Introduction: Cutaneous squamous cell carcinoma (cSCC) is the second most common cutaneous neoplasm, and its incidence is on the rise. While most cSCCs have an excellent prognosis, certain risk factors, especially immunosuppression, have been associated with higher rates of local recurrence (LR), metastasis, and poor prognosis. This study aims to assess the risk factors for LR and metastasis development in cSCC among solid organ transplant recipients (SOTRs) and compare these rates with those in immunocompetent patients. Materials and Methods: A retrospective observational study included cSCC cases from the University Hospital Reina Sofia in Cordoba, Spain, between 2002 and 2019. Demographic, clinical, and histopathological data were collected. Local recurrence and metastasis rates were analyzed, along with progression-free survival. Univariate analyses were performed to identify prognostic factors in SOTRs. Results: Among 849 cSCC cases, we found higher rates of local recurrence and metastasis in tumors developed by SOTRs compared to those in immunocompetent individuals. However, no significant differences in local recurrence, metastasis, or progression-free survival were observed between the two groups. Risk factors for adverse outcomes in SOTRs included tumor size > 2 cm, depth > 4 mm, and a higher Clark level. A total of 34.4% of SOTRs developed a second primary cSCC during the follow-up. Conclusions: In our study, cSCCs in SOTRs did not exhibit statistically significant differences in the rates of adverse outcomes compared to immunocompetent patients. The prognosis of cSCCs in SOTRs may be more related to other tumor-dependent risk factors than to the immunosuppression status itself. Future studies are needed to refine risk stratification and follow-up protocols to ensure the optimal management of high-risk cSCC cases, particularly among immunosuppressed patients.

Simple Summary: This study evaluates the occurrence of second primary neoplasms (SPNs) in individuals with a history of melanoma (MM) and identify factors that increase the risk in our population. A prospective cohort study was conducted, involving 529 MM survivors from January 2005 to August 2021. Among the 529 patients, 89 were diagnosed with SPNs, with 62 being skin tumors and 37 being solid organ tumors. The estimated probability of developing SPNs after MM diagnosis was found to increase over time, reaching 4.1% at 1 year, 11% at 5 years, and 19% at 10 years. Several factors were significantly associated with a higher risk of SPNs, including older age, primary MM location on the face or neck, and the histologic subtype of lentigo maligna MM. We conclude that individuals with primary MM located on the face and neck, as well as those with the histological subtype of lentigo maligna-MM, have a higher risk of developing SPNs. Age also independently influences the risk. Understanding these risk factors can assist in developing MM guidelines that provide specific follow-up recommendations for individuals at the highest risk. (1) Introduction: The association between melanoma (MM) and the occurrence of second primary neoplasms (SPNs) has been extensively studied, with reported incidence rates ranging from 1.5% to 20%. This study aims to evaluate the occurrence of SPNs in patients with a history of primary MM and to describe the factors that make the risk higher in our population. (2) Material and Methods: We conducted a prospective cohort study and calculated the incidence rates and relative risks (RR) for the development of different SPNs in 529 MM survivors from 1 January 2005 to 1 August 2021. Survival and mortality rates were obtained, and the Cox proportional hazards model was used to determine the demographic and MM-related factors that influence the overall risk. (3) Results: Among the 529 patients included, 89 were diagnosed with SPNs (29 prior to MM diagnosis, 11 synchronous, and 49 after MM), resulting in 62 skin tumors and 37 solid organ tumors. The estimated probability of developing SPNs after MM diagnosis was 4.1% at 1 year, 11% at 5 years, and 19% at 10 years. Older age, primary MM location on the face or neck, and histologic subtype of lentigo maligna mm were significantly associated with a higher risk of SPNs. (4) Conclusions: In our population, the risk of developing SPNs was higher in patients with primary MM located on the face and neck and with the histological subtype of lentigo maligna-MM. Age also independently influences the risk. Understanding these hazard factors can aid in the development of MM guidelines with specific follow-up recommendations for individuals with the highest risk.

