Mohs micrographic surgery in immunosuppressed vs immunocompetent patients: Results of a prospective nationwide cohort study (REGESMOHS, Spanish registry of Mohs surgery).

BACKGROUND: Immunosuppressed (IS) patients, particularly solid organ transplant recipients and those on immunosuppressive therapy, face a higher incidence and recurrence of nonmelanoma skin cancers (NMSC), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Mohs micrographic surgery (MMS) is the preferred treatment for high-risk NMSC due to its high cure rate and margin examination capabilities. However, IS patients may experience more complications, such as surgical site infections, and a greater risk of recurrence, making their outcomes a subject of interest. OBJECTIVES: This study aimed to compare IS and immunocompetent (IC) patients undergoing MMS for NMSC in terms of baseline characteristics, intra- and post-surgical complications, and postoperative recurrence rates. METHODS: The study utilized data from the REGESMOHS registry, a 7-year prospective cohort study in Spain. It included 5226 patients, categorizing them into IC (5069) and IS (157) groups. IS patients included solid organ transplant recipients, those on immunosuppressive treatments, individuals with haematological tumours and HIV-positive patients. Patient data, tumour characteristics, surgical details and outcomes were collected and analysed. RESULTS: IS patients demonstrated a higher proportion of SCC, multiple synchronous tumours and tumours invading deeper structures. Complex closures, unfinished MMS and more surgical sections were observed in the IS group. Although intra-operative morbidity was higher among IS patients, this difference became non-significant when adjusted for other variables such as year of surgery, antiplatelet/anticoagulant treatment or type of closure. Importantly, IS patients had a substantially higher recurrence rate (IRR 2.79) compared to IC patients. CONCLUSIONS: This study suggests that IS patients may be at a higher risk of development of AE such as bleeding or tumour necrosis and are at a higher risk of tumour recurrence. Close follow-up and consideration of the specific characteristics of NMSC in IS patients are crucial. Further research with extended follow-up is needed to better understand the long-term outcomes for this patient group.

Development and validation of a model to predict complex Mohs micrographic surgery in clinical practice: REGESMOSH scale.

INTRODUCTION: There is still a need to develop a simple algorithm to identify patients likely to need complex Mohs micrographic surgery (MMS) and optimize MMS schedule. The main objectives of this study are to identify factors associated with a complex MMS and develop a predictor model of the number of stages needed in surgery and the need for a complex closure. MATERIALS AND METHODS: A nationwide prospective cohort study (REGESMOHS, the Spanish Mohs surgery registry) was conducted including all patients with a histological diagnosis of basal cell carcinoma (BCC). Factors related to three or more stages and a complex closure (that needing a flap and/or a graft) were explored and predictive models were constructed and validated to construct the REGESMOSH scale. RESULTS: A total of 5226 patients that underwent MMS were included in the REGESMOHS registry, with 4402 (84%) having a histological diagnosis of BCC. A total of 3689 (88.9%) surgeries only needed one or two stages and 460 (11.1%) required three or more stages. A model to predict the need for three or more stages included tumour dimension, immunosuppression, recurrence, location in risk areas, histological aggressiveness and previous surgery. Regarding the closure type, 1616 (38.8%) surgeries were closed using a non-complex closure technique and 2552 (61.2%) needed a complex closure. A model to predict the need for a complex closure included histological aggressiveness, evolution time, patient age, maximum tumour dimension and location. CONCLUSION: We present a model to predict MMS needing ≥3 stages and a complex closure based on epidemiological and clinical data validated in a large population (with real practice variability) including different centres that could be easily implemented in clinical practice. This model could be used to optimize surgery schedule and properly inform patients about the surgery duration.

Complications Associated with Mohs Micrographic Surgery: Data from the Nationwide Prospective Cohort REGESMOHS.

