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.     

Detection of human papilloma virus type 58 in a case of a perianal Bowen's disease coexistent with adult T-cell leukemia

A case of Bowen's disease (BD) that appeared in the perianal region of a 65-year-old Japanese woman coexistent with chronic adult T cell leukemia (ATL) is described. Histopathological findings revealed that irregularly arranged tumor cells with atypical nuclei throughout the epidermis, which itself disclosed hyperkeratosis, dyskeratotic cells, and clumping cells. Positive staining for HPV antigens was immunohistochemically seen in several nuclei of the tumor cells. Electron microscopic study of the tumor tissue disclosed virus particles of about 50 nm in diameter form the squamous cells. A positive band at 256 bp was obtained by PCR using HPV-L1 primer. The amplified DNA by L1 primer completely corresponded to that of HPV-58.     

Dermoscopic features of hidroacanthoma simplex: Usefulness in distinguishing it from Bowen's disease and seborrheic keratosis

Hidroacanthoma simplex (HAS) is a rare benign eccrine adnexal tumor. HAS is sometimes clinically or pathologically misdiagnosed as squamous cell carcinoma in situ (Bowen's disease; BD), seborrheic keratosis (SK) or other adnexal tumor. To date, there has never been a report focusing on dermoscopic features to distinguish HAS from BD and SK. We found the following dermoscopic findings to be characteristic of HAS: fine black dots/globules (75% of cases) and fine scales arranged annularly (100% of cases). In contrast, glomerular vessels, which are typically observed in BD, were not seen in any of the four cases. Cerebriform appearance and milia‐like cysts, which are typically observed in SK, were also not seen in any of the four cases. The existence of “scattered fine black dots/globules” and “fine scales arranged annularly”, and the absence of the glomerular vessels, may contribute to precise diagnosis of HAS. Even though HAS resembles BD or SK clinically, it can be distinguished from these by the characteristic dermoscopic features.     

Immunocryosurgery ‐ an effective combinational modality for Bowen's disease

Bowen's disease (BD) is widely treated with topical imiquimod or cryosurgery. The present single‐center retrospective study reports on the application of standardized immunocryosurgery (cryosurgery during ongoing topical imiquimod) for the treatment of BD. Daily imiquimod 5% cream was applied on BD lesion and a 5 mm rim around it in 5‐week treatment cycles; cryosurgery (liquid N₂, open spray; 2 cycles, 15 second each) was performed at the end of the second week of each treatment cycle. Between 1/1/2009 and 31/12/2014 21 patients (mean age ± SD: 74.4 ± 8.0 years; 12 males) with 24 lesions (mean maximum diameter ± SD: 45.8 ± 50.9 mm; range: 9–200 mm) completed the protocol. The anatomic distribution of the lesions included face/scalp (Ν = 14), neck/trunk (Ν = 6), and extremities (Ν = 4). Twenty‐one out of twenty‐four lesions with diameter <80 mm cleared after one immunocryosurgery cycle, while the rest three tumors (with the largest diameters: 100, 180, 200 mm) required two treatment cycles for complete response (clearance rate: 100%). After a median follow‐up of 24 months (range: 6–60 months) the overall effectiveness was 91.7%: 22/24 lesions remained in sustained complete remission. With the exception of a variable degree of hypopigmentation, the cosmetic outcome was satisfactory even for extensive lesions. Immunocryosurgery, is feasible and highly efficacious minimally‐invasive treatment alternative for BD.     

Ingenol mebutate gel for the treatment of Bowen's disease: a case report of three patients

We report three Bowen's disease (BD) cases treated with ingenol mebutate (IM), a novel topical chemotherapeutic agent approved for the treatment of actinic keratosis (AK) that is available in two doses: 0.015% and 0.05%. Three women diagnosed with BD exhibited a positive response after 2 or 3 day period of IM treatment, depending on lesion location. In the three cases, clinical resolution was observed 4 or 9 weeks posttreatment, and was confirmed with histopathology. Local skin reactions were common the first week after treatment but they resolved spontaneously. In our opinion these cases, along with another case reported in Germany, support the concept of commencing of clinical trials using IM on patients with BD.     

A case of Bowen's disease showing a clinical tendency toward spontaneous regression

We present a case of Bowen's disease showing a clinical tendency toward spontaneous regression. The patient, a healthy 86-year-old woman, complained that erythema had appeared on her left forearm two years earlier and had gradually enlarged. At the first examination, we observed a well-demarcated, 4 x 3 cm, erythematous plaque, partically covered with crusting and erosions near the wrist. Diagnosis of Bowen's disease was confirmed by a biopsy. Since the patient refused surgery and also discontinued hyperthermic treatment with disposable chemical pocket warmers after a brief trial, we decided to continue the observation of disease progression without any treatment. Two years after the initial visit, the lesion showed a clinical tendency toward spontaneous regression, with a fine erythematous plaque that showed the obscurely demarcated border of the lesion. After three years, although the patient exhibited a similar symptomatic improvement, a skin biopsy showed a few residual tumor cells. At the patient's request, we chose to observe the progress of the lesion. We review the literature of cases of Bowen's disease that have shown a similar tendency toward spontaneous regression, which have been rare.     

