Giant congenital nevus with progressive sclerodermoid reaction in a newborn.

Giant congenital melanocytic nevi are a rare occurrence in the pediatric population. The risk of malignant transformation associated with these lesions has been well established; however, the management strategies for giant congenital nevi remain controversial. We report an unusual sclerodermoid reaction in a giant congenital nevus in a 6-week-old Caucasian girl. Given its abnormal clinical appearance, the entire lesion was excised. The histology was consistent with an atypical compound/sclerosing spindle and epithelioid cell congenital nevus. No evidence of malignant change was seen histologically. The incidence of malignant transformation in giant congenital nevi has been difficult to calculate. Review of the literature yields an incidence of between 4 and 9%, favoring surgical excision of these lesions where possible. Atypical presentations of giant congenital nevi are rare, and we have found no other reported cases with a stromal change similar to that seen in our patient. We hypothesize that this change may represent an atypical host reaction to the nevus cells.

Chromosome abnormalities in malignant melanoma: clinical significance of nonrandom chromosome abnormalities in 206 cases.

We report the cytogenetic abnormalities from a series of 206 primary malignant melanoma specimens referred to a single institution. A total of 169 out of 206 unique cases had chromosome breakpoints. A previously described statistical method was used to detect nonrandom distribution of chromosome breakpoints at the level of chromosome regions. Nonrandom occurrence of chromosome breakpoints (indicating that the observed number of breaks significantly exceeded the expected number of breaks) was detected in 28 regions, suggesting a hierarchy of genetic abnormalities in melanoma. Clinical variables and tumor characteristics were analyzed for associations with the presence of any nonrandom chromosome breakpoints; with individual, nonrandomly involved chromosome regions; and with paired, nonrandomly involved chromosome regions. No nonrandomly involved chromosome regions or pairs of regions appeared to significantly affect survival. These results identify recurring, nonrandom chromosome abnormalities in malignant melanoma. These results suggest that recurring, nonrandom chromosome alterations play a key role in the etiology and/or progression of malignant melanoma and identify targets within the genome for molecular genetic studies.

Lymphomatoid granulomatosis in a 4-year-old boy.

Lymphomatoid granulomatosis is a necrotizing angiocentric and angiodestructive infiltrative process involving primarily the lung, skin, central nervous system, and kidney. The incidence is highest in middle-aged men and is rare in children. We report a case of lymphomatoid granulomatosis involving both skin and lung in a 4-year-old boy. The disease progressed to peripheral T-cell lymphoma, which was unusual in light of recent evidence suggesting a B-cell origin in the majority of cases.

Dermal toxicity of topical (-)epigallocatechin-3-gallate in BALB/c and SKH1 mice.

(-)Epigallocatechin-3-gallate (EGCG), the major polyphenolic component of green tea, inhibits experimental chemical and physical carcinogenesis, yet little toxicological data has been reported. Therefore, we performed studies on the dermal toxicity of EGCG applied in an ointment formulation in mice. Female BALB/c mice were dehaired with a topical depilatory and administered 75 microl EGCG in hydrophilic Ointment U.S.P. at three concentrations (10, 3, and 1%, all w/w) daily for 30 days. At the 10% concentration, gross toxicity was manifested by the formation of erythema and papular lesions by day 5. A 7% reduction in weight was observed by day 15. No toxicity was observed at the two lower concentrations or in the vehicle control group. Also, no toxicity was observed when mice were dehaired by shaving. This study was repeated in female SKH1 mice, an outbred hairless strain that does not require depilation. No toxicity was observed in the SKH1 mice, indicating that daily topical EGCG appears non-toxic in normal skin. However, use of topical depilatories may potentiate dermal toxicity of EGCG.

Expression in normal human tissues of five nucleotide excision repair genes measured simultaneously by multiplex reverse transcription-polymerase chain reaction.

