Faculty Bibliography

PURPOSE/OBJECTIVE:We hypothesized that initial biopsy may understage acral lentiginous melanoma (ALM) and lead to undertreatment or incomplete staging. Understanding this possibility can potentially aid surgical planning and improve primary tumor staging. METHODS:A retrospective review of primary ALMs treated from 2000 to 2017 in the US Melanoma Consortium database was performed. We reviewed pathology characteristics of initial biopsy, final excision specimens, surgical margins, and sentinel lymph node biopsy (SLNB). RESULTS:We identified 418 primary ALMs (321 plantar, 34 palmar, 63 subungual) with initial biopsy and final pathology results. Median final thickness was 1.8 mm (range 0.0-19.0). There was a discrepancy between initial biopsy and final pathology thickness in 180 (43%) patients with a median difference of 1.6 mm (range 0.1-16.4). Final T category was increased in 132 patients (32%), including 47% of initially in situ, 32% of T1, 39% of T2, and 28% of T3 lesions. T category was more likely to be increased in subungual (46%) and palmar (38%) melanomas than plantar (28%, p = 0.01). Among patients upstaged to T2 or higher, 71% had ≤ 1-cm margins taken. Among the 27 patients upstaged to T1b or higher, 8 (30%) did not have a SLNB performed, resulting in incomplete initial staging. CONCLUSIONS:In this large series of ALMs, final T category was frequently increased on final pathology. A high index of suspicion is necessary for lesions initially in situ or T1 and consideration should be given to performing additional punch biopsies, wider margin excisions, and/or SLNB.

BACKGROUND:As a result of the rapidly changing hormonal milieu, changing or newly discovered pigmented skin lesions during pregnancy can be diagnostically challenging. It is important for GPs to be aware of the effect of gestational changes on pigment production and features that should raise concern. OBJECTIVE:The aim of this article is to provide an understanding of common changes that may occur in pigmented lesions during pregnancy, features that are of concern and the management of suspected melanoma in pregnant women. DISCUSSION:In pregnant women, changing naevi should be evaluated using conventional ABCDE melanoma diagnostic criteria, and suspicious lesions should not be attributed solely to a change in the hormonal milieu. In this population, diagnosed melanoma is probably best treated at a specialist centre.

BACKGROUND:Pigmented skin lesions in childhood and adolescence can be diagnostically challenging. It is important for general practitioners to be aware of the spectrum of benign, atypical and malignant pigmented lesions occurring in these patient groups and of features that should raise concern. OBJECTIVE:The aims of this article are to assist recognition of high-risk skin lesions encountered in childhood and adolescence and to provide an understanding of the features and management of suspected melanoma in this population. DISCUSSION:In children and adolescents, there exist a variety of congenital and acquired naevi and other pigmented skin lesions that can be diagnostically problematic. Additionally, conventional detection criteria for melanoma seen in adults are often not present in children and adolescents, making diagnosis more difficult. Melanoma, if diagnosed in these populations, should be treated at a specialist centre whenever possible.

BackgroundMatrix metalloproteinase-23 (MMP-23) can block the voltage-gated potassium channel Kv1.3, whose function is important for sustained Ca2+ signaling during T cell activation. MMP-23 may also alter T cell activity and phenotype through cleavage of proteins affecting cytokine and chemokine signaling. We therefore tested the hypothesis that MMP-23 can negatively regulate the anti-tumor T cell response in human melanoma.MethodsWe characterized MMP-23 expression in primary melanoma patients who received adjuvant immunotherapy. We examined the association of MMP-23 with the anti-tumor immune response - as assessed by the prevalence of tumor-infiltrating lymphocytes and Foxp3+ regulatory T cells. Further, we examined the association between MMP-23 expression and response to immunotherapy. Considering also an in trans mechanism, we examined the association of melanoma MMP-23 and melanoma Kv1.3 expression.ResultsOur data revealed an inverse association between primary melanoma MMP-23 expression and the anti-tumor T cell response, as demonstrated by decreased tumor-infiltrating lymphocytes (TIL) (P inverted question mark= inverted question mark0.05), in particular brisk TILs (P inverted question mark= inverted question mark0.04), and a trend towards an increased proportion of immunosuppressive Foxp3+ regulatory T cells (P inverted question mark= inverted question mark0.07). High melanoma MMP-23 expression is also associated with recurrence in patients treated with immune biologics (P inverted question mark= inverted question mark0.037) but not in those treated with vaccines (P inverted question mark= inverted question mark0.64). Further, high melanoma MMP-23 expression is associated with shorter periods of progression-free survival for patients receiving immune biologics (P inverted question mark= inverted question mark0.025). On the other hand, there is no relationship between melanoma MMP-23 and melanoma Kv1.3 expression (P inverted question mark= inverted question mark0.27).ConclusionsOur data support a role for MMP-23 as a potential immunosuppressive target in melanoma, as well as a possible biomarker for informing melanoma immunotherapies.