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Orphanet Journal of Rare Diseases May 2024Invasive cutaneous squamous cell carcinomas (cSCC) are a leading cause of death in recessive dystrophic epidermolysis bullosa (RDEB), a rare blistering genodermatosis.... (Review)
Review
BACKGROUND
Invasive cutaneous squamous cell carcinomas (cSCC) are a leading cause of death in recessive dystrophic epidermolysis bullosa (RDEB), a rare blistering genodermatosis. Outcomes of RDEB-cSCC therapies have primarily been described in case reports. Systematic studies are scarce. This systematic review aims to assess the pathophysiology, clinical characteristics, and outcomes of RDEB-cSCCs, with a focus on results and mechanisms of recent immunotherapies and anti-EGFR treatments.
RESULTS
A systematic literature search of epidermolysis bullosa and cSCC was performed in February 2024, using PubMed, Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and EudraCT databases. Cases with administration of systematic therapies and unpublished outcomes regarding death were tracked with corresponding authors. Data extraction and risk of bias assessment was performed by two independent reviewers. Of 1132 references in the original search, 163 relevant articles were identified, representing 59 case reports, 7 cohort studies, 49 abstracts, 47 in-vitro/in-vivo experiments, and 1 bioinformatic study. From these, 157 cases of RDEB-cSCCs were included. The majority of RDEB-cSCCs were well-differentiated (64.1%), ulcerated (59.6%), and at least 2 cm in size (77.6%), with a median age at diagnosis of 30 years old (range 6-68.4). Surgery was the primary form of treatment (n = 128), followed by chemotherapy and radiotherapy. Anti-EGFR therapy and immunotherapy was also reported beginning in 2009 and 2019, respectively. Survival time from first cSCC diagnosis to death was available in 50 cases. When stratified by their treatment regimen, median survival time was 1.85 years (surgery + chemotherapy, n = 6), 2 years (surgery only, n = 19), 4.0 years (+ anti-EFGR therapy, n = 10), 4 years (surgery + radiotherapy, n = 9), 4.6 years (+ immunotherapy, n = 4), and 9.5 years (surgery + chemotherapy + radiotherapy; n = 2). Treatment-related adverse events were primarily limited to impaired wound healing for immunotherapies and nausea and fatigue for anti-EGFR therapies.
CONCLUSIONS
Despite the challenges of a limited sample size in a rare disease, this systematic review provides an overview of treatment options for cSCCs in RDEB. When surgical treatment options have been exhausted, the addition of immunotherapy and/or anti-EGFR therapies may extend patient survival. However, it is difficult to attribute extended survival to any single treatment, as multiple therapeutic modalities are often used to treat RDEB-cSCCs.
Topics: Humans; Epidermolysis Bullosa Dystrophica; Skin Neoplasms; Carcinoma, Squamous Cell; Immunotherapy
PubMed: 38769503
DOI: 10.1186/s13023-024-03190-1 -
Archives of Dermatological Research Nov 2023Sentinel lymph node biopsy is increasingly used to detect subclinical nodal metastases in extramammary Paget disease. We performed a comprehensive systematic review of... (Review)
Review
Sentinel lymph node biopsy is increasingly used to detect subclinical nodal metastases in extramammary Paget disease. We performed a comprehensive systematic review of the literature to further explore the role of sentinel lymph node biopsy in extramammary Paget disease. Five databases were searched for relevant terms. Articles were included if they were in English and presented primary data on at least one patient with extramammary Paget disease who underwent sentinel lymph node biopsy in the absence of lymphadenopathy or known metastatic disease. Twenty-eight articles were included, with 366 subjects. Seventy-seven sentinel node biopsies (21.2%) were positive, including 12 in which the primary tumor had microinvasion (15.6%) and 56 with deep invasion (72.7%). Of the positive cases, 11 (14.3%) had no further treatment, 54 (70.1%) underwent nodal dissection, 4 (5.2%) were treated with systemic agents, and 1 (1.3%) had radiation. After a mean follow up of 24 months, 9 subjects with a positive lymph node biopsy experienced nodal recurrence (11.7%), 15 had distant metastases (19.5%), and 13 died of the disease (16.9%). In conclusion, invasive extramammary Paget disease is strongly associated with poor outcomes including nodal metastasis, distant metastasis, and disease specific death. Sentinel lymph node biopsy is a useful tool to screen for subclinical nodal metastases in invasive disease, and can be used to help guide clinical management.
