David N. Silvers

Discordance in the histopathologic diagnosis of difficult melanocytic neoplasms in the clinical setting

Background:  The gold standard for diagnosing melanocytic neoplasms is by histopathologic examination. However, lack of agreement among expert dermatopathologists in evaluating these tumors has been well established in experimental settings.

Identification of PTEN mutations in metastatic melanoma specimens

CONTEXT PTEN,a tumour suppressor gene located on chromosome 10q23, develops somatic mutations in various tumours and tumour cell lines including brain, endometrium, prostate, breast, kidney, thyroid, liver, and melanoma. OBJECTIVES To investigate the mutational profile of this gene further, as well as its role in tumour progression in melanoma. DESIGN, SETTINGS We examined 21 metastatic melanoma samples for 10q23 allelic losses andPTEN sequence alterations. Additionally, we screened these samples for mutations inCDKN2A, a gene in which alterations are well documented in primary melanoma as well as in the germline of familial melanoma. RESULTS Loss of heterozygosity (LOH) at 10q23 was observed in 33% (7/21) of the samples tested. We identified four sequence alterations in PTEN(19%) and two in CDKN2A (9.5%). Of interest, only one case showed mutations in both genes. CONCLUSIONS These data support the notion that PTEN alterations occur in some metastatic melanomas, and that mutation of this gene plays a role in the progression of some forms of melanoma.

Histologic spectrum of neurothekeoma and the value of immunoperoxidase staining for S-100 protein in distinguishing it from melanoma.

Neurothekeoma, a benign cutaneous lesion of probable nerve sheath origin, is divided histologically into two subtypes--myxoid and cellular. However, we believe that neurothekeoma encompasses a wider spectrum of lesions, with the myxoid and cellular subtypes falling at either end of the morphologic spectrum. Because the cellular variant of neurothekeoma sometimes resembles melanoma, it presents a difficult diagnostic problem. We report the histologic and immunohistochemical findings in 14 cases of neurothekeoma and review the findings in 35 additional cases from the literature. A detailed analysis of the histologic spectrum is also included. When examined by immunostains, only the myxoid variants of neurothekeoma stain positively for S-100 protein. We conclude that when the histological differential diagnosis is between cellular neurothekeoma and melanoma, an S-100-positive lesion should be regarded as melanoma.

Nephrogenic Systemic Fibrosis and Its Impact on Abdominal Imaging

The objective of this article is to review the current knowledge about nephrogenic systemic fibrosis (NSF) and how to prevent it. More than 300 cases of NSF in patients with severe chronic renal insufficiency or acute renal failure or in patients undergoing dialysis have been reported in the peer-reviewed literature, with an overwhelming majority occurring within weeks to months after injection of a gadolinium-based contrast agent (GBCA). Because administration of a high dose of a GBCA is a primary risk factor and because most high-dose magnetic resonance (MR) imaging applications involve abdominal imaging (eg, liver and abdominal MR angiography), NSF cases have been associated with abdominal MR imaging. Additional major risk factors for developing NSF include proinflammatory conditions, failure to perform dialysis promptly after GBCA administration, use of nonionic linear contrast agents, hyperphosphatemia, and younger age. Recent recommendations to use GBCAs with caution in patients with acute renal failure, patients receiving dialysis, or patients with an estimated glomerular filtration rate of less than 30 mL/min have resulted in virtually no new NSF cases being reported with onset in 2008 or 2009 in spite of a high level of awareness about this entity. In conclusion, NSF has been virtually eliminated by using caution in administering GBCAs to patients known to have severe or acute renal failure. In these patients, avoid high doses; and for patients undergoing dialysis, schedule MR imaging to occur just before a dialysis session to ensure rapid elimination of gadolinium.

