Eyelid Radiotherapy-Treated Basal and Squamous Cell Carcinomas: A Case Series.

Histologic Safety Margins of Periocular BCC

Cells to Surgery Quiz: December 2018

5-aminolevulinic acid photodynamic therapy for the treatment of basal and squamous cell carcinoma: A systematic review.

Topical photodynamic therapy has been used for the treatment of superficial and nodular basal cell carcinomas, with varying cure rates. This study aims to evaluate the effectiveness of topical photodynamic therapy in the treatment of superficial and nodular basal cell carcinomas in Asian patients treated at the National Skin Centre, Singapore. A retrospective analysis of Asian patients with histologically confirmed basal cell carcinomas and treated with photodynamic therapy was performed. Eight Chinese patients, with an equal gender distribution and mean age of 83.4 years were included. Five of eight basal cell carcinomas were superficial while the remaining three were nodular. The basal cell carcinomas were located in the head and neck in seven patients. The overall clearance rate at 3 months was 87.5% while the clearance rate for superficial and nodular basal cell carcinomas was 100% and 66.6% respectively at 3 months. At 12 months, the overall clearance rate was 85. 7%. This is a retrospective analysis with small patient numbers. In this small series of eight Asian patients, topical photodynamic therapy has been shown to be effective and generally well-tolerated in the treatment of basal cell carcinomas, particularly of the superficial subtype. However, larger studies are needed to evaluate its overall efficacy in Asian patients.

Patients with nevoid basal cell carcinoma syndrome suffer from multiple basal cell carcinomas, requiring numerous surgical procedures that over time leave them with multiple disfiguring scars. Photodynamic therapy with delta-aminolevulinic acid using red light (approximately 630 nm) sources has been reported as effective in treatment of superficial and small nodular basal cell carcinomas. To our knowledge, the blue light source (417 nm peak irradiance) approved by the FDA for treatment of actinic keratoses has not been used for photodynamic therapy with delta-aminolevulinic acid of basal cell carcinoma. We report treatment of two nevoid basal cell carcinoma syndrome patients, women aged 21 and 47, with 20%delta-aminolevulinic acid solution and 417-nm blue light source (irradiance 10 mW/cm(2)). delta-Aminolevulinic acid was applied topically on lesions 1 to 5 hr before light treatment. Lesions were illuminated with 417+/-5-nm blue light for 1000 sec (10 J/cm(2)). Two consecutive treatments 1 week apart were administered as a therapeutic course. Each patient underwent two courses of photodynamic therapy with delta-aminolevulinic acid 2 to 4 months apart. The reported assessment was made 8 months after initial treatment. In most sessions the entire face, rather than visible basal cell carcinomas only, was treated. The treated basal cell carcinomas were clinically subdivided to superficial or nodular type guided by their morphologic features. A total of 9 superficial and 16 nodular basal cell carcinomas on the face and 27 superficial basal cell carcinomas on the lower extremities were treated. Complete clinical response was observed in 8 of 9 (89%) superficial basal cell carcinomas and 5 of 16 (31%) nodular basal cell carcinomas on the face and in 18 of 27 (67%) of superficial basal cell carcinomas on the lower extremities. The remaining 21 lesions showed partial clinical resolution. No new basal cell carcinomas were observed during the 8-month follow-up period in areas treated with a broad application technique. Resolution of the lesions was accompanied by an excellent cosmetic outcome and decreased prominence of old surgical scars in the more severely affected patient. Treatments were well tolerated, but associated with moderate to severe stinging during illumination. To our knowledge this is the first use of photodynamic therapy with delta-aminolevulinic acid with 417-nm blue light for treatment of multiple basal cell carcinomas in patients with nevoid basal cell carcinoma syndrome. Our clinical results demonstrate that the blue light reduces cutaneous tumor burden in such patients. Further studies are needed to confirm that broad-area photodynamic therapy with delta-aminolevulinic acid may eradicate subclinical tumors in nevoid basal cell carcinoma syndrome sufferers, as suggested by a strikingly decreased incidence of new basal cell carcinomas in our patients.

