Deep convolutional neural network with fusion strategy for skin cancer recognition: model development and validation.

We aimed to develop an accurate and efficient skin cancer classification system using deep-learning technology with a relatively small dataset of clinical images. We proposed a novel skin cancer classification method, SkinFLNet, which utilizes model fusion and lifelong learning technologies. The SkinFLNet's deep convolutional neural networks were trained using a dataset of 1215 clinical images of skin tumors diagnosed at Taichung and Taipei Veterans General Hospital between 2015 and 2020. The dataset comprised five categories: benign nevus, seborrheic keratosis, basal cell carcinoma, squamous cell carcinoma, and malignant melanoma. The SkinFLNet's performance was evaluated using 463 clinical images between January and December 2021. SkinFLNet achieved an overall classification accuracy of 85%, precision of 85%, recall of 82%, F-score of 82%, sensitivity of 82%, and specificity of 93%, outperforming other deep convolutional neural network models. We also compared SkinFLNet's performance with that of three board-certified dermatologists, and the average overall performance of SkinFLNet was comparable to, or even better than, the dermatologists. Our study presents an efficient skin cancer classification system utilizing model fusion and lifelong learning technologies that can be trained on a relatively small dataset. This system can potentially improve skin cancer screening accuracy in clinical practice.

Seborrheic keratosis.

Seborrheic keratosis (SK) is the most common benign epidermal tumor in clinical dermatological practice. This review summarizes current knowledge about the clinical and histological appearance, epidemiology, pathogenesis, and treatment of SK. There are different subtypes of SK based on clinical presentation and histologic findings. Several factors, including age, genetic predisposition, and possibly also exposure to ultraviolet radiation, are thought to contribute to the development of SK. The lesions can occur on all areas of the body except for the palms and soles, but the most common sites are the face and upper trunk. The diagnosis is usually made clinically, and in some cases by dermatoscopy or histology. Many patients prefer to have the lesions removed for cosmetic reasons although there is no medical indication. Treatment options include surgical therapy, laser therapy, electrocautery, cryotherapy, and topical drug therapy, which is currently in development. Treatment should be individualized depending on the clinical picture and patient preference.

Effectiveness and safety of topical calcipotriol in the treatment of flat seborrheic keratosis on the face.

Seborrheic keratosis is the most common slow-growing, benign epithelial tumour, usually appearing on sun-exposed areas. Treatment modalities for seborrheic keratosis may be uncomfortable and/or time-consuming. We present a case series of 12 patients with solitary seborrheic keratosis localized on the face treated with 0.005% calcipotriol ointment. The treatment lasted 3-8 months and resulted in complete regression of the lesions. Remission (follow-up period) lasted from 6 to 10 years. We conclude that topical calcipotriol may be a useful treatment option for seborrheic keratosis.

Pigmented Inflamed Seborrheic Keratosis of the Bulbar Conjunctiva.

A 57-year-old Black man presented with the recent onset of a pigmented temporal epibulbar lesion. As pigmentation of conjunctival epithelial lesions is correlated with complexion pigmentation, the lesion was presumed to represent a pigmented ocular surface squamous neoplasia (OSSN). Excisional biopsy, however, revealed a pigmented conjunctival seborrheic keratosis, a rare occurrence. The lesion lacked cytologic atypia. Intralesional processes of dendritic melanocytes were demonstrated by hematoxylin-eosin and Melan-A stains. Melanophages also contributed to clinical pigmentation. Subepithelial lymphocytic infiltration, elevated Ki67 proliferative rate, prominent mitotic activity, and subtle spongiosis afforded evidence of inflammation rather than malignancy in a lesion devoid of cytologic atypia.

High expression level of homocitrulline is correlated with seborrheic keratosis and skin aging.

BACKGROUD: Homocitrulline (Hcit), is involved in the pathological processes of some diseases. However, the role and function of Hcit (CBL) in human skin remains largely obscure. OBJECTIVE: To investigate the correlation of the level of Hcit in seborrheic keratosis, skin aging, and its clinical significance. METHODS: Immunohistochemistry was used to analyze the level of Hcit in skin lesions of seborrheic keratosis (SK), unaffected skin (distant 0.5 centimeters from SK lesion), and normal skin of healthy subjects in the control group. ELISA test was used to detect the serum level of CBL in SK patients and healthy subjects of different ages. RESULTS: Hcit was mainly localized in the nucleus of epidermal cells. In healthy control skin, the expression of Hcit increased with age and showed a positive correlation with age (the correlation coefficient was 0.806, p = 0.0002). The expressional level of Hcit in SK lesions was higher than that in healthy control skin (Z = -3.703, p = 0.0002). The serum level of CBL in healthy subjects and in SK patients increased with age (the correlation coefficient were 0.5763, p = 0.0032; 0.682, p = 0.004. respectively). The serum level of CBL in SK patients was higher than that in healthy subjects (Z = -2.19, p = 0.030). STUDY LIMITATIONS: The small serum sample size in the study. CONCLUSION: The high expressional level of Hcit is correlated with seborrheic keratosis and skin aging. HCit may be one of the potential biomarkers of skin aging.

