Intraepidermal Squamous Cell Carcinoma Research Articles

Intralesional photodynamic therapy induces apoptosis in basal cell carcinoma and Bowen's disease through caspase 3 and granzyme B.

Photodynamic therapy (PDT) is used to treat cutaneous cancers. It may induce cell death through direct and indirect means, including apoptosis, inflammation and certain immune mechanisms, with the depth of penetration as a potential modifying factor. To examine the pathways of apoptosis in the intralesional PDT of basal cell carcinoma (BCC) and intraepidermal squamous cell carcinoma (Bowen's disease). Sixteen patients with superficial or nodular BCC and Bowen's disease were treated with intralesional aminolevulinic acid-PDT. Biopsies were taken at baseline and 24 h post-PDT, and sections were examined by immunohistochemistry for the expression of markers of apoptosis, such as caspase 3, involved in the intrinsic apoptotic pathway, granzyme B, a caspase-independent apoptotic mediator, and the proapoptotic markers BAX and BAK. Apoptotic cells stained with TUNEL showed statistically significant staining at 24 h post PDT (p < 0.01 in both BCC and Bowen's lesions). Caspase 3 (p < 0.01 in BCC and p < 0.05 in Bowen's) and granzyme B (p < 0.01 in BCC and p < 0.01 in Bowen's) were significantly increased at 24 h post-PDT. BAX expression was apparently increased compared to baseline in Bowen's lesions at 24 h post-PDT, whereas Bak was upregulated both in BCC and Bowen's disease at baseline and at 24 h post-PDT. Intralesional PDT induces apoptosis in BCC and Bowen's disease via common and alternative apoptotic pathways involving granzyme B. Proapoptotic factors Bak in both BCC and Bowen and Bax in Bowen's disease appear to increase by intralesional PDT at 24 h.

Knowledge and awareness about Bowen's disease among dental students.

The study aimed to assess the awareness and knowledge about Bowen's disease among dental students. Bowen disease is an infrequent skin disorder and is also referred to as squamous cell carcinoma in situ. It is a noninvasive form of intraepidermal squamous cell carcinoma with flat or slightly raised lesions. An online survey was conducted among 300 dental students between the age group of 18-30 years in the Chennai district based on Bowen's disease. This is the best approach to data collection due to the large population of the city of Chennai and is also appropriate in the current situation where people need to avoid gatherings and close contact. About 78.21% were BDS students and 21.79% were MDS students. In the age group of 10-20 years, 8.97% responded heard about Bowen disease and 3.85% responded not heard. Within the 21-30 years age group, 44.02% responded that Bowen disease is invasive and 20.09% responded noninvasive. Studies showed that the exact occurrence of Bowen's disease is not known. It is found to be more common in men than in women. To conclude, about 65% of participants were aware of Bowen's disease. Nevertheless, patients with Bowen's disease seem to be at an abnormal risk of internal malignancies, and they need to be educated about the various treatments available to prevent the cause as soon as possible.

Bowen disease on the dorsum of the foot associated with human papillomavirus type 16

A 94 years old Japanese female was presented to our hospital with a skin lesion on her left foot. A physical examination found a markedly hyperkeratotic reddish-brown plaque, measuring 3 cm in diameter. A biopsy specimen showed prominent papillomatosis, hyperkeratosis, and atypical keratinocytes throughout the epidermis. Individual cell keratinization, multinucleated keratinocytes, and many keratinocytes with clear cytoplasm were seen. We excised the lesion, and the skin grafting was used for covering the skin defect. We investigated whether human papillomavirus (HPV) was present in the lesion, and HPV 16 DNA was detected using the polymerase chain reaction. Immunohistochemical analysis showed several HPV-positive cells in the upper epidermis. In addition, the tumor cells showed strong and diffuse expression of p16INK4a. Bowen disease (BD) is an intraepidermal squamous cell carcinoma. The precise pathogenesis of BD is unclear, but it involves various factors. HPV infection is one of these factors and is a well-known cause of BD of the genitalia and fingers. It has been shown that some BD lesions occurring at other locations are also associated with HPV. Dysregulation of the Rb/p16INK4a pathway is considered to play an important role in HPV-induced BD, but the precise mechanism remains to be elucidated. J. Med. Invest. 69 : 152-154, February, 2022.