The role of laser and light sources used alone and in conjunction with photodynamic therapy (PDT) for the treatment of nonmelanoma skin cancers (NMSCs) remains unclear. PDT is a newly accepted treatment option for actinic keratoses (AKs) with clearance rates comparable to 5-flourouracil. The purpose of this study was to review literature pertaining to the use of light-emitting technologies and PDT for the treatment of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and AKs. A National Library of Medicine PubMed Internet search of English-language journals was performed using the terms laser, PDT, BCC, SCC, and AK. The search encompassed all English-language clinical trials on human subjects from the mid-1960s to the present using laser and light source therapy and/or topical aminolevulinic acid. Articles were excluded if they contained fewer than 10 patients, had a follow-up time of less than 1 month, used intravenous photosensitizers, or were review articles. A total of 20 papers were included for review (10 for BCC, 4 for AK, and 6 for SCC). Follow-up for these patients ranged from 1 to 36 months. Clearance rates were reported up to 100% for superficial BCCs, AKs, and SCC in situ, and lower (8%) for more invasive SCC. Recurrence rates ranged from to 0% to 31% for superficial BCCs, 16% to 31% for AKs, 0% to 52% for SCC in situ, and 82% for invasive SCC. Precise PDT and laser clearance and recurrence rates for superficial and nodular BCC and SCC treated with laser and PDT are not yet known. From the available data, it appears that PDT may be capable of achieving clearance rates comparable to radiation therapy for BCC. However, with current technology, PDT treatment of BCC remains inferior to surgical excision and Mohs surgery, for which recurrence rates have been reported to be less than 10%. The reported clearance rates currently limit the usefulness of PDT and laser therapy. However, multiple treatments and the use of penetration enhancers may significantly increase the efficacy of 5-aminolevulinic acid-PDT. With regard to SCCs, the risk of metastatic disease restricts the use of laser and PDT. Studies are currently underway with new light sources, photosensitizers, and various therapeutic regimens. At this time, because the reported recurrence rates are significantly higher than those achieved with standard therapies, laser and PDT should be reserved for only those patients who cannot undergo surgical therapy for BCC and SCC.

Micronodular basal cell carcinoma (BCC) may be more difficult to eradicate and prone to recurrence than nodular subtype. The aim of the study was to compare anatomical and histological characteristics of the basal cell carcinomas subtypes and the relationship of the micronodular BCC with other subtypes. Primary BCCs (n = 3074) were classified as superficial, nodular, micronodular, morpheic/infiltrative. The location was head/neck, limbs, chest/abdomen, back or genitals. Fifty-one micronodular BCCs were matched randomly with nodular and infiltrative cases, by age, sex, and tumor site. A modified Clark level was used to classify the tumor depth. Micronodular, nodular and infiltrative BCC were prevalently located in the head/neck (P < 0.0001), while superficial in the other regions (P < 0.0001). The Clark level was comparable between micronodular and infiltrative BCC, while nodular BCC showed a more superficial level than micronodular (P < 0.001) and infiltrative (P < 0.001) BCC. No nodular BCC had level IV and only 37.3% level III, while 92% of both micronodular and infiltrative BCC were level III or IV. The percentage of level IV was 11.8% and 25.5% in micronodular and infiltrative BCC, respectively. In the mid-face/periauricular region, 95.5% of micronodular and 100% of infiltrative cases of were level III or IV, compared to 50% of nodular BCC (P < 0.001). The Clark level of nodular subtype was higher for BCC of mid-face/periauricular than other regions (P < 0.05). It can be concluded that micronodular BCC shows intermediate characteristics compared with nodular and infiltrative subtypes but appears to have a specific individuality making it a distinct subtype.

Treating keratinocyte carcinomas with a combination of imiquimod, 5-fluorouracil, and tretinoin using store-and-forward telemedicine in the age of coronavirus disease 2019 to promote social distancing

For 1378 patients treated in the 11 years 1988-1998 by conventional excision of 1635 basal cell carcinomas, 1516 first index lesions were histologically completely excised. All patients having more than one BCC excised were identified from the data base from 1988 to 2003 to give minimum 5 years follow for last treated primary lesions in 1998. Measured clearance margins around the initial lesions at or near sites of presumptive recurrent lesions were noted and the lesions recorded photographically. All incompletely excised lesions whether or not re-excised were excluded. The median age for all patients was 70 years. Over minimum 5 years follow up, six patients developed nine subsequent lesions contiguous with the scar or graft repair of primary index lesion excision site (probable recurrences). The median interval to recurrence was 41 months (4 months-8 years 10 months), with median lateral clearance margin around the primary tumour of 2 mm (0.3-6.8 mm). A further nine patients developed 11 new lesions near (within 1cm of) the scar or graft of primary index lesion excision site (possible recurrences). The median interval to recurrence was 59 months (1 year-8 years 6 months). The median lateral clearance margin around the primary tumour was 4.1 mm (0.8-5.8 mm). For the two groups combined the maximum recurrence rate expressed as a percentage of index lesions was 1.3% (20/1516). Two thirds of possible and probable recurrences occurred in the temple and forehead, although these sites represented only 22% of all lesions, which may rather suggest new lesions in an area of field change as opposed to residual disease. The measured clearance margins reported here perhaps suggest that some original lesions may well have been completely excised primarily and many 'recurrences' were new primaries. These figures indicate there is a low order of probability for the incidence of recurrent basal cell carcinoma during minimum 5 years follow period after conventional surgical excision and conventional histological assessment of tumour resection margins.

