Surgical excision versus topical 5% 5-fluorouracil and photodynamic therapy in treatment of Bowen's disease: A multicenter randomized controlled trial.

BACKGROUND: Randomized controlled trials comparing the effectiveness of 5-fluorouracil cream, methylaminolevulinate photodynamic therapy (MAL-PDT) and surgical excision in patients with Bowen's disease are lacking. METHODS: In this multicenter noninferiority trial, patients with a histologically proven Bowen's disease of 4-40 mm were randomly assigned to excision with 5 mm margin, 5% 5-fluorouracil cream twice daily for 4 weeks, or 2 sessions of MAL-PDT with 1 week interval. The primary outcome was the proportion of patients with sustained clearance at 12 months after treatment. A noninferiority margin of 22% was used. RESULTS: Between May 2019 and January 2021, 250 patients were randomized. The proportion of patients with sustained clearance was 97.4% (75/77) after excision, 85.7% (66/77) after 5-fluorouracil, and 82.1% (64/78) after MAL-PDT. Absolute differences were -11.7% (95% CI -18.9 to -4.5; P = .0049) for 5-fluorouracil versus excision and -15.4% (95% CI -23.1 to -7.6; P = .00078) for MAL-PDT versus excision. Both noninvasive treatments significantly more often led to good or excellent cosmetic outcome. CONCLUSIONS: Based on our predefined noninferiority margin of 22%, 5-fluorourcail is noninferior to excision and associated with better cosmetic outcome. For MAL-PDT noninferiority to excision cannot be concluded. Therefore, 5-fluorouracil should be preferred over excision and MAL-PDT in treatment of Bowen's disease.

Immunocryosurgery is a safe and feasible treatment for basal cell carcinoma and Bowen disease in renal transplant recipients.

Keratinocyte skin carcinomas (squamous cell carcinoma, basal cell carcinoma [BCC], Bowen disease [BD]) inflict significant morbidity and constitute a treatment challenge in renal transplant recipients (RTR). Immunocryosurgery has shown efficacy >95% in the treatment of BCC and BD in immunocompetent patients. The present study evaluated the safety, feasibility and efficacy, of immunocryosurgery in the treatment of BCC and BD in a series of RTR. During a 3-year period, biopsy-confirmed cases of BCC and BD were treated with a standard immunocryosurgery cycle (5 weeks daily imiquimod and a session of cryosurgery at day 14). Safety was evaluated by comparing graft function markers between immunocryosurgery treated RTR patients and matched controls. Ten BCC (8 nodular, 1 basosquamous, 1 superficial; diameter 6-14 mm; mean 9.2 mm) and nine BD disease lesions in nine patients (7 men, 2 women; age range: 54-70 years, mean: 62.1 years) were treated with immunocryosurgery and followed-up for two to 5 years. Five BCC were located on the "H area" of the face. No patient showed clinical or laboratory signs of transplant dysfunction during treatment or follow-up. Seven out of 10 BCC lesions cleared completely after one 5-week immunocryosurgery cycle, two cleared after repeat and intensified treatment cycles and one responded only partially (clearance rate: 90%). Seven out of nine BD lesions cleared after one 5-week immunocryosurgery cycle and one lesion after two cycles (clearance rate: 88.9%). In conclusion, immunocryosurgery is a safe, feasible and effective minimally invasive treatment alternative to standard surgical modalities for BCC and BD in RTR.

Bowen disease with matrical differentiation: Report of an exceptional histopathologic presentation.

Matrical differentiation is the distinctive feature of pilomatricoma and other purely matrical adnexal neoplasms; additionally, foci of matrical differentiation have been also described in hybrid cysts of Gardner syndrome, as well as in a wide variety of benign and malignant cutaneous tumors, including basal cell carcinoma. We report an exceptional case of Bowen disease exhibiting multiple foci of matrical differentiation, as confirmed by means of immunohistochemical studies. Several types of divergent, non-squamous differentiation have been exceptionally reported in cutaneous squamous cell carcinoma in situ (cSCCIS), including sebaceous, mucinous/glandular, poroid, tricholemmal, and neuroendocrine differentiation; matrical differentiation may be added to this list. Our findings further emphasize the undifferentiated nature of neoplastic cells in cSCCIS.