DNA repair is central to the integrity of the human genome. Reduced DNA repair capacity has been linked to genetic susceptibility to cancer. An adequate expression level of DNA repair genes is essential for normal DNA repair activities. Although there is tissue specificity in the expression, searching for a surrogate tissue is needed for molecular epidemiological studies. In this study, the relative expression levels of five selected human nucleotide excision repair (NER) genes (ERCC1, XPB/ERCC3, XPG/ERCC5, CSB/ERCC6, and XPC) in 20 different types of human normal tissue were simultaneously measured by a new multiplex reverse transcription (RT)-PCR assay using the expression level of the beta-actin gene as an internal control. Transcripts of each of the five NER genes were detectable, but the levels varied in these normal tissues. Both mitogen (phytohemagglutinin)-stimulated and unstimulated human peripheral lymphocytes showed similar expression patterns for the five NER genes. In general, the expression levels of stimulated lymphocytes were also similar to most of the rapidly proliferating tissues, such as the skin, breast, intestine, liver, testis, ovary, placenta, or prostate, but was relatively higher than that of the slowly proliferating or nonproliferating tissues such as adipose, brain, hippocampus, muscle, spleen, or lung. The data suggested that although the five NER genes were expressed at different levels in the normal tissues examined, PHA-stimulated peripheral lymphocytes may be used as a surrogate tissue for estimating expression levels of these genes in proliferating tissues. This new multiplex RT-PCR assay may help detect aberrant expression of these NER genes in both normal and tumor tissues.

Effect of retinol in preventing squamous cell skin cancer in moderate-risk subjects: a randomized, double-blind, controlled trial. Southwest Skin Cancer Prevention Study Group.

We conducted a randomized, double-blind, controlled trial to examine the efficacy of retinol supplementation on the incidence of first new nonmelanoma skin cancer in moderate-risk subjects. A total of 2297 free-living subjects were enrolled; subjects resided in Arizona (median age, 63 years) and had a history of more than 10 actinic keratoses and at most 2 squamous cell carcinoma (SCC) or basal cell carcinoma (BCC) skin cancers. Subjects were randomly assigned to receive oral retinol (25,000 IU) or placebo supplementation daily for up to 5 years. The primary end points for the trial were time to first new SCC or BCC. During a median follow-up time of 3.8 years, we found that 526 subjects had a first new skin cancer. Comparing retinol-supplemented subjects with placebo-supplemented subjects showed a hazard ratio for first new SCC of 0.74 (95% confidence interval, 0.56-0.99; P = 0.04). The hazard ratio of first new BCC for the retinol-supplemented subjects compared with those receiving placebo was 1.06 (95% confidence interval, 0.86-1.32; P = 0.36). Potentially adverse symptoms that were judged to be associated with retinol were rare (approximately 1% higher in the retinol group than in the control group). Therefore, we concluded that daily supplementation with 25,000 IU of retinol was effective in preventing SCC, although it did not prevent BCC.

Trial of retinol and isotretinoin in skin cancer prevention: a randomized, double-blind, controlled trial. Southwest Skin Cancer Prevention Study Group.

The objective of this study was to examine the effect of retinol and isotretinoin on the incidence of nonmelanoma skin cancer in high-risk subjects. A total of 525 participants with a history of at least four basal cell carcinomas (BCCs) and/or cutaneous squamous cell carcinomas (SCCs) were entered into a randomized, double-blind, placebo-controlled trial, performed in free-standing study clinics. Participants were randomly assigned to receive oral retinol (25,000 units), isotretinoin (5-10 mg), or placebo supplementation daily for 3 years. The time to first new occurrence of BCC or cutaneous SCC was used as the outcome measure. During the study period, 319 BCCs and 125 cutaneous SCCs were diagnosed clinically and pathologically. There were no differences between those who received retinol, isotretinoin, or the placebo, with regard to the time to first occurrence or to the total number of tumors noted. No beneficial effects were noted with regard to the prevention of nonmelanoma skin cancer with either retinol or isotretinoin.

Retinoids in prevention of skin cancer.

