45 research outputs found
Immune Disregulation in Cutaneous Squamous Cell Carcinoma of Patients with Recessive Dystrophic Epidermolysis Bullosa: A Single Pilot Study
Background: Cutaneous squamous cell carcinoma (cSCC) is one of the most devastating complications of recessive dystrophic epidermolysis bullosa (RDEB). We recently demonstrated a reduction in immune cell peritumoral infiltration in RDEB patients with cSCC, together with a reduction in CD3+, CD4+, CD68+ and CD20 lymphocytes as compared to primary and secondary cSCC in patients without RDEB. Recently, new molecules, such as high mobility group box 1 (HMGB1), T cell immunoglobulin, mucin domain 3 (TIM-3) and Heme oxygenase-1 (HO-1), have been shown to play a role in antitumoral immunity. Objective: Patients with RDEB are known to be at increased risk of developing skin cancers, including the dreaded squamous cell carcinoma of the. Tendentially, cSCCs that arise in the context of EBDR are more aggressive and lead to statistically significant bad outcomes compared to cSCCs developed on the skin of patients without EBDR. In an attempt to study the microenvironment of these lesions, we conducted an immunohistochemical analysis study of proteins that could be actively involved in the genesis of this type of malignant neoplasms. Methods: In this retrospective study, the OH1-HMGB1-TIM3 activation axis, as correlated to the T lymphocytes cell count, was assessed in biopsy samples from 31 consecutive cases consisting of 12 RDEB patients with cSCC, 12 patients with primary cSCC and 7 RDEB patients with pseudoepitheliomatous cutaneous hyperplasia. Parametric Student’s t-test was applied for normally distributed values, such as CD4+ and CD8+, and non-parametric Mann–Whitney test for non-normally distributed values, such as HMGB-1, TIM-3 and HO-1. Results: In RDEB patients with cSCC and with pseudoepitheliomatous hyperplasia, the expression of CD4 T helper lymphocytes was lower than in the peritumoral infiltrate found in primary cSCC. CD8 cytotoxic T lymphocytes were increased in primary cSCC compared to the other two groups. An increased HMGB1 expression was evident in both primary and RDEB cSCC. TIM3 expression was higher in RDEB patients with cSCC compared to the other two groups. A significantly reduced immunohistochemical expression of HO-1 was evident in the tumoral microenvironment of cSCC-RDEB as compared to primary cSCC. Conclusions: These data suggest that a reduced immune cell peritumoral infiltration in RDEB patients could be responsible, in the complexity of the mechanisms of carcinogenesis and host response, of the particular aggressiveness of the cSCC of RDEB patients, creating a substrate for greater local immunosuppression, which, potentially, can “open the doors” to development and eventual metastasis by this malignant neoplasm
Topical propranolol for a chronic recalcitrant wound
A 68 yearâold patient presented to our attention with a deep ulcerating lesion of the right sole.
He reported the substance loss had manifested after a corticosteroid infiltration at the same site for antiâinflammatory purposes about 11 months before. He reported no other medical condition.
At physical examination a 2 Ă 1 cm ulcer was present, with irregular and undermined borders. The substance loss involved completely the skin and the subcutaneous tissue, sparing the plantar fascia which was left exposed (FIG. 1). No sign of infection was noticeable. The lesion had been treated with a variety of topical and systemic drugs, including advanced dressings, dermal substitute (Integra), and subcutaneous low molecular weight heparin as well as aspirin, with no significant clinical response whatsoever. At time of consultation, vacuumâassisted closure therapy was proposed, but the patient refused. Based on various reports on successful use of topical timolol for chronic ulcers, we discussed the possibility of using a similar offâlabel treatment. With written consent, we started the patient on a three times/day topical application of a galenic preparation of 1% propranololâhydrochloride in a hydrophilic cream, covered by a nonadhering silicone dressing (Adaptic) while withdrawing any other specific treatment. We chose propranolol instead of timolol for the excellent safety profile and minor systemic absorption, as supported by the vast experience on ulcerated infantile hemangiomas 1. After 3 weeks of continued application, the ulcer had dramatically improved, and after another week the lesion had completely healed (FIG. 2). No irritation or other local or systemic adverse effects were noticed. The cream was then suspended; follow up at 1 year did not show any sign of recurrenc
Persistence of superficial basal cell carcinoma during pembrolizumab treatment for metastatic melanoma
The Home-made Biostimulating Thread Lift
Supplemental Digital Content is available in the text