Triple collision tumor comprising Merkel cell carcinoma with an unusual immunophenotype, squamous cell carcinoma in situ, and basal cell carcinoma.

Merkel cell carcinoma (MCC) is a rare, aggressive primary cutaneous neuroendocrine cancer which almost always exhibits the cytokeratin (CK)20+/thyroid transcription factor (TTF)-1- immunophenotype. MCC may occur concurrently with squamous cell carcinoma, Bowen disease, and/or basal cell carcinoma (BCC), with some evidence that MCCs which occur in conjunction with other neoplasms exhibit different immunophenotypes compared to pure MCC cases. We present a case of CK20-/TTF-1+ MCC concurrent with Bowen disease and BCC, and discuss possible differences in the pathogenesis of pure vs combined MCC. We also review the literature for this unusual immunophenotype, noting that most cases occur in combined MCC.

A rare case of Bowen's disease of the nipple: Literature review and management pathway.

INTRODUCTION: Bowen's disease or squamous cell carcinoma in situ is a precursor malignant neoplasm restricted to the epidermis. Clinically and histologically, Bowen's disease of the nipple can resemble Paget's disease. It is crucial to differentiate between the two with immunohistological staining in order to provide the appropriate treatment. This review of Bowen's disease of the nipple will examine the diagnostic and treatment modalities previously used. We also present our own case of Bowen's disease of the nipple and propose a clinical pathway for this rare disease process. METHODS: A review of published literature using MEDLINE, PubMed, and Google Scholar revealed seven articles were identified with a total of eight cases of Bowen's disease of the nipple. RESULTS: Treatment modalities varied within the literature. This ranged from photodynamic therapy to simple mastectomy and sentinel lymph node biopsy. Standard surgical margins are inadequate for Bowen's disease of the nipple, as it has been shown to spread along the lactiferous ducts. Our case is of a 57-year-old female with Bowen's disease of her right nipple, confirmed through immunohistological staining. Wide local excision with immediate full-thickness skin graft reconstruction was performed and is now disease-free with a healed graft. CONCLUSION: There is no accepted management pathway for Bowen's disease of the nipple. We propose a treatment algorithm that involves immunohistological staining to diagnose Bowen's disease of the nipple. This would then be followed by a wide local excision, complete nipple excision including underlying lactiferous ducts and glandular tissue and subsequent reconstruction.

The application of keystone flap combined with vacuum-assisted closure in the repair of sacrococcygeal skin defect after tumor resection.

OBJECTIVE: We aimed to explore the efficacy of keystone flap combined with vacuum-assisted closure (VAC) in the repair of sacrococcygeal wounds. METHODS: This study is a retrospective review of patients undergoing keystone flap reconstruction between January 2014 and January 2018. A standardized data collection template was used to collect related variables. The detailed process of the reconstructive surgery is carefully described in this study. The postoperative healing process was closely observed. RESULTS: Twelve patients underwent keystone flap repair between January 2014 and January 2018. The average wound size before closure measured 7.83 ± 1.93 × 5.28 ± 0.91 cm. All the patients achieved primary wound healing and the flaps survived during the follow-up period, which ranged from 1 to 24 months. No severe complications and obvious scar appeared, and the patients were satisfied with both appearance and function. CONCLUSIONS: The application of keystone flap combined with VAC is a promising way to repair wounds in the sacrococcygeal region with little postoperative complication and similar soft-tissue thickness to the surrounding tissue.

Medial canthal defects following tumour excision: To reconstruct or not to reconstruct?

