The Role of Artificial Intelligence in Early Diagnosis and Molecular Classification of Head and Neck Skin Cancers: A Multidisciplinary Approach.

Cancer remains a significant global health concern, with increasing genetic and metabolic irregularities linked to its onset. Among various forms of cancer, skin cancer, including squamous cell carcinoma, basal cell carcinoma, and melanoma, is on the rise worldwide, often triggered by ultraviolet (UV) radiation. The propensity of skin cancer to metastasize highlights the importance of early detection for successful treatment. This narrative review explores the evolving role of artificial intelligence (AI) in diagnosing head and neck skin cancers from both radiological and pathological perspectives. In the past two decades, AI has made remarkable progress in skin cancer research, driven by advances in computational capabilities, digitalization of medical images, and radiomics data. AI has shown significant promise in image-based diagnosis across various medical domains. In dermatology, AI has played a pivotal role in refining diagnostic and treatment strategies, including genomic risk assessment. This technology offers substantial potential to aid primary clinicians in improving patient outcomes. Studies have demonstrated AI's effectiveness in identifying skin lesions, categorizing them, and assessing their malignancy, contributing to earlier interventions and better prognosis. The rising incidence and mortality rates of skin cancer, coupled with the high cost of treatment, emphasize the need for early diagnosis. Further research and integration of AI into clinical practice are warranted to maximize its benefits in skin cancer diagnosis and treatment.

Spontaneous regression of primary cutaneous diffuse large B-cell lymphoma, leg type: A case series and review of the literature.

Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL, LT) is a subtype of cutaneous B-cell lymphoma with unfavorable prognosis usually requiring aggressive polychemotherapy for disease control. Only single cases of spontaneous regression of PCDLBCL, LT are reported in the literature, peaking 3 months post-biopsy following a clinical history of no longer than 1 year. Here, we report the first case of a spontaneously relapsing and remitting PCDLBCL, LT with complete regression after a clinical history of more than 9 years and thus an atypically indolent clinical course. The female patient presented with recurrent erythematous, non-ulcerated, non-raised plaques of the right lower leg for 6 years. Pathological workup and exclusion of a systemic disease confirmed the diagnosis of PCDLBCL, LT. Due to the history of repeated spontaneous remission, no therapy was initiated. Nine years after first occurrence the patient presented with complete clinical remission lasting for 64 months. We retrospectively identified four additional PCDLBCL, LT patients with spontaneous remission lasting up to 53 months. Our data provide evidence for a distinct PCDLBCL, LT patient subgroup that clinicians should be aware of and warrants a watch-and-wait treatment regime.

Comparison of local flaps versus skin grafts as reconstruction methods for defects in the medial canthal region.

BACKGROUND: The medial canthal region features a complex three-dimensional and internal anatomical structure. When reconstructing a defect in this area, it is crucial to consider both functional and aesthetic aspects, which presents significant challenges. Generally, local flaps are preferred for reconstruction; however, skin grafts can be used when local flaps are not feasible. Therefore, we conducted a comparative analysis of surgical outcomes skin grafts when local flaps were not feasible, to determine which surgical method is more effective for medial canthal region reconstruction. METHODS: Twenty-five patients who underwent medial canthal region reconstruction using skin grafts or local flaps from 2002 to 2021 were enrolled. Patient information was obtained from medical records. Five plastic surgeons evaluated the surgical outcomes based on general appearance, color, contour, and symmetry. RESULTS: Skin grafts were used in eight patients and local flaps were used in 13. Combined reconstructions were employed in four cases. Minor complications arose in four cases but improved with conservative treatment. No major complications were reported. Recurrence of the skin cancer was noted in two cases. All categories showed higher scores for the local flap compared to both skin graft and combined reconstruction; however, the differences were not statistically significant respectively. CONCLUSION: The choice of appropriate surgical methods for reconstructing defects in the medial canthal region depends on various factors, including the patient's overall health, the size and depth of the defect, and the degree of involvement of surrounding structures. When a local flap is not feasible, a skin graft may provide favorable surgical outcomes. Therefore, a skin graft can serve as a viable alternative for reconstructing the medial canthal region.

Australians with chronic lymphocytic leukaemia continue to have high rates of second primary malignancies in the modern era.