BACKGROUND: Large prospective studies on the safety of Mohs micrographic (MMS) surgery are scarce, and most focus on a single type of surgical adverse event. Mid-term scar alterations and functional loss have not been described. OBJECTIVES: To describe the risk of MMS complications and the risk factors for them. METHODS: A nationwide prospective cohort collected all adverse events on consecutive patients in 22 specialised centres. We used multilevel mixed-effects logistic regression to find out factors associated with adverse events. RESULTS: 5,017 patients were included, with 14,421 patient-years of follow-up. 7.0% had some perioperative morbidity and 6.5% had mid-term and scar-related complications. The overall risk of complications was mainly associated with use of antiaggregant/anticoagulant and larger tumours, affecting deeper structures, not reaching a tumour-free border, and requiring complex repair. Age and outpatient setting were not linked to the incidence of adverse events. Risk factors for haemorrhage (0.9%) were therapy with antiaggregant/anticoagulants, tumour size, duration of surgery, and unfinished surgery. Wound necrosis (1.9%) and dehiscence (1.0%) were associated with larger defects and complex closures. Immunosuppression was only associated with an increased risk of necrosis. Surgeries reaching deeper structures, larger tumours and previous surgical treatments were associated with wound infection (0.9%). Aesthetic scar alterations (5.4%) were more common in younger patients, with larger tumours, in H-area, and in flap and complex closures. Risk factors for functional scar alterations (1.7%) were the need for general anaesthesia, larger tumours that had received previous surgery, and flaps or complex closures. CONCLUSIONS: MMS shows a low risk of complications. Most of the risk factors for complications were related to tumour size and depth, and the resulting need for complex surgery. Antiaggregant/anticoagulant intake was associated with a small increase in the risk of haemorrhage, that probably does not justify withdrawal. Age and outpatient setting were not linked to the risk of adverse events.

Expression of microRNA-21 and TIMP-3 in paradoxical psoriasiform reactions during treatment with antitumor necrosis factor agents.

BACKGROUND: Expression of microRNA-21 (miR-21) is increased in psoriasis, leading to reduced levels of epidermal tissue inhibitor of matrix metalloproteinase 3 (TIMP-3), a highly potent inhibitor of the tumor necrosis factor alpha (TNFα) sheddase TACE (TNFα-converting enzyme)/ADAM17. We described the profile of miR-21 and TIMP-3 in paradoxical psoriasiform reactions induced by anti-TNFα drugs and in a control group to elucidate the pathogenesis of this reactions. METHODS: We performed an analytic, cross-sectional, prospective, experimental case-control study. We compared our findings with those of non-induced psoriasis. RESULTS: We included 15 patients with a change of morphology (plaque to guttate psoriasis) and 10 patients with induced psoriasis (six palmoplantar pustulosis and four plaque psoriasis). Consecutive patients with different subtypes of non-induced, non-systemically treated psoriasis were included as a control group. We found that most cases with guttate psoriasis and with induced plaque psoriasis cases showed high expression of TIMP-3 expression and decreased or poorly increased levels of miR-21. The expression pattern was not homogeneous in the cases of induced palmoplantar pustulosis. These profiles differ from those of non-induced psoriasis. CONCLUSION: We conclude that various pro-inflammatory cytokine profiles are involved in the pathogenesis of paradoxical psoriasiform reactions and non-induced psoriasis.

Risk Factors and Rate of Recurrence after Mohs Surgery in Basal Cell and Squamous Cell Carcinomas: A Nationwide Prospective Cohort (REGESMOHS, Spanish Registry of Mohs Surgery).

Randomized studies to assess the efficacy of Mohs micrographic surgery in basal cell and squamous cell carcinomas are limited by methodological and ethical issues and a lack of long follow-up periods. This study presents the "real-life" results of a nationwide 7-years cohort on basal cell carcinoma and squamous cell carcinoma treated with Mohs micrographic surgery. A prospective cohort was conducted in 22 Spanish centres (from July 2013 to February 2020) and a multivariate analysis, including characteristics of patients, tumours, surgeries and follow-up, was performed. A total of 4,402 patients followed up for 12,111 patient-years for basal cell carcinoma, and 371 patients with 915 patient-years of follow-up for squamous cell carcinoma were recruited. Risk factors for recurrence included age, non-primary tumours and more stages or unfinished surgeries for both tumours, and immunosuppression for squamous cell carcinoma. Incidence rates of recurrence were 1.3 per 100 person-years for basal cell carcinoma (95% confidence interval 1.1-1.5) and 4.5 for squamous cell carcinoma (95% confidence interval 3.3-6.1), being constant over time (0-5 years). In conclusion, follow-up strategies should be equally intense for at least the first 5 years, with special attention paid to squamous cell carcinoma (especially in immunosuppressed patients), elderly patients, non-primary tumours, and those procedures requiring more stages, or unfinished surgeries.

Mohs micrographic surgery in dermatofibrosarcoma protuberans: Rate and risk factors for recurrence in a prospective cohort study from the Spanish Registry of Mohs Surgery (REGESMOHS) and review of the literature.

