcinoma, squamous cell carcinoma and Bowen's disease.

Skin lesions of basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and Bowen's disease were immunohistochemically examined using the 1-2B7B monoclonal antibody, which recognizes a 120 kDa polypeptide component found in hemidesmosomes of normal human epidermis and hemidesmosome-like adhesion junction of vascular endothelial cells, to disclose altered characteristics of the interface between the tumor cell aggregate and stromal tissues of the epidermal neoplasms. In BCC, 1-2B7B antigen was rarely expressed at the tumor cell aggregate-stromal tissue interface, where poorly developed hemidesmosometonofibril complexes and a normal-looking lamina densa were detectable. In SCC and Bowen's disease, 1-2B7B antigen was expressed not only along the interface of the tumor nest and stromal tissue, but also in the intercellular space of the desmosomes and other adhesion junction structures that lack associating tonofibrils. In the invading front of SCC, 1-2B7B antigen had partly disappeared from the tumor cell aggregate-stromal tissue interface, where neither hemidesmosomes nor lamina densa were noted. The altered distribution of this hemidesmosomal component in the epidermal neoplasms seems to reflect aberrant interaction of neoplasmic cells and surrounding stromal tissue.