Population-based studies have demonstrated a high risk of second cancers, especially of the skin, among patients with chronic lymphocytic leukaemia (CLL). We describe age-standardised incidence ratios (SIRs) of second primary malignancies (SPM) in Australian patients with relapsed/refractory CLL treated with at least two lines of therapy, including ibrutinib. From December 2014 to November 2017, 156 patients were identified from 13 sites enrolled in the Australasian Lymphoma and Related Diseases Registry, and 111 had follow-up data on rates of SPM. At 38.4 months from ibrutinib therapy commencement, 25% experienced any SPM. SIR for melanoma and all cancers (excluding nonmelanomatous skin cancers) were 15.8 (95% confidence interval (CI): 7.0-35.3) and 4.6 (95% CI: 3.1-6.9) respectively. These data highlight the importance of primary preventive interventions and surveillance, particularly as survival from CLL continues to improve.

Understanding Active Photoprotection: DNA-Repair Enzymes and Antioxidants.

The detrimental effects of ultraviolet radiation (UVR) on human skin are well-documented, encompassing DNA damage, oxidative stress, and an increased risk of carcinogenesis. Conventional photoprotective measures predominantly rely on filters, which scatter or absorb UV radiation, yet fail to address the cellular damage incurred post-exposure. To fill this gap, antioxidant molecules and DNA-repair enzymes have been extensively researched, offering a paradigm shift towards active photoprotection capable of both preventing and reversing UV-induced damage. In the current review, we focused on "active photoprotection", assessing the state-of-the-art, latest advancements and scientific data from clinical trials and in vivo models concerning the use of DNA-repair enzymes and naturally occurring antioxidant molecules.

Incidence and mortality trends of primary cutaneous melanoma: A 50-year Rochester Epidemiologic Project study.

Background: National cancer reporting-based registry data, although robust, lacks granularity for incidence trends. Expert opinion remains conflicted regarding the possibility of melanoma overdiagnosis in the context of rising incidence without a corresponding rise in mortality. Objective: To characterize 10- and 50-year trends in melanoma incidence and mortality. Methods: Multicenter, population-based epidemiologic study utilizing the Rochester Epidemiology Project for Olmsted County, Minnesota residents diagnosed with melanoma from 01/01/1970 to 12/21/2020. Age- and sex-adjusted incidence and disease-specific mortality are calculated. Results: Two thousand three hundred ten primary cutaneous melanomas were identified. Current age- and sex-adjusted incidence rates increased 11.1-fold since 1970s (P < .001). Over the last decade, there is an overall 1.21-fold (P < .002) increase, with a 1.36-fold increase (P < .002) among females and no significant increase among males (1.09-fold increase, P < .329). Melanoma-specific mortality decreased from 26.7% in 1970s to 1.5% in 2010s, with a hazard ratio (HR) reduction of 0.73 (P < .001) per 5-year period. Increased mortality was associated with Breslow thickness (HR 1.35, P < .001), age at diagnosis (HR 1.13, P = .001) left anatomic site (HR 1.98, P = .016), and nodular histogenic subtype (HR 3.08, P < .001). Limitations: Retrospective nature and focused geographic investigation. Conclusion: Melanoma incidence has continued to increase over the past decade, most significantly in females aged 40+. Trend variations among age and sex cohorts suggests external factors beyond overdiagnosis may be responsible. Disease-specific mortality of melanoma continues to decrease over the last 50 years.

Covering skin defects with a xenogeneic collagen matrix in comparison with a skin graft - A multicenter randomized controlled trial.

The objective of this study was to analyze, in a randomized controlled multicenter trial, whether a xenogeneic collagen matrix (XCM) could be used to cover skin defects. Patients with the need for skin excisions were recruited and randomized to treatment with a skin graft after a period of granulation or to treatment with an XCM. The results were evaluated by two independent observers on the Patient and Observer Scar Assessment Scale. On this scale, scars are ranked from 1 to 10 in six different categories. Results range from 6 to 60, with lower scores representing scars closer to normal skin. The results 6 months after reconstruction were used as primary endpoint and compared in a non-inferiority approach. A total of 39 wounds in the head and neck region were analyzed. The mean results were 16.55 (standard deviation 6.8) for XCM and 16.83 (standard deviation 8.21) in the control group. The result of the XCM was not significantly inferior to the result of the skin graft (p = 0.91). Within the limitations of the study, it seems that the use of xenogeneic collagen matrices is a viable alternative to other approaches in small skin defects, and therefore should be taken into account whenever the reduction of patient morbidity to a minimum is the priority. TRIAL REGISTRATION: This trial was registered in the German Clinical Trials Register under registration identification number DRKS00010930 and can be found under the following URLs: https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00010930. https://trialsearch.who.int/Trial2.aspx?TrialID=DRKS00010930.

Invasion risk of cutaneous squamous cell carcinoma in situ by histological subtype: a retrospective cohort study.

