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The Journal of Investigative Dermatology Dec 2023Keratoacanthoma (KA) is a common keratinocyte neoplasm that is regularly classified as a type of cutaneous squamous cell carcinoma (cSCC) despite demonstrating benign...
Keratoacanthoma (KA) is a common keratinocyte neoplasm that is regularly classified as a type of cutaneous squamous cell carcinoma (cSCC) despite demonstrating benign behavior. Differentiating KA from well-differentiated cSCC is difficult in many cases due to the substantial overlap of clinical and histological features. Currently, no reliable discriminating markers have been defined, and consequently, KAs are often treated similarly to cSCC, creating unnecessary surgical morbidity and healthcare costs. In this study, we used RNA sequencing to identify key differences in transcriptomes between KA and cSCC, which suggested divergent keratinocyte populations between each tumor. Imaging mass cytometry was then used to identify single-cell tissue characteristics, including cellular phenotype, frequency, topography, functional status, and interactions between KA and well-differentiated cSCC. We found that cSCC had significantly increased proportions of Ki67+ keratinocytes among tumor keratinocytes, which were dispersed significantly throughout non-basal keratinocyte communities. In cSCC, regulatory T-cells were more prevalent and held greater suppressive capacity. Furthermore, cSCC regulatory T-cells, tumor-associated macrophages, and fibroblasts had significant associations with Ki67 keratinocytes as opposed to avoidances with KA, indicating a more immunosuppressive environment. Our data suggest that multicellular spatial features can serve as a foundation to enhance the histological discrimination of ambiguous KA and cSCC lesions.
Topics: Humans; Carcinoma, Squamous Cell; Keratoacanthoma; Ki-67 Antigen; Skin Neoplasms; Keratinocytes
PubMed: 37419445
DOI: 10.1016/j.jid.2023.06.192 -
Pathology Oct 2023Keratoacanthoma (KA) is widely considered a benign, usually self-resolving, neoplasm distinct from cutaneous squamous cell carcinoma (cSCC), while some consider KA to be...
Keratoacanthoma (KA) is widely considered a benign, usually self-resolving, neoplasm distinct from cutaneous squamous cell carcinoma (cSCC), while some consider KA to be indistinguishable from cSCC. Published studies indicate utility for p16, p53, Ki-67 immunostaining and elastic van Gieson (EVG) in the assessment of KA and cSCC. We compared clinical features and staining patterns for p16, p53, Ki-67 and EVG in fully excised KA, cSCC with KA-like features (cSCC-KAL) and other cSCC (cSCC-OTHER). Significant differences between KA, cSCC-KAL and cSCC-OTHER were found for head and neck location (20%, 86%, 84%), and duration <5 months (95%, 63%, 36%). KA shows both a mosaic pattern for p16 (>25-90% of neoplasm area) and peripheral graded pattern for p53 (up to 50% moderate and strong nuclear staining) in 92% compared with 0% of cSCC-KAL and 0% of cSCC-OTHER. In contrast, a highly aberrant pattern (usually null) for one or both p16 and p53, was present in 0% of KA, 83.8% of cSCC-KAL and 90.9% of cSCC-OTHER. Abnormal distribution of Ki-67 beyond the peripheral 1-3 cells was uncommon in KA (4.2%) and common in cSCC-KAL (67.6%) and cSCC-OTHER (88.4%). Moderate to striking entrapment of elastic and collagen fibres was present in the majority of KA (84%), cSCC-KAL (81%) and cSCC-OTHER (65%). KA are clinically distinct neoplasms typically of short duration occurring preferentially outside the head and neck and generally lacking aberrations of p16, p53 and Ki-67, compared with cSCC that have high rates of aberrant or highly aberrant p16, p53 and Ki-67, but EVG lacked specificity.
Topics: Humans; Keratoacanthoma; Carcinoma, Squamous Cell; Skin Neoplasms; Ki-67 Antigen; Tumor Suppressor Protein p53; Immunohistochemistry; Staining and Labeling
PubMed: 37573161
DOI: 10.1016/j.pathol.2023.07.001 -
Journal of Cutaneous Pathology Oct 2023Immune-mediated regression of melanocytic neoplasms is predominantly lymphocytic, driven by CD8+ anti-tumoral T-cells and, rarely, natural killer cells. Histopathologic...
