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.     

Bowen's diseases and basal cell carcinomas in a patient.

Bowen's disease is a well-known precancerous lesion, in which invasive squamous carcinoma may develop. However, it is rare that Bowen's disease, basal cell carcinoma, and internal malignancy develop in a single patient. We report a case of a 54-year-old male patient with Bowen's disease, basal cell carcinoma of the skin, and squamous cell carcinoma of the lung. Multiple scaly erythematous patches had developed several years earlier and were diagnosed as Bowen's disease by skin biopsy. The number of lesions increased and, five months ago, a right lower lobectomy was done for squamous cell carcinoma which was detected on a chest X-ray. Skin biopsies of two different sites revealed Bowen's disease and basal cell carcinoma. The arsenic level was increased in his hair specimen. Cryotherapy was applied.     

Invasive squamous cell carcinoma after treatment of carcinoma in situ with 5% imiquimod cream

Squamous cell carcinoma in situ has the potential to progress to invasive squamous cell carcinoma. This report presents two cases of punch biopsy-proven squamous cell carcinoma in situ, treated with once-daily application of 5% imiquimod cream for 6 weeks. Both patients developed moderate local inflammatory reactions during treatment. The first patient demonstrated clinical clearance of the scalp lesion after treatment. Two months later, he re-presented with a subcutaneous nodule at the same site. Histology was consistent with recurrent squamous cell carcinoma. Five months following excision of the recurrent tumour, he presented with metastatic squamous cell carcinoma to a cervical lymph node. The second patient had low-grade chronic lymphocytic leukaemia and presented with squamous cell carcinoma in situ of the leg that failed to clear clinically after treatment with imiquimod. He presented 4 months later with a focus of invasive squamous cell carcinoma within the lesion.     

Epidermotropic metastases from squamous cell carcinoma of the lower female genital tract mimicking primary Bowen's carcinoma

Epidermotropic metastases from internal malignancies are exceedingly rare. We report a striking example of epidermotropic metastatic carcinoma of the lower female genital tract to the skin of the abdomen and groin. Atypical cells were scattered throughout the epidermis, mimicking Bowen's disease. Focally, islands of atypical squamous cells were also found in the adjacent dermis. Histopathologically, the lesion resembled a primary invasive squamous cell carcinoma. However, the clinical history of a metastatic carcinoma of the genitalia and the clinical presentation with multiple lesions militated against a primary squamous cell carcinoma and favored interpretation of the lesions as epidermotropic metastases.     

鲍温病继发鳞状细胞癌一例

患者，女，71岁。左背部皮肤增生物5年，表面丘疹半年。疣状物和红斑处的皮肤镜分别提示鲍温病和鳞癌表现，结合组织病理诊断鲍温病继发高分化鳞状细胞癌。手术切除，随访1年无复发。     

鲍温病及鳞状细胞癌转移1例

报告1例砷中毒男性患者，56岁，因白血病曾服用含砷剂中药。初发手指疣状增生，以后左肋部、手掌见角化性斑疹、丘疹。组织病理提示左手指鳞状细胞癌、肋部、手掌鲍温病。治疗：手术切除并放疗，半年后复发，左前臂皮肤出现结节并淋巴结转移。     

Immunohistological analysis of P53 expression in human skin tumors.

The p53 expression in various skin tumors was immunohistologically evaluated using two mouse monoclonal anti-p53 antibodies, PAb421 and PAb1801. The p53 expression was not detected in the normal epidermal cells. Nuclear staining suggested that the p53 expression was observed in 10 of 26 squamous cell carcinomas (SCCs) from 24 patients, in one undifferentiated carcinoma, one proliferating trichilemmal cyst, one malignant proliferating trichilemmal tumor and in one metastatic carcinoma of breast cancer. None off four cases of Bowen's disease (SCC in situ) showed nuclear staining. In the SCCs, five of 20 primary lesions, three of four recurrent lesions and both of two metastatic lesions had positive nuclei. There was one case of SCC in which a primary lesion was negative but a recurrent lesion was positive. Thus, p53 expression was more frequently observed in SCCs at more clinically advanced stages. This may suggest that p53 has some relevance to progression of SCC. Nuclear staining was not detected in any of the following cases: two cases of seborrheic keratosis, one eccrine poroma, one keratoacanthoma, 11 basal cell epitheliomas, two mammary Paget's disease, three genital Paget's disease, one sebaceous carcinoma, four malignant melanomas, six lymphomas, two leukemia cutis and two angiosarcomas.     

