Histological deep margins in cutaneous squamous cell carcinoma of the scalp and risk of recurrence.

BACKGROUND: Consensus is lacking on adequate deep histological margins in cutaneous squamous cell carcinoma (cSCC). Deep clearance for tumours located on the scalp is limited by anatomic constraints. OBJECTIVE: To determine whether clear but close deep histological margins (<1 mm) confer a higher risk of recurrence in cSCCs of the scalp treated by wide local excision, compared to deep histological margins ≥1 mm. METHODS: Multicentre retrospective observational cohort study and multivariate competing risk analysis to evaluate risk factors for recurrence. RESULTS: In total, 295 patients with 338 cSCCs were included. Close deep histological margins were not associated with an increased cumulative incidence of recurrence (subhazard ratio [SHR] 1.96 [95% CI 0.87-4.41]). However, an increased risk of recurrence was observed for those tumours that presented concurrent invasion of the galea aponeurotica and close deep margins, as opposed to patients without these factors (SHR 3.52 [1.24-10.01]). Tumours with clear but close peripheral margins (<1 mm) also had higher risk of recurrence (SHR 5.01 [1.68-14.97]). LIMITATIONS: Retrospective observational study based on pathology reports. CONCLUSION: Deep histological margins <1 mm do not confer a greater risk of recurrence as long as the tumour is completely excised and the galea aponeurotica is not involved. Surgical excision of cSCC on the scalp should include the galea to ensure proper assessment of deep margins.

Case Report: Localized bullous pemphigoid induced by local triggers: a case series and a proposal for diagnostic criteria based on a literature review.

Introduction: Localized bullous pemphigoid (LBP) is an infrequent bullous pemphigoid (BP) variant restricted to a body region. According to the most compelling evidence, LBP occurs in patients with pre-existent serum antibodies against the basement membrane zone, which occasionally acquire the capacity to induce disease after the influence of different local factors acting as triggers. Methods: We hereby present a multicenter cohort of 7 patients with LBP developed after local triggers: radiotherapy, thermal burns, surgery, rosacea, edema and a paretic leg. In addition, we conducted a review of the literature, and we propose a set of diagnostic criteria for LBP, also based on our case series and the 2022 BP guidelines from the European Academy of Dermatology and Venereology. Results: During follow-up, three of the patients from our series evolved to a generalized BP, with only one requiring hospitalization. Our literature search retrieved 47 articles including a total of 108 patients with LBP, with a 63% with a potential local precipitating factor previous to their diagnosis. LBP mostly affected older females, and a subsequent generalized progression occurred in 16.7% of the cases. The most frequently involved areas were the lower limbs. Radiation therapy and surgery were responsible for the inducement of nearly 2 in 3 cases of LBP. We observed a significantly higher risk of generalization in cases where the trigger led to the developing of LBP earlier (p=0.016). Our statistical analysis did not detect any other prognosis factor for generalization when assessing direct immunofluorescence, histological and serological results, or other patient related factors. Conclusion: LBP should be suspected in patients with recurrent localized bullous eruptions. The presence of a trauma history in the same anatomic area is reported in most cases.

Prognostic factors for satellitosis or in-transit metastasis in cutaneous squamous cell carcinoma: A multicentric cohort study.

BACKGROUND: Satellitosis or in-transit metastasis (S-ITM) has clinical outcomes comparable to node-positivity in cutaneous squamous cell carcinoma (cSCC). There is a need to stratify the risk groups. OBJECTIVE: To determine which prognostic factors of S-ITM confer an increased risk of relapse and cSCC-specific-death. METHODS: A retrospective, multicenter cohort study. Patients with cSCC developing S-ITM were included. Multivariate competing risk analysis evaluated which factors were associated with relapse and specific death. RESULTS: Of a total of 111 patients with cSCC and S-ITM, 86 patients were included for analysis. An S-ITM size of ≥20 mm, >5 S-ITM lesions, and a primary tumor deep invasion was associated with an increased cumulative incidence of relapse (subhazard ratio [SHR]: 2.89 [95% CI, 1.44-5.83; P = .003], 2.32 [95% CI, 1.13-4.77; P = .021], and 2.863 [95% CI, 1.25-6.55; P = .013]), respectively. Several >5 S-ITM lesions were also associated with an increased probability of specific death (SHR: 3.48 [95% CI, 1.18-10.2; P = .023]). LIMITATIONS: Retrospective study and heterogeneity of treatments. CONCLUSION: The size and the number of S-ITM lesions confer an increased risk of relapse and the number of S-ITM an increased risk of specific-death in patients with cSCC presenting with S-ITM. These results provide new prognostic information and can be considered in the staging guidelines.