Unrecognized Bowen’s disease in previously treated condylomata acuminata: indication of a common etiology?

Bowen's disease (BD) is an intraepidermal squamous cell carcinoma (SCC) with the capacity to become invasive SCC giving rise to distant metastasis. In rare cases it can be associated with human papillomavirus (HPV) infection, specifically with HPV types 16, 18, 31, 32, and 34. Here we report a case of an immunocompetent white male, age 37, with an erythematous, irregularly-shaped patch in his suprapubic region, appearing 1 year after treatment for condylomata acuminata with cryotherapy and podophyllin in the same area. At the time of clinically active disease, a urethral smear was positive for high-risk HPV types. The lesion was considered a scar by several physicians because it emerged in an area of previous postinflammatory hyperpigmentation. The aim of this report is to raise awareness of the emerging causative association between anogenital HPV infection and the development of BD, which was the possible etiological agent in the case of the patient presented here. Hereby we also advocate primary preventive measures in terms of safe sexual habits and HPV vaccination.

Pink plaque on the hypogastrium

Bowen’s disease is a type of intraepidermal squamous cell carcinoma usually affecting the elderly and occurring on sun-exposed areas, such as the face, scalp, and limbs. The development of Bowen’s disease in other locations such as the abdomen is rare. In these cases, dermoscopy proves to be a helpful tool in making the diagnosis [1]. A 65-year-old male with no previous medical history presented himself with a nonhealing asymptomatic lesion on the abdomen slowly growing for the last ten years. A dermatological examination revealed a 6-cm well-limited erythematous plaque on the hypogastrium with peripheral pigmentation (Fig. 1). Dermoscopy found central keratin as well as white shiny structures, including white shiny lines, white shiny areas, and rosettes (Fig. 2) as well as brown linear globules and dots on the periphery and looped vessels (Fig. 3). Bowen’s disease was the most likely diagnosis, which was confirmed by histopathology. The patient underwent surgery for excision of the lesion with 5-mm margins.

Treatment of erythroplasia of Queyrat: current status and advances

Erythroplasia of Queyrat (EQ) , an in situ intraepidermal squamous cell carcinoma, is considered as Bowen′s disease of the glans and prepuce. EQ is seen almost exclusively in uncircumcised middle-aged or older men, and may progress into invasive squamous cell carcinoma in about 33% of patients. Effective treatments include local excision, Mohs surgery, partial or total penectomy, topical 5-fluorouracil 5% ointment or imiquimod 5% cream, cryotherapy, radiotherapy, laser therapy, photodynamic therapy, and so on. Traditional topical treatment is simple to operate and easily accepted by patients, but recurrence is frequent. Recently, photodynamic therapy and laser therapy have developed rapidly and become the first-line therapy of EQ. However, surgical treatment is still considered the golden standard therapy for EQ with reduced recurrence. The recurrence rate is lower than 2% in patients with EQ of the glans and prepuce after removal of lesions, but the appearance and function of the penis are usually affected by surgical operation. The selection of treatment approaches depends on the immune status of, lesional sites in and will of patients. Key words: Erythroplasia; Neoplasms, squamous cell; Surgical procedures, operative; External application drugs; Clinical protocols

Current status of and advances in the treatment of Bowen's disease

Bowen's disease,an intraepidermal squamous cell carcinoma,can progress into invasive squamous cell carcinoma.It can be treated by surgical and nonsurgical methods.Surgical methods involve simple excision,Mohs micrographic surgery,electrodesiccation and curettage; nonsurgical methods include medical treatment,radiotherapy,cryotherapy,photodynamic therapy and other combined therapies.Surgical methods are the first choice for the treatment of Bowen's disease.For patients not suitable for surgery and lesions at specific sites,medical treatment and photodynamic therapy can be used. Key words: Bowen's disease;  Dermatologic surgical procedures;  Therapeutics