Expression of moesin and its associated molecule CD44 in epithelial skin tumors

Moesin, one of the ERM (ezrin; radixin; moesin) family members, is directly associated with the cytoplasmic domain of CD44, which is now thought to be related to the metastatic potential of tumor cells. Using immunohistochemistry we investigated the expression of moesin in normal epidermis and various kinds of epithelial skin tumors: squamous cell carcinoma, verrucous carcinoma, Bowen's disease, solar keratosis, keratoacanthoma, basal cell carcinoma, and extramammary Paget's disease. Normal skin showed positive epidermal staining for moesin with the exception of the stratum corneum. The expression of moesin varied with the type of skin tumor. In basal cell carcinoma, Bowen's disease, and extramammary Paget's disease, moesin expression was either faint or negative. In contrast to Bowen's disease, invasive squamous cell carcinoma showed more intense and heterogeneous staining of the cytoplasm and the cell membrane. Verrucous carcinoma was weakly positive, with a tendency for the moesin to be distributed in the cell membrane. The staining pattern of moesin varied among the different kinds of epithelial skin tumors, and its expression was generally similar to that of the standard form of CD44. These results suggest that moesin is closely inter-related with CD44 in epithelial skin cells as seen in other cellular systems, and that the variable pattern of moesin staining among the skin tumor cells could reflect expression disorders associated with the transformation.     

Hyperthermic treatment of Bowen's disease with disposable chemical pocket warmers: a report of 8 cases

Bowen's disease is a form of squamous cell carcinoma in situ, in which local hyperthermia may be efficacious. We studied 8 patients with Bowen's disease to ascertain whether hyperthermia can be effective against it. As a heat source, disposable chemical pocket warmers were applied daily with pressure directly to the lesion site while the patient was awake, and the clinical course was observed for 4 to 5 months. The lesion was then excised and examined to determine the histopathologic effects. The results showed efficacy in 6 cases, in which the nodular and invasive lesions and the erythematous patches abated; then the lesions disappeared, leaving deposits of pigment (complete remission). In one case, the signs improved by at least 50% (partial remission); in the other case, there was only slight palliation (no response). As for the posttreatment histopathologic effects, tumor cells were eliminated in 3 cases, isolated tumor cells were seen in 3 cases, and there was no change in 2. Although the treatment did not yield perfect results, it represents a major improvement of hyperthermic therapy and is one effective method of treating Bowen's disease.     

E-cadherin expression in skin tumors using an AMeX immunohistostaining method

The AMeX (acetone-methylbenzoate-xylene) method results in good preservation of tissue and morphological details, almost equivalent to that of routinely processed formalin-fixed and paraffin-embedded tissue specimens, and of antigenicity equivalent to that of fresh frozen tissue specimens. It has been reported that the expression of the cell-cell adhesion molecule E-cadherin is often decreased in some types of carcinomas. A decrease in E-cadherin expression is associated with the invasive or metastatic potential of tumor cells. We immunohistochemically examined the expression of E-cadherin with anti-E-cadherin monoclonal antibody in various skin tumors (25 basal cell carcinomas, 11 squamous cell carcinomas, 9 keratoacanthomas, and 11 Bowen's disease) using the AMeX method and found that this method preserved antigenicity well without pretreatment. E-cadherin expression was decreased in 18.2% of squamous cell carcinomas and 33.3% of keratoacanthomas. On the other hand, it was preserved in almost all Bowen's disease and basal cell carcinomas. From the results of our study, we suggest that Bowen's disease and basal cell carcinoma do not have much metastatic potential due to retention of high levels of E-cadherin expression. We hope to apply the AMeX method to other immunohistochemical examinations because this is a very useful staining method.     