Characterization of patients, surgery procedures and the risk factors for dermatofibrosarcoma protuberans (DFSP) recurrences is poorly defined. In this study, we aimed to describe the demographics, tumor characteristics and interventions of DFSP treated with Mohs micrographic surgery (MSS) to determine the rate and risk factors for recurrence. Data were collected from REGESMOHS, a nationwide prospective cohort study of patients treated with MMS in Spain. From July 2013 to February 2020, 163 patients with DFSP who underwent MMS were included. DFSP was mostly located on trunk and extremities. Recurrent tumors had deeper tumor invasion and required higher number of MMS stages. Paraffin MMS was the most frequently used technique. Overall recurrence rate was 0.97 cases/100 person-years (95% IC = 0.36-2.57). No differences were found in epidemiological, tumor, surgery characteristics or surgical technique (frozen or paraffin MMS [p = 0.6641]) in terms of recurrence. Median follow-up time was 28.6 months with 414 patient-years of follow-up. In conclusion, we found an overall low recurrence rate of DFSP treated with MMS. None of the studied risk factors, including MMS techniques, was associated with higher risk for recurrence.

Geometric border as a marker for melanoma diagnosis: Study of 200 consecutive melanocytic lesions.

The ABCD rule has long been proposed as a guidance for malignant melanoma (MM) diagnosis. We aimed to define a new simple, straightforward tool that could be useful in early melanoma detection and must be validated in further studies. We conducted a prospective historic cohort study of 200 melanocytic lesions classifying them according to the presence of geometric borders. Sixty-four percent of the MM and 31% of the melanocytic nevi presented with geometric borders. Lesions with two straight borders that formed a noncurvilinear angle presented a 2.1-fold higher risk of being malignant after excision. When comparing melanomas with geometric and nongeometric border, we found a tendency toward better prognostic markers in the geometric lesions. Lesions located in the extremities and melanoma subtype SSM were more common in the geometric group. Regarding pathologic features, a deeper Breslow (mean, 3.8 vs 1.4 mm), presence of ulceration (25% vs 5%) and a higher number of mitosis was found in the nongeometric group. On the other hand, more regression was found in the geometric group while both groups showed similar degree of lymphovascular infiltration. We propose geometric border as another clinical criterion to take into account when suspecting MM, which must be validated in further studies. The ABCDE rule could be completed with a G for geometry.

Mohs Surgery Outside Usual Indications: A Review.

The body of literature supporting the use of Mohs micrographic surgery (MMS) in tumors outside the main indications (basal cell carcinoma, squamous cell carcinoma, dermatofibrosacroma protuberans, lentigo maligna) is constantly growing, but it is still based on case reports, case series, or at best institutional case series that focus on a single malignancy. Our aim in this review was to assess use of MMS in an array of rare tumors outside the usual indications. A review was performed using the MEDLINE database and the search engine ClinicalKey®. We reviewed the use of MMS on atypical fibroxanthoma (AFX)/malignant fibrous histiocytoma, microcystic adnexal carcinoma, extramammary Paget's disease, Merkel cell carcinoma, pocrine/eccrine carcinoma/porocarcinoma, trichilemmal carcinoma, leiomyosarcoma, and angiosarcoma. Mohs micrographic surgery appears to be scarcely used in these tumors due to their low incidence. It is mainly performed for tumors in the H-zone of the face, and can be performed safely. The overall recurrence rate is lower compared with simple or wide local excision. MMS should be used in a more generalized fashion for these tumors.

Differences of Mohs micrographic surgery in basal cell carcinoma versus squamous cell carcinoma.

BACKGROUND: The two main tumors treated with Mohs micrographic surgery (MMS) are basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). There are no studies analyzing whether MMS is different when treating these two types of tumors. OBJECTIVE: We aim to compare the characteristics of the patients, the tumors, and MMS, and first-year follow-up of MMS in BCC and SCC. METHODS: REGESMOHS is a prospective cohort study of patients treated with MMS. The participating centers are 19 Spanish hospitals where at least one MMS is performed per week. Data on characteristics of the patients, tumors, and surgery were recorded. The follow-up was done with two visits: the first visit within 1 month after surgery and the second one within the first year. RESULTS: From July 2013 to April 2017, a total of 2,669 patients who underwent MMS were included in the registry. Of them, 2,448 (93%) were diagnosed with BCC, and 181 (7%) were diagnosed with SCC. Patients with SCC were older than those with BCC (median age 73 years vs. 68 years) and presented immunosuppression more frequently. The tumor size was significantly larger in the SCC group. Regarding surgery, deeper invasion was more frequent in SCC, resulting in larger defects. Despite this, SCC did not require more stages to get clear margins or more time in the operating room. Incomplete Mohs was more frequent in the SCC group (6%) than in the BCC group (2%). The incidence of perioperative complications was higher when treating SCC. There were more relapses in the first-year follow-up in the SCC group. CONCLUSION: There are significant differences when comparing MMS in BCC and SCC. Knowledge of these differences can help to prepare the patient and plan the surgery, optimizing results.