Radyoterapi iyi yanıt veren Bowen hastalığı olgusu

Bowen"s disease is a form of intraepidermal squamous cell carcinoma which is known as carsinoma in situ. The head, neck, and extremities are the most commonly affected anatomic locations. Treatment options for Bowen"s disease include observation, surgery, cryotherapy, electrodesiccation and curettage, topical application of 5-fluorouracil or imiquimod, Moh"s micrographic surgery, photodynamic therapy, and radiotherapy. Radiation therapy is advantageous in patients who refuse surgery, for large or multiple lesions, for lesions in cosmetically sensitive areas, and in patients who are predisposed to formation of keloids, with a high cure rate cited in the literature. Here we report a 70-year-old man who was diagnosed as Bowen"s disease and completely healed with the treatment of radiotherapy. By means of this case report, we will review the current literature and empasize that radiotherapy is an effective treatment alternative for Bowen's disease in the suitable lesions.

Successful Treatment of Bowen’s Disease with Topical Maxacalcitol

Since Bowen’s disease, an intraepidermal squamous cell carcinoma, occurs frequently in elderly people, surgical treatment is sometimes difficult. Therefore, an alternative treatment is required due to other underlying diseases. We report here the case of an elderly man with Bowen’s disease who declined surgical treatment due to concerns of postoperative bleeding secondary to anticoagulation. Occlusive dressing therapy with maxacalcitol, an active vitamin D3 derivative, resulted in clinical resolution. We investigated the mechanism of anti-tumour activity of this vitamin D3 ointment in Bowen’s disease.

Long‐term follow‐up of metil aminolevulinate (MAL)‐PDT in difficult‐to‐treat cutaneous Bowen’s disease

Bowen's disease (BD) is a form of intraepidermal squamous cell carcinoma, which is clinically characterized by gradually enlarging, well-demarcated erythematous plaques with irregular borders and surface crusting or scaling, affecting primarily the elderly. BD often presents with lesions difficult to treat with standard therapy as surgery, cryosurgery, or 5-fluorouracil (5-FU) for the risk of significantly poor cosmetic outcome, failure rate, and adverse events, related mainly to the age of the patients. Topical PDT with methyl aminolevulinate (MAL) represents a valid and approved therapy for BD lesions in many cases, especially for lesions located at poor healing sites or for large patches of disease, due to its high efficacy coupled with good tolerability and tissue-sparing attitude. In this study, we sought to investigate the efficacy, safety, and cosmetic outcome of MAL-PDT in a series of patients with BD lesions which were challenging to treat for clinical, surgical, and patient-related reasons, such as size of the lesion, difficult surgical approach for anatomical sites, or age of patients and request of the best cosmetic result. We also performed a long-term follow-up to assess recurrence rates and eventual late-onset adverse events.

Immunohistochemical Staining of p16 in Squamous Cell Carcinomas of the Genital and Extragenital Area

Background and objectives Positive immunostaining for the tumor suppressor protein p16 is associated with the presence of mucosal or alfa subtypes of human papillomavirus (HPV) in cervical and genital squamous cell carcinoma (SCC). The aim of this study was to determine whether p16 immunostaining is also associated with mucosal HPV in extragenital SCC. Material and methods Paraffin sections of lesions located in the genital region (8 genital warts, 3 intraepidermal SCCs, and 7 invasive SCCs) and extragenital area (29 intraepidermal SCCs corresponding to Bowen disease and 10 invasive SCCs) were stained for p16 by immunohistochemistry. Mucosal HPV was detected by polymerase chain reaction (PCR). Results In the genital area, p16 immunostaining was negative in genital warts and positive in all 3 intraepidermal SCCs and 2 invasive SCCs (29%). Mucosal HPV was detected in 6 genital warts and 2 intraepidermal SCCs (100% after exclusion of 3 lesions that could not be analyzed by PCR) and in the 2 invasive SCCs that were positive for p16. In the extragenital area, 19 intraepidermal SCCs (95%) and 2 invasive SCCs (20%) were immunopositive for p16. Mucosal HPV was detected in 4 intraepidermal SCCs (p16 immunopositive) and 1 invasive SCC (p16 immunonegative). In intraepidermal SCCs, p16 immunostaining facilitated the identification of dermal microinfiltration or invasion of normal skin appendages. Conclusions According to our results, unlike in genital SCCs, p16 immunopositivity is independent of the presence of HPV in extragenital SCCs. Compared with intraepidermal SCCs, the absence of p16 protein in invasive SCCs in the extragenital area would indicate progression of the disease.