A Case of Double Cancer: A Squamous Cell Carcinoma Arising from a Long Pierced Site on the Left Earlobe and a Solid Tubular Carcinoma of the Left Breast

A 43-year-old woman presented with a well differentiated squamous cell carcinoma of the left earlobe where a small hole for pierced type earrings had been made about 20 years earlier. A year after the removal of the tumor, a metastasis of a moderately differentiated squamous cell carcinoma to the left cervical lymph nodes was detected. A month later, a solid tubular carcinoma of the left breast was found. A modified radical neck dissection and a quadrantectomy with an axillary lymph node dissection were performed. A total of 5 courses of peplomycine-mitomycine combinated therapy with 26 Gy of radiotherapy was administered for the cervical lesion. A month of postoperative chemotherapy with tegafur-uracil and medroxyprogesterone acetate and a total of 56 Gy of radiotherapy to the mammary lesion were added. She has been well without recurrence for about a year after the operations. This case is not only a rare double cancer, a combination of a squamous cell carcinoma and a solid tubular carcinoma, but may also be the first case of a squamous cell carcinoma arising at a long pierced site on an earlobe for pierced type earrings.     

Occurrence of Langerhans cells and expression of class II antigens on keratinocytes in malignant and benign epithelial tumors of the skin: an immunohistopathologic study with monoclonal antibodies

We used an avidin-biotin complex immunoperoxidase technique with various monoclonal antibodies to determine Langerhans cell densities, class II antigen expression on keratinocytes, and phenotypes of other infiltrating cells in several malignant and benign epithelial tumors of the skin. Our observations indicate (1) there are few Langerhans cells in nests of basal cell carcinoma and squamous cell carcinoma; (2) there are increased Langerhans cell densities in seborrheic keratoses, verrucous epidermal nevus, and Bowen's disease; (3) there is an expression of class II molecules on the keratinocytes and cancer cells of basal cell carcinoma, squamous cell carcinoma, Bowen's disease, seborrheic keratosis, and verrucous epidermal nevus; and (4) there is a netlike staining of the keratinocyte surface with OKM5 in the epidermal lesion of seborrheic keratosis, verrucous epidermal nevus, and Bowen's disease, as well as in the epidermis adjacent to the basal cell carcinoma and squamous cell carcinoma nests.     

Treatment of Bowen's disease of the digit with carbon dioxide laser

BACKGROUND: Therapy for Bowen's disease is essential to prevent invasive squamous cell carcinoma and metastases. Surgical excision is preferred because of the low relapse rate, but it may result in scar contracture, especially in the digit. OBJECTIVE: This study was undertaken to evaluate the effectiveness of carbon dioxide laser for Bowen's disease of the digit. METHODS: Patients with biopsy-proven Bowen's disease of the digits were recruited from the Department of Dermatology, Siriraj Hospital during the period 1992-1998. Risk factors were assessed. The lesion and 4 mm of surrounding clinically uninvolved skin were vaporized by means of the carbon dioxide laser. Wounds were managed by second intention. Patients were followed up at 1 week, 4 weeks, 6 months, and yearly thereafter if applicable. RESULTS: During this 7-year period, only 6 patients with Bowen's disease of the digits were identified. Four of the 6 had a long history of exposure to arsenic from herbal medicines. Postoperative clinical appearance was mild atrophic skin and hypopigmentation. No functional impairment was found. Biopsy specimens taken after treatment showed a slightly thinned epidermis and mild fibrosis in the papillary dermis. There has been no evidence of recurrence in the 6 months to 7.7 years since surgery. CONCLUSION: At least 67% of the patients affected by Bowen's disease of the digits had chronic arsenicism. It may be the earliest presentation of chronic arsenicism. Carbon dioxide laser provides ease of surgery, excellent cosmesis, preservation of function, and effective treatment for patients with Bowen's disease of the digits.     

