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.

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.

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.

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.

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.

Syringocystadenoma papilliferum. A plasmacytotropic tumor.

Seven cases of syringocystadenoma papilliferum were studied by immunohistochemical methods for the presence of IgG, IgA, IgM, and secretory component in tumor epithelial cells and IgG, IgA, and IgM in plasma cells underlying the tumor epithelium. Six of seven cases showed IgA positivity within epithelial cells, one case showed faint intraepithelial IgG staining, and none stained for IgM. Four of five cases were positive for secretory component. The plasma cells were predominantly of the IgG and IgA class. These findings suggest that the association of plasma cells with this tumor is a consequence of epithelial attraction via a mechanism similar to that utilized by glands of the normal secretory immune system.

Subacute cutaneous lupus erythematosus and discoid lupus erythematosus. Comparative histopathologic findings.

Subacute cutaneous lupus erythematosus (SCLE) is a recently described distinct subset of lupus erythematosus (LE) having characteristic clinical, serologic, and genetic findings. This study describes the histopathologic characteristics of SCLE and determines whether it could be differentiated from discoid lupus erythematosus (DLE) on histopathologic grounds alone. Biopsy specimens from 33 patients having either SCLE or DLE, as defined by strict clinical criteria, were examined without knowledge of the clinical diagnosis. Histologic discrimination between SCLE and DLE was accomplished in 82%. The specimens from DLE lesions had substantially more hyperkeratosis, basement membrane thickening, follicular plugging, and superficial and deep inflammatory cell infiltrate, while SCLE had more epidermal atrophy. The histopathologic differences between SCLE and DLE further support the concept that SCLE is distinct from DLE and should be considered a unique subset of LE.

Murine graft-versus-host skin disease: a chronologic and quantitative analysis of two histologic patterns.

Human graft-versus-host disease (GVHD) has several cutaneous manifestations, including a lichenoid and a sclerotic injury pattern. A versatile animal model of graft-versus-host skin disease (GVHSD) would facilitate study of the pathophysiology of these two cutaneous injury patterns. We have examined two murine chimeras histologically and have found two distinct patterns. Allogeneically transplanted B1/6 mice show a prolonged lichenoid-interface dermatitis that eventuates in clinical alopecia, whereas LP/J recipients of allogeneic cells do not show hair loss. Their histopathology consists of an early lichenoid phase that abates and is replaced by dermal sclerosis. Because of the versatility of the mouse as a laboratory animal, we feel that this model provides an excellent opportunity to define the immunopathologic mechanisms responsible for skin injury in GVHD. In addition, an understanding of the pathogenesis of the T cell-dependent, lichenoid, and sclerotic patterns of tissue injury in GVHSD might well provide insight into the pathogenesis of the GVHSD analogs, cutaneous lupus erythematosus and scleroderma.

Herpes gestationis: clinical and histologic features of twenty-eight cases.

We have studied 28 patients with well-documented herpes gestationis (HG) to determine the frequency of complications and to review the histopathology, immunopathology, and clinical parameters of disease. The frequency of miscarriages and other maternal complications in our series was not extraordinary. Fetal complications were similarly limited. Less than 5% of infants had cutaneous lesions, and no other untoward fetal complications were apparent. Although the clinical features of our patients largely paralleled those typically reported for patients with HG, several variants of disease were noted. We report one woman with immunofluorescence-confirmed HG who had no clinical disease during a subsequent pregnancy. We also identified cases in which the characteristic vesiculobullous lesions of HG never developed. Instead, four women had urticarial papules or plaques throughout their clinical courses. HG was verified in these four women by typical immunofluorescent findings and by recurrent, classical disease during subsequent pregnancies in two. In addition, two women were identified with recurrent HG during pregnancies by different husbands.

Amyloidosis presenting as priapism.

A sixty-five-year-old white man presented with sudden onset of painful, priapism. Review of pathologic specimens at the time of surgical decompression revealed massive amyloid infiltration. Purpura, organ enlargement, gastrointestinal bleeding, and congestive heart failure developed subsequently. Postmortem examination revealed widespread amyloidosis. To our knowledge this is the first report of amyloidosis presenting with priapism.