Epigenetic Silencing of Tumor Suppressor miR-124 Directly Supports STAT3 Activation in Cutaneous T-Cell Lymphoma.

Increasing evidence supports a potential role for STAT3 as a tumor driver in cutaneous T-cell lymphomas (CTCL). The mechanisms leading to STAT3 activation are not fully understood; however, we recently found that miR-124, a known STAT3 regulator, is robustly silenced in MF tumor-stage and CTCL cells. OBJECTIVE: We studied here whether deregulation of miR-124 contributes to STAT3 pathway activation in CTCL. METHODS: We measured the effect of ectopic mir-124 expression in active phosphorylated STAT3 (p-STAT3) levels and evaluated the transcriptional impact of miR-124-dependent STAT3 pathway regulation by expression microarray analysis. RESULTS: We found that ectopic expression of miR-124 results in massive downregulation of activated STAT3 in different CTCL lines, which resulted in a significant alteration of genetic signatures related with gene transcription and proliferation such as MYC and E2F. CONCLUSIONS: Our study highlights the importance of the miR-124/STAT3 axis in CTCL and demonstrates that the STAT3 pathway is regulated through epigenetic mechanisms in these cells. Since deregulated STAT3 signaling has a major impact on CTCL initiation and progression, a better understanding of the molecular basis of the miR-124/STAT3 axis may provide useful information for future personalized therapies.

The natural history of cutaneous sarcoidosis. Clinical spectrum and histological analysis of 40 cases.

BACKGROUND: Cutaneous lesions of sarcoidosis can allow physicians to establish the diagnosis of a systemic disease, but the need of monitoring patients presenting skin limited sarcoidosis in order to detect further extracutaneous involvement has rarely been evaluated. OBJECTIVES: To review clinical and histological features of patients with cutaneous sarcoidosis and the risk of progression to systemic disease. To characterize the phenotype of patients with isolated cutaneous sarcoidosis and to assess the temporal relationship between cutaneous and systemic disease. METHODS: Retrospective review of a series of patients with cutaneous sarcoidosis. Clinical, histopathological, and evolutive features were reviewed. RESULTS: Forty patients were included in the study. Systemic disease was present in 82.5% of patients. Previous or concurrent cutaneous involvement occurred in 81.8% of them. Seven out of 14 patients with cutaneous lesions evolved to a systemic sarcoidosis in a mean time of 6 years, with a range between 4 and 9 years. No clinical or histological differences were found between patients with systemic sarcoidosis and those who showed persistent isolated cutaneous lesions. CONCLUSIONS: Sarcoidosis may be manifested as an isolated cutaneous disorder. No clinical or histopathological features seem to be helpful to discriminate cases of a persistent isolated cutaneous disease from those that will develop systemic involvement. Since the development of systemic involvement in cases of isolated cutaneous sarcoidosis can occur many years afterward, careful monitoring seems advisable, and a long follow-up is recommended.

Persistent cutaneous ulcers after Yttrium-90 synovectomy, an unusual complication: two case reports and a review of the literature.

Development of persistent deep cutaneous ulceration is a rare and serious complication of radiosynovectomy, an extended procedure used in the treatment of chronic synovitis. Cutaneous radiation necrosis is a rare complication of synovectomy, probably as a result of radiocolloid para-articular injection. This rare phenomenon should be suspected when an ulcer adjacent to an articulation appears several days or even months after a radiation synovectomy. It can turn into a challenging diagnosis for rheumatologists, orthopaedists and dermatologists, especially in those cases with a late development of the skin lesions. Recognition of this potential side effect is important in order to establish a proper therapeutic strategy and avoid unnecessary treatments. Surgical excision appears to be the treatment of choice. We report two patients with knee osteoarthritis treated with intra-articular injection of Yttrium-90 who developed persistent cutaneous ulcers secondary to radiation necrosis.

Persistent cutaneous abdominal ulcerations secondary to diffuse dermal angiomatosis: an underestimated sign for severe atherosclerosis: A case report.

BACKGROUND: Diffuse dermal angiomatosis (DDA) is a rare, acquired, reactive vascular proliferation, clinically characterized by livedoid erythematous-violaceous plaques, which frequently evolve to ulceration and necrosis. Histopathologically, it is manifested by a diffuse proliferation of endothelial cells within the full thickness of the dermis. DDA has been mainly associated with severe peripheral atherosclerosis. METHODS: We report a 63-year-old woman who presented with multiple erythematous-violaceous plaques with central deep skin ulcers on thighs, lower abdomen, and perianal area, associated with intermittent claudication, low-grade fever, and weight loss. Initially, the clinical picture along with positive cultures for Klebsiella pneumoniae suggested a multifocal ecthyma gangrenosum; nevertheless, a skin biopsy showed a diffuse dermal proliferation of endothelial cells interstitially arranged between collagen bundles. A computed tomography scan revealed severe aortic atheromatosis with complete luminal occlusion of the infrarenal aorta and common iliac arteries. RESULTS: The diagnosis of DDA secondary to severe atherosclerosis was established. The patient underwent a left axillofemoral bypass surgery with a rapidly healing of the ulcers in the next weeks. CONCLUSIONS: DDA should be considered in the differential diagnosis of livedoid ischemic lesions. Recognition of DDA as a cutaneous sign of severe peripheral vascular disease is important for both dermatologists and internists. Recognition of risk factors and their management with an early intervention to correct tissue ischemia can be curative.