Topics: Humans; Sentinel Lymph Node Biopsy; Lymphatic Metastasis; Paget Disease, Extramammary; Skin Neoplasms
PubMed: 37266674
DOI: 10.1007/s00403-023-02649-8 -
Journal of the European Academy of... May 2024Dermoscopy of the nail unit (onychoscopy) is a method which allows for non-invasive observation of the nail structures, increasing the accuracy of clinical diagnosis.... (Review)
Review
Dermoscopy of the nail unit (onychoscopy) is a method which allows for non-invasive observation of the nail structures, increasing the accuracy of clinical diagnosis. Currently, it is used in evaluation of both inflammatory and neoplastic conditions of the nail unit. However, in contrast to the skin, the anatomy of the nail unit prevents direct observation of nail bed or nail matrix structure during classic onychoscopy. Intra-operative onychoscopy is a variant of the technique which uses direct visualization of the nail unit structures after nail plate avulsion. The aim of this systematic review was to summarize the current state of knowledge on intra-operative onychoscopy. The MEDLINE, EMBASE and Cochrane databases were systematically searched in January 2024. All types of study designs assessing intra-operative dermoscopy of the nail unit were included in this study. The risk of bias in included studies was assessed using the Joanna Briggs Institute critical appraisal tools. The qualitative synthesis of 19 studies totalling a number of 218 cases in 217 patients included the following entities: melanoma, nevus, hypermelanosis (melanocytic activation), melanocytic hyperplasia, melanophages accumulation, squamous cell carcinoma, glomus tumour, lichen planus, onychomatricoma, onychomycosis and subungual exostosis. The main limitation of the study was a relatively low number of identified studies, most with low levels of evidence. Intra-operative onychoscopy does not replace histologic examination, though it may be useful in determining the modality of surgical diagnostic procedures.
PubMed: 38717320
DOI: 10.1111/jdv.20078 -
Cureus Jan 2024The purpose of this systematic review is to summarize all existing evidence, regarding the immunohistochemical expression of REV-7 in different human cancer pathology... (Review)
Review
The purpose of this systematic review is to summarize all existing evidence, regarding the immunohistochemical expression of REV-7 in different human cancer pathology specimens. Moreover, the association of REV-7 expression with disease severity (clinical course), patients' survival, prognosis, and response to various treatments, such as chemotherapy and irradiation, was investigated. Three databases (PubMed, Scopus, and Cochrane) were systematically screened, from inception to September 2, 2023, as suggested by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Only studies using immunohistochemical staining for REV-7 in paraffin-embedded cancer tissues were included. Nine studies met the inclusion criteria and were included in the final qualitative synthesis. All nine studies were retrospective and non-comparative ones. Selected studies reported immunohistochemical expression of REV-7 in different types of cancer, including testicular cancer, ovarian cancer, esophagus squamous cell carcinoma, prostate cancer, colorectal cancer, diffuse large B-cell lymphoma, breast cancer, lung cancer, and skin cancer. High REV-7 expression was associated with faster disease progression, resistance to available treatment options, and worse prognosis in the majority of included studies. These results indicate that immunohistochemical staining of REV-7 protein could potentially be used as a predictive tissue marker in certain cases. Promising results, arising from REV-7 inactivation experiments, render REV-7 targeting a potential therapeutic strategy for future cancer management, especially in the cases of chemoresistant or radioresistant disease.
PubMed: 38371007
DOI: 10.7759/cureus.52542 -
Pediatric Transplantation Feb 2024There is a well-documented risk of secondary cutaneous malignancies following allogeneic hematopoietic stem cell transplant (HSCT), but data on risk in pediatric...
BACKGROUND
There is a well-documented risk of secondary cutaneous malignancies following allogeneic hematopoietic stem cell transplant (HSCT), but data on risk in pediatric populations are limited. The objective of this study is to perform a systematic review of reported features and outcomes of skin cancers in pediatric allogeneic HSCT recipients.
METHODS
MEDLINE, EMBASE, CINAHL, Cochrane, and Web of Science were systematically searched (Prospero CRD42022342139). Studies reporting cutaneous cancer outcomes were included if the age at transplant was ≤19 years. Titles, abstracts, and full-text articles were screened in duplicate.