Immune-mediated regression of melanocytic neoplasms is predominantly lymphocytic, driven by CD8+ anti-tumoral T-cells and, rarely, natural killer cells. Histopathologic features of regression include effacement of the epidermis, replacement of tumor cells by a fibrotic stroma, varying degrees of chronic inflammation (usually lymphocytes) and melanophages, as well as vascular ectasia and angioplasia. The understanding of regression and the complex immune response in melanoma has led to the development of targeted immunotherapy in melanoma. Here, we report a case of near-complete regression of a melanocytic neoplasm associated with neutrophilic and eosinophilic inflammation, suggesting a non-traditional pathway of regression that has yet to be explored.
Topics: Humans; Skin Neoplasms; Melanoma; Epidermis; Lymphocytes; Inflammation
PubMed: 37448109
DOI: 10.1111/cup.14492 -
Open Veterinary Journal Jan 2024Cutaneous neoplastic disorders are often observed in small mammal pets, such as dogs, regardless of their gender.
BACKGROUND
Cutaneous neoplastic disorders are often observed in small mammal pets, such as dogs, regardless of their gender.
AIM
An important objective of this work was to give a full account of the clinical, pathological, and immune-histochemical features of several skin tumors in dogs.
METHODS
This study was a case series in the hospital clinic, Faculty of Veterinary Medicine, Zagazig University, Egypt. Twenty-five dogs (14 males and 11 females) were examined clinically during the period from March 2022 to October 2023. The skin swelling was collected from affected animals and then subjected to a detailed histopathological study to record the different gross and microscopic findings and confirm the diagnosis by immunohistochemistry.
RESULTS
Skin neoplasia in dogs was exposed to various clinical signs, and the dogs' ages ranged between 3 and 11 years. Concerning tumor features, the majority of neoplasms were malignant (65.52%) more than benign (34.48%). The study revealed the presence of 29 cases of dogs showed neoplasia with different prevalence rates including squamous cell carcinoma (13.79%), mast cell tumor (6.89%), basal cell tumors (10.34%), histiocytoma (6.89%), trichoepithelioma (10.34%), transmissible venereal tumor (10.34%), trichilemmoma (3.44%), scalp paraganglioma (3.44%), pilomatricoma (10.34%), malignant melanomas (17.24%), and miscellaneous cases as fat necrosis (6.89%), in males and females dogs with different histopathological lesions and immunohistochemistry expressions for pan-cytokeratin (CK), melanocyte-differentiation antigens (S100 protein), and synaptophysin.
CONCLUSION
Malignant melanomas (17.24%) are the extremely common cutaneous tumors diagnosed in this study. Meanwhile, benign tumors such as trichilemmoma, trichoepithelioma, pilomatricoma, and paraganglioma are less frequent in dogs.
Topics: Humans; Male; Female; Dogs; Animals; Melanoma; Pilomatrixoma; Egypt; Skin Neoplasms; Paraganglioma; Mammals; Dog Diseases
PubMed: 38633166
DOI: 10.5455/OVJ.2024.v14.i1.44 -
Equine Veterinary Journal Jan 2024The sarcoid is the most common equine cutaneous neoplasm. Evidence-based treatment of this condition is often lacking, and selection of treatment modality based on... (Review)
Review
BACKGROUND
The sarcoid is the most common equine cutaneous neoplasm. Evidence-based treatment of this condition is often lacking, and selection of treatment modality based on clinical experience or anecdotal evidence.
OBJECTIVES
To assess the quality of the currently available best evidence regarding the treatment of the equine sarcoid.
STUDY DESIGN
Systematic review.
METHODS
In compliance with PRISMA guidelines, literature searches were performed in PUBMED, Web of Science, CAB Abstracts, EMBASE (Ovid) and Scopus in April 2021. Included papers were required to describe an interventional study examining sarcoid treatment strategy, of level 4 evidence or greater. The case definition required confirmation of at least some included lesions on histopathology, and a minimum of 6 months of follow-up was required on treated cases. Studies were assessed by two independent reviewers (KO, CD). Data extraction was performed manually, followed by risk of bias assessment. Methodological quality was assessed using the GRADE system.
RESULTS
In total, 10 studies were included in the review. Case definition was confirmed via histopathology in all included lesions in 60% of papers. Time to follow-up was variably reported. Overall risk of bias ranged from 'some concerns' to 'critical'. Reported sarcoid regression rate ranged from 28% to 100% on an individual sarcoid level, and 9%-100% on a whole horse level. Transient local inflammation was reported following most treatment strategies, with further adverse events reported infrequently.