Cutaneous squamous cell carcinoma: a comprehensive clinicopathologic classification--part two

Cutaneous squamous cell carcinoma (SCC) includes many subtypes with widely varying clinical behaviors, ranging from indolent to aggressive tumors with significant metastatic potential. However, the tendency for pathologists and clinicians alike is to refer to all squamoid neoplasms as generic SCC. No definitive, comprehensive clinicopathological system dividing cutaneous SCCs into categories based upon their aggressiveness has yet been promulgated. Therefore, we have proposed the following based upon the malignant potential of SCC variants, separating them into categories of low (< or = 2% metastatic rate), intermediate (3-10%), high (greater than 10%), and indeterminate behavior. Low-risk SCCs include SCC arising in actinic keratosis, HPV-associated SCC, tricholemmal carcinoma, and spindle cell SCC (unassociated with radiation). Intermediate-risk SCCs include adenoid (acantholytic) SCC, intraepidermal epithelioma with invasion, and lymphoepithelioma-like carcinoma of the skin. High-risk subtypes include de novo SCC, SCC arising in association with predisposing factors (radiation, burn scars, and immunosuppression), invasive Bowen's disease, adenosquamous carcinoma, and malignant proliferating pilar tumors. The indeterminate category includes signet ring cell SCC, follicular SCC, papillary SCC, SCC arising in adnexal cysts, squamoid eccrine ductal carcinoma, and clear-cell SCC. Subclassification of SCC into these risk-based categories, along with enumeration of other factors including tumor size, differentiation, depth of invasion, and perineural invasion will provide prognostically relevant information and facilitate the most optimal treatment for patients.     

Cutaneous squamous cell carcinoma: a comprehensive clinicopathologic classification. Part one

Cutaneous squamous cell carcinoma (SCC) includes many subtypes with widely varying clinical behaviors, ranging from indolent to aggressive tumors with significant metastatic potential. However, the tendency for pathologists and clinicians alike is to refer to all squamoid neoplasms as generic SCC. No definitive, comprehensive clinicopathological system dividing cutaneous SCCs into categories based upon their aggressiveness has yet been promulgated. Therefore, we have proposed the following based upon the malignant potential of SCC variants, separating them into categories of low (< or = 2% metastatic rate), intermediate (3-10%), high (greater than 10%), and indeterminate behavior. Low-risk SCCs include SCC arising in actinic keratosis, HPV-associated SCC, tricholemmal carcinoma, and spindle cell SCC (unassociated with radiation). Intermediate-risk SCCs include adenoid (acantholytic) SCC, intraepidermal epithelioma with invasion, and lymphoepithelioma-like carcinoma of the skin. High-risk subtypes include de novo SCC, SCC arising in association with predisposing factors (radiation, burn scars, and immunosuppression), invasive Bowen's disease, adenosquamous carcinoma, and malignant proliferating pilar tumors. The indeterminate category includes signet ring cell SCC, follicular SCC, papillary SCC, SCC arising in adnexal cysts, squamoid eccrine ductal carcinoma, and clear-cell SCC. Subclassification of SCC into these risk-based categories, along with enumeration of other factors including tumor size, differentiation, depth of invasion, and perineural invasion will provide prognostically relevant information and facilitate the most optimal treatment for patients.     

Spontaneous regression of recurrent and metastatic Merkel cell carcinoma

Merkel cell carcinoma (MCC) is a malignant neuroendocrine tumor with a high rate of recurrence and metastasis. Despite its high degree of malignancy, spontaneous regression has been documented. We report an 87-year-old woman who presented with recurrent MCC on her left cheek and regional lymph node metastasis. Although she received no treatment due to her poor condition, the recurrent metastatic lesion regressed spontaneously within 2 months.     