AIMS: Cutaneous squamous cell carcinoma in situ (SCCis) can be classified histopathologically into four subtypes: full-thickness (FT), hypertrophic actinic keratosis (HAK), Bowenoid, and acantholytic types. 3%-5% of SCCis lesions progress to invasive squamous cell carcinoma (iSCC), however progression risk by subtype has not been assessed. Aim one of this study is to quantitatively assess the risk of iSCC associated with each histological subtype of SCCis. Aim two is to evaluate if the histological grade of iSCC differs among subtypes of the associated SCCis. METHODS: The pathology information system at our institution was queried for cutaneous SCCis cases with and without associated iSCC from 2020 to 2022. The study group consisted of 65 cases of SCCis with associated iSCC and control group 65 randomly selected cases of SCCis without invasion. For each case SCCis subtype was classified as FT, HAK, Bowenoid or acantholytic type. iSCCs were classified as low grade if well to moderately differentiated (LG) and high grade (HG) if moderately to poorly differentiated. RESULTS: iSCC was most often associated with HAK-type SCCis, followed by acantholytic and FT-type SCCis, with Bowenoid type rarely associated with iSCC. 41% (14/34) of iSCCs associated with HAK-type SCCis were HG compared with 84% (21/25) for FT-type SCCis. CONCLUSIONS: iSCC is most often associated with HAK-type SCCis, followed by acantholytic and FT-types, and rarely with Bowenoid type. HG invasive SCC is most often associated with FT-type, and LG with HAK-type SCCis. Stratifying SCCis by subtype can inform clinical management.

Localized Merkel cell carcinoma treatment considerations: a response to the forty-year experience at the Peter MacCallum cancer centre.

Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine tumour of the skin with poor prognosis and rising global incidence. A recently published article in BMC Cancer, titled "Merkel cell carcinoma: a forty-year experience at the Peter MacCallum Cancer Centre" (Wang et al.), provides a contemporary analysis of locoregional disease outcomes in Australia which highlights the comparative effectiveness of radiotherapy for excisions with involved margins versus wide local excision. There is a persistent lack of clear, well-defined guidelines to manage MCC in Australia despite experiencing the highest rates globally. The advanced age at onset also provides inherent challenges for optimal management and often, a case-by-case approach is necessary based on patient preferences, baseline function and fitness for surgery. This paper responds to the recently published article by Wang et al. and will expand the discourse regarding management of localized MCC. Specifically, we will discuss the surgical excision approaches; alternative treatment options for MCC including radiotherapy, Mohs micrographic surgery and novel immunotherapy agents being investigated through several clinical trials.

Is thermography an effective screening tool for differentiating benign and malignant skin lesions in the head and neck? A systematic review.

The aim of this study was to assess, through a systematic review, the status of infrared thermography (IRT) as a diagnostic tool for skin neoplasms of the head and neck region and in order to validate its effectiveness in differentiating benign and malignant lesions. A search was carried out in the LILACS, PubMed/MEDLINE, SCOPUS, Web of Science and EMBASE databases including studies published between 2004 and 2024, written in the Latin-Roman alphabet. Accuracy studies with patients aged 18 years or over presenting benign and malignant lesions in the head and neck region that evaluated the performance of IRT in differentiating these lesions were included. Lesions of mesenchymal origin and studies that did not mention histopathological diagnosis were excluded. The systematic review protocol was registered in the PROSPERO database (CRD42023416079). Reviewers independently analyzed titles, abstracts, and full-texts. After extracting data, the risk of bias of the selected studies was assessed using the QUADAS - 2 tool. Results were narratively synthesized and the certainty of evidence was measured using the GRADE approach. The search resulted in 1,587 records and three studies were included. Only one of the assessed studies used static IRT, while the other two studies used cold thermal stress. All studies had an uncertain risk of bias. In general, studies have shown wide variation in the accuracy of IRT for differentiating between malignant and benign lesions, with a low level of certainty in the evidence for both specificity and sensitivity.

The hidden Australian skin cancer epidemic, high-risk cutaneous squamous cell carcinoma: a narrative review.

Deaths from non-melanoma skin cancers (NMSCs) have almost doubled in Australia in recent years. Cutaneous squamous cell carcinoma (cSCC) constitutes approximately 20% of NMSCs, but is responsible for most of the deaths. Most skin cancers are easy to diagnose and treat and therefore cSCC are often trivialised; however, there is a high-risk subgroup of cSCC (HRcSCC) that is associated with a high risk of metastasis and death. The definition of early HRcSCC and our ability to identify them is evolving. Many significant prognostic factors have been identified, but a universally accepted prognostic index does not exist. Guidelines for workup, treatment, and follow-up leave many important decisions open to broad interpretation by the treating physician or multidisciplinary team. Some of the treatments used for metastatic cSCC are not supported by robust evidence and the prognosis of metastatic cSCC is guarded. In this review, we highlight the rapid rise in NMSC deaths and discuss some of the deficiencies in our knowledge of how to define, diagnose, stage, and manage HRcSCC.

