Histological evaluation of residual basal cell carcinoma after shave biopsy prior to Mohs micrographic surgery.

BACKGROUND: Patients who are referred for Mohs surgery after pre-operative biopsy has been performed show in some cases no clinical or pathological evidence of tumour persistence. We have previously shown that 25% of these patients show no residual skin cancer either basal cell carcinoma or squamous cell carcinoma. The reasons for 'disappearance' of the tumour may be true non-persistence or false non-persistence because of wrong-site Mohs surgery. OBJECTIVE: To determine the incidence of residual basal cell carcinoma after shave biopsy of primary nodular basal cell carcinoma prior to Mohs micrographic surgery. METHODS: A prospective unblinded study was performed on patients undergoing Mohs surgery for primary nodular basal cell carcinoma. The tumour was removed as a shaved excision using a No. 15 blade at the clinical borders like a shave biopsy (Mohs shave). The bases of the tumors were excised and then sectioned vertically at the middle and cut to the periphery at 10-15 µm intervals till the edge. RESULTS: Fifty-one patients were evaluated. In 40 patients, residual basal cell carcinoma was found at the base of the shave excision site (78.4%). CONCLUSIONS: Pre-operative shave biopsy performed during Mohs surgery for primary nodular basal cell carcinoma is 'curative' in 22% of the patients.

Identification of the molecular target for the suppression of contact hypersensitivity by ultraviolet radiation.

This study was conducted to explore the involvement of DNA damage in the suppression of contact hypersensitivity (CHS) by UV irradiation. The opossum, Monodelphis domestica, was used because cells of these marsupials have an enzyme that is activated by visible light (photoreactivating enzyme) and repairs ultraviolet radiation (UVR)-induced pyrimidine dimers in DNA. A single dose of 1,500 J/m2 of UVB (280-320 nm) radiation, representing 2 minimal erythema doses, was administered to the dorsal skin of opossums. This treatment prevented the opossums from developing a CHS response to dinitrofluorobenze (DNFB) applied either at the site of irradiation or an unirradiated site. In addition, this dose of UVR decreased the number of ATPase+ epidermal Langerhans cells in the dorsal epidermis to approximately 3% of that in unirradiated skin at the time of DNFB application. Treatment of the animals with wavelengths that activate the repair enzyme (320-500 nm, photoreactivating light, PRL) for 120 min immediately after UV irradiation inhibited the UVR-induced suppression of CHS almost completely. Exposure to PRL before UVR did not prevent UVR-induced suppression of CHS. PRL treatment after UV irradiation also prevented the decrease in the number of ATPase+ Langerhans cells. Measurements of lesions in DNA indicated that PRL treatment removed around 85% of the UVR-induced pyrimidine dimers. These data provide direct evidence that DNA, and most likely, the pyrimidine dimer, is the primary molecular target for the UVB-induced suppression of contact hypersensitivity to haptens applied to irradiated or unexposed skin.

Alterations in Langerhans cells and Thy-1+ dendritic epidermal cells in murine epidermis during the evolution of ultraviolet radiation-induced skin cancers.

To understand the role of cutaneous immune cells in host resistance to the induction and growth of skin cancer, we investigated the number and morphology of murine dendritic epidermal cells (dEC) during the evolution of ultraviolet (UVA) UV-induced skin cancers. Female C3H/HeN mice were treated topically with 8-methoxypsoralen followed by ultraviolet A (UVA) radiation 3 times/week or irradiated with UVB radiation 3 times/week. In both psoralen plus UVA- and UVB-treated mice, ATPase+ and Ia+ Langerhans cells almost completely disappeared from the treated skin during the early latency period of tumor development (4 weeks) but reappeared in the epidermis late in the latency period (between 15 and 22 weeks). The ATPase+ cells that reappeared in the epidermis had a rounder, less dendritic morphology than normal Langerhans cells. Thy-1+ dEC were totally depleted from the epidermis in both treatment groups at the end of first week of treatment and were nearly absent from the skin during the entire latency period. After tumors appeared (29 weeks), Thy-1+ dEC were still absent or detected only in small numbers in skin surrounding the tumors. ATPase+ and Ia+ cells present in skin around the tumors constituted 60 to 80% of the number in nonirradiated skin. Mice that received UVA radiation alone developed no tumors. ATPase+ and Ia+ Langerhans cells and Thy-1+ dEC were detected in UVA-treated epidermis after 22 weeks and 43 weeks, although the numbers were lower than those in unirradiated mice. Most psoralen plus UVA-induced tumors (81%) were squamous cell carcinomas, whereas only 24% of UVB-induced tumors were of this histological type. Our results demonstrate that UV-induced skin cancers developed in the presence of ATPase+ and Ia+ cells in the epidermis and in the absence of Thy-1+ dEC.