Acute bacterial septic vasculopathy.

OBJECTIVES: The frequency and clinicopathologic characteristics of cutaneous lesions in sepsis are not well known. This study aimed to analyze cutaneous lesions in bacterial septic vasculopathy. METHODS: The study population comprised 32 patients with bacterial sepsis, cutaneous lesions, and skin biopsy-proven septic vasculopathy. The clinical and histologic characteristics of the lesions were analyzed. Findings in non-immunosuppressed patients (NISPs) and immunosuppressed patients (ISPs) were compared. RESULTS: Nine of 32 patients were immunosuppressed. The foci of sepsis were variable; in 17 patients, the focus was not identified. Although Neisseria meningitidis was the most common causal agent, several microorganisms were identified. Cutaneous manifestations were an early event in 90.6% of patients. The most common skin signs were purpuric lesions and petechiae. Overall mortality was 28.1%; 65.5% of patients survived without sequelae. Skin biopsies showed thrombi in 100% of cases. Other common findings were inflammatory infiltrate, blood extravasation, and epidermal involvement. Bacteria within the vascular wall were seen in 21.9% of cases and fibrinoid necrosis in 25%. A comparison of ISPs with NISPs disclosed that meningococcemia was more common in the latter group, and the presence of pustules was more common in the former. Histopathology testing revealed that fibrinoid necrosis and bacterial invasion of the vessel wall were more common in ISPs than in NISPs. Conclusions Several microorganisms can cause septic vasculopathy. Clinical presentation is variable and does not depend on the microorganism or the pathogenic mechanism. Histopathologically, septic vasculopathy is a thrombo-occlusive vasculopathy with variable morphology. Cutaneous lesions are an early event and allow for rapid diagnosis.

Infective panniculitis.

Infective panniculitides are infections of the subcutaneous fat induced by any kind of micro-organism. They have rarely been considered as an entity within the spectrum of the panniculitis. Because of the increase in the immunosuppressive population, cutaneous infections' incidence is growing and atypical clinical presentations can be found. In this article, we analyze the etiology, clinical picture, histopathologic findings, diagnostics tools, and treatment of the more relevant infective panniculitis. We divide them according to the causative micro-organisms in bacterial, mycobacterial, fungal, and viral panniculitis.

Late skin reaction to iodixanol (Visipaque): clinical manifestations, patch test study, and histopathological evaluation.

Late reactions to iodinated contrast media are frequent. Cutaneous manifestations are the commonest, in which maculopapular exanthema, a type of cutaneous presentation, is widespread. Controversy exists about the utility of the skin test in the management of these reactions. The aim of this study is to analyse the clinical characteristics, the histopathological findings, and the results of the patch test in patients who developed a late skin reaction (LSR) to the nonionic, dimeric, iodinated contrast media Visipaque. We retrospectively reviewed the patients with LSR to Visipaque, seen in the Dermatology Department between 1999 and 2005. A total of 12 patients participated in this study (7 men and 5 women), ages ranging from 39 to 76 years (mean 56). 11 of the patients had significant medical history. All the patients developed a maculopapular exanthema between 2 hr and 3 days after the radiological examination, involving the trunk and proximal limbs, although some of the patients showed involvement of distal areas. The skin biopsy, performed in 6 patients, showed nonspecific findings consistent with drug reaction. In 3 patients, patch tests to Visipaque and iodixanol were positive. The most frequent manifestation of LSR to iodixanol is a maculopapular exanthema, involving the trunk and the limbs, although distal involvement can be seen. Histopathological findings are nonspecific and cannot be distinguished from other drug reaction. Patch tests have a limited value, and in cases where they were negative, reintroduction of the drug triggered a new LSR.