Two chemoprevention randomized clinical trials were begun in 1984 to evaluate retinoids in the prevention of skin cancers. Moderate risk subjects with a history of at least 10 actinic keratoses and at most two prior skin cancers were enrolled in the SKICAP-AK trial and randomized to 25,000 IU retinol or placebo daily for 5 years. High risk subjects with a history of at least four prior skin cancers were enrolled in the SKICAP-S/B trial and randomized to receive 25,000 IU retinol, 5-10 mg isotretinoin or placebo daily for 3 years. Data from the SKICAP-AK trial indicate that retinol reduces incidence of first new squamous cell skin cancers but had no effect on the incidence of first new basal cell skin cancer. The effect of retinoids had no significant benefit on squamous or basal cell skin cancers in the high risk subjects on the SKICAP-S/B trial, although intervention duration was less than planned. Daily retinol was effective in preventing squamous cell cancers in moderate risk subjects.

Design and recruitment for retinoid skin cancer prevention (SKICAP) trials. The Southwest Skin Cancer Prevention Study Group.

The retinoid skin cancer prevention (SKICAP) trials are a set of double-blind, randomized, placebo-controlled clinical trials. The SKICAP-actinic keratoses (AK) trial tests the hypothesis that daily supplementation of retinol (25,000 IU) for 5 years reduces the incidence of skin cancers in high-risk individuals, those with a history of greater than ten clinically or pathologically diagnosed AK and, at most, one prior pathologically confirmed cutaneous squamous cell carcinoma (SCC) or basal cell carcinoma (BCC). The SKICAP-SCC/BCC (S/B) trial tests the hypothesis that daily supplementation of retinol (25,000 IU) or 13-cis-retinoic acid (5 or 10 mg) for 3 years reduces skin cancer incidence in very high-risk individuals, those with a history of at least four pathologically confirmed SCCs or BCCs. Between 1984 and 1988, 2800 participants were enrolled at two clinics on the SKICAP-AK trial; and between 1985 and 1990, a total of 719 participants were enrolled at four clinics on the SKICAP-S/B trial. The initial recruitment strategy was referral by dermatologists, but low accrual necessitated the use of other strategies to achieve enrollment goals, which included involving additional clinics and using paid trial-specific advertisements in print and electronic media. Thirteen % of the SKICAP-AK participants and 36% of the SKICAP-S/B participants were enrolled through dermatologist referral, whereas paid advertisements resulted in enrollment of 87% of SKICAP-AK and 43% of SKICAP-S/B participants. A population-based skin cancer registry was used to identify and enroll the remaining 21% of the SKICAP-S/B participants.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of the p53 gene in human precancerous actinic keratosis lesions and squamous cell cancers.

A biomarker of skin cancer would be beneficial in evaluating the efficacy of potential cancer chemoprevention agents. To this end, we investigated the tumor suppressor gene p53 in precancerous actinic keratosis lesions (AK) and malignant squamous cell carcinomas (SCCs) using polymerase chain reaction and single-strand conformation polymorphism analysis (PCR-SSCP) techniques. In addition, p53 protein expression was evaluated using immunohistochemistical analysis with the PAB 1801 monoclonal antibody. Nine out of 13 (69%) SCCs and 8 of 15 (53%) AKs were positive for p53 mutations. In contrast, normal skin samples were negative for p53 mutations. Sequence analysis of AKs and SCCs showed primarily C to T transition mutations. Nuclear immunochemical staining for p53 was observed in 12/15 (80%) AK and 12/13 (92%) SSCs. These results suggest that p53 mutations may be involved in the malignant conversion of AKs to SCCs and that p53 may be useful as a biomarker to study the potential modulatory effects of cancer chemopreventive agents against skin cancer.

Ciprofloxacin-induced granulomatous interstitial nephritis and localized elastolysis.