Relationship between α-genus human papillomavirus and non-genital seborrheic keratosis: Report of new cases and updated review.

BACKGROUND: Seborrheic keratoses (SK) are the most common acquired benign tumor that affects middle-aged or older adults with great cosmetic concern. Clinical and histopathological similarities of SK and common warts have been addressed by investigating the possible presence of human papillomavirus (HPV) DNA in SK. Previous studies suggested the association between α-genus HPV and SK located on genital skin, whereas the causal relationship between α-HPV and non-genital SK remains controversial. AIM: This study aimed to clarify the pathogenic involvement of α-HPV in the development of non-genital SK. METHODS: We analyzed α-HPV DNA prevalence and HPV genotypes using a PCR-based microarray on 51 skin samples presenting with histologically confirmed SK without any malignant changes. Correlation between the histological subtype of SK and their HPV DNA-positive reactivity was also evaluated. RESULTS: Of 51 non-genital SK, two (3.9%) skin samples were positive for α-HPV DNA; high-risk HPV 31 and low-risk HPV 42 were found. Evaluation of HPV prevalence in different histological types of SK showed that both HPV-positive cases were acanthotic type; 14.3% of acanthotic SK lesions were positive, while all of the other types were negative for α-HPV. CONCLUSIONS: This study demonstrates that α-HPV positivity is very rare in common non-genital SK. The rare α-HPV-positive SK lesions histologically belonged to the acanthotic type, implying a potential impact of HPV infection on epidermal hyperproliferation. Although a possible association cannot be excluded, our findings suggest that α-HPV is not a major causative factor for non-genital SK.

Melanocytes as the source of the increased melanisation in pigmented epithelial tumours: a holistic approach.

BACKGROUND: We aimed to elucidate the causes of the increased melanisation in basal cell carcinoma (BCC) and seborrheic keratosis (SK), and the role of melanocytes in this process. METHODS: This study was a retrospective-cohort study conducted in the pathology department of a university hospital between January 2019 and October 2020. Forty-nine SK and 30 pigmented BCC were included in our study. SRY-box transcription factor 10 (SOX10), CD68, and Masson-Fontana staining was used for analysis in all samples. A representative section of each specimen was photographed under ×400 magnification to facilitate the assessments of the morphology of the melanocytes and their following morphometric parameters: density, nuclear diameter, and distribution. The density of pigmented keratinocytes in the lesional epidermis was scored. The nuclear diameters of melanocytes located in the nonlesional epidermis, the density of the melanophages, and the presence or absence of ulceration and solar elastosis were also recorded. RESULTS: The morphometric findings confirmed a statistically significant increase in melanocyte density in the BCC group compared with that in the SK group (p < 0.001). Moreover, the nuclear minor diameters in the melanocytes of the BCC sections were significantly higher than those in the SK specimens (p < 0.001). The epidermal melanocytes were distributed diffusely in almost all BCC specimens (96.7%), whereas they were mainly limited to the basal layer in the majority of the SK sections (59.2%). The number of epidermal melanised keratinocytes with a score of 3 was significantly higher in the SK group (n = 31; 63.2%) than in the BCC group (n = 6; 20%) (p = 0.001), and they were the main cells representing the pigmented appearance of the tumours. No significant difference was found between both tumour groups in terms of their melanophage density scores (p = 0.206). DISCUSSION: This study is the first step towards an objective quantification of the melanocytes in pigmented epithelial tumours and may provide a morphological background for future studies on these skin lesions.

Seborrheic Keratosis With Malignant Transformation (Invasive or Noninvasive Squamous Cell Carcinoma Arising in Seborrheic Keratosis): A Clinicopathologic and Immunohistochemical Study of 11 Cases.