The appearance of morphea after vaccination has been reported to date as single and deep lesions that appear exactly at the site of the skin puncture. It was therefore postulated that the origin could be the trauma related to the injection. The aim of this article is to review the various hypotheses offered in the published literature about generalized morphea following vaccination. We present two cases of generalized morphea after COVID-19 vaccination and review the published literature on immune-related cutaneous reactions. As previously reported, antigenic cross-reactivity between vaccine spike proteins and human tissues could cause certain immune-mediated diseases, including generalized morphea. Herein we report two cases of generalized morphea probably induced by the COVID-19 vaccine, given the temporal relationship with its administration. In summary, environmental factors such as vaccination against SARS-COV-2 could induce an immune system dysregulation, which would have an important role in the pathogenesis of morphea. We present two cases of generalized morphea probably induced by the COVID-19 vaccine, given the time elapsed between vaccination and the onset of the skin lesions.

Colony-stimulating factor 1 receptor (CSF1R) inhibitors represent a new class of immune-modulatory drugs, mostly investigated in clinical trials in different malignant neoplasms. Four patients, diagnosed with recurrent or advanced malignant neoplasm and treated with a combination of anti-programmed death ligand 1 and anti-CSF1R monoclonal antibodies, developed an asymptomatic cutaneous eruption characterized by an ill-defined pseudoedematous to waxy diffuse infiltration with a reticular cobblestone-like pattern. Histopathological examination revealed diffuse mucin deposition involving the superficial and mid-dermis with fragmented and scattered elastic fibers. The exact pathogenic mechanisms implicated in the development of mucin deposits in patients treated with CSF1R inhibitors remain to be elucidated. A reduced degradation and clearance of components of the extracellular matrix by macrophages secondary to CSF1 pathway inhibition may be hypothesized. Shredding and fragmentation of elastic fibers may be a result of the increased accumulation of mucopolysaccharides. This observation illustrates the new spectrum of skin-related toxicities secondary to new targeting therapies. This may contribute to a better understanding of the underlying pathogenic mechanisms in skin diseases characterized by a persistent dermal glycosaminoglycan deposition.

Background: Organ transplant recipients (OTR) have a higher risk of actinic keratosis (AK) and keratinocyte carcinomas (KC). There are no clinical trials assessing the effectiveness of daylight photodynamic therapy (DPDT) to prevent new AK and KC in OTR. Objectives: To determine whether repeated treatments of field cancerization with DPDT are effective in preventing new AK and KC in OTR. Methods: A randomized, intra-subject controlled, evaluator-blind, split-face and/or scalp trial, from April 2016 to October 2018. Participants were OTR older than 18 years, 1-year posttransplant, with at least 5 AK on each hemi-face/hemi-scalp. One side received six field treatments with DPDT: two sessions 15 days apart at baseline, two at 3 months and two at 9 months after baseline. Control side received lesion-directed treatment with cryotherapy (double freeze-thaw) at baseline, 3 and 9 months. Total number of lesions (AK and KC) at 21 months, number of new AK and KC at 3, 9, 15 and 21 months and treatment preferences were analysed. Results: Of 24 men included, 23 were analysed at 3 months; and 21, at 9, 15 and 21 months. Mean (SD) age was 69.8 years (9.2). The total number of lesions at 21 months was 4.7 (4.3) for DPDT and 5.8 (5.0) for control side; P = 0.09. DPDT showed significantly lower means [SD] of new lesions compared to control side at 3 months (4.2 [3.4] vs. 6.8 [4.8]; P < 0.001), 9 months (3.0 [3.3] vs. 4.3 [3.4]; P = 0.04) and 15 months (3.0 [4.6] vs. 4.8 [5.0]; P = 0.02), and non-significant at 21 months (3.7 [3.5] vs. 5.0 [4.5]; P = 0.06). Most participants preferred DPDT. Conclusion: DPDT showed potential effectiveness in preventing new AK and KC in OTR by consecutive treatments of field cancerization. The preference for DPDT could facilitate adherence to the long-term treatment necessary in these patients.