A Sub-Group of Kidney-Transplant Recipients with Highly Aggressive Squamous Cell Carcinoma Expressing Phosphorylated Serine392p53.

Cutaneous squamous cell carcinomas in kidney-transplant recipients are frequent, with an increasing incidence linked to long immunosuppression durations and exposure to ultraviolet radiation. p53 is at the cornerstone of ultraviolet-induced DNA damage, but the role of p53 post-translational modifications in this context is not yet deciphered. Here, we investigated the phosphorylation status of p53 at Serine 392 in 25 cutaneous squamous cell carcinomas in kidney-transplant recipients, compared with 22 non-transplanted patients. Cutaneous squamous cell carcinomas in transplanted patients occurred after a median period of 19 years of immunosuppression, with a median number of 15 cutaneous squamous cell carcinomas and more aggressive histological and clinical characteristics. There was no significant difference between Ki67, p53, and pSer392p53 expression in the two groups. Using principal component analysis, we identified a cluster of exclusively transplanted patients with a median of 23 years of immunosuppression duration, significantly more aggressive biological characteristics, and higher pSer392p53 expression. pSer392p53 was expressed in the whole tumor, suggesting an early carcinogenic event in the course of prolonged immunosuppression. This high, diffuse pSer392p53 expression, corresponding to a high level of DNA damage, might be useful to identify aggressive cutaneous squamous cell carcinomas in kidney-transplant recipients to treat them more aggressively.

Impact of Mogamulizumab in Real-Life Advanced Cutaneous T-Cell Lymphomas: A Multicentric Retrospective Cohort Study.

BACKGROUND: Advanced mycosis fungoides (MF) and Sézary syndrome (SS) are rare, aggressive cutaneous T-cell lymphomas that may be difficult to treat. Mogamulizumab is a recent monoclonal antibody targeting the CCR4 receptor expressed on the surface of Sézary cells. It can be prescribed in MF/SS stages III to IV in the second line after systemic therapy or in stages IB-II after two unsuccessful systemic therapies. We lack data on long-term efficiency and potential side effects in real-life conditions. Our study aims to determine efficacy considering the median PFS of advanced CTCL with mogamulizumab. Secondary objectives were to consider tolerance and estimate delay until side effects appeared. METHODS: Data on patients with advanced cutaneous T-cell lymphomas were collected since French Authorization, in six French university hospitals. Patients were followed until they stopped mogamulizumab because of relapse or toxicity. For those still treated by mogamulizumab, the end point was 1 September 2021. We excluded 3 patients as they had already been included in the MAVORIC study and data was not available. RESULTS: The median time of follow-up was 11.6 months. Of the 21 patients included, we reported four full-response patients, eight in partial response, one in stability, three in progression, and five were deceased. One patient had visceral progression, and seven had new lymphadenopathy. Progression-free survival was estimated at 22 months. Twenty patients presented adverse events, of which 10 were severe, i.e., grade III-IV. The median time between the introduction of mogamulizumab and the first adverse event was 21 days. CONCLUSIONS: Our study suggests that mogamulizumab can give patients with advanced refractory CTCL a consequent PFS, estimated at 22 months. The long-term safety of mogamulizumab was determined to be acceptable since we reported few grade III-IV AEs, comparable with other studies. No other study using real-life data has been performed to investigate the AEs of mogamulizumab.

Revisiting detection of in-transit metastases in melanoma patients using digital 18F-FDG PET/CT with small-voxel reconstruction.

AIM: To evaluate the use of digital 18F-FDG PET/CT with small-voxels reconstruction for detecting in-transit metastases in melanoma patients with primary lesion located on the upper or lower limbs, in comparison with standard reconstruction and European Association of Nuclear Medicine Research limited (EARL)-compliant reconstruction mimicking former generation PET systems. METHODS: Forty-six PET examinations acquired in list mode on a Vereos digital PET/CT system were reconstructed with (1) the standard reconstruction [2 iterations, 10 subsets (2i10s), point-spread function (PSF) modelling and time-of-flight enabled, no post-filtering and voxel size of 2 mm], (2) a small-voxel reconstruction using 1 mm voxels otherwise using the same parameters, (3) an EARL-compliant reconstruction mimicking a former generation system. Comparison of results across these reconstructions was made for a blind randomized review using a 3-point scale for the presence of in-transit metastases and image quality as well as for tumour-to-background (T/B) ratios and noise level in reference organs. RESULTS: Seven of the thirty-two EARL-compliant images classified as negative moved to positive on 1mmPSF images, and 5 of the 6 EARL-compliant images classified as indeterminate moved to positive on 1mmPSF images (P = 0.01). Amongst a total of 20 PET examinations classified as positive using the 1mmPSF reconstruction, fifteen were considered true positive, five false positive results occurred. Twenty-four patients with 1 mm PSF images were classified as negative, none of those under active surveillance experienced in-transit metastases during the 17 months following their PET examination. The positive likelihood ratio for the 1 mm reconstruction was much higher than that observed for EARL-compliant images (14.7 vs 7.82). Importantly, negative likelihood ratios for the 1 mm and 1mmPSF reconstruction were almost perfect. Compared to EARL-compliant data, T/B ratios extracted from the 1mmPSF showed a 2.84-fold increase (P < 0.001). A similar pattern of statistically significant increase was observed for noise level in organs of reference. Image quality for the torso was found to be significantly lower for 1mmPSF reconstruction (P = 0.03). Image quality for the limbs was found to be better for 1mmPSF (P < 0.001). CONCLUSION: Digital PET with small-voxel reconstruction brings an additional value for the detection of in-transit metastases by reducing the number of indeterminate findings and making up for falsely negative scans using former generation PET systems. An acquisition encompassing lower or upper limbs as appropriate should be performed.