Cytokeratin 10-negative nested pattern enables sure distinction of clonal seborrheic keratosis from pagetoid Bowen's disease

Background: The histopathologic pattern of clonal seborrheic keratosis (SK) is quite similar to the nested pattern of pagetoid Bowen's disease [squamous cell carcinoma in situ (SCCIS)], and differentiation between the two can be challenging, especially when only small pieces are available for interpretation. Methods: Eleven examples of clonal SK and 13 examples of pagetoid SCCIS were examined histopathologically (tabulating necrotic keratinocytes, suprabasal mitoses, infiltrate, parakeratosis housing plump nuclei, crowding of nuclei) and immunohistochemically (using Ki‐67, bcl‐2, cytokeratin 7 and cytokeratin 10). Sensitivity, specificity, p‐values (Fisher's exact test, two‐tailed) and positive/negative likelihood ratios (+LR/?LR) were calculated. Results: Significant differences were seen with regard to crowding (p = 0.0009) and mitoses (p = 0.0006); however, only complete absence of necrotic keratinocytes or of crowding appeared to be diagnostically convincing for a diagnosis of clonal SK (?LR < 0.01). Significant differences were also seen with bcl‐2 (p = 0.0005) and cytokeratin 10 antibodies (p < 0.00001). Both markers displayed a typical nested pattern in clonal SK, nests being bcl‐2‐positive and cytokeratin 10‐negative. Cytokeratin 10‐negative nests were the most convincing criterion for differentiation between clonal SK and pagetoid SCCIS (+LR > 10, ?LR < 0.01). Conclusions: The most reliable marker to distinguish clonal SK from pagetoid SCCIS is cytokeratin 10 when it spares nests. Other criteria that assist in the differential diagnosis are bcl‐2 expression, absence of crowding and of mitoses. Böer‐Auer A, Jones M, Lyasnichaya OV. Cytokeratin 10‐negative nested pattern enables sure distinction of clonal seborrheic keratosis from pagetoid Bowen's disease.     

A case of multiple Bowen's disease with squamous cell carcinoma of the larynx and adenocarcionoma of the prostate

Bowen's disease, or cutaneous squamous cell carcinoma in situ, has been regarded as a cutaneous marker for internal malignancy. However, the relationship of Bowen's disease to visceral cancers remains controversial. We present a 76-year-old male with multiple lesions of Bowen's disease, who later developed laryngeal cancer and subsequent prostate cancer with distant metastases. Efforts to detect possible common etiologic agents including human papillomavirus and chronic arsenicism revealed no association between Bowen's disease and the internal malignancies. Despite the controversy, we suggest that a conservative cancer workup is ethically indicated in patients with multiple Bowen's disease.     

Identification of a human papillomavirus type 58 lineage in multiple Bowen's disease on the fingers: Case report and published work review

Human papillomavirus (HPV) has been detected in some cases of Bowen's disease, particularly on the fingers and genitalia. HPV‐58 is classified as a high‐risk mucosal type and accounts for a high percentage of cervical cancer in Asia. Moreover, several HPV‐58 lineages, including sublineage A1, have a high prevalence in Asia. However, the nature of HPV‐58‐associated skin cancer is still unknown. Here, we report a case of a Japanese patient with multiple Bowen's disease on the fingers. A 33‐year‐old man presented with multiple reddish‐brown scaly plaques on his left middle finger and right ring finger. All lesions were surgically excised, and the diagnosis of Bowen's disease was made. We performed Sanger sequencing using DNA extracted from paraffin‐embedded samples and identified HPV‐58 sublineage A1. Additionally, we review previous reports on HPV‐58‐associated skin cancers, including our case, showing a high regional prevalence in Asia. Further studies would be needed to reveal the relationship between HPV‐58 lineages and carcinogenesis in the skin.     

Human papillomavirus associated with Bowen's disease of the finger

We report here a case of Bowen's disease that developed in the periungual area of the left ring finger of a 55-year-old Japanese male. Because the histology of the lesion mimicked in part the features of a common wart, a PCR-based analysis of human papillomavirus (HPV) DNA and sequencing of viral DNA of PCR-amplified fragments were performed. The lesion contained HPV11 and 16 DNA, and HPV was suspected to play a role in the development of the lesion.     