MAIN LIMITATIONS
Review methodology excluded a large proportion of available literature regarding the equine sarcoid. Significant heterogeneity between included studies prevented quantitative synthesis and most included papers were at significant risk of bias, indirectness, and imprecision.
CONCLUSIONS
There is insufficient evidence currently available to recommend one sarcoid treatment over another. There is an urgent need for sufficiently powered, randomised, placebo-controlled trials in order to allow more definitive comparison of the efficacy of different treatment strategies.
Topics: Animals; Horses; Skin Neoplasms; Horse Diseases
PubMed: 36917551
DOI: 10.1111/evj.13935 -
The American Journal of Dermatopathology Aug 2023Deep penetrating nevi (DPN), particularly those showing combined features, or combined deep penetrating nevi (CDPN), may show histopathological resemblance to blue nevus...
Deep penetrating nevi (DPN), particularly those showing combined features, or combined deep penetrating nevi (CDPN), may show histopathological resemblance to blue nevus (BN) and melanoma. Preferentially Expressed Antigen in MElanoma (PRAME) is a marker that helps distinguish melanoma from benign melanocytic lesions. Lymphoid enhancer-binding factor 1 (LEF1) has been proposed to be used in conjunction with β-catenin for diagnosis of DPN. The immunohistochemical expression of PRAME and LEF1 was evaluated in 10 DPN (including 6 CDPN and 2 DPN-like proliferations with atypical features), 16 BN (including combined and cellular BN), and 2 melanomas with features of DPN or BN. PRAME was negative in most DPN (n = 10/10, n = 9/10, one case with discrepancy between readers) and all BN (n = 16/16), while the 2 melanomas included were positive (n = 2/2). All DPN were positive for LEF1 (n = 9/9) while only a subset of BN were positive (n = 6/16, P = 0.0028; n = 5/16, P = 0.001, per both readers). LEF1 seemed to be easier to interpret than β-catenin because of its nuclear pattern of expression. The expression of LEF1 in the regular nevus component of combined BN presents a potential pitfall in practice because it may lead to misinterpretation of LEF1 as positive in the BN component of the lesion. However, a subset (approximately one-third) of combined BN seemed to show true LEF1 expression. Taking into account pitfalls in interpretation, the combinatorial panel of PRAME and LEF1, in addition to conventional histopathological features, may be useful to distinguish CDPN from combined BN and other benign and malignant mimics.
Topics: Humans; Nevus, Blue; beta Catenin; Skin Neoplasms; Lymphoid Enhancer-Binding Factor 1; Melanoma; Nevus, Epithelioid and Spindle Cell; Nevus; Transcription Factors; Diagnosis, Differential; Antigens, Neoplasm
PubMed: 37462205
DOI: 10.1097/DAD.0000000000002488 -
Journal of the European Academy of... Jul 2024In recent years, new approaches for optimal patient management of cancer have focused on patient-centered care, with integration of tumour-directed treatment and... (Review)
Review
In recent years, new approaches for optimal patient management of cancer have focused on patient-centered care, with integration of tumour-directed treatment and patient-directed supportive and palliative care throughout the disease journey from prevention through screening, diagnosis, treatment, and follow-up. In 2022, at the International Forum of Dermatology (IFD), a scientific session was entirely dedicated to highlight recent developments on patient-centered approaches in skin cancer. An international panel of different groups of participants involved in a patient's journey on the management of skin cancer presented and discussed challenges and barriers that persist in the field of skin cancer prevention and care pathways. Although primary prevention remains a crucial step in the prevention of melanoma, the different surveys performed during the last 20 years demonstrate that the use of sunscreen increases very slowly. Secondary prevention that includes skin screening and diagnostic measures may benefit from the development of digital tools. To improve adherence, patients need accurate, reliable information about their disease and the treatment options, and this type of content that can also be made available on digital tools. Shared decision-making is a hallmark of a patient-centered approach and requires health care providers who can communicate well to patients and their families, underscoring the pivotal role of health care professionals all through the patient journey. Health care providers have a crucial role in supporting patients through their journey in skin cancer. They will benefit from mobile apps and technologies that have been developed recently to address challenges in skin cancer prevention, detection and care, including those that are primarily directed to the patient. However, more peer-reviewed studies are needed as well as regulations to ensure that apps are accurate, reliable, and up to date.
