Non-Invasive Gene Expression Testing to Rule Out Melanoma.

The Pigmented Lesion Assay (PLA) is a gene expression test that helps rule out melanoma and has the potential to reduce the need for surgical biopsies of atypical pigmented skin lesions. Utilizing a new technological platform for the non-invasive profiling of skin, the assay analyzes samples collected from adhesive patches for expression of two key genes (PRAME and LINC00518) known to be overexpressed in melanoma. The test result is binary (positive/negative) based on the detection of one or both genes. PLA positive cases are generally biopsied to establish the histopathologic diagosis, while PLA negative cases are considered for ongoing monitoring. The combination of visual inspection with histopathology, the current gold standard for melanoma diagnosis, has a relatively low negative predictive value (NPV) of approximately 83%, meaning that 17% of melanomas will be interpreted as benign lesions. In contrast, the PLA has a very high NPV (>99%). Further, with its high specificity (69-91%), use of the PLA can reduce the number of false positive samples subjected to histopathology review. By adding the PLA to the current care pathway, the number of surgical biopsies needed to find a melanoma (number needed to biopsy) is markedly reduced from 20-25 biopsies for dermatologists and 39 biopsies for physician assistants, to an average of 2.7. To date, unnecessary surgical procedures of benign lesions have been reduced by 88% based on a sample of more than 20,000 analyzed cases. This has resulted in fewer missed melanomas and significant cost savings to health care systems.

Actikerall™ (5-Fluorouracil 0.5% and Salicylic Acid 10%) Topical Solution for Patient-directed Treatment of Actinic Keratoses.

Actinic keratosis (AK), a common cutaneous lesion with the potential to transform into squamous cell carcinoma, has traditionally been treated with ablative and/or surgical procedures. Recently, a topical formulation combining 0.5% 5-fluorouracil with 10% salicylic acid (5-FU-SA) was introduced in Europe under the trade name Actikerall™ for the treatment of grade I/II AKs. In a single randomized phase III trial, 5-FU-SA was shown to be superior to diclofenac 3% gel in hyaluronic acid, as measured by the histological clearance of one defined lesion (72% vs. 59.1%) and by complete clinical clearance (55.4% vs. 32.0%). 5-FU-SA should be applied once daily to a total area of up to 25 cm(2), which may include the lesion(s) and a small area of surrounding skin (rim of healthy skin should not exceed 0.5 cm), for up to 12 weeks. The most common side effects are local inflammation and pruritus at the application site, and no serious adverse effects have been reported to date. Now commercially available in Canada, 5-FU-SA represents a patientapplied therapeutic option for the treatment of both overt and subclinical AKs.

The role of cosmeceuticals in antiaging therapy.

As baby boomers get older, they have shown an increasing interest in maintaining a youthful appearance. As a result, there has been a corresponding increase in topical antiaging formulations, which are commonly referred to as cosmeceuticals. These products come with a seemingly limitless number of key active ingredients and claims of reducing the signs of aging and/or maintaining a youthful appearance. This paper reviews the more common cosmeceutical ingredients.

Imiquimod 5% cream for the treatment of actinic keratoses.

Actinic keratoses (AKs) are premalignant inflammatory skin lesions with the potential to transform into squamous cell carcinoma (SCC). There are several treatment options available for patients presenting with multiple AKs. Imiquimod is believed to stimulate and enhance host immune responses locally against skin tumors and viral infections. Five clinical studies to date have demonstrated its safety and efficacy in the treatment of actinic keratoses. Long-term follow-up studies examining recurrence rates are limited.

Cutaneous melanomas that defy conventional prognostic indicators.