Laissez-faire following excision of peri-ocular tumours has been described, but is not universally well established. We describe our experience with laissez-faire for managing medial canthal defects following tumour excision and compare our outcomes with full thickness skin grafts. Retrospective comparative case series of 68 patients who underwent reconstruction of a medial canthal defect using laissez-faire with sutured Sorbsan (LFS) (n = 36) or a full thickness skin graft (FTSG) (n = 32) at the same centre. Tumour diagnosis, defect size, time taken to epithelialise, functional and cosmetic outcomes, complications, follow-up duration and any secondary interventions were recorded. Basal call carcinoma was the most common neoplasm excised (63/68, 93%). Defect size ranged from 7 × 5 mm to 25 × 10 mm. Mean time for wound epithelialisation in LFS group was 33 days. Mean duration of follow-up was 32 months (range 1-80 months) for LFS and 30 months (range 6-60 months) for FTSG. Good functional and cosmetic outcomes were achieved in all 68 patients. Review of clinical photographs showed epicanthic fold in 2 patients and visible scar in 1 patient in the LFS group and 3 cases of hypopigmented scar and 7 hypertrophic scars in the FTSG group. No cases required secondary intervention. There were no cases of postoperative infection. LFS in the medial canthal region is less likely to lead to hypertrophic scarring or cicatricial sequelae compared to FTSG (p = 0.02). Both techniques are associated with excellent functional and aesthetic outcomes even for larger defects.

Targeted ablation of perianal high-grade dysplasia in men who have sex with men: an alternative to mapping and wide local excision.

BACKGROUND: Perianal high-grade dysplasia (Bowen disease) is traditionally treated with mapping and wide excision with possible grafting rather than local ablation. OBJECTIVE: The aim of this study is to examine the results of high-grade perianal dysplasia ablation. DATA SOURCES: Data for this study were derived from a retrospective chart review at a surgical practice screening and treating patients for high-grade dysplasia between July 1998 and June 2013. STUDY SELECTION: The patients included were men who have sex with men and are undergoing perianal dysplasia ablation. INTERVENTION: Ablation of perianal dysplasia with electrocautery, laser, or infrared coagulation was performed. MAIN OUTCOME MEASURES: The primary outcomes measured were the recurrence of perianal dysplasia postablation and factors affecting recurrence. RESULTS: Seventy HIV-positive and 11 HIV-negative patients enrolled; the median ages were 44.7 and 42.8 years. Median follow-up times for HIV-positive and HIV-negative patients were 4.62 and 3.53 years, and the median numbers of treatments were 4 and 1, p = 0.004. The median number of lesions treated was 1 for both groups. Only 1 HIV-negative patient had a recurrence 8 months after treatment. For HIV-positive patients, the Kaplan-Meier probability of recurrence at 1, 3, and 5 years was 38% (95% CI 26-50), 59% (95% CI 47-72), and 68% (95% CI 55-81) after the first ablation with no difference for subsequent treatments. HIV-positive patients had a relative risk of perianal high-grade squamous intraepithelial lesions of 3.72 (95% CI 2.10-6.60) compared with HIV-negative patients (p ≤ 0.0001). In multivariate analysis, only each increase in intra-anal high-grade squamous intraepithelial lesions significantly increased recurrence (HR 1.13, 95% CI 1.00-1.28, p = 0.002). Only 3 patients with perianal high-grade squamous intraepithelial lesions did not have canal dysplasia. Perianal cancer developed in 3 after being lost to follow-up. LIMITATIONS: This is a retrospective analysis of 1 experienced surgeon's results. No precise way exists to accurately determine the size of the disease. CONCLUSIONS: Perianal dysplasia can be successfully ablated, but recurrence remains high. Almost all patients have anal canal dysplasia. HIV-positive patients are at the greatest risk for disease and recurrence. An increased number of high-grade canal lesions increases recurrence.

Skin tumour surgery in primary care: do general practitioners need to improve their surgical skills?