Perioperative management of facial reconstruction surgery in patients with end-stage renal disease undergoing dialysis.

BACKGROUND: The rising incidence of dialysis-dependent end-stage renal disease (ESRD) has underscored the need for collaboration between plastic surgeons and nephrologists, particularly concerning preoperative and postoperative management for facial reconstruction. This collaboration is essential due to a scarcity of comprehensive information in this domain. METHODS: A study initiated in January 2015 involved 10 ESRD cases on dialysis undergoing Mohs micrographic surgery for facial skin cancer, followed by reconstructive surgery under general anesthesia. To ensure surgical safety, rigorous measures were enacted, encompassing laboratory testing, nephrology consultations, and preoperative dialysis admission. Throughout surgery, meticulous control was exercised over vital signs, electrolytes, bleeding risk, and pain management (excluding nonsteroidal anti-inflammatory drugs). Postoperative assessments included monitoring flap integrity, hematoma formation, infection, and cardiovascular risk through plasma creatinine levels. RESULTS: Adherence to the proposed guidelines yielded a notable absence of postoperative wound complications. Postoperative plasma creatinine levels exhibited an average decrease of 1.10 mg/dL compared to preoperative levels, indicating improved renal function. Importantly, no cardiopulmonary complications or 30-day mortality were observed. In ESRD patients, creatinine levels decreased significantly postoperatively compared to the preoperative levels (p< 0.05), indicating favorable outcomes. CONCLUSION: The consistent application of guidelines for admission, anesthesia, and surgery yielded robust and stable outcomes across all patients. In particular, the findings support the importance of adjusting dialysis schedules. Despite the limited sample size in this study, these findings underscore the effectiveness of a collaborative and meticulous approach for plastic surgeons performing surgery on dialysis-dependent patients, ensuring successful outcomes.

Primary cutaneous mucinous carcinoma in a periorbital lesion: two case reports and literature review.

Primary cutaneous mucinous carcinoma (PCMC) is a rare malignancy of the sweat glands that most commonly affects the periorbital area. It is characterized by slow growth over a prolonged period, and its morphology can be easily confused with a benign tumor, such as an epidermal cyst. Consequently, many patients experience recurrence after undergoing multiple resections. However, there are few reports concerning the surgical management of PCMC. We present two cases of PCMC originating in the periorbital area. The first case involved a 76-year-old man with a mass measuring 3.0× 1.5 cm that had been increasing in size. The second case was a 61-year-old man with two masses, each measuring 1.0× 1.0 cm, that were also growing. Both patients underwent wide excision with a 5-mm safety margin, which was determined based on the widest view of the cross-section of the mass on the magnetic resonance imaging. Subsequently, based on the intraoperative frozen biopsy results, both patients underwent additional excision with a 5-mm safety margin in only one direction. This report shows that, when determining the surgical margin of PCMC in periorbital area, employing imaging modalities and intraoperative frozen biopsies can be helpful for narrowing the surgical margin.

Development and Validation of Adaptable Skin Cancer Classification System Using Dynamically Expandable Representation.

OBJECTIVES: Skin cancer is a prevalent type of malignancy, necessitating efficient diagnostic tools. This study aimed to develop an automated skin lesion classification model using the dynamically expandable representation (DER) incremental learning algorithm. This algorithm adapts to new data and expands its classification capabilities, with the goal of creating a scalable and efficient system for diagnosing skin cancer. METHODS: The DER model with incremental learning was applied to the HAM10000 and ISIC 2019 datasets. Validation involved two steps: initially, training and evaluating the HAM10000 dataset against a fixed ResNet-50; subsequently, performing external validation of the trained model using the ISIC 2019 dataset. The model's performance was assessed using precision, recall, the F1-score, and area under the precision-recall curve. RESULTS: The developed skin lesion classification model demonstrated high accuracy and reliability across various types of skin lesions, achieving a weighted-average precision, recall, and F1-score of 0.918, 0.808, and 0.847, respectively. The model's discrimination performance was reflected in an average area under the curve (AUC) value of 0.943. Further external validation with the ISIC 2019 dataset confirmed the model's effectiveness, as shown by an AUC of 0.911. CONCLUSIONS: This study presents an optimized skin lesion classification model based on the DER algorithm, which shows high performance in disease classification with the potential to expand its classification range. The model demonstrated robust results in external validation, indicating its adaptability to new disease classes.

