Bowen's Disease Research Articles

Relationship Between PD-L1, PD-1, CD8 and Clinicopathological Factors in Primary SCCs.

Squamous cell carcinoma of the skin (SCCs) is the second most common skin cancer, with continuously increasing incidence. Programmed cell death ligand 1 (PD-L1), programmed cell death 1 receptor (PD-1), and CD8 expression in primary SCCs have not been described in many studies. We investigated the association between PD-L1, PD-1, CD8, and clinicopathological prognostic factors for recurrence, metastasis, and mortality of SCCs. Immunohistochemically stained sections of 100 primary SCCs divided into two groups according to diameter of the tumors (<20 mm and >20 mm) were assessed. Recombinant rabbit anti-PD-L1 antibody [SP142] - C-terminal, rabbit monoclonal anti-PD1 antibody [NAT105], and FLEX Mono Mo A-Hu CD8, cl C8/144B, RTU were used. We did not establish statistically significant differences between PD-L1, PD-1, CD8 expression, and high-risk clinicopathological features - tumor size >20 mm, depth >6 mm, poor tumor cell differentiation, perineural/lymphovascular invasion, low/absent lymphocyte stromal reaction. In primary SCCs, the expression of PD-L1, PD-1, and CD8 are not associated with high-risk clinicopathological factors. We suggest that these immunohistochemical markers are more significant in advanced cases and metastatic tissues.

Lipidomics revealed alterations in glycerophospholipid metabolism in skin squamous cell carcinoma.

Skin squamous cell carcinoma (SCC) is a prevalent malignancy, and dysregulated lipid metabolism has been implicated in its pathogenesis. However, detailed characterization of lipid alterations in SCC remains limited. We analyzed lipid metabolic variations in tissue samples from 34 SCC patients and adjacent healthy tissues (located more than 1 cm from the tumor margin) using liquid chromatography-mass spectrometry (LC-MS). Data visualization and discriminatory lipid profiles were identified using principal component analysis (PCA) and sparse partial least squares discriminant analysis (sPLS-DA). Key lipids involved in the SCC metabolism were identified and further validated using an external data set (from a previous study, which similarly explored lipid profiles in oral SCC using lipidomics approaches). Pathway enrichment analysis was conducted to elucidate the metabolic pathways associated with these key lipids. Eight lipids were identified by comparing SCC and healthy tissues including PI(16:0/22:4), PI(18:1/20:4), PE(16:0/20:4), PE(16:0/22:5), PE(16:0/22:6), PE(18:1/20:3), PC(18:1/20:2), and PC(18:2/20:2), as confirmed by independent datasets. All of these lipids were upregulated in SCC tumor tissues. Pathway enrichment analysis revealed significant alterations in glycerophospholipid metabolic pathways, particularly affecting the metabolism of diacylglycerophosphocholines, glycerophosphoethanolamines, and glycerophosphoinositols. Our findings reveal that dysregulated glycerophospholipid metabolism plays a pivotal role in the development of SCC.

Application of in vivo reflectance confocal microscopy in the diagnosis of Bowen's disease.

Bowen's disease (BD) is a relatively rare early-stage squamous cell carcinoma in situ, most commonly affecting the middle-aged and elderly, and occurring on the skin or mucous membranes of various parts of the body. Its onset is concealed, the course of the disease is chronic, and some patients have malignant tumors outside the skin; therefore, it is necessary to diagnose and evaluate the disease at an early stage. This study aimed to investigate the application of reflectance confocal microscopy (RCM) in the diagnosis of BD. We performed RCM imaging on the lesion site and underwent skin biopsy for histological diagnosis of 92 patients initially diagnosed with BD in clinic. A retrospective analysis of the RCM result as well as the histological examination revealed that after analyzing RCM images, out of 92 biopsy lesions, 61 were diagnosed with BD, of which 54 were consistent with RCM diagnosis. Among the 59 cases diagnosed with BD by RCM, 54 cases were consistent with the histological diagnosis. Afterwards, we analyzed the RCM characteristics in patients with BD verified by biopsy, and compared the RCM images of two different lesions, classic Bowen's disease and pigmented Bowen's disease, and further summarized the key points of BD under RCM. Finally, we focused on the differential characteristics between BD and other skin diseases in RCM. RCM is of great value in the diagnosis of BD. RESEARCH HIGHLIGHTS: A retrospective study of RCM and histological diagnosis in patients with clinical diagnosis of BD. Analyze the RCM characteristics of skin lesions verified by biopsy. RCM is of great value in the diagnosis and differentiation of BD.