Tumor thickness is usually an accurate prognostic indicator for the patient with melanoma. However, very thin primary melanomas occasionally recur locally or metastasize, whereas some patients with very thick primary melanomas survive far longer than expected. There is also a group of patients with primary melanomas of various thicknesses who relapse after a very long disease-free interval. The large database of the Sydney Melanoma Unit which now contains comprehensive long-term follow-up on more than 13,000 patients treated over a 45-year period, has provided a unique opportunity to study melanomas that defy conventional prognostic indicators. Recurrence developed in 2.8% of melanoma patients classified as stage I (pTNM staging system) and with very thin lesions (< 0.50 mm). These recurrences developed more frequently in women than men and histologically were found to be associated with ulceration, high mitotic activity, and invasion to Clark's level IV, but not with regression. Concurrent lymph node metastases (stage III) were present in 3.1% of patients with very thin lesions (< 0.50 mm). In this group, most patients were men, and every lesion displayed regression. Total survival exceeded 15 years in 15.7% of stage II and III patients with very thick lesions (> 5.5 mm). In 1.7% of patients with lesions of any thickness, the disease-free interval before relapse was > 15 years. Neither in patients with very thick lesions surviving for > 15 years, nor in those with a disease-free interval of > 15 years was it consistently possible to show the presence or absence of any of the histological features usually considered to be of prognostic significance.

An open study to assess the efficacy and safety of topical 3% diclofenac in a 2.5% hyaluronic acid gel for the treatment of actinic keratoses.

BACKGROUND: Actinic keratoses are potential precursors of invasive squamous cell carcinoma; therefore, treatment is often recommended. Current topical treatments may cause considerable discomfort, pain, or skin irritation. This study was established to explore the role, if any, of topical 3% diclofenac in 2.5% hyaluronic acid gel in the management of actinic keratoses. OBSERVATIONS: An open-label study was conducted of topical 3% diclofenac in 2.5% hyaluronic acid gel applied to 1 or more actinic keratoses. Patients were instructed to apply 1.0 g of the gel twice daily for as many as 180 days. Treatment was stopped earlier than 180 days if lesions were assessed as cleared. Twenty-nine adults were treated for periods of 33 to 176 days (median, 62 days). Of the 29 subjects, 27 were reevaluated 30 days after drug therapy discontinuation. Of the 27 patients, 22 (81%) had a complete response and another 4 (15%) showed marked clinical improvement. The preparation was generally well tolerated, although in 7 patients (24%) an irritant-type contact dermatitis developed, which was confined to the treatment site. CONCLUSION: Topical 3% diclofenac in 2.5% hyaluronic acid gel may be a clinically useful topical agent for the treatment of actinic keratoses.

Total-body photographs of dysplastic nevi.

A method of taking total-body photographs to document dysplastic nevi is described. A set of 24 views is taken. These 35-mm color slide transparencies are projected onto a rearview screen at the time of subsequent follow-up examinations. A comparison between the baseline photographs and the current clinical findings allows the physician to detect thin malignant melanomas in a curable stage.

Clinical significance of skin biopsies in the diagnosis and management of graft-vs-host disease in early postallogeneic bone marrow transplantation.

OBJECTIVE: To determine the value of skin biopsies in the management of suspected graft-vs-host disease (GVHD) within 30 days of allogeneic bone marrow transplantation (BMT). DESIGN: Retrospective study based on review of a BMT database. SETTING: Leukemia/BMT ward of a tertiary care, university teaching hospital. PATIENTS: One hundred and eighty-seven consecutive patients who received allogeneic BMT between January 1, 1994, and June 30, 1997, at Vancouver General Hospital, Vancouver, British Columbia. MAIN OUTCOME MEASURES: (1) Skin biopsy frequency for patients with rashes suggestive of acute GVHD; (2) clinical significance of skin biopsy in the management of patients with suspected acute GVHD after BMT; (3) relationship between severity of clinical GVHD and the likelihood to receive GVHD therapy; and (4) relationship between biopsy status or biopsy result and outcome of BMT (acute and chronic GVHD, transplant-related mortality, and overall and event-free survival). RESULTS: During the early post-BMT period (<30 days after BMT), 88 patients had rashes suggestive of acute GVHD; of these, 51 (58%) underwent skin biopsy to confirm the diagnosis. Skin biopsies were performed more often for higher clinical stages of cutaneous GVHD. There was no significant difference between the patients with positive biopsy findings and those with negative findings, either in the clinical severity of acute GVHD or in likelihood to receive treatment for GVHD. Most (85%) of the patients who underwent biopsies and received GVHD therapy had treatment initiated before skin biopsies were performed or before the results were available. The higher the clinical grade of overall acute GVHD, the more likely it was that the patients were treated for GVHD (P<.001). The outcome of BMT was not influenced by the skin biopsy status or biopsy result. CONCLUSIONS: The biopsy findings correlated poorly with the clinical severity of skin rash suggestive of acute GVHD soon after BMT. The decision to treat suspected acute GVHD depended not on skin biopsy findings but rather on clinical severity of acute GVHD. In this regard, skin biopsy has a limited role in the management of patients early after allogeneic BMT.

