Dermatofluoroscopy diagnostics in different pigmented skin lesions: Strengths and weaknesses.

BACKGROUND: The melanin fluorescence of skin lesions is measurable with two-photon excitation, a process termed dermatofluoroscopy, which has shown a shift from the green spectra in benign melanocytic lesions to the red spectra in melanoma. This study addressed the question as to which kind of pigmented lesions can be correctly diagnosed as melanin-bearing malignant tumors. METHODS: 476 pigmented lesions including 101 cutaneous melanomas were analyzed with dermatofluoroscopy, measuring the melanin fluorescence in a grid-like fashion with a separation of measurement points of 0.2 mm. The results of the dermatofluoroscopy are presented as a diagnostic score with a cut-off score of ≥ 28 for the diagnosis of melanin-bearing malignant tumors, and were compared to the gold standard of histopathology. RESULTS: A highly significant difference (p < 0.0001) between the diagnostic scores of different skin tumors was found. Dermatofluoroscopy scores showed the highest sensitivity for melanomas (92.1 %). Interestingly, most pigmented basal cell carcinomas (BCCs, 88.9 %) were diagnosed as melanin-bearing malignant tumors. A higher sensitivity for the correct diagnosis was observed in older patients (≥ 53 years, p = 0.003), in patients with skin tanning (p = 0.025), and in patients with freckles during childhood (p = 0.046). CONCLUSIONS: Two-photon fluorescence is an innovative technique for the diagnosis of pigmented skin lesions, and shows a high sensitivity for detection of melanomas and pigmented BCCs.

Anti-vascular endothelial growth factor antibody bevacizumab in conjunction with chemotherapy in metastasising melanoma.

PURPOSE: The combination of the antiangiogenic antibody bevacizumab with standard chemotherapy has improved the prognosis in patients with metastastic colorectal cancer and other advanced cancers. The role of combined anti-VEGF and chemotherapy in metastastic melanoma is just starting to be elucidated. METHODS: We tested this notion in three patients with advanced and therapy-refractory melanoma. RESULTS: Interestingly, two patients achieved objective regressions after three courses of therapy; the third patient, albeit progressing demonstrated a pronounced liquid necrosis in bulky lymphnode metastasis. CONCLUSION: Further studies are warranted to scrutinize these impressive therapeutic effects on the combination of bevacizumab and chemotherapy in melanoma.

The monoclonal antibody SM5-1 recognizes a fibronectin variant which is widely expressed in melanoma.

BACKGROUND: Previously we have generated the monoclonal antibody SM5-1 by using a subtractive immunization protocol of human melanoma. This antibody exhibits a high sensitivity for primary melanomas of 99% (248/250 tested) and for metastatic melanoma of 96% (146/151 tested) in paraffin embedded sections. This reactivity is superior to the one obtained by HMB-45, anti-MelanA or anti-Tyrosinase and is comparable to anti-S100. However, as compared to anti-S100, the antibody SM5-1 is highly specific for melanocytic lesions since 40 different neoplasms were found to be negative for SM5-1 by immunohistochemistry. The antigen recognized by SM5-1 is unknown. METHODS: In order to characterize the antigen recognized by mAb SM5-1, a cDNA library was constructed from the metastatic human melanoma cell line SMMUpos in the Uni-ZAP lambda phage and screened by mAb SM5-1. The cDNA clones identified by this approach were then sequenced and subsequently analyzed. RESULTS: Sequence analysis of nine independent overlapping clones (length 3100-5600 bp) represent fibronectin cDNA including the ED-A, but not the ED-B region which are produced by alternative splicing. The 89aa splicing variant of the IIICS region was found in 8/9 clones and the 120aa splicing variant in 1/9 clones, both of which are included in the CS1 region of fibronectin being involved in melanoma cell adhesion and spreading. CONCLUSION: The molecule recognized by SM5-1 is a melanoma associated FN variant expressed by virtually all primary and metastatic melanomas and may play an important role in melanoma formation and progression. This antibody is therefore not only of value in immunohistochemistry, but potentially also for diagnostic imaging and immunotherapy.