Faculty Bibliography

We present a 21-year-old primigravida woman with a several-week history of pruritic, edematous, targetoid plaques that appeared initially on the abdomen, flanks, and legs and that progressed to involve the inner aspects of the upper arms and lateral aspects of the chest. The histopathologic findings showed perivascular and interstitial dermatitis with eosinophils and vacuolar changes with linear C3 deposition at the basement-membrane zone on direct immunofluorescence study. A diagnosis of pemphigoid gestationis was made. Pemphigoid gestationis is a rare, bullous dermatosis of pregnancy that may be associated with prematurity and small-for-gestational age birth weights. The diagnosis is often made with direct immunofluorescence studies of perilesional skin. Oral glucocorticoids remain the gold standard of therapy in moderate-to-severe cases. The edematous papules and plaques of pemphigoid gestationis may be particularly difficult to distinguish from polymorphic eruption of pregnancy; therefore, immunofluorescence studies are prudent. Prompt recognition and appropriate management may reduce morbidity of this disease, which often recurs with subsequent pregnancies.

Desquamative inflammatory vaginitis (DIV) is a chronic disorder associated with yellow vaginal discharge, vulvovaginal burning and pruritus, and dyspareunia. The cause of DIV is unknown; however, infectious, hormonal, and inflammatory etiologies have been proposed. In this series, we observe the association of DIV and vitamin D deficiency by reporting 4 cases of women with DIV and vitamin D deficiency associated with Crohn disease. We further show that the DIV symptoms resolve when the circulating concentrations of 25-hydroxyvitamin D (25-HD) returned to normal. These data provide further support for the notion that DIV can be associated with vitamin D deficiency and DIV symptoms reflect altered vaginal mucous membrane function

A 61-year-old-man presented with a sudden onset of multiple, hyperpigmented papules with a central punctum on the face, chest, upper back, and arms. Histopathologic examination showed infundibular cysts. These findings are consistent with a diagnosis of multiple eruptive milia, which is a rare disorder that is characterized by the sudden development of crops of milia over weeks to months. They are more extensive in number and distribution than they are in primary milia. Milia may present spontaneously without a known cause, as part of an inherited familial condition, or as part of a genodermatosis. The etiologies are uncertain, and treatment options are varied

Androgen receptor (AR) is expressed in both stromal and epithelial cells of the prostate. The majority of studies on AR expression and function in prostate cancer is focused on malignant epithelial cells rather than stromal cells. In this study, we examined the levels of stromal AR in androgen-dependent and -independent prostate cancer and the function of stromal AR in prostate cancer growth and invasion. We showed that stromal AR levels were decreased in the areas surrounding cancerous tissue, especially in androgen-independent cancer. Using two telomerase-immortalized human stromal cell lines, one AR-positive and the other AR-negative, we demonstrated that stromal cells lacking AR stimulated cell proliferation of co-cultured prostate cancer cells in vitro and enhanced tumour growth in vivo when co-injected with PC3 epithelial cells in nude mice. In contrast, stromal cells expressing AR suppressed prostate cancer growth in vitro and in vivo. In parallel with cancer growth, in vitro invasion assays revealed that stromal cells lacking AR increased the invasion ability of PC3 cell by one order of magnitude, while stromal cells expressing AR reduced this effect. These results indicate a negative regulation of prostate cancer growth and invasion by stromal AR. This provides potentially new mechanistic insights into the failure of androgen ablation therapy, and the reactivation of stromal AR could be a novel therapeutic approach for treating hormone refractory prostate cancer.