Management of close/positive margins in cutaneous squamous cell carcinoma of the head and neck: a systematised review

Introduction: The authors reviewed close/positive margins in cutaneous squamous cell carcinoma of the head and neck, ensuing recurrence, regional or systemic metastasis, mortality and follow-up management. Methods: The design was a systematised review from January 2000 to July 2021. The MEDLINE database was searched with 15 articles out of 3104 meeting the inclusion criteria. Pertinent references underpinning the National Comprehensive Cancer Network’s Squamous Cell Skin Cancer Guidelines Version 2.2022 were reviewed. Results: Overall, there were 13,671 cutaneous squamous cell carcinoma lesions. We found pooled rates for positive excision (14.6% at 99% CI [12.97, 16.26]), ensuing recurrence (14.7% at 99% CI [13.51, 15.83]), regional or systemic metastasis (33.8% at 99% CI [33.77, 33.87]), and mortality (46.6% at 99% CI [42.53, 50.65]). Positive excisions most frequently involved the deep margin (73.7%), nose (34.5%) and ear (33.14%). Re-excision of positive margins appeared to confer worse recurrence (35.4%). We found pooled rates for close/positive excision (17% at 99% CI [15.22, 18.84]), ensuing recurrence (17% at 99% CI [15.76, 18.16]), regional or systemic metastasis (30.4% at 99% CI [26.15, 34.73]), and mortality (46.6% at 99% CI [42.53, 50.65]). Mean follow up was 51 months. Surgical re-excision with adequate margins appeared to be most efficacious, followed by radiotherapy. Chemoradiation and chemotherapy appeared less efficacious. Conclusion: Surgical re-excision with adequate margins remains the gold standard for close/positive margins in cutaneous squamous cell carcinoma of the head and neck, followed by radiotherapy.

Giant Bowen’s disease of anterior abdominal wall with invasive squamous cell carcinoma-A rare case report

A 65 years old male presented to the out-patient department of Dermatology with complaints of a large verruco-erosive lesion on left anterior abdominal wall for 15 years. A wedge incision biopsy was done which showed features of Bowen’s disease. The patient was referred to department of General Surgery where a complete excision was done. The final histopathology report confirmed the diagnosis of Bowen disease with a focus of invasive carcinoma component. This case report is unusual for its clinical presentation, duration and location of the lesion.

Analysis of the consistency of doctors’ opinions in the assessment of dermatoscopic images of actinic keratosis, Bowen’s disease, keratoacanthoma and squamous cell cancer

Background. Squamous cell skin cancer (SCSC) is the most dangerous tumor of all non-melanocytic skin neoplasms due to its aggressive course with destructive growth and frequent metastasis. Another characteristic feature of SCSC is the presence of precancerous conditions such as actinic keratosis, arsenic keratosis and PUVA-keratosis. In the gradual increase in the degree of keratinocyte dysplasia to the development of invasive forms of skin malignancies, the following continuum of diseases can be distinguished: actinic keratosis — Bowen’s disease — keratoacanthoma — SCSC. Dermatoscopic signs of each of the listed nosologies can also occur in other diseases of this chain, which can complicate diagnosis and lead to erroneous patient management tactics. Aim. To determine the consistency of dermatologists’ opinions in assessing dermatoscopic images of actinic keratosis, Bowen’s disease, keratoacanthoma and SCSC, depending on work experience. Methods. The study was conducted on the basis of the Scientific and Practical Center for the Diagnosis and Treatment of Skin Tumors of the Federal State Budgetary Educational Institution “PIMU” of the Ministry of Health of the Russian Federation. Based on the literature data, we compiled a generalized list of possible dermatoscopic signs of actinic keratosis, Bowen’s disease, keratoacanthoma, SCSC and analyzed dermatoscopic images of 85 elements of actinic keratosis, 28 — of Bowen’s disease, 10 — of keratoacanthoma and 24 — of SCSC. 10 dermatovenerologists participated in the study, half of whom (Group 1) had experience in the field of dermatoscopy for more than 4 years, and the other half (Group 2) — for less than 4 years. Results. The study reveals statistically significant deviations in the frequencies of dermatoscopic signs between the two groups of specialists when analyzing images of actinic keratosis and Bowen’s disease. Differences in the frequency of detection of keratoacanthoma and SCSC signs between specialists with more than 4 years of experience in the field of dermatoscopy and less than 4 years’ experience have not been found. Conclusion. Taking into account the average number of signs, the statistically justified result of the analysis is the inference that the average group frequencies in Group 1 and Group 2 are equal. The conclusion is that the opinions of specialists in the field of dermatoscopy are highly consistent, regardless of work experience. This indicates the high diagnostic value of the method, despite its subjective nature.

