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Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy that is associated with an increased risk of developing cutaneous malignancies. Clinical outcomes for these malignancies, including melanoma and keratinocyte cancers (KC), are worse for patients with CLL. Individuals with CLL develop an immunodeficiency of both the adaptive and innate immune system, which plays a role in the increased prevalence of skin cancers. This review focuses on the complex interplay between genetics, immunity, and pathogens that influence the cellular composition and biology of skin tumors and their microenvironment in CLL patients, and in comparison with other chronic hematological malignancies. It is paramount for dermatologists to be aware of the association between CLL (and chronic hematological malignancies more broadly) and cutaneous malignancies. This is a high-risk population who require regular and vigorous dermatologic follow-up., (© 2024 Japanese Dermatological Association.)

Nicotinamide (NAM), an amide form of vitamin B3, replenishes cellular energy after ultraviolet radiation (UVR) exposure, thereby enhancing DNA repair and reducing UVR's immunosuppressive effects. NAM reduces actinic keratoses and new keratinocyte cancers in high risk individuals, but its effects on melanoma are unknown. Melanomas arising on NAM or placebo within the ONTRAC skin cancer chemoprevention trial (Oral Nicotinamide To Reduce Actinic Cancer) were examined by immunohistochemistry. The effects of NAM (50 μM, 5 mM and 20 mM) on the viability, proliferation and invasiveness of four human melanoma cell lines and on the viability and proliferation of two human melanocyte lines, with and without UV irradiation were also investigated. 50 μM NAM did not affect viability, proliferation or invasion of melanoma or melanocyte cell lines, whereas concentrations too high to be achievable in vivo reduced viability and proliferation. Nicotinamide did not enhance melanoma viability, proliferation or invasiveness in vitro, providing additional confidence in its safety for use in clinical trials in high risk patients. Peritumoral and tumour infiltrating CD4+ and CD8+ lymphocytes were significantly increased in melanomas arising on NAM compared to those arising on placebo. Given the chemopreventive activity of nicotinamide against keratinocyte cancers, its DNA repair enhancing effects in melanocytes and now its potential enhancement of tumour-infiltrating lymphocytes and lack of adverse effects on melanoma cell growth and proliferation, clinical trials of nicotinamide for melanoma chemoprevention are now indicated.

Ultraviolet radiation (UVR) causes DNA damage in melanocytes by producing photolesions such as cyclobutane pyrimidine dimers and 8-oxo-7-hydrodeoxyguanosine. The production of reactive oxygen species by UVR also induces inflammatory cytokines that, together with the inherent immunosuppressive properties of UVR, propagate carcinogenesis. Nicotinamide (Vitamin B 3 ) enhances DNA repair, modulates the inflammatory environment produced by UVR, and reduces UV-induced immunosuppression. As nicotinamide reduces the incidence of actinic keratoses and nonmelanoma skin cancers in high-risk individuals and enhances repair of DNA damage in melanocytes, it is a promising agent for the chemoprevention of melanoma in high-risk populations., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Nicotinamide (vitamin B 3 ) has a range of photoprotective effects in vitro and in vivo; it enhances DNA repair, reduces UV radiation-induced suppression of skin immune responses, modulates inflammatory cytokine production and skin barrier function and restores cellular energy levels after UV exposure. Pharmacological doses of nicotinamide have been shown to reduce actinic keratoses and nonmelanoma skin cancer incidence in high-risk individuals, making this a nontoxic and accessible option for skin cancer chemoprevention in this population., (© 2017 The Australasian College of Dermatologists.)

Primary upper gastrointestinal tract melanoma is a rare but well recognised entity, with a poor prognosis because of delay in diagnosis. Furthermore, it may be difficult to determine whether a gastrointestinal melanoma represents a metastasis or a primary tumour. We report a 67-year-old man with a primary oesophageal melanoma, treated with surgical resection, who remains disease-free two years post resection.

Topical diphencyprone (DPCP) can be used to treat in transit and cutaneously metastastatic melanoma. To date, 50 patients have received DPCP therapy for at least 1 month at our institution, with complete clearance of cutaneous disease in 46% and partial response in a further 38% of patients. Topical immunotherapy with DPCP is inexpensive and well-tolerated and should be considered in patients with skin metastases unsuitable for or refractory to other forms of therapy., (© 2013 Wiley Periodicals, Inc.)

The authors provide an update on a previously reported patient with in-transit metastatic melanoma of the scalp treated with topical diphencyprone (DPCP). Molecular studies implicate the thymus-derived TH17 lymphocyte subset in a remarkable immunotherapeutic regression. The authors performed RT-PCR of total RNA from paraffin-embedded tissue before and after treatment with DPCP. Before treatment with DPCP, the authors found elevated expression of IL 17C/D/E/F; after treatment there was no detectable expression. Conversely, increased expression of PLZF/CD27 and CTLA4 was seen after treatment with no expression before treatment. No expression of IL17A/B, CD7, RORgTand FoxP3 were before or after treatment. Conclusions are limited to only the time samples were obtained. Remarkable regression of an in-transit metastatic melanoma treated with the immunomodulatory agent DPCP showed gain and loss of gene expression of the TH17 pathway. Further study of this pathway from NK to NK-T to TH7 and TH1 cells both with and without accessory or dendritic cells will improve understanding of contact sensitizers as topical immunomodulators.

Topical immunotherapy with contact sensitizers for metastatic melanoma was first reported more than 30 years ago. Diphencyprone (DPCP) immunotherapy is frequently used to treat cutaneous warts and alopecia areata, and we have previously reported the use of DPCP as a single agent to successfully treat extensive, radiotherapy-resistant melanoma metastases on the scalp. We now report DPCP treatment of a further six patients with cutaneous metastatic melanoma. Of seven patients treated with DPCP thus far, four have demonstrated complete responses of their cutaneous lesions and three have had partial responses. The treatment was well-tolerated by all patients. Topical immunotherapy with DPCP is inexpensive and relatively non-invasive and should be considered in patients with locally advanced skin metastases that are unsuitable for other therapies.

Diphencyprone is a potent contact sensitizer sometimes used to treat alopecia areata and cutaneous warts. A patient with previous primary nodular melanoma on the scalp developed extensive, confluent cutaneous metastases near the primary site, unsuitable for treatment with surgery or radiotherapy. Topical treatment with diphencyprone as a single agent resulted in regression of all lesions, and the patient remains well 18 months later. Topical immunotherapy with diphencyprone was an inexpensive and well-tolerated treatment for extensive cutaneous melanoma metastases in our patient unsuitable for other therapies.

Initial reports suggest that positron emission tomography with [18F]fluorodeoxyglucose (FDG-PET) may offer greater diagnostic accuracy and versatility than conventional radiology in staging patients with metastatic melanoma. We reviewed the first 100 melanoma patients to have PET imaging at our institution. PET findings were correlated with all other available results, including plain X-ray, computed tomography (CT), magnetic resonance (MR) imaging, bone scintigraphy, clinical findings and histopathology. A total of 415 metastatic lesions were evaluated, 388 (93%) of which were detected by PET. In 20 patients, PET detected 24 metastases up to 6 months earlier than conventional imaging or physical examination. Selection of surgical or medical management was specifically influenced by PET findings in 22 patients, and PET was used to clarify another 12 cases where CT was inconclusive. In nine patients undergoing chemotherapy, PET was used to assess response to treatment. We conclude that FDG-PET can accurately detect metastatic melanoma with a single non-invasive scan, and can demonstrate some metastases months before conventional imaging techniques. PET can improve the selection of patients for surgery, has potential for monitoring response to treatment and may prove a cost-effective means of staging melanoma patients.