High-risk mucosal human papillomavirus-associated squamous cell carcinoma of the fingers presents distinctive clinicopathological characteristics and outcomes: a bicentric retrospective study.

BACKGROUND: High-risk mucosal human papillomavirus (HR-HPV) seems to play a role in cutaneous squamous cell carcinoma (cSCC), particularly in nail tumours, where genitodigital transmission has been suggested. The role of HR-HPV in nonungual cSCC of the finger needs to be clarified. AIM: To evaluate the prevalence, clinicopathological characteristics, surrogates and outcomes of HR-HPV in cSCC of the finger. METHODS: This was an observational bicentric study including patients with an excised in situ or invasive cSCC located on the finger. Differences in HR-HPV and non-HR-HPV tumours were evaluated. RESULTS: Forty-five patients (45 tumours) were included. HR-HPV was detected in 33% of cases (22% HPV type 16). The mean age was lower in patients with HR-HPV than in those with non-HR-HPV (62·4 vs. 81·1 years, P = 0·001). HR-HPV tumours were smaller (10 mm vs. 15 mm, P = 0·07) and more frequently intraepidermal (60% vs. 20%, P = 0·004). The absence of elastosis (P = 0·030) and inflammation (P = 0·026) and the presence of basaloid morphology (P = 0·003) were surrogates of HR-HPV detection. Mean p16 positivity was 61% in HR-HPV and 36% in non-HR-HPV tumours (P = 0·061). Recurrence after surgery was more common in HR-HPV tumours (58% vs. 34%), although this was not statistically significant. HR-HPV was detected in 27% of the nonungual tumours. CONCLUSION: HR-HPV-associated cSCC of the finger appears in younger patients, is smaller and is less infiltrative than non-HR-HPV tumours. The presence of a basaloid morphology and the absence of elastosis and inflammation could be used as markers for HR-HPV detection. The high prevalence of HR-HPV in nonungual cSCC suggests its aetiopathogenic role in these tumours.

Diagnostic Accuracy of Image-guided Biopsies for Diagnosis of Metastatic Melanoma in a Real-life Setting.

Early detection of melanoma metastasis is essential in order to initiate treatment and improve patient prognosis. The aim of this study was to determine the diagnostic accuracy of different image-guided biopsy techniques in patients with melanoma. A cohort study of patients diagnosed with melanoma who had undergone image-guided biopsies (ultrasound-guided fine-needle aspiration cytology, ultrasound-guided core-needle biopsy, computerized tomography--guided fine-needle aspiration cytology and computerized tomography-guided core-needle biopsy) to detect melanoma metastasis between 2004 and 2021 was conducted. The reference standard was histological confirmation and/or clinical-radiological follow-up. Sensitivity, specificity, positive and negative predictive values were calculated. A total of 600 image--guided biopsies performed on 460 patients were included for analysis. Locoregional lesions represented 459 (76.5%) biopsies, and 141 (23.5%) were distant lesions. Of the included biopsies, 49 (8.2%) were insufficient for diagnosis. Overall, sensitivity and specificity were 92% (95% confidence interval 89-94) and 96% (95% confidence interval 91-99), respectively. Sensitivity sub-analyses revealed lower diagnostic accuracy values in the lung, inguinal lymph nodes, and computerized tomography-guided lesions under 1 cm. Limitations include spontaneous metastasis regression and arbitrary minimum follow-up period. Image-guided biopsies in patients with melanoma have high sensitivity and specificity for detection of regional or distant metastasis. Tissue type, location and tumour burden may influence the diagnostic accuracy of the test.

Severe blistering eruptions induced by immune checkpoint inhibitors: a multicentre international study of 32 cases.

Among dermatologic adverse events induced by immune checkpoint inhibitors (ICI), bullous life-threatening reactions are rare. To better define the clinical and histological features, treatment, and prognosis of ICI-related severe blistering cutaneous eruptions. This retrospective case series was conducted between 2014/05/15 and 2021/04/15 by the dermatology departments of four international registries involved in drug reactions. Inclusion criteria were age ≥18 years old, skin eruption with blisters with detachment covering ≥1% body surface area and at least one mucous membrane involved, available pictures, and ICI as suspect drug. Autoimmune bullous disorders were excluded. Each participant medical team gave his own diagnosis conclusion: epidermal necrolysis (EN), severe lichenoid dermatosis (LD), or unclassified dermatosis (UD). After a standardized review of pictures, cases were reclassified by four experts in EN or LD/UD. Skin biopsies were blindly reviewed. Thirty-two patients were included. Median time to onset was 52 days (3-420 days). Cases were originally diagnosed as EN in 21 cases and LD/UD in 11 cases. After review by experts, 10/21 EN were reclassified as LD/UD. The following manifestations were more frequent or severe in EN: fever, purpuric macules, blisters, ocular involvement, and maximal detachment. Most patients were treated with topical with or without systemic corticosteroids. Eight patients (25%) died in the acute phase. The culprit ICI was not resumed in 92% of cases. In three patients, another ICI was given with a good tolerance. Histology did not reveal significant differences between groups. Severe blistering cutaneous drug reactions induced by ICI are often overdiagnosed as EN. Consensus for management is pending.