Mutant Nrf2E79Q enhances the promotion and progression of a subset of oncogenic Ras keratinocytes and skin tumors

Squamous cell carcinomas (SCCs), including lung, head & neck, bladder, and skin SCCs often display constitutive activation of the KEAP1-NRF2 pathway. Constitutive activation is achieved through multiple mechanisms, including activating mutations in NFE2L2 (NRF2). To determine the functional consequences of Nrf2 activation on skin SCC development, we assessed the effects of mutant Nrf2E79Q expression, one of the most common activating mutations in human SCCs, on tumor promotion and progression in the mouse skin multistage carcinogenesis model using a DMBA-initiation/TPA-promotion protocol where the Hras A->T mutation (Q61L) is the canonical driver mutation. Nrf2E79Q expression was temporally and conditionally activated in the epidermis at two stages of tumor development: 1) after DMBA initiation in the epidermis but before cutaneous tumor development and 2) in pre-existing DMBA-initiated/TPA-promoted squamous papillomas. Expression of Nrf2E79Q in the epidermis after DMBA initiation but before tumor occurrence inhibited the development/promotion of 70% of squamous papillomas. However, the remaining papillomas often displayed non-canonical Hras and Kras mutations and enhanced progression to SCCs compared to control mice expressing wildtype Nrf2. Nrf2E79Q expression in pre-existing tumors caused rapid regression of 60% of papillomas. The remaining papillomas displayed the expected canonical Hras A->T mutation (Q61L) and enhanced progression to SCCs. These results demonstrate that mutant Nrf2E79Q enhances the promotion and progression of a subset of skin tumors and alters the frequency and diversity of oncogenic Ras mutations when expressed early after initiation.

Genetically predicted TWEAK mediates the association between lipidome and Keratinocyte Carcinomas.

Reports suggest that lipid profiles may be linked to the likelihood of developing skin cancer, yet the exact causal relationship is still unknown. This study aimed to examine the connection between lipidome and skin cancers, as well as investigate any possible mediators. A two-sample Mendelian randomization (MR) analysis was conducted on 179 lipidomes and each skin cancer based on a genome-wide association study (GWAS), including melanoma, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). Then, Bayesian weighted MR was performed to verify the analysis results of two-sample MR. Moreover, a two-step MR was employed to investigate the impact of TNF-like weak inducer of apoptosis (TWEAK)-mediated lipidome on skin cancer rates. MR analysis identified higher genetically predicted phosphatidylcholine (PC) (17:0_18:2) could reduce the risk of skin tumors, including BCC (OR=0.9149, 95% CI: 0.8667-0.9658), SCC (OR=0.9343, 95% CI: 0.9087-0.9606) and melanoma (OR=0.9982, 95% CI: 0.9966-0.9997). The proportion of PC (17:0_18:2) predicted by TWEAK-mediated genetic prediction was 6.6 % in BCC and 7.6% in SCC. The causal relationship between PC (17:0_18:2) and melanoma was not mediated by TWEAK. This study identified a negative causal relationship between PC (17:0_18:2) and keratinocyte carcinomas, a small part of which was mediated by TWEAK, and most of the remaining mediating factors are still unclear. Further research on other risk factors is needed in the future.

Naringenin as potent anticancer phytocompound in breast carcinoma: from mechanistic approach to nanoformulations based therapeutics.

The bioactive compounds present in citrus fruits are gaining broader acceptance in oncology. Numerous studies have deciphered naringenin's antioxidant and anticancer potential in human and animal studies. Naringenin (NGE) potentially suppresses cancer progression, thereby improving the health of cancer patients. The pleiotropic anticancer properties of naringenin include inhibition of the synthesis of growth factors and cytokines, inhibition of the cell cycle, and modification of several cellular signaling pathways. As an herbal remedy, naringenin has significant pharmacological properties, such as anti-inflammatory, antioxidant, neuroprotective, hepatoprotective, and anti-cancer activities. The inactivation of carcinogens following treatment with pure naringenin, naringenin-loaded nanoparticles, and naringenin combined with anti-cancer agents was demonstrated by data in vitro and in vivo studies. These studies included colon cancer, lung neoplasms, breast cancer, leukemia and lymphoma, pancreatic cancer, prostate tumors, oral squamous cell carcinoma, liver cancer, brain tumors, skin cancer, cervical and ovarian cancers, bladder neoplasms, gastric cancer, and osteosarcoma. The effects of naringenin on processes related to inflammation, apoptosis, proliferation, angiogenesis, metastasis, and invasion in breast cancer are covered in this narrative review, along with its potential to develop novel and secure anticancer medications.