In‐transit recurrence of Merkel cell carcinoma associated with Bowen's disease: The first reported case successfully treated by avelumab

A 65‐year‐old Japanese man presented with a dome‐shaped nodule, the base of which was contiguous with a dull brown plaque, on the left leg. After local excision of the cutaneous lesion and left inguinal lymph node dissection, several dermal and subcutaneous nodules developed successively on the left lower extremity. Hematoxylin–eosin staining of the primary cutaneous lesion demonstrated uniform neoplastic cells arranged in a trabecular pattern extending from the dermis to subcutis. Mitotic figures were abundant. Although the overlying epidermis was substantially intact, the Merkel cells had invaded the epidermis, resulting in Pautrier‐like microabscesses. The hyperplastic epidermis adjacent to the nodule consisted of abnormally growing atypical keratinocytes. The enlarged left inguinal lymph node and successive secondary nodules contained Merkel cells similar to those in the primary nodule. Immunohistochemically, most tumor cells were positive for CAM5.2, synaptophysin, chromogranin A, CD56 and vimentin. The tumor cells in the left inguinal lymph node were positive for CAM5.2, synaptophysin and cytokeratin 20 but negative for CM2B4, and less than 1% of the cells expressed programmed cell death ligand 1. The patient was treated with avelumab, which showed significant efficacy against the in‐transit recurrence. Two months later, all nodules had disappeared completely. We describe a case of in‐transit recurrence of Merkel cell carcinoma that was associated histologically with Bowen's disease and was successfully treated with avelumab. Although accumulation of additional cases is needed, avelumab therapy may be a useful treatment for in‐transit recurrence of Merkel cell carcinoma.     

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.     

Treatment of giant Bowen's disease with sequential use of photodynamic therapy and imiquimod cream

We present a 79-year-old man with a 2-year history of Bowen's disease. The 10 × 10 plaque was located on the right frontotemporal area. The patient was treated with two photodynamic therapy (PDT) sessions, performed 1 week apart, followed by five times per week application of imiquimod 5% cream for 6 consecutive weeks. Complete clinical and histological response was achieved 3 months after treatment was completed. The patient remains recurrence free 12 months after treatment. Cosmetic outcome was evaluated as fair because of residual erythema. Long-term follow-up is mandatory for assessment of recurrences. Further studies are needed in order to confirm the improved outcome using the combination of PDT and imiquimod cream.     

Efficacy of Imiquimod 3.75% for the treatment of extensive Bowen's disease of the face in an elderly patient

Bowen's disease is a cutaneous squamous cell carcinoma (SCC) in situ with a potential risk of progression to invasive SCC. Despite the high number of approved treatments, elderly patients with extensive lesions of critical sites may represent a therapeutical challenge, especially in cases of treatment failure or recalcitrant disease. Here, we report the successfully use of topical Imiquimod 3.75% to treat an extensive Bowen's disease of the cheek in an elderly.     

A cardiac allograft recipient with Bowen's disease on a finger and concurrent perianal bowenoid papulosis

We report a patient who developed Bowen's disease of the finger and bowenoid papulosis of the perianal area after cardiac transplantation. Human papillomavirus (HPV) type 16 only, not any skin-related or epidermodysplasia verruciformis-related types, was detected in both lesions by in situ hybridization and polymerase chain reaction. The same virus type was identified in both the tumor of the finger and the perianal area, which suggests contact transmission. HPV 16 has often been associated with malignant changes and may be at least one source of the malignancies that are more common in immunosuppressed patients. The presence of a potentially oncogenic type of the HPV in an immunosuppressed patient highlights the importance of regular follow-up of such patients.     

Bowen's Disease: Statistical Study of a 10 Year Period

According to histological records, a total of 74 patients were diagnosed with Bowen's disease (B.d.) between 1 January 1984 and 31 December 1993 at the Department of Dermatology of Kitasato University. There was slight female predominance (36 ♂, 38 ♀), and 73% of the patients were older than 60 years; the mean age was 66.8 years. Fifteen patients had multiple (two-five) lesions. In 13 patients, other benign skin lesions were also found. Arsenic exposure as etiologic factor could have been present in 2 cases. Only 3 patients had other associated malignant tumors, which does not confirm the paraneoplastic nature of B.d. One-fifth of the lesions were on sun-exposed areas (head, neck and hands). Although we excluded invasive carcinomas from our statistical study, we mention the 8 invasive carcinomas developing from B.d. in that period. Histopathological classification of B.d. is uncommon. Classifying our cases by Darier's histopathological classification, 63.3% of them belonged to the lenticular type. The malignant potential of different histopathological types of B.d. needs further investigation.     

Arsenic keratosis and pigmentation accompanied by multiple Bowen's disease and genitourinary cancer in a psoriasis patient

We report a case of arsenic keratosis and pigmentation accompained by multiple Bowen's disease and genitourinary cancer in a 64-year-old man. He was a psoriasis patient with a history of herbal medication for about thirty years. He showed multiple hyperkeratotic plaques on the bilateral palms, soles, and multiple, brownish, scaly, elevated papules on the back in addition to diffuse hyperpigmentation. Biopsy confirmed arsenic keratosis and Bowen's disease. Transitional cell carcinoma was also detected on his ureter and bladder during follow-up. The skin lesions were treated with topical 5-fluorouracil, etretinate, and excision with improvement.