18F-FDG PET/CT versus Diagnostic Contrast-Enhanced CT for Follow-Up of Stage IV Melanoma Patients Treated by Immune Checkpoint Inhibitors: Frequency and Management of Discordances over a 3-Year Period in a University Hospital.

AIM: To perform a comprehensive analysis of discordances between contrast-enhanced CT (ceCT) and 18F-FDG PET/CT in the evaluation of the extra-cerebral treatment monitoring in patients with stage IV melanoma. MATERIALS AND METHODS: We conducted a retrospective monocentric observational study over a 3-year period in patients referred for 18F-FDG PET/CT and ceCT in the framework of therapy monitoring of immune checkpoint (ICIs) as of January 2017. Imaging reports were analyzed by two physicians in consensus. The anatomical site responsible for discordances, as well as induced changes in treatment were noted. RESULTS: Eighty patients were included and 195 pairs of scans analyzed. Overall, discordances occurred in 65 cases (33%). Eighty percent of the discordances (52/65) were due to 18F-FDG PET/CT scans upstaging the patient. Amongst these discordances, 17/52 (33%) led to change in patient's management, the most frequent being radiotherapy of a progressing site. ceCT represented 13/65 (20%) of discordances and induced changes in patients' management in 2/13 cases (15%). The most frequent anatomical site involved was subcutaneous for 18F-FDG PET/CT findings and lung or liver for ceCT. CONCLUSIONS: Treatment monitoring with 18F-FDG PET/CT is more efficient than ceCT and has a greater impact in patient's management.

Dermoscopic Features of Toenail Onychomycosis.

BACKGROUND: Onychomycosis is the most common infectious nail disorder. Direct mycologic examination is still the cornerstone of diagnosis; however, it may take several weeks to obtain a result. Recently some dermoscopic patterns that can be useful in the diagnosis of onychomycosis were described. However, published data on dermoscopic features of onychomycosis are still limited. METHODS: We performed a prospective dermoscopic study of patients with positive fungal culture between April and December 2016. Patients with a final diagnosis of psoriasis or lichen planus were excluded from the study. Dermoscopy (polarized and nonpolarized) was performed. RESULTS: Thirty-seven patients were enrolled, 24 women and 13 men (median ± SD age, 48.6 ± 16.1 years). Nail samples were culture positive for Trichophyton rubrum (89.2%), Trichophyton interdigitale (8.1%), and Candida albicans (2.7%). Distal and lateral subungual onychomycosis was the most frequent clinical subtype (59.5%). The most frequent dermoscopic features were subungual keratosis (73.0%), distal subungual longitudinal striae (70.3%), spikes of the proximal margin of an onycholytic area (59.5%), transverse superficial leukonychia (29.7%), and linear hemorrhage (13.5%). Brown chromonychia was most frequently seen with nonpolarized dermoscopy (66.6% versus 24%; P = .027). CONCLUSIONS: Specific dermoscopic signs of onychomycosis are mostly related to the proximal invasion of the nail plate. Detection of these signs is simple and can, in some cases, help avoid mycologic testing.

Retronychia Clinical Features and Surgical Treatment.

Retronychia is a newly described condition characterized by the embedding of the nail plate into the proximal nail fold. It mainly affects the great toe unilaterally as a result of mechanical factors. It is rarely reported, and its pathogenesis is not fully understood. Nail plate avulsion represents both a diagnostic and a therapeutic approach. We describe a 34-year-old woman with a medical history of congenital malalignment of the toenails, diagnosed as having retronychia, and emphasize the disease pathogenesis and surgical procedure.