Tinción inmunohistoquímica p16 en carcinomas epidermoides del área genital y extragenital

Background and objectives Positive immunostaining for the tumor suppressor protein p16 is associated with the presence of mucosal or αsubtypes of human papillomavirus (HPV) in cervical and genital squamous cell carcinoma (SCC). The aim of this study was to determine whether p16 immunostaining is also associated with mucosal HPV in extragenital SCC. Material and methods Paraffin sections of lesions located in the genital region (8 genital warts, 3 intraepidermal SCCs, and 7 invasive SCCs) and extragenital area (29 intraepidermal SCCs corresponding to Bowen disease and 10 invasive SCCs) were stained for p16 by immunohistochemistry. Mucosal HPV was detected by polymerase chain reaction (PCR). Results In the genital area, p16 immunostaining was negative in genital warts and positive in all 3 intraepidermal SCCs and 2 invasive SCCs (29%). Mucosal HPV was detected in 6 genital warts and 2 intraepidermal SCCs (100% after exclusion of 3 lesions that could not be analyzed by PCR) and in the 2 invasive SCCs that were positive for p16. In the extragenital area, 19 intraepidermal SCCs (95%) and 2 invasive SCCs (20%) were immunopositive for p16. Mucosal HPV was detected in 4 intraepidermal SCCs (p16 immunopositive) and 1 invasive SCC (p16 immunonegative). In intraepidermal SCCs, p16 immunostaining facilitated the identification of dermal microinfiltration or invasion of normal skin appendages. Conclusions According to our results, unlike in genital SCCs, p16 immunopositivity is independent of the presence of HPV in extragenital SCCs. Compared with intraepidermal SCCs, the absence of p16 protein in invasive SCCs in the extragenital area would indicate progression of the disease.

P60b Epidemiological trends in non melanoma skin cancer in a Mediterranean population

Introduction Non melanoma skin cancer (NMSC) is the most common malignancy occurring in the Caucasian race. Sun exposure and advanced age are the most important risk factors in the development of these tumors. Currently, more epidemiological data are needed to determine the true distribution in the Mediterranean population. The objective of this study is to estimate the incidence of histologically proven basal cell carcinoma in a cohort of Spanish patients and to assess the risk of relapse and the time to development of subsequent cutaneous tumors after 10 years of follow-up. Methods Patients were retrospectively studied from 1997 to 2007. Data analysis included sex, age, immune status, tumor location, histology (subtype, vascular and/or neural involvement and status of surgical margins), time to relapse and incidence of new skin tumors during follow-up. Information was collected from histological reports and the clinical database from a tertiary care hospital in Madrid, Spain that serves a population of roughly 750 000 inhabitants in a specific sanitary area. Results We have studied 106 patients with a confirmed diagnosis of basal cell carcinoma, 48 of them (45,3%) were males and 58 (54,7%) females. The median age was 66,25 years old (range 41–91) and the mean size 185,09 mm2. Solid basal cell carcinoma was the most common histological type (41,5%). The most frequent locations were the inferior aspect of the nose (17%), temporal area of the scalp (15%), upper part of the nose (10,4%) and right frontal area of the scalp (7,5%). After conventional surgery, 19 (17,9%), 9 (8,5%) and 3 (2,8%) patients had involvement of a lateral, deep and both margins, respectively. After a mean follow-up of 115 months, we recorded 13 cases of first relapse (12,26%), 6 of them (46,15%) diagnosed before 16,80 months (range 2,59–85,26) and 2 cases of second relapse (1,89%) at 7,20 and 52,10 months. Thirty patients presented a second primary cutaneous tumor, the most frequent one being solid basal cell carcinoma, seen in 11 patients (10,4%), followed by intraepidermal squamous cell carcinoma observed in 7 patients (6,6%). Roughly 50% of the second tumors appeared in the first 37 months (range 3,98–137,33). Immunosuppression was present in 11 patients (10,4%) and 25 (24,5%) were diagnosed of a synchronous or metachronous malignant solid neoplasia. Conclusion We have carried out a cohort study to assess, in addition to the incidence and distribution of basal cell carcinoma, the risk of relapse and the development of new tumors. We have studied a stable population of patients, not biased by hospital referral, during a follow-up time period of 10 years. We provide key epidemiological data on the most common cutaneous malignancy in a Mediterranean population where limited information is currently available.