ABSTRACT: Seborrheic keratosis is a common benign neoplasm composed of basaloid keratinocytes. However, little is known about the malignant transformation of the tumor. Eleven cases of seborrheic keratosis with malignant transformation were analyzed. The 11 patients included 5 male patients and 6 female patients with a median age of 75 years at diagnosis (68-90 years). The tumors arose at various sites from the scalp (n = 3) to the lower leg (n = 2). The median tumor size was 12 (10-32) and 40 (20-75) mm in 7 noninvasive and 4 invasive cases, respectively. One patient exhibited in-transit skin metastasis. Histopathology of the malignant components resembled porocarcinoma or inverted follicular keratosis. Bowenoid and pagetoid spreading was frequently observed. The malignant components expressed cytokeratin 5/6 (100%) and GATA3 (73%), but not cytokeratin 7 (0%), cytokeratin 19 (9%), BerEP4 (0%), c-kit (0%), and NUT (0%). No significant immunoreactivity of YAP1 was observed in any of the cases. Mutant-type immunostaining of p53 and PTEN was observed in 91% and 82% of the cases, respectively. An increase in p16 expression was seen in 6 (86%) of the 7 cases with noninvasive carcinoma, although a loss of p16 immunoexpression was seen in the invasive carcinoma component in 3 (75%) of the 4 cases. This study demonstrated that seborrheic keratosis can undergo malignant transformation, particularly in large-sized lesions in elderly patients. Malignant components mimic porocarcinoma or inverted follicular keratosis. Malignant transformation induced by TP53 and PTEN mutations and tumor invasion by CDKN2A inactivating mutations are suggested in this study.

Update of pathophysiology and treatment options of seborrheic keratosis.

Seborrheic keratosis (SK) is a common, benign tumor that can occur on everybody site and can be conservatively managed. Cosmetic concerns, especially when a lesion involves the facial area, are the most common reason for excision. SK shows male gender preponderance and increasing age is an independent association with the condition. Even though more prevalent in the elderly, it has also been reported in younger age groups like adolescents and young adults. Precise pathogenesis is still obscure, but ultra-violet exposure represents a predisposing factor to SK by altering the biochemical concentration and expression of factors like Glutamine deaminases, endothelin, and stem cell factor. Moreover, the accumulation of amyloid-associated protein has also been postulated. Involvement of genitalia has been associated with human papillomavirus infection. Recently, Merkel cell polyomavirus nucleic acid was also detected in SK. Several oncogenic mutations involving FGFR-3 and FOXN1 have been identified. SKs are usually classified clinically and histologically. Dermatoscopy is a noninvasive alternative diagnostic technique widely used in differentiating SK from other benign and malignant tumors. In terms of treatment, topical agents, shave dissection, cryosurgery, electrodesiccation, laser application and curettage under local anesthesia are safe methods for eradication of SKs, mostly for cosmetic purposes. Though generally safe, the latter techniques may occasionally cause post-procedure depigmentation, scarring, and recurrence. Nanosecond-pulsed electric field technology is a promising new technique with fewer side-effects.

Clonal-pattern Seborrheic Keratosis: Risk of Recurrence and Progression to Carcinoma.

Seborrheic keratosis is a benign epidermal tumor. Seborrheic keratosis with clonal pattern (CPSK) displays histologic features distinct from other subtypes of SK (non-CPSK). We sought to quantitatively assess the risk of recurrence and progression to squamous cell carcinoma (SCC), either in situ or invasive, of incompletely excised CPSKs. We studied all 244 cases from 238 patients of "seborrheic keratosis, clonal pattern" diagnosed in our institution over a 10-year period (2008-2018). Demographic, clinical, pathologic, and follow-up data were gleaned from electronic health records. Following glass slide review, CPSK lesions were divided into 2 groups: CPSK with cytologic atypia and CPSK without cytologic atypia. For comparison, 107 non-CPSKs were studied as controls. The minimum follow-up period was 2 years (median=4 y). All lesions were incompletely excised. Eighteen of 244 CPSKs (7.4%) recurred at or adjacent to the site of initial partial removal compared with 1.9% of non-CPSKs. Five of the 18 (28%) recurrent CPSKs recurred as CPSK, 11 (61%) as SCC in situ, and 3 (17%) as invasive SCC. The mean time to recurrence was 3.1 years. Two non-CPSKs recurred as non-CPSKs. Overall CPSKs were more likely to recur than non-CPSKs ( P =0.04). CPSKs with atypia were more likely to recur than CPSKs without atypia ( P =0.03). The upgrade rate to SCC at least in situ of all recurrent CPSK lesions with atypia was 78%. Our results suggest that pathologists should report the presence of clonal pattern when observed in seborrheic keratoses, indicate the presence of atypia, and provide lesional margin assessment.

Study on the correlation of high expression level of HuD with seborrheic keratosis and skin aging.