RESULTS
Out of 824 citations that were screened, 12 articles were selected for analysis. The final sample included 67 pediatric HSCT recipients, comprising 65 allogeneic transplant recipients and 2 cases of HSCT with an unknown donor type. The median age at transplant and skin cancer diagnosis were 7.4 and 13 years, respectively. Out of the 67 pediatric HSCT recipients, some patients developed more than one lesion, resulting in 71 lesions. The most common skin cancer type was cutaneous squamous cell carcinoma (32 lesions), followed by basal cell carcinoma (25 lesions). The median latency period between HSCT and skin cancer diagnosis ranged from 0 to 29 years. Identified risk factors for skin cancers included younger age at the time of transplant, exposure to total body irradiation, prolonged post-transplant immunosuppression, graft versus host disease, and sunburn.
CONCLUSION
Skin cancers are reported in pediatric allogeneic HSCT recipients, and the risk appears to be increased. More data are needed to better characterize this risk.
Topics: Humans; Child; Young Adult; Adult; Skin Neoplasms; Carcinoma, Squamous Cell; Hematopoietic Stem Cell Transplantation; Graft vs Host Disease; Transplantation, Homologous; Disease Progression
PubMed: 37786978
DOI: 10.1111/petr.14618 -
Cancer Treatment and Research... 2024The management of periocular basal cell carcinoma (BCC) is challenging due to its proximity to the eyeball. Vismodegib, a Hedgehog pathway inhibitor, has emerged as a... (Review)
Review
The management of periocular basal cell carcinoma (BCC) is challenging due to its proximity to the eyeball. Vismodegib, a Hedgehog pathway inhibitor, has emerged as a therapeutic option for locally advanced and metastatic BCC. To critically appraise the relevant evidence, we conducted a systematic review of observational and experimental studies assessing the efficacy and safety of vismodegib for periocular BCC. Thirty-seven trials, including 435 patients, were eligible. No randomized trials were retrieved. Complete and overall clinical response rates were 20-88 % and 68-100 %, respectively. Disease progression was observed at a maximum rate of 14 %. Recurrence rates varied between 0 % and 31 %. The most common side effects were muscle cramps, dysgeusia, weight loss and alopecia. Treatment with vismodegib improved health-related quality of life. In conclusion, vismodegib represents an important novel treatment for advanced periocular BCC, with good response rates and acceptable tolerability profile. Nevertheless, its full potential needs clarification through randomized controlled trials.
Topics: Humans; Anilides; Antineoplastic Agents; Carcinoma, Basal Cell; Pyridines; Quality of Life; Skin Neoplasms
PubMed: 38367414
DOI: 10.1016/j.ctarc.2024.100796 -
The American Journal of Dermatopathology Sep 2023Signet-ring cell/histiocytoid carcinoma (SRCHC) is a rare appendageal tumor, mainly considering eyelids, more rarely axillae. This article describes 2 novel SRCHC cases...
Signet-Ring Cell/Histiocytoid Carcinoma: Report of Two Cases and Systematic Review of the Literature on the Epidemiology, Clinical Characteristics, and Pathological and Molecular Findings.
Signet-ring cell/histiocytoid carcinoma (SRCHC) is a rare appendageal tumor, mainly considering eyelids, more rarely axillae. This article describes 2 novel SRCHC cases of 71- and 66-year-old men and systematically reviews the literature on SRCHC. Of all cases reported in the literature, 73 (91.2%) were men and 7 (8.8%) were women. The median age at diagnosis was 71 years. Skin changes were located in the eyelids (68%) and axillae (32%). In all tested cases, SRCHC cells expressed CK7, CKAE1/AE3, EMA, CAM5.2, and AR and PIK3CA mutations. Future research should determine whether AR/PIK3CA-targeted therapies influence patients' survival.