The Use of Imiquimod in the Treatment of Periocular Tumours

Purpose: To review our experience with 5% topical Imiquimod in the treatment of periocular tumours.Methods: Imiquimod, an imidazoquinoline, is an immune response modifier which has been shown to have potent anti-viral and anti-tumour activity. We present a retrospective case series of 5 patients who received topical Imiquimod for various eyelid tumours. Two patients were diagnosed with basal cell carcinoma of the eyelid, one patient with actinic keratosis, one with intraepidermal squamous cell carcinoma (Bowen’s disease) and one patient had concomitant squamous cell carcinoma and intraepidermal squamous cell carcinoma.Results: All 5 patients, with various eyelid neoplastic/pre-neoplastic pathology, responded well with clinical resolution, to treatment with topical Imiquimod. There were few adverse reactions to periocular use of 5% Imiquimod, with only 1 patient developing a chemical conjunctivitis which resolved on dose reduction.Conclusions: There is limited experience and published literature on the use of topical 5% Imiquimod in the treatment of periocular tumours. In our experience, it is a safe and effective treatment for periocular lesions, including actinic keratosis, intraepidermal squamous cell carcinoma, basal cell carcinoma and squamous cell carcinoma. To our knowledge, this is the first published description of the successful use of 5% Imiquimod in treating moderately differentiated squamous cell carcinoma of the eyelid.

Bowen's disease treated by carbon dioxide laser. A series of 44 patients

Background: Bowen's disease is a common form of intraepidermal (in situ) squamous cell carcinoma of the skin and mucous membrane. Treatment with destruction of the epidermis by any method is necessary to prevent invasive squamous cell carcinoma. Objective: To report our experience with CO2 laser vaporization in the treatment of Bowen's disease and try to identify which factors could have any influence on results. Methods: A total of 44 patients were treated with the CO2 laser in superpulsed mode, focalized at 2 W/cm2. Results: In 86.3% of patients, a unique treatment session was required. ‘Clearance after one treatment’ was achieved in 86.3% of the total series of patients and only 7.9% of these patients developed recurrence of the lesion. In 11.3% of the cases, there was ‘clearance after more than one treatment’ without clinical recurrences in any of these patients during the follow‐up. ‘No response’ was achieved in 2.2% of the total series of patients. Conclusion: We conclude that the CO2 laser in superpulsed mode is an effective, efficient, safe, functional and good cosmetics treatment for Bowen's disease and it provides the same recurrence rate as other more aggressive or more expensive modalities of treatment.