Blood pressure levels decrease during Mohs micrographic surgery.

BACKGROUND: A common practice is not to operate on patients with elevated blood pressure (BP) levels to avoid cardiovascular and cerebrovascular complications. We therefore designed a study to evaluate the effect of prolonged surgery under local anesthesia on BP levels, and to compare the outcome of patients with elevated BP to those with normal BP. METHODS: We studied 121 patients (65 males) with a mean age of 60 ++/-14 years (range 31-89) who were referred for Mohs micrographic surgery (MMS) during 2 consecutive months. Forty six patients had a history of hypertension. Blood pressure was measured in all subjects in the supine position with an automated device 5 times during surgery. RESULTS: Blood pressure decreased significantly during surgery from 152 +/- 2/85 +/- 1 mm Hg at baseline to 139 +/- 2/79 +/- 1 at the end of the surgery (p < .05). Forty two patients (34%) had elevated BP levels at baseline whereas only 18 patients had these levels at the end of the first stage. There was no difference in surgery outcomes between those with elevated and those with normal BP levels at baseline. CONCLUSIONS: Blood pressure levels decrease during MMS under local anesthesia and the outcome of patients with elevated BP is good. Thus, patients with elevated BP can safely undergo surgery under local anesthesia.

Effect of psoralens and ultraviolet radiation on murine dendritic epidermal cells.

Monofunctional psoralens produce less phototoxicity than bifunctional psoralens after ultraviolet A (UVA) irradiation. We investigated the effect of repetitive treatments with angelicin (isopsoralen), a monofunctional psoralen, plus UVA radiation (IPUVA) on the number and morphology of dendritic epidermal cells (dEC). This effect was compared with that of 8-methoxypsoralen plus UVA radiation (PUVA), UVA alone, and UVB radiation. C3H/HeN mice were treated topically with the drugs three times/wk for 4 consecutive wk; followed each time by 1 or 2.5 J/cm2 of UVA radiation. Other groups of mice were treated with the drugs alone, UVA alone, or 0.81 J/cm2 of UVB. Epidermal sheets were stained for ATPase, Ia, and Thy-1 markers. Mice treated with PUVA and UVB exhibited severe phototoxicity, whereas no overt phototoxicity was observed in mice treated with IPUVA, UVA alone, or the drugs alone. Early during the PUVA and UVA treatments the ATPase marker was lost from dEC, followed by loss of the Ia marker; the Ia marker was lost before the ATPase marker from dEC in animals treated with IPUVA. At the end of the treatment, however, nearly total depletion of ATPase+, Ia+, and Thy-1+ dEC was observed in mice treated with PUVA and IPUVA. UVB radiation caused rapid depletion of Thy-1+ dEC as well as ATPase+ and Ia+ cells. During treatments with IPUVA, PUVA, UVA, and UVB, the Langerhans cells became rounded and lost their dendrites. These changes were quantitated by image analysis. We conclude that alterations of cutaneous immune cells can occur in the absence of overt phototoxicity, and that monofunctional and bifunctional psoralens plus low dose of UVA radiation may have different effects on dEC markers.

The sensitivity of Langerhans cells to simulated solar radiation in basal cell carcinoma patients.

The role of Langerhans cells (LC) in host resistance against the induction and growth of nonmelanoma skin cancers is still obscure. The purpose of this study was to investigate the sensitivity of LC to simulated solar radiation in patients with basal cell carcinoma (BCC). Thirty-four patients (31-74 years old) with at least one histologically diagnosed BCC on a sun-exposed area and 21 healthy volunteers (29-62 years old) were included in the study. Patients and control subjects were given 10 graded doses of simulated solar UV radiation (10-75 mJ/cm2) on the lower back using a 12S solar simulator with a WG 320 filter. Twenty-four hours later, the minimal erythema dose (MED) was determined and shave biopsies were taken from the site given 1.25 X MED and from adjacent, unirradiated skin. Epidermal sheets were stained for LC using the ATPase method. The mean value of the MED of the BCC patients was 25 +/- 2 mJ/cm2 and that of controls was 29 +/- 3 mJ/cm2 (p greater than 0.05). The number of ATPase+ LC was significantly decreased (p less than 0.05), and their morphology was altered in the irradiated skin of nearly all individuals. However, there was no significant difference in the average reduction of LC in the patients (32% +/- 3%) compared with that of control subjects (32% +/- 4%). The depletion of LC ranged from 0% to 74% in different individuals, all of whom were given 1.25 MED. Furthermore, no correlation was found between the percentage decrease in ATPase+ cells and the dose of UV radiation required to produce erythema. Our results indicate that the ability of UV radiation to cause erythema was unrelated to the magnitude of its effects on LC number or morphology. Second, the morphologic alterations of LC in BCC patients after UV irradiation do not differ from those observed in normal individuals. Third, as a group, patients with BCC do not have a significantly lower MED than cancer-free subjects.

