Demographic, behavioural and physician-related determinants of early melanoma detection in a low-incidence population.

BACKGROUND: Knowledge of the factors that influence early detection of melanoma is important in developing strategies to reduce associated mortality. OBJECTIVES: To identify sociodemographic, behavioural and medical care-related factors associated with melanoma thickness in a low-incidence population but with a high case fatality. PATIENTS AND METHODS: In a multicentre, retrospective, survey-based study of 202 patients with a recent diagnosis of invasive melanoma (< 1 year), we collected data on demographic and behavioural factors, attitudes towards prevention, access to medical care, frequency of skin self-examination (SSE) and physician skin examination (PSE) in relation to melanoma thickness. RESULTS: Thinner tumours (≤ 1 mm, 80 melanomas) were associated with female sex (P ≤ 0.049), nonnodular (superficial spreading melanoma, lentigo maligna melanoma, acral lentiginous melanoma) histological subtypes (P < 0.001), absence of ulceration (P ≤ 0.001), and location other than lower extremity or trunk location (P ≤ 0.004). Patients married at the time of diagnosis or who performed SSE during the year prior to diagnosis were more likely to have thinner tumours than those who did not [odds ratio (OR) 3.45, 95% confidence interval (CI) 1.48-8.04 and OR 2.43, 95% CI 1.10-5.34, respectively]. Full-body skin examination by a physician was not significantly associated with thinner melanoma (OR 1.99, 95% CI 0.66-6.07). CONCLUSIONS: SSE was shown to be an important factor in the detection of thin melanoma, in contrast to partial or full-body PSE, which did not show any statistically significant effect on tumour thickness.

Reliability of quantification measures of actinic keratosis.

BACKGROUND: Enumerating actinic keratoses (AKs) is highly variable but important to standardize as new therapies are emerging. OBJECTIVES: To assess the reliability of four different methods used to quantify AKs and to investigate whether a consensus meeting affects the reliability. METHODS: This was a single-blinded study of 12 experienced dermatologist raters counting AKs on the face and ears of nine subjects before and after a consensus meeting. Raters were recruited from investigators of a multicentre Veterans Affairs cooperative study. The intraclass correlation coefficient (ICC) among raters for pre- and post-consensus evaluations was the primary outcome measure. RESULTS: Of the four assessment methods, the 'total count' method had the greatest ICC for both pre- (0·18, P = 0·04) and post-consensus (0·66, P = < 0·0001) assessments. Total count was also the only pre-consensus ICC for which the null hypothesis of no association among assessments was rejected. CONCLUSIONS: Total AK count appears to be the most reliable measure of quantifying AKs on the face and ears. Educational consensus discussion prior to assessment improves reliability of this measure.

Developing indications for the use of sentinel lymph node biopsy and adjuvant high-dose interferon alfa-2b in melanoma.

OBJECTIVES: To convene a multidisciplinary panel of dermatologists, surgical oncologists, and medical oncologists to formally review available data on the sentinel lymph node (SLN) biopsy procedure and high-dose adjuvant interferon alfa-2b therapy for patients with melanoma and to rate the "appropriateness," "inappropriateness," or "uncertainty" of the procedure and therapy to guide clinical decision making in practice. PARTICIPANTS: The panel comprised 13 specialists (4 dermatologists, 4 oncologists, and 5 surgeons) from geographically diverse areas who practiced in community-based settings (n = 8) and academic institutions (n = 5). Participants were chosen based on recommendations from the relevant specialty organizations. EVIDENCE: A formal literature review was conducted by investigators at Protocare Sciences Inc, Santa Monica, Calif, on the risks and benefits of performing an SLN biopsy in patients with stage I or II melanoma and adjuvant interferon alfa-2b therapy in patients with stage II or III disease. The MEDLINE database was searched from 1966 through July 2000, and supplemental information was obtained from various cancer societies and cancer research groups. Panel participants were queried on additional sources of relevant information. Unpublished, presented data were included in abstract form on 1 recently closed clinical trial. CONSENSUS PROCESS: The RAND/UCLA Appropriateness Method was used to review and rate multiple clinical scenarios for the use of SLN biopsy and interferon alfa-2b therapy. The consensus method did not force agreement. CONCLUSIONS: The panel rated 104 clinical scenarios and concluded that the SLN biopsy procedure was appropriate for primary melanomas deeper than 1.0 mm and for tumors 1 mm or less when histologic ulceration was present and/or classified as Clark level 4 or higher. The SLN biopsy was deemed inappropriate for nonulcerated Clark level 2 or 3 melanomas 0.75 mm or less in depth and uncertain in tumors 0.76 to 1.0 mm deep unless they were ulcerated or Clark level 4 or higher. Interferon alfa-2b therapy was deemed appropriate for patients with regional nodal and/or in-transit metastasis and for node-negative patients with primary melanomas deeper than 4 mm. The panel considered the use of interferon alfa-2b therapy uncertain in patients with ulcerated intermediate primary tumors (2.01-4.0 mm in depth) and inappropriate for node-negative patients with nonulcerated tumors less than 4.0 mm deep. Specialty-specific ratings were conducted as well.