Histopathology of incipient intraepidermal squamous cell carcinoma (“actinic keratosis”)

Actinic keratoses (AKs) are proliferations of transformed, neoplastic keratinocytes confined to the epidermis induced by exposure to ultraviolet (UV) radiation in sunlight. They are extremely prevalent and are seen in most middle-aged to elderly Caucasian persons with a history of significant sun exposure. These lesions are currently termed AKs while they remain confined to the epidermis, but when they extend more deeply to involve the papillary and/or reticular dermis, they are termed squamous cell carcinoma (SCC). The term AK was developed on the basis of clinical appearance and texture of these lesions without regard to histopathology or pathobiology. This study was based on a current and historical literature review. AKs and SCC represent the same disease process at different stages of evolution. Neoplastic transformation occurs in keratinocytes exposed to UV radiation manifest primarily as mutations in the p53 gene. In time, these cells proliferate in the epidermis and eventually extend into the dermis at which point metastatic spread can occur. Cytologic atypia is visible in early stages and is identical to that seen in SCC that is present in the dermis or in metastatic lesions. This sequence of events is directly analogous to that of evolving carcinoma of the uterine cervix that has been termed cervical intraepithelial neoplasia. AKs are malignant neoplasms in evolution and demonstrate histologic and molecular genetic features of malignancy. Because the name currently used to describe these lesions does not reflect the pathobiology of the process, we propose that a new, more appropriate name be given to these lesions. We propose that a classification scheme analogous to that used by gynecologists for evolving carcinoma of the uterine cervix using the terminology "keratinocytic intraepidermal neoplasia" or another term such as "solar keratotic intraepidermal SCC" be used to define these lesions and that the term actinic (solar) keratosis be eliminated.

Toxicity of Vesicant Agents Scheduled for Destruction by the Chemical Stockpile Disposal Program

The vesicant agents of the unitary chemical munitions stockpile include various formulations of sulfur mustard [bis-(2-chloroethyl) sulfide; agents H, HD, and HT] and small quantities of the organic arsenical Lewisite [dichloro(2-chlorovinyl) arsine; agent L]. These agents can be dispersed in liquid, aerosol, or vapor form and are capable of producing severe chemical burns upon direct contact with tissue. Moist tissues such as the eyes, respiratory tract, and axillary areas are particularly affected. Available data summarizing acute dose response in humans and laboratory animals are summarized. Vesicant agents are also capable of generating delayed effects such as chronic bronchitis, carcinogenesis, or keratitis/keratopathy of the eye under appropriate conditions of exposure and dose. These effects may not become manifest until years following exposure. Risk analysis derived from carcinogenesis data indicates that sulfur mustard possesses a carcinogenic potency similar to that of benzo[a]pyrene. Because mustard agents are alkylating compounds, they destroy individual cells by reaction with cellular proteins, enzymes, RNA, and DNA. Once begun, tissue reaction is irreversible. Mustard agents are mutagenic; data for cellular and laboratory animal assays are presented. Reproductive effects have not been demonstrated in the offspring of laboratory rats. Acute Lewisite exposure has been implicated in cases of Bowen's disease, an intraepidermal squamous cell carcinoma. Lewisite is not known to generate reproductive or teratogenic effects.

Toxicity of vesicant agents scheduled for destruction by the Chemical Stockpile Disposal Program.

The vesicant agents of the unitary chemical munitions stockpile include various formulations of sulfur mustard [bis-(2-chloroethyl) sulfide; agents H, HD, and HT] and small quantities of the organic arsenical Lewisite [dichloro(2-chlorovinyl) arsine; agent L]. These agents can be dispersed in liquid, aerosol, or vapor form and are capable of producing severe chemical burns upon direct contact with tissue. Moist tissues such as the eyes, respiratory tract, and axillary areas are particularly affected. Available data summarizing acute dose response in humans and laboratory animals are summarized. Vesicant agents are also capable of generating delayed effects such as chronic bronchitis, carcinogenesis, or keratitis/keratopathy of the eye under appropriate conditions of exposure and dose. These effects may not become manifest until years following exposure. Risk analysis derived from carcinogenesis data indicates that sulfur mustard possesses a carcinogenic potency similar to that of benzo[a]pyrene. Because mustard agents are alkylating compounds, they destroy individual cells by reaction with cellular proteins, enzymes, RNA, and DNA. Once begun, tissue reaction is irreversible. Mustard agents are mutagenic; data for cellular and laboratory animal assays are presented. Reproductive effects have not been demonstrated in the offspring of laboratory rats. Acute Lewisite exposure has been implicated in cases of Bowen's disease, an intraepidermal squamous cell carcinoma. Lewisite is not known to generate reproductive or teratogenic effects.