BACKGROUND: Currently, most studies of ELAV (Embryonic Lethal, Abnormal Vision, Drosophila)-like protein 4 (Hu antigen D, HuD) focus on nervous system-related diseases; the role of HuD in the occurrence of skin aging and seborrheic keratosis (SK) has not been reported. OBJECTIVE: To explore the role of HuD in the occurrence of SK and skin aging and its related clinical significance. METHODS: The expression levels of HuD in the skin and blood of healthy people at different ages, SK lesions, and perilesional skin of SK patients were detected by both immunohistochemistry and Western blotting. The mRNA expression levels of HuD in the skin and blood of healthy peoples at different ages were detected by quantitative real-time reverse transcription-polymerase chain reaction. The expression level of HuD was compared with the skin of healthy people, SK lesion, and perilesional skin of SK patients of the same age. RESULTS: The immunohistochemistry and Western blotting showed that the expression levels of HuD in SK lesions were higher than those in healthy skin and perilesional skin. The immunohistochemical staining intensity, protein and mRNA expression levels of HuD in the skin and blood of healthy people were correlated with age, which gradually increased with increasing age. CONCLUSION: HuD is highly expressed in SK lesion and aged skin, indicating that a higher HuD expression level is correlated with occurrence of SK and aging skin; however, its mechanism needs to be further studied.

Cutaneous Ganglioneuromas With Overlying Epidermal Hyperplasia: A Case Series Presentation and Proposal of Potential Etiopathogenesis.

ABSTRACT: Cutaneous ganglioneuromas (GNs) are exceptionally uncommon tumors, and many reported cases describe association with overlying epidermal hyperplasia that may be interpreted as seborrheic keratosis (SK) or SK-like proliferation. We report 5 cases of cutaneous GN in adult patients; all of which were discovered incidentally in the immediate vicinity of epidermal hyperplasia. A review of the literature demonstrates the current-although likely imperfect-understanding of the etiopathogenesis of both SK and GN in the skin. We explore the putative pathophysiologies of other common, well-characterized skin lesions and, taking them into account, provide rationale for the coexistence of cutaneous GN with overlying SK and SK-like epidermal changes. However, we ultimately acknowledge a dilemma of causality and, given the rarity of their co-occurrence, objectively question whether occasional cameo appearances by GN lying subjacent to SK and SK-like hyperplasia may be due merely to chance.

In vivo evaluation of facial papule dermatoses with reflectance confocal microscopy in children.

BACKGROUND: Molluscum contagiosum (MC), milia, keratosis pilaris (KP), verruca plana (VP), seborrheic keratosis (SK), and juvenile xanthogranuloma (JXG) are common papule dermatoses on the face of children that have a similar appearance. In vivo evaluation of facial papule dermatoses with reflectance confocal microscopy (RCM) is helpful in the diagnosis of these ambiguous lesions in children. The purpose of this study was to clarify the RCM characteristics of MC, milia, KP, VP, SK, and JXG and explore the clinical application value of RCM for these common facial papule dermatoses. METHODS: We recruited 113 patients referred for unequivocal facial papule dermatosis, including 21 patients with MC, 17 patients with milia, 19 patients with KP, 36 patients with VP, 8 patients with SK, and 12 patients with JXG. We evaluated the characteristics and distinguishing features of the six kinds of facial papule dermatoses using RCM. RESULTS: The main RCM features of the six dermatoses included a well-demarcated border of the lesion area. MC, milia and KP all manifested cyst-like structures, and their distinguishing features were the location of the cystic structures and the refractive index of the contents. Although VP, SK, and JXG did not have obvious cystoid structures, VP was typically characterized by uniformly distributed petal-like structures with a medium-to-high refractive index in the epidermis. With regard to SK, the characteristic features were an obviously thickened epidermis and cobblestone-like structures. JXG was mainly characterized by multiple large round and ovoid cells with a foamy cytoplasm, and discoid-shaped multinucleated large cells were diffusely distributed in the dermis. CONCLUSION: RCM allows the real-time visualization of major key diagnostic and distinguishing features of common facial papule dermatoses in children, including MC, milia, KP, VP, SK, and JXG.

Ungual seborrheic keratosis with longitudinal melanonychia: A case report.

In this paper, we report the case of a 71-year-old man with an 8-year history of melanonychia on the right little finger, who referred to our hospital because the color of pigmented area had gradually darkened and the width had expanded. Physical examination revealed longitudinal melanonychia with brown color (4 mm in width). Dermoscopic examination revealed multiple white round clods and splinter hemorrhages. No micro-Hutchinson sign was observed. We performed a punch biopsy (diameter 3 mm) of the nail matrix for diagnosis. Histopathological examination revealed irregular acanthosis of epithelium of the nail bed and distal matrix, which consisted of basaloid cells without nuclear atypia. Several zones exhibited cell whorls reminiscent of squamous eddies. The whorls were composed of large pink cells arranged in an onion peel-like fashion. The basaloid cells tested negative for human papillomavirus in situ hybridization and p16 staining. The morphology of white round clods (milia-like cysts in metaphoric term) observed in dermoscopic analysis corresponded to squamous eddies in histopathology. Considering these features, ungual seborrheic keratosis (SK) with longitudinal melanonychia was diagnosed, which is an atypical site for SK. We suggest that the dermoscopic finding of milia-like cysts may be useful for the diagnosis of ungual SK.