Case report A 33-year-old woman was referred to our centre for therapeutic advice concerning multiple slow-growing skin lesions on the scalp and face. In 2003, the clinical diagnosis of nevoid basal cell carcinoma (NBCCS) was made based on a history of odontogenic keratocysts, distinct craniofacial features (frontal bossing, hypertelorism and coarse face), calcification of the falx cerebri and dura mater, segmentation defect of cervical vertebrae C5-C6, seizures, cardiac fibroma and mesenteric cysts. Genetic testing with DHPLC technique on leucocytes confirmed a germline mutation in patched 1 (PTCH1) gene on chromosome 9q22.3 in 2007. The first dermatological examination in 2009 revealed multiple lesions in the head and neck region, most of them clinically suspect for nodular or nodulo-ulcerative basal cell carcinomas (BCCs). Lesions suspect for superficial BCCs were predominantly observed on the lower limbs and to a lesser extent in the head and neck region. Patient presented also with dermal naevi, in the face and neck region, which could be differentiated from small nodular BCCs through dermoscopy. We did not observe palmoplantar pits, milia or epidermal cysts. The BCCs, which clinically presented as nodular or nodulo-ulcerative lesions, were treated with surgical excision to ensure optimal cure rate. In total 19 lesions were removed. Histological review showed 17 nodular BCCs and 2 BCCs of the superficial type. Non-surgical treatments, such as topical 5-fluorouracil and topical 5% imiquimod or photodynamic therapy which offer better cosmetic outcome, are treatment options for superficial BCCs. The therapeutic challenge in this genetically impaired patient lies in the expected development of a large number of BCCs with repeated occurrence throughout life. Radiotherapy should be avoided in the treatment of BCC in NBCCS since ionizing radiation may lead to the development of new BCCs in the field of irradiation. In this patient, for whom oral contraception is prohibited due to a history of thrombophilia, oral retinoids are relatively contra-indicated due to their teratogenic effects. In this regard, hedgehog/smoothened inhibitor molecules may provide a long-term option in the treatment of early lesions, in order to avoid surgery with its possible functional defects and unaesthetic consequences. These molecules bind with high affinity to Smoothened protein and substitute for the lost protein PTCH1 function by inhibiting Hedgehog pathway activation. Since available oral molecules are reserved for locally advanced or metastatic BCCs, we opted for inclusion in a clinical trial concerning a topical specific Smoothened inhibitor.

Demarcation of nonmelanoma skin cancer margins in thick excisions using multispectral polarized light imaging.

Non-melanoma skin cancer (NMSC) is generally considered to be a worldwide epidemic. Current estimates predict that between 0.9 and 1.2 million new cases will be diagnosed each year in the United States of America (USA), which is one-third of all cancers diagnosed (1). In Australia, the incidence of NMSC continues to rise and it now affects at least 1% to 2% of the population annually (1, 2). NMSC tends to affect Caucasians particularly in areas exposed to sunlight, such as the head, neck and back of the hands. There is an increased risk with fair skin, blue eyes and a history of repeated sunburns (1). There are two main forms of NMSC, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), which account for 80% and 16% respectively (1). The majority of BCCs present as two varieties. Nodular BCC (nBCC) appears mostly on the head and neck and accounts for approximately 60% of all BCCs (3). Most of the remainder are superficial BCC (sBCC), which occur on the trunk and extremities (4, 5). Standard treatments for BCCs include excision, curettage and electrodesiccation, and cryosurgery (6). Other forms of treatment such as Mohs micrographic surgery, intralesional interferon (7) and radiotherapy, may be used depending on the nature, site and size of the tumor (6). Actinic keratosis (AK) is considered by some to be the earliest clinically recognizable manifestation of SCC in situ (8, 9). The risk of progression of AK to invasive SCC has been reported as ranging from 0.25 to 20% within 10 – 25 years (8, 10, 11). Sun avoidance measures and sunscreen protection are the first steps in the therapy of AK. The conventional approaches for treating AKs include cryotherapy, electrodesiccation and curettage, excision, CO2 laser therapy, 5-fluorouracil (5-FU), chemical peels and photodynamic therapy (12). Recently, topical immunotherapy in the form of imiquimod 5% cream has demonstrated efficacy for the treatment of BCC and AK. Imiquimod, an immune response modifier, has demonstrated in pre-clinical studies to have both antiviral and antitumor activity in vivo (13). It is currently recommended for the treatment of external genital warts induced by human papillomavirus (14 – 16). This paper reviews the evidence of the safety and efficacy of imiquimod for the treatment of BCC and AK. IMIQUIMOD FOR THE TREATMENT OF BASAL CELL CARCINOMA