A 64-year-old man presented with a superficial, well-demarcated, skin-colored tumor on the left posterior scalp that measured 4 x 5 x 6 cm. The tumor was nearly hairless, rubbery, non-tender, and mobile over the underlying subcutaneous tissues. The lesion had grown slowly since arising approximately 30 years ago. Treatment options were declined in the past. However, with relatively more rapid growth over the past five years, the nodule began to cause intermittent pain and interfere with the patient's ability to lie on his back. The patient denied a history of similar lesions in himself or his family. A biopsy specimen showed a ruptured proliferating trichilemmal cyst with focal calcification. Complete excision is recommended for all benign proliferating variants owing to their potential for locally aggressive behavior and malignant transformation

We report a rare case of granular cell tumor in the scrotum. Granular cell tumors are soft-tissue neoplasms originating from Schwann cells that rarely affect male external genitalia. They are essentially benign; therefore, the treatment is complete excision of the lesion. Although never previously reported in the male external genitalia, malignant variants exist in 2% of cases. Because the clinical presentation is not specific, the diagnosis of malignant granular cell tumors can be made only by the pathologist. To our knowledge, only 5 other cases in the scrotum and 19 cases described in the penis have been reported

Ultraviolet light exposure is the major risk factor for the development of squamous cell carcinoma in Caucasians. Mutations in the tumor suppressor gene p53 have been identified in both squamous cell carcinomas and basal cell carcinomas. The human homolog of the Drosophila patched gene, has been shown to be mutated in sporadic basal cell carcinomas; however, mutations in the patched gene have not been found in squamous cell carcinoma. In this study, we screened a total of 20 squamous cell carcinoma samples for mutations in the patched gene. Using polymerase chain reaction-single strand conformation polymorphism as an initial screening method, we identified one non-sense mutation, two mis-sense mutations and three silent mutations in five squamous cell carcinoma samples. In one squamous cell carcinoma sample, we identified a tandem GG-->AA transitional change at nucleotide 3152 in exon 18 of the patched gene that resulted in a premature stop codon at codon 1051. The three squamous cell carcinoma samples containing non-sense and mis-sense mutations were isolated from individuals with histories of multiple basal cell carcinoma. Sequence analysis of the p53 gene in these five squamous cell carcinoma samples identified one CC-->TT and three C-->T ultraviolet-specific nucleotide changes. Our study provides evidence that the patched gene is mutated in squamous cell carcinoma from individuals with a history of multiple basal cell carcinoma. The identification of ultraviolet-specific nucleotide changes in both tumor suppressor genes supports the notion that ultraviolet exposure plays an important part in the development of squamous cell carcinoma.

Basal cell carcinoma (BCC) is the most common skin cancer in the Western world. Ultraviolet (UV) exposure, race, age, gender, and decreased DNA repair capacity are known risk factors for the development of BCC. Of these, UVB irradiation from sunlight is the most significant risk factor. The incidence of sporadic BCC increases in individuals older than age 55, with the greatest incidence reported in individuals who are older than 70, and is rare in individuals who are younger than 30. In this study, we analyzed 24 BCC samples from individuals who had BCC diagnosed by the age of 30. Fifteen single-stranded conformation polymorphism variants in the PTCH gene were identified in 13 BCC samples. Sequence analysis of these single-stranded conformation polymorphism variants revealed 13 single nucleotide changes, one AT insertion, and one 15-bp deletion. Most of these nucleotide changes (nine of 15) were predicted to result in truncated PTCH proteins. Fifteen p53 mutations were also found in 11 of the 24 BCC samples. Thirty-three percent (five of 15) and 60% (nine of 15) of the nucleotide changes in the PTCH and p53 genes, respectively, were UV-specific C-->T and CC-->TT nucleotide changes. Our data demonstrate that the p53 and PTCH genes are both implicated in the development of early-onset BCC. The identification of UV-specific nucleotide changes in both tumor suppressor genes suggests that UV exposure is an important risk factor in early onset of BCC.

UVB irradiation is known to produce DNA damage at mutation hotspots in the p53 tumor suppressor gene, leading to the development of skin cancers. Mutations in the PTCH tumor suppressor gene, which is known to be responsible for the development of nevoid basal cell carcinoma syndrome, have also been identified in sporadic basal cell carcinomas (BCCs). We describe the case of an 80-year-old welder in whom 3 novel p53 mutations, as well as UV-specific PTCH mutations, were detected in two BCC samples from sun-exposed skin. The simultaneous presence of UV-specific p53 and PTCH mutations in the same BCC sample has not previously been reported.