Localized chrysiasis induced by laser therapy.

BACKGROUND: Chrysiasis is a rare blue-gray skin discoloration that occurs in sun-exposed sites of some patients who receive gold salts. A unique case of localized chrysiasis developed immediately after Q-switched ruby laser (694 nm) irradiation for postinflammatory hyperpigmentation secondary to granuloma faciale in a patient who was receiving long-term gold sodium thiomalate therapy for psoriatic arthritis. Skin biopsy specimens showed striking changes in the ultrastructural characteristics of cutaneous gold deposits following laser treatment. OBSERVATIONS: A blue-gray skin discoloration developed immediately after laser exposure and persisted unchanged after 1 year. Transmission electron microscopy of skin biopsy specimens showed electron-dense gold deposits. Before laser irradiation, these deposits were 106 +/- 35 (mean +/- SD) nm in diameter and faceted, consistent with a crystalline structure. Posttreatment deposits were round, smaller, measured 16 +/- 4 nm, and resembled colloidal gold. Identical findings were observed in an area of sun-protected skin treated with the Q-switched ruby laser; irradiation with a pulsed dye laser at 585 nm had no effect. CONCLUSIONS: Localized chrysiasis was induced in a patient receiving parenteral gold therapy who underwent treatment with a Q-switched ruby laser. This form of chrysiasis resulted from a structural alteration in dermal gold deposits. A similar physiochemical modification in gold deposits induced by UV light may explain the localization of chrysiasis to sun-exposed skin in affected patients.

Sinonasal malignant melanoma--a clinicopathologic analysis of 18 cases.

Sinonasal melanoma is a rare malignancy. We present the clinicopathologic review of 18 cases seen at the British Columbia Cancer Agency between 1976 and 1992: 13 men and five women, mean age 66 years (range 32-88). Patients presented with nasal obstruction and bleeding (n = 8), obstruction alone (n = 4), bleeding alone (n = 5) or pain (n = 1). Those with bleeding presented with a shorter duration of symptoms than those with obstruction alone. All patients with obstruction alone died of their disease, while all patients with bleeding alone are alive or have died of an unrelated cause; four out of eight patients with both obstruction and bleeding are alive. There was no significant relationship between treatment modality and outcome. Histologic subtypes included epithelioid (n = 10), spindle-cell (n = 4), small-cell (n = 3) and pleomorphic (n = 1). Eight out of 11 cases from whom samples of paraffin-embedded tissue were available showed more prominent staining for HMB-45 than for S-100. In two cases, only rare (< 0.1%) cells stained for S-100. Cell type, mitotic rate and P53 expression were unrelated to disease outcome. Six out of seven patients with < or = 10% of cells showing intense staining for PCNA were alive or had died of an unrelated cause, while three out of four with > 10% staining died of their disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical features of dysplastic nevi.

The clinical features of 100 dysplastic nevi were tabulated. Although certain characteristics were present in most or all of these melanocytic nevi, there was a marked heterogeneity of other clinical features. The preponderant type of large (greater than or equal to 8 mm) melanocytic nevus in patients with classic dysplastic nevi is a papule or plaque with the following characteristics: multicoloration (various shades of tans, browns, reds, or black); slightly raised height for its broad diameter; mamillated surface; and lack of hypertrichosis. An atlas illustrates some of the clinical varieties of melanocytic nevi in this syndrome.

Topical 3% diclofenac in 2.5% hyaluronan gel for the treatment of actinic keratoses.

Actinic Keratoses (AKs) are epidermal skin lesions that have the potential to develop into squamous cell carcinoma. Many of the treatment options available can cause discomfort, pain or skin irritation. Topical 3% diclofenac in 2.5% hyaluronan gel (Solaraze, Bioglan Pharma) is a relatively new treatment that has been shown to be effective and well tolerated for the treatment of AKs.