Real-time high-resolution millimeter-wave imaging for in-vivo skin cancer diagnosis.

High-resolution millimeter-wave imaging (HR-MMWI), with its high discrimination contrast and sufficient penetration depth, can potentially provide affordable tissue diagnostic information noninvasively. In this study, we evaluate the application of a real-time system of HR-MMWI for in-vivo skin cancer diagnosis. 136 benign and malignant skin lesions from 71 patients, including melanoma, basal cell carcinoma, squamous cell carcinoma, actinic keratosis, melanocytic nevi, angiokeratoma, dermatofibroma, solar lentigo, and seborrheic keratosis were measured. Lesions were classified using a 3-D principal component analysis followed by five classifiers including linear discriminant analysis (LDA), K-nearest neighbor (KNN) with different K-values, linear and Gaussian support vector machine (LSVM and GSVM) with different margin factors, and multilayer perception (MLP). Our results suggested that the best classification was achieved by using five PCA components followed by MLP with 97% sensitivity and 98% specificity. Our findings establish that real-time millimeter-wave imaging can be used to distinguish malignant tissues from benign skin lesions with high diagnostic accuracy comparable with clinical examination and other methods.

SEBORRHEIC KERATOSIS: CURRENT STATE OF THE PROBLEM.

OBJECTIVE: The aim is to identify age, gender, clinical and morphological features of seborrheic keratosis. PATIENTS AND METHODS: Material and methods: The study used biopsy material from 196 patients with a clinical diagnosis of "Seborrheic keratosis". In all cases, when studying directions for pathohistological examination, the authors analyzed gender and age characteristics, as well as localization of seborrheic keratosis. The resulting material was fixed in a 10% solution of neutral formalin (ph 7.4) for 24-48 hours. The procedure was carried out according to the generally accepted technique and the material was embedded in paraffin. Sections of 4-5×10-6m thick were made from paraffin blocks for staining with hematoxylin and eosin. The microspecimens were examined using an Olympus BX-41 microscope (Japan). RESULTS: Results: The study revealed a modern feature of seborrheic keratosis -"rejuvenation" of this tumor, as evidenced by its predominant development in patients aged 31 to 50 years. Seborrheic keratosis is more common in men, and is localized mainly on the skin of the face, scalp, neck and back. When diagnosing seborrheic keratosis, the author notes a significant discrepancy between clinical and morphological diagnoses, which actualizes the problem of improving the available clinical research methods and emphasizes the importance of morphological research. Hyperkeratotic and acanthotic histological variants of seborrheic keratosis are the most common. The case of seborrheic keratosis with malignancy and transformation into squamous cell carcinoma, identified by the author, should develop oncological alertness in doctors and patients. CONCLUSION: Conclusions: The study revealed age, gender, clinical and morphological features of seborrheic keratosis, which will contribute to a better understanding of this pathology by the doctors of various specialties, and improve the treatment and diagnostic process.

Utility of 30% hydrogen peroxide in the treatment of seborrheic keratosis.

BACKGROUND: Hydrogen peroxide (H2 O2 ) has been used in medicine as an antiseptic, but at a higher concentration of 40%, it is used as a chemical cauterant for seborrheic keratoses (SKs). Its action and hence utility at 30% is unexplored. It can serve as a relatively inexpensive modality of treatment for SKs. OBJECTIVES: To evaluate the efficacy and side effects of 30% H2 O2 as a chemical cauterant in SKs. METHODS: Seborrheic keratoses were treated with 30% H2 O2 methodically. Posttreatment assessment was done for the lesion thickness, patient satisfaction, and side effects like burning, itching, edema, crusting, vesiculation, erosion, ulceration, and pigmentary changes. RESULTS: Complete clearance was noted in 25 (49%) lesions, after a single session. Five (9%) lesions responded poorly. Patient satisfaction was excellent with 34 (66.7%) lesions. Side effects noted were burning, pruritus, erythema, edema, and crusting. However, none of them was severe. Dryness, vesiculation, and scarring were reported by none. CONCLUSIONS: H2 O2 30% can be used as a chemical cauterant with minimal side effects.