9:45-10:00. Positron Emission Tomography (PET) is Superior to Computerized Tomography (CT) for Metastatic Staging in Melanoma Patients.

PET provides diagnostic information currently not available with traditional imaging. Retrospective analysis was performed of 104 patients with primary or recurrent melanoma who underwent PET for staging to determine sensitivity/specificity compared to body CT. 157 PET and 70 CT scans were analyzed with a mean follow up of 26 months. Metastatic events were confirmed with positive histology (73%) or documented disease progression.PET demonstrated 86% sensitivity and 97% specificity in 41 patients with metastasis. CT showed 57% sensitivity and 70% specificity in 30 patients with metastasis. Exclusion of areas not evaluated on CT (head, neck/supraclavicular, and extremities) increased CT sensitivity to 68%. Fifty-three patients underwent 67 consecutive CT and PET scans that detected 132 metastases in 30 individuals. PET detected a greater percentage of metastases (83%) compared to CT (56%), and specifically, in the soft tissue, neck, peripheral/mediastinal/intraabdominal lymph nodes, and small bowel. PET detected 100% of mediastinal metastasis while CT detected only 67%. Surprisingly, PET detected 84% of lung parenchymal metastasis compared to 72% with CT.PET is more sensitive and specific than CT for detection of melanoma metastasis and should be considered the primary staging study upon suspicion of recurrent disease. PET shows greater ability to detect soft tissue, small bowel, and lymph node metastasis that do not meet criteria designated as abnormal by CT. Likewise, CT does not routinely evaluate the supraclavicular area, neck, or upper/lower extremities. However, even when these sites are excluded from comparative analysis, PET is superior to CT in detecting melanoma metastasis.

Characterization of circulating T cells specific for tumor-associated antigens in melanoma patients.

We identified circulating CD8+ T-cell populations specific for the tumor-associated antigens (TAAs) MART-1 (27-35) or tyrosinase (368-376) in six of eleven patients with metastatic melanoma using peptide/HLA-A*0201 tetramers. These TAA-specific populations were of two phenotypically distinct types: one, typical for memory/effector T cells; the other, a previously undescribed phenotype expressing both naive and effector cell markers. This latter type represented more than 2% of the total CD8+ T cells in one patient, permitting detailed phenotypic and functional analysis. Although these cells have many of the hallmarks of effector T cells, they were functionally unresponsive, unable to directly lyse melanoma target cells or produce cytokines in response to mitogens. In contrast, CD8+ T cells from the same patient were able to lyse EBV-pulsed target cells and showed robust allogeneic responses. Thus, the clonally expanded TAA-specific population seems to have been selectively rendered anergic in vivo. Peptide stimulation of the TAA-specific T-cell populations in other patients failed to induce substantial upregulation of CD69 expression, indicating that these cells may also have functional defects, leading to blunted activation responses. These data demonstrate that systemic TAA-specific T-cell responses can develop de novo in cancer patients, but that antigen-specific unresponsiveness may explain why such cells are unable to control tumor growth.

Infiltrative basal cell carcinoma occurring in sites of biopsy-proven nodular basal cell carcinoma.

