Agreement of dermatopathologists in the evaluation of clinically difficult melanocytic lesions: how golden is the 'gold standard'?

BACKGROUND: The 'gold standard' for the diagnosis of melanocytic lesions is dermatopathology. Although most of the diagnostic criteria are clearly defined, the interpretation of histopathology slides may be subject to interobserver variability. OBJECTIVES: The aim of this study was to determine the variability among dermatopathologists in the interpretation of clinically difficult melanocytic lesions. METHODS: This study used the database of MelaFind®, a computer-vision system for the diagnosis of melanoma. All lesions were surgically removed and sent for independent evaluation by four dermatopathologists. Agreement was calculated using kappa statistics. RESULTS: A total of 1,249 pigmented melanocytic lesions were included. There was a substantial agreement among expert dermatopathologists: two-category kappa was 0.80 (melanoma vs. non-melanoma) and three-category kappa was 0.62 (malignant vs. borderline vs. benign melanocytic lesions). The agreement was significantly greater for patients ≥40 years (three-category kappa = 0.67) than for younger patients (kappa = 0.49). In addition, the agreement was significantly lower for patients with atypical mole syndrome (AMS) (kappa = 0.31) than for patients without AMS (kappa = 0.76). LIMITATIONS: The data were limited by the inclusion/exclusion criteria of the MelaFind® study. This might represent a selection bias. The agreement was evaluated using kappa statistics. This is a standard method for evaluating agreement among pathologists, but might be considered controversial by some statisticians. CONCLUSIONS: Expert dermatopathologists have a high level of agreement when diagnosing clinically difficult melanocytic lesions. However, even among expert dermatopathologists, the current 'gold standard' is not perfect. Our results indicate that lesions from younger patients and patients with AMS may be more problematic for the dermatopathologists, suggesting that improved diagnostic criteria are needed for such patients.

Dermatoscopy of lentigo maligna.

Lentigo maligna and LMM require different dermatoscopic criteria for evaluation. The ease and accessibility of examining these lesions with dermatoscopy coupled with the clinical pathologic correlation afforded by the biopsy techniques discussed allow the practitioner to become proficient and prescient with the use of dermatoscopy. The criteria mentioned here are relatively new but are present and detectable in most cases of LM and LMM. The fact that there is some overlap among pigmented actinic keratosis, squamous cell carcinoma in situ, and lichenoid keratosis lesions should not detract or deter the physician from using dermatoscopy. Clinically, these lesions also usually will be equivocal and will require close clinical scrutiny and biopsies. If given the choice of using skin surface microscopy for one class of lesion only, one might well choose LM lesions because of their otherwise subtle nature and the clues that can be unlocked with oil immersion, illumination, and magnification, along with knowledge of these new criteria.

Improvement of early recognition of lentigo maligna using dermatoscopy.

BACKGROUND: The clinical differentiation between lentigo senilis/initial seborrheic keratosis and lentigo maligna on the face can be difficult. OBJECTIVE: Our purpose was to determine whether dermatoscopy (eg, skin surface microscopy at 10x magnification) can reliably differentiate between these entities. METHODS: Dermatoscopic slides of 87 consecutive patients presenting 37 malignant and 50 benign pigmented skin lesions on the face were analyzed with the use of 27 dermatoscopic criteria. RESULTS: Univariate analysis selected two criteria specific for lentigo maligna: asymmetric pigmented follicular openings and dark (brown or black) rhomboidal structures. Location-specific importance in relation to facial location was attributed to the color "slate-gray, " especially in combination with structures such as dots, globules, streaks, and homogeneous areas. Multivariate analysis (logistic regression model) revealed the 4 most important features to be asymmetric pigmented follicular openings, dark rhomboidal structures, slate-gray globules, and slate-gray dots with a sensitivity of 89% and a specificity of 96%. CONCLUSION: Three conclusions can be drawn from our study: With a set of 4 dermatoscopic features, early lentigo maligna can be detected with high accuracy; dermatoscopic features on the face differ from criteria used in other locations; and our progression growth model for lentigo maligna delineates the different steps of malignant growth in lentigo maligna.

