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Nevus-associated lentigo maligna and lentigo maligna melanoma (NALMM) are rarely described in the literature and are considered an incidental finding. This study aimed to evaluate the frequency of NALMM and its clinicopathological features. A total of 201 histopathology reports were reviewed and among them 20% of the samples corresponded to NALMM, with females overrepresented in this group (p = 0.02). A significant association was also observed between NALMM with the presence of multiple nevi (p = 0.01), and dysplastic nevi (p = 0.04). Moreover, the risk of developing a second melanoma of nevus-associated type was 4.3 times higher in patients with NALMM. These results indicate that NALMM is more frequent than previously reported, suggesting that the associated nevus could interact or even act as a precursor for LM/LMM. Future studies with larger samples allied to techniques like confocal microscopy and molecular analysis are essential to determine this biological link between nevus and LM/LMM.

[This corrects the article DOI: 10.1371/journal.pone.0205517.].

Radiotherapy is often used to treat lentigo maligna. However, the long-term efficacy and safety of radiotherapy approaches have not been thoroughly evaluated. We aimed to evaluate the long-term efficacy and safety of ultrasoft X-ray/Grenz ray treatment in those patients. A total of 161 lesions from 159 patients received treatment with Grenz ray between 2005 and 2007. Follow-up of recurrence was performed 10 years after the final treatment. In the study setting, the cure rates were 97% for primary therapy with Grenz ray alone and 100% when Grenz ray was combined with partial or radical excision. The treatment is well tolerated, simple to perform, and has an excellent cosmetic outcome, with 94% of patients pleased with the results. Grenz ray is painless, effective, and safe for use when surgery is not feasible. Thus, Grenz ray can be considered as a standard treatment option for lentigo maligna.

Sjogren’s syndrome is classically characterized by symptoms of keratoconjunctivitis sicca and xerostomia, secondary to lymphocytic infiltration of the salivary and lacrimal glands. Cutaneous findings of this disease are infrequently discussed and thus rarely considered among patients without the typical symptomatology. However, these patients can develop xerosis, alopecia, vitiligo, papular or nodular lesions, or cutaneous vasculitis. A 56-year-old Asian female presented with intermittent cutaneous erythematous lesions of her bilateral pinna and preauricular areas. Despite initial symptom presentation causing concern for tumid lupus versus cutaneous T cell lymphoma versus relapsing polychondritis, extensive serologic and histopathologic workup eventually indicated a likely diagnosis of Sjogren’s syndrome. This case brings to light that Sjogren’s syndrome is truly a multi-systemic disease and can present with primarily extra glandular cutaneous symptoms. When approaching the workup of a new patient, it is absolutely vital to maintain a broad differential and keep in mind that overlap syndromes among multiple autoimmune diseases do exist as well.

Nevus-associated lentigo maligna and lentigo maligna melanoma (NALMM) are rarely described in the literature and are considered an incidental finding. This study aimed to evaluate the frequency of NALMM and its clinicopathological features. A total of 201 histopathology reports were reviewed and among them 20% of the samples corresponded to NALMM, with females overrepresented in this group (p = 0.02). A significant association was also observed between NALMM with the presence of multiple nevi (p = 0.01), and dysplastic nevi (p = 0.04). Moreover, the risk of developing a second melanoma of nevus-associated type was 4.3 times higher in patients with NALMM. These results indicate that NALMM is more frequent than previously reported, suggesting that the associated nevus could interact or even act as a precursor for LM/LMM. Future studies with larger samples allied to techniques like confocal microscopy and molecular analysis are essential to determine this biological link between nevus and LM/LMM. [ABSTRACT FROM AUTHOR]

Ligand-activated plasma membrane receptors follow pathways of endocytosis through the endosomal sorting apparatus. Receptors cluster in clathrin-coated pits that bud inwards and enter the cell as clathrin-coated vesicles. These vesicles travel through the acidic endosome whereby receptors and ligands are sorted to be either recycled or degraded. The traditional paradigm postulated that the endocytosis role lay in signal termination through the removal of the receptor from the cell surface. It is now becoming clear that the internalization process governs more than receptor signal cessation and instead reigns over the entire spatial and temporal wiring of receptor signaling. Governing the localization, the post-translational modifications, and the scaffolding of receptors and downstream signal components established the endosomal platform as the master regulator of receptor function. Confinement of components within or between distinct organelles means that the endosome instructs the cell on how to interpret and translate the signal emanating from any given receptor complex into biological effects. This review explores this emerging paradigm with respect to the cancer-relevant insulin-like growth factor type 1 receptor (IGF-1R) and discusses how this perspective could inform future targeting strategies.

Despite enormous international efforts, skin melanoma is still a major clinical challenge. Melanoma takes a top place among the most common cancer types and it has one of the most rapidly increasing incidences in many countries around the world. Until recent years, there have been limited options for effective systemic treatment of disseminated melanoma. However, lately, we have experienced a rapid advancement in the understanding of the biology and molecular background of the disease. This has led to new molecular classifications and the development of more effective targeted therapies adapted to distinct melanoma subtypes. Not only are these treatments more effective but they can be rationally prescribed to the patients standing to benefit. As such, melanoma management has now become one of the most developed for personalized medicine. The aim of the present paper is to summarize the current knowledge on melanoma molecular classification, predictive markers, combination therapies, as well as emerging new treatments.

Although clinical guidelines exist, the management of patients with cutaneous melanoma (CM) is a complex process that may vary between different care providers with potential dysfunctions ultimately mirrored in the overall patient satisfaction. The aim of the present study was to investigate the CM management as related to lead times, surgical quality and diagnosis communication with the hypothesis that the care may differ between providers and disparities may impact patient satisfaction. Medical records of 181 patients were retrospectively analyzed with parallel patient satisfaction evaluation by telephone interviews. Overall mean lead times from initial diagnosis until completion of all surgery and histopathology reports were 80-100 days and delays occurred at every step of the process. General practitioners performed excision biopsies faster however this was mitigated by slower histopathology processing. University level CM care showed less lag time between excision biopsy, wide local excision for thick melanomas and histopathology confirmation. University level care operated with twice the surgical margin as compared to general practitioners and non-university level specialists. Male patients had larger excision biopsy margins and significantly shorter lead times than female patients. Patient satisfaction rates were generally higher in the academic hospitals as compared to general practitioners and non-university dermatology clinics. Surprisingly, there was no correlation between lead times and patient satisfaction. Taken together, CM show substantial variation and caution should be practiced when using patient satisfaction as a quality indicator.

Statins are notorious for causing myalgia and sometimes mild elevation of CPK (creatine phosphokinase). Herein, we present a case of necrotizing autoimmune myopathy induced by statins. The patient was on therapy with atorvastatin for about six years before she started developing myalgia and mild elevation in CPK that resolved after discontinuation of therapy. Since her cardiovascular risk was high and she had hypercholesterolemia, three months after CPK levels normalization, she was re-challenged with pravastatin. Few months later, she again presented severe myalgia, weakness, and elevated CPK levels. Hence, medication was discontinued, and she undergone an extensive workup for possible causes of inflammatory myopathies that revealed necrotizing autoimmune myopathy. Our case report offers an excellent source of “identification patterns” of muscular autoimmune disease which can be easily mistaken as common side effect of a drug.