BACKGROUND: Due to a rapid increase in the incidence of skin cancer, it seems inevitable that general practitioners (GPs) will play a larger role in skin cancer care. OBJECTIVES: To assess surgical procedures used by GPs in skin tumour management. METHODS: We performed a retrospective study of 1,898 pathology reports of skin tumours excised by GPs in 2009. RESULTS: In 22.9% no diagnosis was provided on the application form. Mostly, once-off excisions (no preceding biopsy) were performed, 7% of the excised lesions were malignant, and 35% of incisions were incomplete. Excisions in the face and neck region were incomplete in 65.4%; 22% of melanomas were biopsied or shaved. CONCLUSION: This study underlines the difficulties in skin tumour management in primary care. To stimulate adequate resource use, the number of excisions of benign lesions could be lowered, and pretreatment biopsy in non-melanoma skin cancer management should be encouraged. GPs should be aware of their limitations and consider referral of high-risk malignancies.

Bowen's disease of the nail apparatus: a series of 8 patients and a literature review.

Bowen's disease of the nail apparatus is uncommon. Since often characteristic clinical features are missing, diagnosis and treatment are delayed. We have analyzed our patients' files from January 2001 to July 2015 for this disorder. We identified eight patients with Bowen's disease of the nail apparatus, six male and two female individuals. Fingers were more often affected than toes. The disease does not respect the anatomical borders of the nail apparatus. Therefore, we performed delayed Mohs surgery with skin grafts in seven patients and with second intention healing in one patient. Two relapses were noted but only one ate the same digit. Since relapses occurred after 2-3 years, a follow-up of such patients seems justified.

Bowen's disease: A six-year retrospective study of treatment with emphasis on resection margins.

Bowen's disease is an in situ squamous cell carcinoma of the skin with various treatment modalities available. A major advantage of surgical excision is the opportunity to histologically examine the resection margins. There is no consensus about the most appropriate margin. This retrospective study evaluates the clearance rates achieved by excision with a 5 mm margin and estimates how that might change after fictitiously reducing the resection margin by 1 or 2 mm. Patients with histologically confirmed Bowen's disease were selected at the Maastricht University Medical Centre from 2002 until 2007. Surgical margins and complete excision rates were evaluated and histological slides were re-examined. To our knowledge this is the first study investigating the safety margin for Bowen's disease. As Bowen's disease is not an invasive disease, minimisation of healthy tissue excision is desirable. Our data show that a hypothetical reduction of the safety margin from 5 mm to 4 or 3 mm decreases the complete excision rate from 94.4% to 87% and 74.1%, respectively.

Histology of melanoma and nonmelanoma skin cancer.

Incidence of skin tumors is increasing among elderly patients, and the multi-morbidities which occur in the elderly are a great challenge for dermatologists. Basis of every treatment of skin cancer patients is a reliable diagnosis. Therefore, histopathology serves as the gold standard in clinical dermatooncology and dermatologic surgery. This chapter provides a comprehensive review on the main types of melanoma and nonmelanoma skin cancers, including precursor lesions.

Restoration of glans penis defect by a bipedicled foreskin flap.

Plastic surgeons reconstruct hard and soft tissues in many parts of the human body. Penile reconstruction is unique in that the target tissue has to be soft but intermittently rigid. There are many ways to treat penile defects. The ideal reconstruction must take into considerations sensation, cosmesis, and erectile functions. There is limited literature available on the management of penile glans defect. In this report, we present the reconstruction of penile glans defect, after surgical excision of Bowen disease, using a bipedicled foreskin flap of bucket handle type. It is easy to perform and highly effective, and importantly, both cosmetic and functional outcomes at 1-year follow-up were quite satisfactory.

Two-stage posterior cross-labial transposition flap: a novel technique for labium minus reconstruction.