[Inaugural Scalp Metastasis of Pulmonary Squamous Cell Carcinoma: 
A Rare Case Report and Literature Review].

Distant cutaneous metastasis of primary lung squamous cell carcinoma is an exceedingly rare event, with scalp metastasis as the initial clinical presentation even rarer. Scalp skin metastases are prone to be misdiagnosed as other scalp disorders, yet their appearance signifies the deterioration and poor prognosis of lung cancer. This case report documents a female patient presenting initially with scalp folliculitis in dermatology, who was subsequently diagnosed with malignant lung tumor through radiological imaging and referred to Department of Thoracic Surgery. Pathological examination of the excised lesion from the scalp revealed distant metastasis of lung cancer. A review of similar cases reported in literature was conducted. This article aims to enhance understanding and awareness of skin metastasis in lung cancer, to emphasize the importance of this condition, and to improve early recognition and precise diagnosis. It is crucial to prevent clinical misdiagnosis and ensure appropriate treatment, finally leading to improve the prognosis of the patients.
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Depth of invasion analysis to predict acral melanoma outcomes.

BACKGROUND: Acral melanoma is a subtype with worse outcomes. The Breslow micrometric measurement is the most critical parameter in planning treatment and predicting outcomes. However, for acral lentiginous melanoma, the value of the Breslow thickness is a matter of debate. Depth of Invasion (DOI) is a well-established measure for staging oral squamous cell carcinoma. OBJECTIVE: This study compared DOI and Breslow thickness for predicting acral melanoma outcomes. METHODS: We performed a retrospective cross-sectional study of 71 acral melanoma lesions subjected to sentinel lymph node biopsy at one Brazilian referral center. RESULTS: Cox model univariate analysis showed that both DOI and Breslow thickness predicted melanoma specific survival (HR 1.12; p = 0.0255 and HR 1.144; p = 0.0006, respectively), although Kaplan Meier curve was only significant for Breslow (χ2 = 5.792; p = 0.0161) and not for DOI (χ2 = 0.2556; p = 0.6132). Sentinel lymph node status and presence or absence of ulceration also predicted specific survival in patients with acral melanoma (χ2 = 6.3514; p = 0.0117 and χ2 = 4.2793; p = 0.0386, respectively). Multivariate analysis, however, demonstrated that Breslow depth was the only independent parameter for predicting acral melanoma specific survival (HR 1.144; p = 0.0006). CONCLUSION: Even though Breslow thickness remains the main predictor for survival in acral melanoma, it is not a perfect parameter. The introduction of DOI in this context opens new perspectives for predicting acral melanoma outcomes.

Efficacy and safety of 0.5% colchicine cream versus 5% 5-fluorouracil cream in the treatment of cutaneous field cancerization: a randomized clinical trial.

BACKGROUND: 5-Fluorouracil (5-FU) is a first-line drug to treat cutaneous field cancerization (CFC). There are few clinical trials with topical colchicine (COL). OBJECTIVE: To evaluate the effectiveness of 0.5% COL cream versus 5% 5-FU cream in the treatment of CFC. METHOD: This was a randomized, open, self-controlled clinical trial. Forty-five patients (90 forearms), with three to ten actinic keratoses (AK) on each forearm, used 0.5% COL cream 2×/day for seven days on one forearm, and 5% 5-FU cream 2× /day, for 21 days, on the other forearm. The dosages were defined based on previous clinical trials for each drug. Adverse effects were evaluated after 14 days and outcomes after 90 days of inclusion. The primary outcome was complete AK clearance and the secondary outcomes were: partial clearance (≥50%), reduction in AK count, assessment of the Forearm Photoaging Scale (FPS), AK Severity Score (AKSS), and adverse effects. RESULTS: After 90 days, there was complete clearance of AK in 37% (95% CI 24%-49%) and partial clearance in 85% (95% CI 76%-93%) of the forearms treated with 5-FU,versus 17% (95% CI 7%-27%) and 78% (95% CI 66%-88%) for COL (p > 0.07). There was a percentage reduction of 75% in the AK count of the forearms treated with 5-FU (95% CI 66%-83%) and 64% in those treated with COL (95% CI 55%-72%). Regarding FPS and AKSS, there was improvement in both groups, with no difference regarding FPS (p = 0.654), and 5-FU superiority for AKSS (p = 0.012). STUDY LIMITATIONS: Single-center study. CONCLUSIONS: 5-FU and COL are effective for treating CFC, with neither showing superiority regarding the reduction in AK counts.