Topics: Humans; Patient-Centered Care; Skin Neoplasms; Decision Making, Shared; Melanoma; Sunscreening Agents
PubMed: 38923012
DOI: 10.1111/jdv.19573 -
Journal of the National Cancer Institute Sep 2023Adjuvant treatments with PD-1 and BRAF+MEK inhibitors statistically significantly prolong recurrence-free survival in stage III cutaneous melanoma. Yet, the effect on...
BACKGROUND
Adjuvant treatments with PD-1 and BRAF+MEK inhibitors statistically significantly prolong recurrence-free survival in stage III cutaneous melanoma. Yet, the effect on overall survival is still unclear. Based on recurrence-free survival outcomes, these treatments have been approved and widely implemented. The treatments have considerable side effects and costs, and overall survival effect remains a highly anticipated outcome.
METHODS
Clinical and histopathological parameters were obtained from the Swedish Melanoma Registry for patients diagnosed with stage III melanoma between 2016 and 2020. The patients were divided depending on if they were diagnosed before or from July 2018, based on the timepoint when adjuvant treatment was introduced in Sweden. Patients were followed up until the end of 2021. In this cohort study, melanoma-specific and overall survival were calculated using the Kaplan-Meier method and Cox-regression analyses.
RESULTS
There were 1371 patients diagnosed with stage III primary melanoma in Sweden in 2016-2020. The 2-year overall survival rates, comparing the 634 patients in the precohort and the 737 in the postcohort, were 84.3% (95% confidence interval [CI] = 81.4% to 87.3%) and 86.1% (95% CI = 83.4% to 89.0%), respectively, with an adjusted hazard ratio of 0.91 (95% CI = 0.70 to 1.19, P = .51). Further, no statistically significant overall or melanoma-specific survival differences were seen when comparing the precohort and the postcohort in different subgroups for age, sex, or tumor characteristics.
CONCLUSIONS
In this nationwide population-based and registry-based study, no survival benefit was detected in patients diagnosed before or after the implementation of adjuvant treatment in stage III melanoma. These findings encourage a careful assessment of the current recommendations on adjuvant treatment.
Topics: Humans; Melanoma; Skin Neoplasms; Cohort Studies; Adjuvants, Immunologic; Registries; Neoplasm Staging; Melanoma, Cutaneous Malignant
PubMed: 37227040
DOI: 10.1093/jnci/djad081 -
Annals of Surgical Oncology Sep 2023
Topics: Humans; Metastasectomy; Melanoma; Skin Neoplasms; Neoplasm Staging
PubMed: 37326813
DOI: 10.1245/s10434-023-13760-5 -
Journal of the American Academy of... Dec 2023Metastasis of cutaneous squamous cell carcinoma (cSCC) is uncommon. Current staging methods are reported to have sub-optimal performances in metastasis prediction....
BACKGROUND
Metastasis of cutaneous squamous cell carcinoma (cSCC) is uncommon. Current staging methods are reported to have sub-optimal performances in metastasis prediction. Accurate identification of patients with tumors at high risk of metastasis would have a significant impact on management.
OBJECTIVE
To develop a robust and validated gene expression profile signature for predicting primary cSCC metastatic risk using an unbiased whole transcriptome discovery-driven approach.
METHODS
Archival formalin-fixed paraffin-embedded primary cSCC with perilesional normal tissue from 237 immunocompetent patients (151 nonmetastasizing and 86 metastasizing) were collected retrospectively from four centers. TempO-seq was used to probe the whole transcriptome and machine learning algorithms were applied to derive predictive signatures, with a 3:1 split for training and testing datasets.
RESULTS
A 20-gene prognostic model was developed and validated, with an accuracy of 86.0%, sensitivity of 85.7%, specificity of 86.1%, and positive predictive value of 78.3% in the testing set, providing more stable, accurate prediction than pathological staging systems. A linear predictor was also developed, significantly correlating with metastatic risk.
LIMITATIONS
This was a retrospective 4-center study and larger prospective multicenter studies are now required.
CONCLUSION
The 20-gene signature prediction is accurate, with the potential to be incorporated into clinical workflows for cSCC.
Topics: Humans; Carcinoma, Squamous Cell; Prognosis; Retrospective Studies; Skin Neoplasms; Transcriptome; Prospective Studies; Neoplasm Staging
PubMed: 37586461
DOI: 10.1016/j.jaad.2023.08.012