PRAME immunohistochemistry as an adjunct for diagnosis and histological margin assessment in lentigo maligna.

AIMS: Lentigo maligna (LM), the most common type of melanoma in situ, is a diagnostically challenging lesion for pathologists due to abundant background melanocytic hyperplasia in sun-damaged skin. Currently, no laboratory methods reliably distinguish benign from malignant melanocytes. However, preferentially expressed antigen in melanoma (PRAME) has shown promise in this regard, and could potentially be applied to diagnosis and margin assessment in difficult cases of LM. METHODS AND RESULTS: Ninety-six cases with a diagnosis of LM (n = 77) or no residual LM (n = 19) following initial biopsy were identified and stained with an antibody directed towards PRAME. Immunohistochemistry (IHC) was scored as positive or negative, and measurement of histological margins by PRAME was performed and compared to the measurement of histological margins using conventional methods [haematoxylin and eosin (H&E) and/or sex-determining region Y-box 10 (SOX10) and/or Melan-A]. Of cases with LM, 93.5% (72 of 77) were PRAME+ and 94.7% (18 of 19) of cases with no residual LM were PRAME- . Of the 35 cases with no margin involvement by PRAME or conventional assessment, 14 cases (40.0%) had no difference in measurement, 17 (48.6%) had a difference of 1 mm or less and four (11.4%) differed by between 1 and 3.5 mm. There was a high correlation between margin assessment methods (r = 0.97, P < 0.0001). CONCLUSIONS: PRAME IHC is a sensitive (93.5%) and specific (94.7%) method for diagnosing LM on biopsy and excision, and measurement of histological margins by PRAME shows a high correlation with conventional methods for margin assessment. Furthermore, the nuclear expression of PRAME makes it a good target for use in dual-colour IHC stains.

Expression of soluble adenylyl cyclase in lentigo maligna: use of immunohistochemistry with anti-soluble adenylyl cyclase antibody (R21) in diagnosis of lentigo maligna and assessment of margins.

CONTEXT: Soluble adenylyl cyclase (sAC) is an enzyme that generates cyclic adenosine monophosphate, a signaling molecule involved in regulating melanocyte functions. R21, a mouse monoclonal antibody against sAC, shows a striking pan-nuclear staining in lentigo maligna, indicating possible utility for diagnosis and margin assessment. OBJECTIVE: To evaluate R21 in the diagnosis and evaluation of margins in lentigo maligna. DESIGN: Thirty one re-excision specimens for lentigo maligna were evaluated for R21 expression using previously published protocol. In addition, 153 cases including 41 lentigo malignas, 30 non-lentigo maligna-type melanomas, 38 lentigos, and 44 nevi were evaluated using a modified stringent protocol to eliminate all nonmelanocyte staining. RESULTS: The sensitivity of nuclear staining with R21 in lentigo maligna was 87.8%. Nuclear expression of sAC was observed in 40% of other melanomas and 2.3% of benign nevi. R21 did not stain nuclei of resting melanocytes but was observed in 28.9% of melanocytic hyperplasias. These cases were easily distinguished from lentigo maligna in routine sections. R21 staining facilitated extent of the lesion in resection margins. In cases examined under the less stringent conditions, interpretation was facilitated by comparing R21 and Mart1/Melan A staining. Greater than 9 pan-nuclear staining melanocytes within one high-power field along with a pan-nuclear sAC/Melan A ratio greater than 0.5 was consistent with a positive margin whereas 5 or less pan-nuclear staining melanocytes along with a sAC/Melan A ratio of less than 0.3 constituted a negative margin. CONCLUSION: R21 is a useful diagnostic adjunct in the diagnosis and evaluation of margins in re-excision specimens in lentigo maligna.

Assessment of the optimal interval for and sensitivity of short-term sequential digital dermoscopy monitoring for the diagnosis of melanoma.

OBJECTIVE: To determine whether 6 weeks could replace 3 months for short-term sequential digital dermoscopy imaging (ST-SDDI) of suspicious melanocytic lesions and determine the proportion of melanomas missed. DESIGN: Consecutive lesions (n = 2602) undergoing ST-SDDI monitored from 1859 patients were included. Half of the patients underwent 6-week monitoring followed by 3-month monitoring (range, 2.5-4.5 months) if changes were not seen. The remainder underwent 3-month monitoring only. Any change during this time led to excision. Lesions unchanged were then followed up over time. SETTING: A tertiary referral institution. MAIN OUTCOME MEASURES: The proportion of changed melanomas (sensitivity) and odds ratios (ORs) for melanoma of changed lesions. RESULTS: Eighty-one melanomas were detected using ST-SDDI (Breslow thickness: median, in situ; maximum, 0.8 mm). Of 39 melanomas detected using ST-SDDI in the 6-week monitored lesions, 27 (69%) were detected at 6 weeks and 12 (31%) at 3 months. The OR for melanoma for a lesion changing at 6 weeks was 19 (95% confidence interval [CI], 10-35), and the overall OR for melanoma for a lesion changing during the short-term monitoring period (6 weeks to 4.5 months) was 47 (95% CI, 23-94). For lesions remaining unchanged at 3 months, 99.2% (1118 of 1127 lesions) were shown to be benign as defined by an unremarkable further follow-up. Seventy-five percent (15 of 20) of the lentigo maligna melanomas, 93% (40 of 43) of other in situ melanomas, and 96% (26 of 27) of the invasive melanomas were detected using ST-SDDI. Conclusion Three months remains the standard interval for ST-SDDI, where the sensitivity for the diagnosis of melanoma for changed (non-lentigo maligna) lesions is high but not 100%.