Techniques for a structural analysis of dermatoscopic imagery.

Techniques were developed for automated detection and characterization of dermatoscopic structures, including the pigment network and brown globules. These techniques incorporate algorithms for grayscale shape extraction based on differential geometry developed by Steger, a snake algorithm, and a modification of the region competition strategy of Zhu and Yuille. A novel approach was developed for global segmentation of pigmented lesions, based on stabilized inverse diffusion equations. Procedures for detection of air bubbles and hairs in dermatoscopic images are also reported.

Nonsurgical treatment of basal cell carcinomas with intralesional 5-fluorouracil/epinephrine injectable gel.

BACKGROUND: To develop a nonsurgical treatment alternative for basal cell carcinomas (BCCs), we evaluated intralesional sustained-release chemotherapy with 5-fluorouracil/epinephrine injectable gel (5-FU/epi gel). OBJECTIVE: To optimize the dose and treatment schedule, we compared the safety, tolerance, and efficacy of six treatment regimens of 5-FU/epi gel in patients with BCCs. METHODS: Two doses and four treatment schedules of 5-FU/epi gel were compared in an open-label, randomized study of 122 patients with biopsy-proven BCCs. One BCC per patient was treated for up to 4 to 6 weeks, then observed for 3 months at which time the tumor site was completely excised for histologic examination. RESULTS: Overall, 91% of evaluable treated tumors (106 of 116) in all regimens had histologically confirmed complete tumor resolution. No clinically significant treatment-related systemic adverse events occurred. The best response rate, tolerance, and patient compliance with assigned dose were in patients receiving 0.5 ml of 5-FU/epi gel three times a week for 2 weeks. The complete response rate based on histologic assessment in this group was 100%. CONCLUSION: Results demonstrate that treatment of BCC with 5-FU/epi gel is both safe and effective, may result in histologically confirmed complete response rates comparable to surgery, and provides a nonsurgical treatment alternative in selected patients.

The ABCD rule of dermatoscopy. High prospective value in the diagnosis of doubtful melanocytic skin lesions.

BACKGROUND: The difficulties in accurately assessing pigmented skin lesions are ever present in practice. The recently described ABCD rule of dermatoscopy (skin surface microscopy at x10 magnification), based on the criteria asymmetry (A), border (B), color (C), and differential structure (D), improved diagnostic accuracy when applied retrospectively to clinical slides. OBJECTIVE: A study was designed to evaluate the prospective value of the ABCD rule of dermatoscopy in melanocytic lesions. METHODS: In 172 melanocytic pigmented skin lesions, the criteria of the ABCD rule of dermatoscopy were analyzed with a semiquantitative scoring system before excision. RESULTS: According to the retrospectively determined threshold, tumors with a score higher than 5.45 (64/69 melanomas [92.8%]) were classified as malignant, whereas lesions with a lower score were considered as benign (93/103 melanocytic nevi [90.3%]). Negative predictive value for melanoma (True-Negative divided by [True-Negative+False-Negative]) was 95.8%, whereas positive predictive value (True-Positive divided by [True-Positive+False-Positive]) was 85.3%. Diagnostic accuracy for melanoma (True-Positive divided by [True-Positive+False-Positive+False-Negative]) was 80.0%, compared with 64.4% by the naked eye. Melanoma showed a mean final dermatoscopy score of 6.79 (SD, +/- 0.92), significantly differing from melanocytic nevi (mean score, 4.27 +/- 0.99; p < 0.01, U test). CONCLUSION: The ABCD rule can be easily learned and rapidly calculated, and has proven to be reliable. It should be routinely applied to all equivocal pigmented skin lesions to reach a more objective and reproducible diagnosis and to obtain this assessment preoperatively.