Ciprofloxacin is known to cause acute interstitial nephritis. We report the first case of ciprofloxacin-induced granulomatous interstitial nephritis and localized elastolysis. The patient presented with acute renal failure and skin lesions following a 14-day course of ciprofloxacin administered for cellulitis. The patient had symmetric, palm-sized, tender violaceous plaques on both axillae. The renal biopsy revealed granulomatous interstitial disease. A skin biopsy revealed an elastolytic process with histocytic infiltration and calcification. After discontinuing ciprofloxacin and starting a short course of steroid therapy, the skin lesion and renal function improved promptly. The nephritis relapsed after prednisone was discontinued and responded to a second course of steroid therapy. Ciprofloxacin, like penicillin, can cause granulomatous interstitial nephritis and elastolysis. A prolonged course of steroid therapy may be indicated in patients with ciprofloxacin-induced granulomatous interstitial nephritis to avoid early relapse.

Benign pigmented apocrine vulvar hamartomas.

Pigmented vulvar lesions were observed in a child during a sexual abuse evaluation. Gross examination of the lesions appeared most consistent with bowenoid papulosis; however, biopsy confirmed the lesions to be pigmented apocrine hamartomas. To our knowledge, these rare and benign tumors have never been described as pigmented, but should be added to the differential diagnosis of pigmented vulvar lesions.

Histologic evaluation of rat mammary tumor necrosis by interstitial Nd:YAG laser hyperthermia.

The extent of coagulative necrosis caused by interstitial laser hyperthermia was measured for different quantities of laser energy in a rat mammary tumor model. Continuous wave Nd:YAG laser at a power level of 5 W was focused onto a 600 mu diameter bare tip quartz fiber and placed inside a 19-gauge needle, which allowed the para-axial flow of normal saline at 1 cc/min. A microthermocouple soldered to the outside of the probe continuously provided the interstitial temperature. After the probe was inserted into the tumor, it was withdrawn as laser energy was administered at a rate sufficient to maintain the temperature within 42-45 degrees C. Tumors were excised after 48 hours, fixed in formalin, cut in 3 mm slices, and the coagulated surfaces measured microscopically. Laser fiber transmission loss was 1% per 1,000 J of laser energy and the average time required to coagulate 1 cc of tumor was 2 minutes. There was a statistically significant correlation between the volume of tumor necrosis and the level of laser irradiation (r = 0.71, P less than 0.001). It is concluded that the described technique is an efficient method of tumor coagulation by interstitial laser hyperthermia and proportionally larger volumes of necrosis are created with greater amounts of laser energy.

The role of radiotherapy in the treatment of malignant sweat gland neoplasms.

Malignant sweat gland neoplasms are rare tumors. Historically, the principal mode of treatment has been local surgical excision. Eight published studies show that greater than 50% of patients develop either local tumor recurrence after surgery or regional lymph node metastases. Most patients have evidence of locoregional failure before distant metastases are detected. Three patients were recently referred to the University of Arizona Cancer Center for consideration of irradiation after resection of such tumors. In two patients, the tumor was located on the scalp and, in one patient, on the alar surface of the nose. Their ages ranged from 19 to 60 years. All underwent surgical resection followed by high-dose irradiation of the surgical bed (approximately 70 Gy) and regional lymphatic chains (approximately 50 Gy). Two patients remain disease-free at 27 and 35 months, respectively, after completion of treatment; the third died of rapidly progressive systemic metastases. A review of the literature is provided focusing on treatment success and predominant patterns of recurrence. Finally, a rational approach for evaluation of patients that might benefit from local irradiation is presented.

Protection of fiber function by para-axial fluid flow in interstitial laser therapy of malignant tumors.

In the past, interstitial laser therapy frequently has failed because of the damage to the bare fiber tip due to intense heat generated at the point of contact. Using a rat mammary tumor model, we describe a method of placing a 600 micron fiber inside a gauge 19 needle cannula after its insertion into the tumor. With this device continuous wave Nd:YAG laser is delivered to the target tumor while 0.9% saline flows para-axially into the tumor. Significant coagulation necrosis was induced with 500 joules at 5 watts, 100 seconds and 1 cc per minute of saline while the needle-fiber is pulled out of the tumor by 10 mm. The mean transmission loss after 500 joules was 2% in ten experiments. The tumor edema due to 1.5 ml of saline was transient. We conclude that successful hyperthermic coagulation necrosis by Nd:YAG laser can be achieved with minimal transmission loss by employing the above technique.