Bowenoid epidermotropic metastatic squamous cell carcinoma

Epidermotropic metastatic squamous cell carcinoma produced full-thickness cellular atypia of bowenoid carcinoma in situ or vulvar intraepithelial neoplasia, grade 3 (VIN 3), in a 73-year-old woman who had past history of uterine cervical carcinoma. The presence of intravascular tumor cell nests and areas showing smooth continuity of the malignant squamous cell nodules with the adjoining benign epidermis supported the possibility of the epidermotropic metastasis. To our knowledge, metastatic epidermotropic squamous carcinoma clinicopathologically simulating primary Bowen's disease has not been reported.     

Trichilemmal tumor arising in a seborrheic keratosis: analysis of cell kinetics by BrdU staining.

We report a case of a 74-year-old male with a trichilemmal tumor arising in a seborrheic keratosis on the buttock and the results of a cell kinetic study of this tumor using a BrdU staining method. The incidence of trichilemmal tumor arising in a seborrheic keratosis seems to be extremely rare. The labeling index of this tumor was 12.0%; this was a level intermediate between normal epidermis and a variety of hyperproliferative skin diseases such as squamous cell carcinoma, Bowen's disease, and psoriasis vulgaris. DNA replicating cells were present in the germinative layers in normal epidermis and the benign hyperproliferative skin diseases, psoriasis vulgaris. In contrast, DNA replicating cells were found throughout the entire epidermis in premalignant and malignant tumors such as in Bowen's disease and squamous cell carcinoma. In this case, DNA replicating cells were localized mainly in the basal and parabasal cell layers, but also seen in the upper squamous layers. These findings suggest that this trichilemmal tumor had a malignant tendency, though it was slow-growing and relatively benign in nature.     

Proton radiotherapy of skin carcinomas

Summary At the Proton Medical Research Center, University of Tsukuba, we performed a pilot study of protonbeam radiotherapy in 12 patients with the following types of carcinoma: Bowen's disease (4), oral verrucous carcinoma (5), and squamous cell carcinoma (3). They received total doses of 51–99.2 Gy in fractions of 2–12.5 Gy. All of the tumours responded well to the treatment. All four lesions of Bowen's disease, three of the five oral verrucous carcinomas, and the three squamous cell carcinomas completely regressed following irradiation. Two squamous cell carcinomas recurred during the followup period. One recurrent squamous cell carcinoma was successfully treated by a salvage surgical operation, and in the other case the patient refused further therapy. In two verrucous carcinomas there was 90% regression of tumour volume. No severe radiation-related complication occurred. As proton radiotherapy produces good local tumour control without significant morbidity to the surrounding normal tissues, it may prove to be a useful therapeutic modality for the treatment of skin carcinomas.     

尖锐湿疣、鲍恩样丘疹病、Bowen病及外阴鳞状细胞癌皮损中端粒酶的表达

目的 探讨端粒酶在正常组织、良性增殖性疾病及恶性肿瘤中的表达情况及其临床意义。方法 采用免疫组化方法检测皮损中端粒酶逆转录酶(hTERT)蛋白的表达情况,并对所有鲍恩样丘疹病和Bowen病病例进行组织病理分析。结果 正常人对照组、尖锐湿疣组及外阴鳞状细胞癌组中任两组间hTERT表达强度差异均有统计学意义,其阳性率依次增高。鲍恩样丘疹病组较尖锐湿疣组hTERT表达强度高,两组差异有统计学意义;虽与Bowen病组比较差异无统计学意义,但较外阴鳞状细胞癌组表达强度低,差异有统计学意义。组织病理上,Bowen病比鲍恩样丘疹病细胞异形性更明显。结论 端粒酶在正常组织、良性增殖性疾病及恶性肿瘤中的表达强度呈梯度升高,提示端粒酶激活在细胞增生及永生化中均发挥重要作用。