Distinctive asymmetry of the labia minora is an underestimated complication that can be congenital, post-traumatic, or occur after oncological intervention or aesthetic labioplasty. Affected women can be restricted functionally and in their sense of self-worth, aesthetic appearance and sexual life. In presenting this case of post-oncological labia minora asymmetry, we demonstrate our method of the two-stage posterior cross-labial transposition flap as a reliable technique for unilateral labium minus reconstruction.

Nailbed HPV-related Bowen's disease in a man living with HIV.

Human papillomavirus (HPV) is a common sexually transmitted infection with wide-ranging clinical manifestations. High-risk anogenital HPV genotypes have also been reported to cause extragenital disease. We describe the case of a 69-year-old male patient living with HIV who was diagnosed with HPV-16 associated Bowen's Disease (BD) of the right middle finger nailbed, despite good virologic control and immune reconstitution. The lesion was managed surgically with adjunctive post-exposure HPV vaccination. This case adds to the growing body of evidence of extra-genital HPV disease attributable to anogenital genotypes in people living with HIV.

Cathepsin K expression in basal cell carcinoma.

BACKGROUND: Cathepsin K is a cysteine protease with strong collagenolytic and elastolytic properties. Recently, cathepsin K expression in tumour cells of malignant melanoma and in the stromal cells of squamous cell carcinoma of the skin has been reported to play an important role in tumour progression. However, its expression profile in basal cell carcinoma (BCC) has not yet been clarified. OBJECTIVE: The aim of this study is to examine the expression profile of cathepsin K in both the tumour cells and the peritumoural stromal cells of BCC in comparison with its expression in normal skin. METHODS: Fifty consecutive operative cases of BCC, 10 cases of actinic keratosis, 10 cases of Bowen's disease and five normal skin tissues were assessed for cathepsin K expression by immunohistochemical methods. RESULTS: In normal skin, cathepsin K expression was observed in the stratum corneum, mature sebaceous cells and outer root sheath of the hair follicles. Cathepsin K was expressed in the tumour cells of all BCC cases, in which 90% showed diffuse expression (>51% of tumour cells), as well as in the peritumoural stromal cells in all BCC cases. Focal cathepsin K expression was observed in the tumour cells of Bowen's disease (2/10 cases), but not in any of actinic keratosis (0/10 cases). CONCLUSION: Cathepsin K expression may contribute to tumour invasion and peculiar histopathological features, such as fibromucinous stroma around the tumour nests by mediating extracellular matrix degradation in BCC.

[Clinical analysis for 18 cases of vulvar Bowen's disease].

OBJECTIVE: To analyse the clinical and pathological characteristics, diagnosis, treatment and prognosis of vulvar Bowen's disease. METHODS: Clinical data including pathological characteristics, diagnosis, treatment methods and follow-up of 18 cases with vulvar Bowen's disease admitted to Cancer Hospital, Chinese Academy of Medical Sciences during January 1991 to June 2011 were retrospectively analyzed. RESULTS: The median age of the 18 patients was 37 years (range:23 to 64 years) . Sixteen patients had symptoms of vulvar itching and two patients had no symptom. Five cases were single neoplasm focus and the other 13 cases were multiple focuses. The diagnosis of vulvar Bowen's disease was according to the pathological diagnosis. Its diagnostic characteristic was giant round or ovoid cells with mono nucleolus in the whole layer of epidermis. All the patients received operation, eleven with simple vulvectomy and other seven cases with lumpectomy. The median follow-up time was 123 months (range: 5 to 197 months). Relapse was found in two cases. One patient relapsed five months postoperation and received vulvectomy. Another patient relapsed fifteen moths post-operation and received lumpectomy again. And they were follow-up for 192 months and 55 months respectively after second operation without relapse. CONCLUSIONS: The diagnostic characteristic of vulvar Bowen's disease is giant round or ovoid cell with mono nucleolus in the whole layer of epidermis, itsdiagnosis is according to the pathological diagnosis. Operation could get very good curative effect for patients with primary vulvar Bowen's disease and even for the recurrent patients. The prognosis of vulvar Bowen's disease is good.