Topics: Male; Humans; Female; Aged; Immunohistochemistry; Carcinoma, Signet Ring Cell; Skin Neoplasms; Eyelid Neoplasms; Skin
PubMed: 37506279
DOI: 10.1097/DAD.0000000000002495 -
The British Journal of Dermatology May 2024
Topics: Aged; Female; Humans; Male; Carcinoma, Merkel Cell; Incidence; Skin Neoplasms
PubMed: 38758058
DOI: 10.1093/bjd/ljae159 -
Annals of Plastic Surgery Jun 2024Nevus sebaceous (NS) is a rare congenital skin lesion affecting approximately 0.3% of all newborns. Although benign, NS lesions can harbor malignant secondary tumors.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Nevus sebaceous (NS) is a rare congenital skin lesion affecting approximately 0.3% of all newborns. Although benign, NS lesions can harbor malignant secondary tumors. The published rate of development of these malignant tumors varies. This meta-analysis aimed to identify the rate of malignant and benign secondary neoplasms occurring in NS.
METHODS
A literature search was conducted using PubMed, Embase, and Web of Science from inception to April 2023. Eligible studies reported incidence or risk of secondary neoplasms in patients with NS. Two independent reviewers screened studies, extracted data, and assessed the quality of included studies. The primary outcome was the pooled incidence of secondary neoplasms. Studies with sample sizes greater than 50 patients were eligible for meta-analysis using the random-effects model.
RESULTS
Twenty-eight studies were identified, 22 of which were eligible for meta-analysis. The overall rate of secondary neoplasms was 12.8% (95% confidence interval [Cl], 9.2%-17.6%). The rates of development of malignant and benign tumors were 2.4% (95% CI, 1.4%-4.1%) and 10.3% (95% CI, 7.5%-13.9%), respectively. The rate of development of basal cell carcinoma was 1.7% (95% CI, 0.9%-3.2%), whereas the rate of the development of syringocystadenoma papilliferum was 3.6% (95% CI, 2.5%-5.3%) and that if trichoblastoma was 2.6% (95% CI, 1.7%-3.8%).
CONCLUSIONS
Although the rate of development of malignant tumors within a primary NS lesion is low, it is not negligible. Prophylactic early excision remains a viable approach to prevent secondary malignant neoplasms, address cosmetic and functional complications, and preempt the need for complex reconstruction in the future. We propose that resection of NS lesions in childhood remains a reasonable first-line option in the appropriate patient keeping in mind that it may leave an undesirable scar.
Topics: Humans; Skin Neoplasms; Incidence; Neoplasms, Second Primary; Nevus, Sebaceous of Jadassohn; Nevus
PubMed: 38725109
DOI: 10.1097/SAP.0000000000003879 -
Experimental Dermatology Jan 2024Patients with advanced cutaneous squamous cell carcinoma (cSCC) who are not eligible for or who fail to respond to anti-PD1 immunotherapy have few treatment options.... (Meta-Analysis)
Meta-Analysis
Patients with advanced cutaneous squamous cell carcinoma (cSCC) who are not eligible for or who fail to respond to anti-PD1 immunotherapy have few treatment options. Epidermal growth factor receptor (EGFR) inhibitors have been investigated as a therapeutic option for advanced cSCC; however, data are limited to small single-arm trials or retrospective studies. A systematic review and meta-analysis was conducted to PRISMA guidelines (CRD42023394300). Studies reporting on outcomes of EGFR inhibition in advanced cSCC were identified. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and adverse event (AE) rate were pooled using a random effects model and the inverse variance method. Twelve studies (six prospective, six retrospective) were identified, representing 324 patients. Pooled ORR was 26% (95% confidence interval [CI] 18-36), median PFS was 4.8 months (95% CI 3.9-6.6) and median OS was 11.7 months (95% CI 9.2-14.1). Any grade AEs occurred in 93% of patients (95% CI 85-97) while grade 3 and higher AEs occurred in 30% (95% CI 14-54). These results were similar between anti-EGFR monoclonal antibodies (MAbs) and tyrosine kinase inhibitors (TKIs). EGFR inhibitors can be considered in patients with advanced cSCC who are contraindicated for or progress on first-line anti-PD1 immunotherapy. Future studies should evaluate their activity and safety following anti-PD1, identify predictive biomarkers for their efficacy and explore combination approaches.
Topics: Humans; Carcinoma, Squamous Cell; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Retrospective Studies; Prospective Studies; Skin Neoplasms; Protein Kinase Inhibitors; Antineoplastic Agents; ErbB Receptors
PubMed: 37971204
DOI: 10.1111/exd.14978