Lewisite: its chemistry, toxicology, and biological effects.

Lewisite is an organic arsenical war gas which is a vesicant with attendant toxicities due to its ability to combine with thiol groups which are essential for activity of a variety of enzymes. Although Lewisite has been designated as a "suspected carcinogen," the indictment is not supported by the available scientific evidence. Indeed, the unwarranted conclusion is based on one specific case history of a former German soldier whose lower right leg was exposed to liquid Lewisite in 1940 with subsequent development of intraepidermal squamous cell carcinoma, and the examination of death certificates of former workers at a Japanese factory that manufactured a variety of war gases including mustard gas, hydrocyanic acid, chloracetophenome, phosgene, diphenylcyanarsine and Lewisite. It is difficult to comprehend why Lewisite was selected out of this group of toxic chemicals as one of those responsible for respiratory cancer in these workers. It would appear to be a difficult task, indeed, to disengage a specific worker from one of the other of several gases at the workplace and assign a specific gas-induced death. The evidence that organic arsenicals are carcinogenic is weak. Although the weight of evidence is such that inorganic arsenical derivatives are considered weak mutagens, the evidence that organic arsenicals are mutagenic is poor. Recent examination of the mutagenic potential of Lewisite using the Ames test has shown that Lewisite is not mutagenic under these circumstances. While oral administration of arsenical compounds, whether inorganic or organic, does not induce teratogenicity except at very high dose levels which are associated with some degree of maternal toxicity, parenteral administration has been associated with teratogenicity but information of maternal toxicity has not always been available. Indeed, maternal toxicity should be considered as an important diagnostic tool in assessing whether a chemical is teratogenic. The significance of parenteral routes for inducing teratogenicity is also problematical. Recently, Lewisite has been shown not to be teratogenic in either rats or rabbits. A monograph on arsenic, succinctly states that "no human epidemiological investigations have been conducted on the carcinogenicity of organic arsenic compounds" (WHO 1981). Indeed, the lack of such evidence eminating from epidemiological sources or from animal studies is resounding. At present, there is no evidence that Lewisite is either carcinogenic, mutagenic or teratogenic. A review of toxicological studies of other organic arsenicals has produced no evidence that they might be carcinogenic, mutagenic or teratogenic.

Bowen's disease and 5-fluorouracil

Sixty-six confirmed cases of Bowen's disease (intraepidermal squamous cell carcinoma) were seen from 1965 through 1976: twenty-four cases were treated surgically-four by excision (two recurrences) and twenty by desiccation and curettage (four recurrences); one was treated with x-ray radiation; and forty-one were treated with topical 5-fluorouracil (5-FU) (three recurrences). Of the six surgical recurrences (25% recurrence), one was retreated by desiccation and curettage and five with 5-FU. Of the three recurrences after 5-FU (8% recurrence), all three were successfully retreated with 5-FU. In view of the generally high recurrence rate after all treatment modalities in Bowen's disease, related to both the ill-defined lateral margins and the frequent follicular involvement with the Bowen's process, prolonged treatment time is required for success with 5-FU. Treatment times employed were 4 to 12 weeks, with a median of 9 weeks. 5-FU concentration ranged from 1% to 3 % in propylene glycol. A 1% concentration of 5-FU was generally adequate on the face, except for occasional recalcitrant areas, such as the nose and eyebrow. A concentration of 2.5% to 3.0% was usually necessary for treatment of Bowen's disease on the other body areas.