Childhood Vulvar Mucous Membrane Pemphigoid.

BACKGROUND: Autoimmune bullous diseases in childhood are a diagnostic challenge. CASE: We present the case of an 11-year-old girl with recurrent vulvar erosions since early childhood. She had been referred to a child abuse unit under the suspicion of sexual abuse. She responded well to dapsone and topical corticosteroids. SUMMARY AND CONCLUSION: Our review focuses on previously reported cases of pemphigoid (bullous or mucous membrane) in childhood with exclusively genital involvement. We also summarize mucous membrane pemphigoid cases diagnosed during childhood. There seems to be a differentiated form of pemphigoid predominantly affecting girls with exclusively vulvar involvement and with good prognosis. Dermatologic evaluation and a skin biopsy with direct immunofluorescence are key to diagnosing a mucous membrane pemphigoid. Further antigenic studies are needed to nosologically classify the disease properly.

Assessment of Sclerodermoid Chronic Graft-versus-host Disease with Colour Doppler Ultrasound.

Sclerodermoid chronic graft-versus-host disease (scGVHD) is a severe complication of allogeneic haema-- topoietic stem cell transplantation. The aim of this study was to investigate the usefulness of high-frequency ultrasound of the skin in assessing the inflammatory patterns and prognosis of patients with scGVHD. A prospective study was carried out with patients who developed scGVHD in the period June 2016 to April 2018. Clinical and ultrasound examinations were performed on the first visit and at 6-month follow-up. A total of 24 patients were included in the study. A 6-month follow-up high-frequency ultrasound of the skin was performed on 20 of the 24 patients. Abnormal B-mode findings in high-frequency ultrasound of the skin consisted of hypoechogenic dermis, hypoechogenicity of septa and hyperechogenicity of lobules in hypodermis. No differences were observed in these basal parameters between treatment progressive/non-responding and inactive/responding scGVHD groups of patients. Basal Doppler showing increased vascular flow with a systolic peak ≥10 cm/s and a vascular resistance index ≥ 0.70 was observed only in those patients who developed progressive/non-responding scGVHD (62.5% vs 0% p = 0.006). In conclusion, Doppler ultrasound is a useful tool to assess the inflammatory activity and outcome of scGVHD. These findings could enhance patient management and help to guide treatment decisions.

Skin Manifestations in COVID-19: Prevalence and Relationship with Disease Severity.

BACKGROUND: Data on the clinical patterns and histopathology of SARS-CoV-2 related skin lesions, as well as on their relationship with the severity of COVID-19 are limited. METHODS AND MATERIALS: Retrospective analysis of a prospectively collected cohort of patients with SARS-CoV-2 infection in a teaching hospital in Barcelona, Spain, from 1 April to 1 May 2020. Clinical, microbiological and therapeutic characteristics, clinicopathological patterns of skin lesions, and direct immunofluorescence and immunohistochemical findings in skin biopsies were analyzed. RESULTS: Fifty-eight out of the 2761 patients (2.1%) either consulting to the emergency room or admitted to the hospital for COVID-19 suspicion during the study period presented COVID-19 related skin lesions. Cutaneous lesions could be categorized into six patterns represented by the acronym "GROUCH": Generalized maculo-papular (20.7%), Grover's disease and other papulo-vesicular eruptions (13.8%), livedo Reticularis (6.9%), Other eruptions (22.4%), Urticarial (6.9%), and CHilblain-like (29.3%). Skin biopsies were performed in 72.4%, including direct immunofluorescence in 71.4% and immunohistochemistry in 28.6%. Patients with chilblain-like lesions exhibited a characteristic histology and were significantly younger and presented lower rates of systemic symptoms, radiological lung infiltrates and analytical abnormalities, and hospital and ICU admission compared to the rest of patients. CONCLUSION: Cutaneous lesions in patients with COVID-19 appear to be relatively rare and varied. Patients with chilblain-like lesions have a characteristic clinicopathological pattern and a less severe presentation of COVID-19.