BACKGROUND Patients with nevoid basal cell carcinoma syndrome suffer from multiple basal cell carcinomas, requiring numerous surgical procedures that over time leave them with multiple disfiguring scars. Photodynamic therapy with δ-aminolevulinic acid using red light (∼630 nm) sources has been reported as effective in treatment of superficial and small nodular basal cell carcinomas. To our knowledge, the blue light source (417 nm peak irradiance) approved by the FDA for treatment of actinic keratoses has not been used for photodynamic therapy with δ-aminolevulinic acid of basal cell carcinoma. OBJECTIVE We report treatment of two nevoid basal cell carcinoma syndrome patients, women aged 21 and 47, with 20%δ-aminolevulinic acid solution and 417-nm blue light source (irradiance 10 mW/cm2). METHODS δ-Aminolevulinic acid was applied topically on lesions 1 to 5 hr before light treatment. Lesions were illuminated with 417±5-nm blue light for 1000 sec (10 J/cm2). Two consecutive treatments 1 week apart were administered as a therapeutic course. Each patient underwent two courses of photodynamic therapy with δ-aminolevulinic acid 2 to 4 months apart. The reported assessment was made 8 months after initial treatment. In most sessions the entire face, rather than visible basal cell carcinomas only, was treated. The treated basal cell carcinomas were clinically subdivided to superficial or nodular type guided by their morphologic features. A total of 9 superficial and 16 nodular basal cell carcinomas on the face and 27 superficial basal cell carcinomas on the lower extremities were treated. RESULTS Complete clinical response was observed in 8 of 9 (89%) superficial basal cell carcinomas and 5 of 16 (31%) nodular basal cell carcinomas on the face and in 18 of 27 (67%) of superficial basal cell carcinomas on the lower extremities. The remaining 21 lesions showed partial clinical resolution. No new basal cell carcinomas were observed during the 8-month follow-up period in areas treated with a broad application technique. Resolution of the lesions was accompanied by an excellent cosmetic outcome and decreased prominence of old surgical scars in the more severely affected patient. Treatments were well tolerated, but associated with moderate to severe stinging during illumination. CONCLUSION To our knowledge this is the first use of photodynamic therapy with δ-aminolevulinic acid with 417-nm blue light for treatment of multiple basal cell carcinomas in patients with nevoid basal cell carcinoma syndrome. Our clinical results demonstrate that the blue light reduces cutaneous tumor burden in such patients. Further studies are needed to confirm that broad-area photodynamic therapy with δ-aminolevulinic acid may eradicate subclinical tumors in nevoid basal cell carcinoma syndrome sufferers, as suggested by a strikingly decreased incidence of new basal cell carcinomas in our patients.

Ocular hazards of blue-light therapy in dermatology

The incidence of nonmelanoma skin cancer is increasing rapidly among elderly persons, but little is known about its incidence in the population younger than 40 years. To estimate the sex- and age-specific incidences of basal cell carcinoma and squamous cell carcinoma in persons younger than 40 years in Olmsted County, Minnesota, and to evaluate change in incidence over time; to describe the clinical presentation, rate of recurrence and metastasis, and histologic characteristics of these tumors in this population-based sample. Population-based retrospective incidence case review. Residents of Olmsted County, Minnesota, a population with comprehensive medical records captured through the Rochester Epidemiology Project. Patients younger than 40 years with basal cell carcinoma or squamous cell carcinoma diagnosed between 1976 and 2003. Incident basal cell carcinomas and squamous cell carcinomas and change in incidence of these tumors over time. During the study period, 451 incident basal cell carcinomas were diagnosed in 417 patients and 70 incident squamous cell carcinomas were diagnosed in 68 patients. Of these tumors, 328 were histologically confirmed basal cell carcinomas and 51 were histologically confirmed squamous cell carcinomas. Overall, the age-adjusted incidence of basal cell carcinoma per 100,000 persons was 25.9 (95% confidence interval [CI], 22.6-29.2) for women and 20.9 (95% CI, 17.8-23.9) for men. The incidence of basal cell carcinoma increased significantly during the study period among women (P<.001) but not men (P = .19). Nodular basal cell carcinoma was the most common histologic subtype; 43.0% of tumors were solely nodular basal cell carcinoma and 11.0% had a mixed composition, including the nodular subtype. The incidence of squamous cell carcinoma was similar in men and women, with an average age- and sex-adjusted incidence per 100 000 persons of 3.9 (95% CI, 3.0-4.8); the incidence of squamous cell carcinoma increased significantly over the study period among both women (P = .01) and men (P = .04). This population-based study demonstrated an increase in the incidence of nonmelanoma skin cancer among young women and men residing in Olmsted County, Minnesota. There was a disproportionate increase in basal cell carcinoma in young women. This increase may lead to an exponential increase in the overall occurrence of nonmelanoma skin cancers over time as this population ages, which emphasizes the need to focus on skin cancer prevention in young adults.