Over 200 basal cell carcinomas (BCCs) are biopsied and subsequently excised each year at the Veterans Affairs Palo Alto Health Care System (VAPAHCS). A focal infiltrative pattern developed in the region of the biopsy scar in the re-excision specimens of 20 cases out of approximately 400 BCCs (< 5%) examined histopathologically over a 2-year period. The patient population included predominantly male, elderly Caucasians (mean age 71), and all tumors fulfilled clinical and histologic criteria for nodular BCC at the time of initial punch or shave biopsy. No patient showed recurrence of tumor following simple re-excision with 2-3 mm surgical margins, with a mean follow up of 25.4 months after excisional surgery. These neoplasms had a more benign clinical course, possibly related to scar formation in healing sites of previously biopsied nodular BCC, rather than true aggressive-growth BCC. The authors conclude that a focal infiltrative pattern in a re-excision specimen may occur histologically as a scar-induced pattern which mimics an aggressive-growth BCC, but does not appear to have the same prognosis. We believe this is an important histologic observation, as recognition of biopsy scar changes in an excisional specimen of BCC may help to distinguish it from true aggressive-growth BCC.

Increased proportion of aggressive-growth basal cell carcinoma in the Veterans Affairs population of Palo Alto, California.

BACKGROUND: We have noted a high frequency of aggressive-growth basal cell carcinomas (BCCS) in our patient population. Subtypes observed with increased frequency include morpheaform, infiltrative, and micronodular. OBJECTIVE: Our purpose was to examine the frequency of histologic subtypes of all BCCs seen in the dermatology clinics in the Veterans Affairs Palo Alto Health Care System in an 18-month period. METHODS: We reviewed 432 consecutive primary BCC biopsy specimens taken from 252 patients. RESULTS: Aggressive-growth BCC was observed in 20.7% of biopsy specimens, including 13.4% morpheaform, 5.7% infiltrative, and 1.6% micronodular subtypes. The mean age of the patient population was 70 years, with a standard deviation of 9.1 years. CONCLUSION: Our observed percentage of aggressive-growth BCC is substantially higher than in most other large studies. A high frequency of aggressive-growth BCC coupled with the increasing incidence of nonmelanoma skin cancer may have significant implications for future health care resource allocation.

Malignant melanoma from the dermatologic perspective.

Early recognition and treatment of thin cutaneous melanomas (stages Ia and Ib) have contributed to a decreased case-fatality rate during the past several decades. The only known preventable risk factor for melanoma is sun protection in childhood, which directly affects the number of melanocytic nevi developing in an adult. Additional risk factors, clinical features, and the malignant potential of precursor lesions are discussed. The four major clinicopathologic subtypes of melanoma are described with recommendations for appropriate biopsy techniques for suspected melanoma. Nationwide skin cancer screenings by dermatologists and greater public awareness of the warning signs of melanoma have enhanced detection of early melanoma and have promoted chances for a cure.

Scleredema revisited. A poststreptococcal complication.

Scleredema is a rare connective disease which must be differentiated from scleroderma in childhood. Scleredema is characterized by thickening of the dermis of the neck, head, and upper trunk. We report a case of scleredema in an 8-year-old boy with coincident streptococcal colonization. The patient report demonstrates many of the common features of scleredema, including an associated streptococcal infection, a relatively benign presentation of illness, and the characteristic mucopolysaccharide intradermal staining on skin biopsy. The literature on scleredema is reviewed, focusing on the disease course, differential diagnosis, and an overview of the proposed three subgroups of scleredema. The association of scleredema to a prior streptococcal infection is explored, and a proposed autoimmune pathophysiology of the disease, as it relates to streptococcal infection, is presented.

Cutaneous nodules of Mycobacterium chelonae in an immunosuppressed patient with preexisting pulmonary colonization.

A 30-year-old immunocompromised man with known pulmonary Mycobacterium chelonae colonization developed a systemic infection with cutaneous manifestations. The eruption consisted of multiple, nontender, subcutaneous nodules on the extremities. A diagnosis of disseminated M. chelonae was made on the basis of recovery of M. chelonae subspecies abscessus from blood and bronchoalveolar lavage fluid and histologic evidence of acid-fast bacilli in a skin biopsy specimen. We believe this is the first reported case of disseminated M. chelonae infection in an immunocompromised host in whom a primary source of the infection was identified.