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Background: Spindle cell melanoma (SCM) including desmoplastic melanoma (DM) is a rare variant of malignant melanoma that may present diagnostic difficulties particularly when staining with S100 is negative, weak, focal, or a combination of these. Conventional melanocytic markers in SCM are usually negative., Objective: We sought to compare the staining of p75 nerve growth factor receptor (NGF-R) and S100 in SCMs., Methods: We evaluated the staining of p75 NGF-R and S100 in 13 cases of SCMs: 3 SCMs without desmoplasia, 5 pure DMs, and 5 combined DMs with a conventional component., Results: Staining with p75 NGF-R was positive in 13 of 13 (100%) cases of SCMs. In 3 cases the intensity of staining and the percentage of cells staining with this marker were greater than those with S100. One case of SCM was negative for S100 but demonstrated strong expression of p75 NGF-R. One case was focally and weakly positive with S100 but expressed strong positive staining with p75 NGF-R. Absence of staining with p75 NGF-R was noted in the conventional round cell component of two of 5 (40%) combined DMs whereas the same areas were strongly positive for human melanoma black (HMB)-45 and Melan-A. In 5 of 5 (100%) cases of combined DMs the desmoplastic component stained positive with p75 NGF-R, demonstrating an inverse relationship with the staining of conventional melanocytic markers., Limitations: Small study size was a limitation., Conclusion: p75 NGF-R exhibits superior staining characteristics and greater sensitivity in identifying SCM and DMs than S100. P75 NGF-R may be a useful diagnostic and ancillary stain in addition to S100., (Copyright © 2009 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Purpose: The recent identification of toll-like receptors (TLRs) and respective ligands allows the evaluation of novel dendritic cell (DC) -activating strategies. Stimulation of TLR9 directly activates human plasmacytoid DCs (PDCs) and indirectly induces potent innate immune responses in preclinical tumor models. We performed an open-label, multicenter, single-arm, phase II pilot trial with a TLR9-stimulating oligodeoxynucleotide in melanoma patients., Patients and Methods: Patients with unresectable stage IIIb/c or stage IV melanoma received 6 mg PF-3512676 weekly by subcutaneous injection for 24 weeks or until disease progression to evaluate safety as well as clinical and immunologic activity. Clinical and laboratory safety assessments were performed weekly; blood samples for immunological measurements were taken every 8 weeks. Tumor measurements were performed according to Response Evaluation Criteria in Solid Tumors., Results: Twenty patients received PF-3512676 for a mean of 10.9 weeks with a mean of 10.7 injections. Laboratory and nonlaboratory adverse events were limited, transient, and did not result in any withdrawals. Two patients experienced a confirmed partial response; one response is ongoing for 140+ weeks. Three patients experienced stable disease. Immunologic measurements revealed induction of an activated phenotype of PDC, elevation of serum levels of 2',5'-oligoadenylate, a surrogate marker of type I interferon production, and significant stimulation of natural killer cell cytotoxicity (the latter was associated with clinical benefit)., Conclusion: These results indicate that TLR9-targeted therapy can stimulate innate immune responses in cancer patients, identify biomarkers that may be associated with TLR9-induced tumor regression, and encourage the design of follow-up studies to evaluate the ability of this therapeutic approach to target human cancer.