Cutaneous lesions of disseminated histoplasmosis in human immunodeficiency virus-infected patients

Disseminated histoplasmosis is being diagnosed more frequently in persons infected with the human immunodeficiency virus and is often the initial manifestation of the acquired immunodeficiency syndrome (AIDS). Disease-related cutaneous features of HIV-associated disseminated histoplasmosis are defined as mucocutaneous lesions from which fungal organisms were either cultured or demonstrated histopathologically. We report four HIV-seropositive patients with disseminated histoplasmosis who had culture-positive skin or oral lesions of histoplasmosis and review the specific cutaneous manifestations of HIV-associated disseminated histoplasmosis. Including our patients, disease-related skin and/or mucosal lesions were present in 11% of patients (26% of 239) with HIV-associated disseminated histoplasmosis. The possibility of disseminated histoplasmosis should be considered in all HIV-infected persons and in persons with AIDS risk factors who have fever, weight loss, hepatosplenomegaly, and new cutaneous lesions. An early skin or mucosal biopsy specimen for crushed tissue preparation, histologic evaluation, and fungal culture is a simple, rapid diagnostic procedure.

Invasive Trichophyton rubrum resembling blastomycosis infection in the immunocompromised host

A 55-year-old renal transplant recipient with onychomycosis and chronic tinea pedis presented with tender nodules on his left medial heel. He then developed papules and nodules on his right foot and calf. A skin biopsy demonstrated periodic acid-Schiff (PAS) positive, thick walled round cells, 2 to 6 microm in diameter, in the dermis. Skin biopsy culture grew Trichophyton rubrum. T. rubrum has been described as an invasive pathogen in immunocompromised hosts. The clinical presentation, histopathology, and early fungal culture growth suggested Blastomyces dermititidis in the differential diagnosis before the final identification of T. rubrum.

Role of PTCH and p53 Genes in Early-Onset Basal 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.

Melanocytic nevi in neonates

The histologic features of seven congenital nevi within 3 months of birth were studied, together with the ultrastructural features of one of the lesions examined microscopically within 48 hours of birth. All seven lesions showed melanocytic hyperplasia within the epidermis and within pilosebaceous and eccrine sweat units. Nevus cells within the dermis were located in proximity to the adnexae. Melanocytic hyperplasia within the epidermis showed a variety of patterns, at least one of which simulated the atypical melanocytic hyperplasia seen in the superficial spreading type of melanoma. The fine structure of the melanosomes in one case studied by electron microscopy resembled hair-bulb melanosomes. They were distinctly different from melanosomes characteristic of epidermal melanocytes, nevus cells, or melanoma cells.

Intralesional Corticosteroid Therapy of Chalazia

Twelve adult patients with 17 chalazia underwent trial intralesional injection of triamcinolone acetonide. Seven chalazia resolved within two weeks after only one injection, and another six after two injections. Two lesions failed to respond to two injections, and two lesions responded to one injection, but either recurred or another lesion developed. Patients were satisfied with the procedure, which appears to be a safe, convenient, and effective altefnative to chalazion surgery.

Skin Resurfacing of the Face with the Erbium:YAG Laser

background. Laser resurfacing of facial skin is a very popular method of rhytide and scar removal. Until recently, the most effective tool utilized for these purposes was the pulsed char‐free carbon dioxide laser. These lasers, however, produce thermal damage related to prolonged wound healing. The Erbium (Er): YAG laser, with its 2940‐nm wavelength and maximal water absorption, has been recently introduced for laser resurfacing of the facial skin. objective. In this study, specific parameters for Er:YAG laser treatment of rhytides were evaluated clinically and histologically. methods. Fifteen patients were treated with the Er:YAG laser. Perioral, periorbital, and total face rhytides were treated. All patients were treated with 0.8–1.0 J, 5‐mm spot size, with the final fluences of 4–5 J/cm2. Patients were evaluated daily after treatment for 7 days and weekly for 2 months for erythema, healing time, improvement, and pigmentary changes. Histologic evaluation of preauricular human facial ex vivo skin was done to determine the penetration of multiple passes of Er:YAG laser in human facial skin. results. All patients showed some degree of improvement of their rhytides. Reepithelialization occurred between 3 and 8 days. All evidence of erythema resolved between 3 and 6 weeks after treatment. The level of tissue ablation was determined to be down to: the granular layer after one pass; to the basal cell layer after two passes, to the papillary dermis after three to four passes, and deeper into the papillary and superficial reticular dermis after five to six passes. conclusion. The Er.YAG laser plays a significant role in the treatment of superficial and mid‐depth rhytides.