Excision repair of pyrimidine dimers induced by simulated solar radiation in the skin of patients with basal cell carcinoma.

One prominent lesion induced in DNA by ultraviolet (UV) radiation is the cyclobutyl pyrimidine dimer formed between adjacent pyrimidines on the same DNA strand. We investigated whether people who have developed basal cell carcinoma on sun-exposed skin have an altered ability to repair UV-induced pyrimidine dimers in DNA. Twenty-two patients with at least one basal cell carcinoma, aged 31-84 years, and 19 healthy volunteers, aged 25-61 years, took part in the study. Both groups were given one minimal erythema dose (MED) of simulated solar radiation on the lower back. DNA was extracted from the irradiated skin 0 to 6 h later, and the number of UV-induced pyrimidine dimers was determined using a dimer-specific endonuclease. At time 0, the average number of dimers per unit of DNA was similar in the two groups. After 6 h, an average of 22 +/- 4% of the dimers were removed in the group with basal cell carcinoma compared to 33 +/- 4% in the cancer-free group. In the basal cell carcinoma group, only 23% of the patients repaired more than 30% of the dimers after 6 h, compared with 53% of the cancer-free subjects (p less than 0.05). We conclude that patients who develop basal cell carcinoma on sun-exposed skin may have a decreased ability to repair pyrimidine dimers induced in skin exposed to simulated solar radiation.

Ultraviolet radiation-induced damage to human Langerhans cells in vivo is not reversed by ultraviolet A or visible light.

Exposure of human skin in vivo to UVB radiation induces pyrimidine dimers in DNA and alters the morphology and function of epidermal Langerhans cells. Cells in human skin have been reported to contain a photoreactivation repair mechanism that, following exposure to UVA or visible light, repairs UVB-induced pyrimidine dimers. The purpose of this study was to determine whether exposure to photoreactivating light would also reverse the UVB-induced morphologic alterations in human Langerhans cells. The skin of eight healthy volunteers was exposed to a low dose of UVB radiation (between 0.75 and 1.5 times the minimal erythema dose), and immediately thereafter exposed to photoreactivating light from either BLB fluorescent lamps (UVA radiation) or incandescent bulbs (visible light). After exposure to UVB radiation, the number of ATPase+ epidermal Langerhans cells was reduced in all subjects to between 21% and 65% of that in unirradiated skin, and the majority of the remaining cells exhibited morphologic alterations. Exposure of the UVB-irradiated skin to photoreactivating light did not reverse or reduce these effects. We conclude that UVB-induced morphologic alterations of human Langerhans cells are not subject to photoreactivation. These results imply either that pyrimidine dimers are not involved in these effects of UVB irradiation, or that photoreactivation does not occur in human Langerhans cells in situ.

Variations in the number and morphology of Langerhans' cells in the epidermal component of squamous cell carcinomas.

We investigated the number and morphology of Langerhans' cells in the epidermal component of squamous cell carcinomas located on the sun-exposed skin of 10 patients. Using adenosine triphosphatase-stained epidermis from the tumors, we compared the Langerhans' cells in squamous cell carcinoma with those in nontumorous skin specimens from the same patient. The nontumorous skin specimen was obtained from either sun-exposed perilesional or non-sun-exposed sites. In three patients a normal number and almost normal morphology of Langerhans' cells were observed within the epidermal component of the tumor. One patient showed a normal number but a profound alteration of the morphology of the cells. In the remaining six patients, a significant decrease in the number of Langerhans' cells was observed. Langerhans' cells within the epidermal component of the tumors of these patients exhibited morphologic alterations in that they were mainly round or oval rather than highly dendritic. In none of our patients was the number of Langerhans' cells in the tumor increased. We conclude that a decreased number and altered morphology of Langerhans' cells occur in some, but not all, squamous cell carcinomas of the skin, and that there is no apparent difference between the number of Langerhans' cells in sun-exposed vs unexposed skin from the same individual.

Local suppression of contact hypersensitivity in mice by a monofunctional psoralen plus UVA radiation.

Monofunctional psoralens, plus UVA radiation are not erythemogenic and are less mutagenic than bifunctional psoralens plus UVA radiation. Thus, they have received considerable attention in recent years as potential therapeutic agents for various skin diseases. The purpose of this study was to examine the immunologic side effects following treatment of mice with a monofunctional psoralen plus UVA radiation. We report that angelicin plus UVA radiation suppressed the induction of contact hypersensitivity to dinitrofluorobenzene. This decreased immune response was associated with the presence of splenic suppressor cells that transferred suppression to normal recipients. Treatment with angelicin and UVA radiation also decreased the number of Thy-1+ and Ia+ dendritic epidermal cells in the treated site. We conclude that although this monofunctional psoralen is not phototoxic, it has immunosuppressive activity in mice.

Analysis of laboratory data in acne patients treated with isotretinoin: is there really a need to perform routine laboratory tests?

INTRODUCTION: Isotretinoin has been used to treat acne since 1982. Its current indications in the package insert are limited and many physicians still feel uncomfortable prescribing it because of its side effects. Serum levels of liver enzymes and lipids are carried out as a routine in most clinics both before and during treatment. AIMS: Our objective was to evaluate the effect of isotretinoin on serum lipids, liver function and other laboratory parameters in order to assess the necessity to perform routine laboratory tests. METHODS: Computerized medical files of 1292 patients in private practice that received isotretinoin for acne were analyzed. RESULTS: 907 patients completed a treatment course of 5 to 9 months. Serum levels of liver enzymes were not elevated to a degree necessitating discontinuation of treatment. Only 1.5% of the patients had serum triglyceride levels above 400 mg%. No laboratory abnormalities were a cause for discontinuation of treatment. During a 6-year follow up only 3.5% of patients received a second course of therapy with isotretinoin. CONCLUSIONS: Aside from its teratogenic effect, isotretinoin is a safe and excellent drug for acne therapy. It should be prescribed for any inflammatory acne and in our opinion there is no need for a routine laboratory follow-up in young, healthy patients aside from a pregnancy test in females. At present, isotretinoin should be considered as the drug of choice for moderate to severe acne.

Multiple dermal fibroblasts in patients with pruritic urticarial papules and plaques of pregnancy. A clue to the etiology?

We have recently demonstrated that in pruritic urticarial papules and plaques of pregnancy (PUPPP) there are multiple dermal fibroblasts with no deposition of mucin. We suggest that in the dermis of patients with PUPPP there is a deposition of a substance that induces fibroblasts proliferation. We assume that this substance (marked as F-substance) is a product of the placenta, which is released to the maternal circulation during pregnancy.

Pruritic urticarial papules and plaques of pregnancy. A review of 21 cases.

Twenty-one patients with pruritic urticarial papules and plaques of pregnancy (PUPPP) were reviewed. Direct immunofluorescence (DIF) examination was negative in all patients. DIF in patients with PUPPP is a useful and reliable laboratory aid in distinguishing this peculiar dermatosis from herpes gestationis.

Mask phenomenon: postemesis facial purpura.

A bizarre form of purpura seen on the face and neck after vigorous vomiting is described. Physicians should be familiar with this form of purpura since patients are very concerned about the mask that appears suddenly. Recovery is spontaneous, and no treatment is needed.

Basal cell carcinoma occurring at the site of a strawberry hemangioma.

A twenty-seven-year-old white woman presented with a basal cell carcinoma at the former site of a strawberry hemangioma. The strawberry hemangioma had been treated in infancy with dry ice. The lesion spontaneously regressed and left no visible scar. To our knowledge, this is the first reported association of basal cell carcinoma and strawberry hemangioma.

Lack of association between varicocele and angiokeratoma of the scrotum (Fordyce).

Angiokeratoma of the scrotum is thought to be associated with varicocele. Our study population consisted of young soldiers and adult reservists. The young population was screened during routine medical examination for the existence of varicocele or angiomas on the scrotum, while the adult reservists, who according to their medical records had varicocele, were randomly questioned for the existence of any kind of spots or lesions on their scrota. We found no association between varicocele and angiokeratoma of the scrotum. Since the prevalence of varicocele is high, it is possible that in the reported cases the association of varicocele and angiokeratoma of the scrotum was coincidental.

Skin diseases unique to the pregnant woman.

Skin disorders are often associated with pregnancy. Most of these disorders are physiologic but some are pathologic. The following review focuses on skin diseases that are unique to pregnancy.