Incidence and geographic differences in keratinocyte carcinoma and Bowen's disease in office‐based dermatological practice between 2013 and 2022: A nationwide Danish registry‐based study

AbstractBackgroundRates of keratinocyte carcinoma (KC) across Europe are impacted by population demographics and geography. Regional differences in KC occurrence exist, but few European studies investigate incidences of specific subtypes in the secondary healthcare sector on a national level.ObjectivesTo determine geographical differences in incidence rate and lifetime risk of KC subtypes across Denmark, including nodular and superficial basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and the KC precursor, Bowen's disease (BD), identified in office‐based dermatological practice.MethodsBased on a nationwide registry (The Danish Skin Cancer Registry), all patients in Denmark's five regions with a histologically‐ or clinically verified KC or BD registered in a state‐funded office‐based dermatology practice between 2013 and 2022 were included. Trends in national‐ and region‐specific age and sex standardised tumour incidence rates (STIR) were calculated. Further, national lifetime risk of each tumour subtype was estimated.ResultsBetween 2013 and 2022, the combined STIR for KC/BD rose 172% nationally from 180 to 489 per 100,000 person‐years (PY). This increase reflected rising rates of nodular BCC, SCC, and BD, while superficial BCC incidence was relatively stable. Regional differences in STIR for combined KC/BD were observed, with the Capital Region and North Jutland generally demonstrating higher rates than Zealand, Southern‐ and Central Denmark (e.g., North Jutland vs. Southern Denmark: 714 vs. 405/100,000PY). While the estimated lifetime risk of developing at least one KC or BD tumour was 21.8%, risk varied with tumour subtype, resulting in subtype‐specific risks of 16.4%, 5.1%, 1.9% and 1.3% for nodular BCC, superficial BCC, SCC, and BD, respectively.ConclusionsIn Denmark's secondary dermatological care sector, incidence of nodular BCC, SCC and BD continues to rise with an overall lifetime risk nearing 22%. While KC incidence is increasing in Denmark, the study detected differences in geographical trends and rate increases of specific tumour subtypes.

Targeting of S-phase kinase associated protein 2 stabilized tumor suppressors leading to apoptotic cell death in squamous skin cancer cells

S-phase kinase-associated protein 2 (Skp2) is an F-box protein overexpressed in human cancers and linked with poor prognosis. It triggers cancer pathogenesis, including stemness and drug resistance. In this study, we have explored the potential role of Skp2 targeting in restoring the expression of tumor suppressors in human cutaneous squamous cell carcinoma (cSCC) cells. Our results showed that genetic and pharmacological Skp2 targeting markedly suppressed cSCC cell proliferation, colony growth, spheroid formation, and enhanced sensitization to chemotherapeutic drugs. Further, western blot results demonstrated restoration of tumor suppressor (KLF4) and CDKI (p21) and suppression of vimentin and survivin in Skp2-knocked-down cSCC cells. Importantly, we also explored that Skp2 targeting potentiates apoptosis of cSCC cells through MAPK signaling. Moreover, co-targeting of Skp2 and PI3K/AKT resulted in increased cancer cell death. Interestingly, curcumin, a well-known naturally derived anticancer agent, also inhibits Skp2 expression with concomitant CDKI upregulation. In line, curcumin suppressed cSCC cell growth through ROS-mediated apoptosis, while the use of N-acetyl cysteine (NAC) reversed curcumin-induced cell death. Curcumin treatment also sensitized cSCC cells to conventional anticancer drugs, such as cisplatin and doxorubicin. Altogether, these data suggest that Skp2 targeting restores the functioning of tumor suppressors, inhibits the expression of genes associated with cell proliferation and stemness, and sensitizes cancer cells to anticancer drugs. Thus, genetic, and pharmacological ablation of Skp2 can be an important strategy for attenuating cancer pathogenesis and associated complications in skin squamous cell carcinoma.

Pigmented nonmelanoma skin cancers of the genital area: adiagnostic and therapeutic challenge - monocentric experience and review of the literature.

Nonmelanoma skin cancers (NMSC), comprising basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), are typically encountered on photo-exposed skin. Nevertheless, several cases of NMSC have been described in covered areas such as the genital region; furthermore, some of these lesions may express a variable degree of pigmentation. Due to the existence of mucosal melanoma, an accurate diagnosis is paramount. In this narrative review, we focused our attention on management and - in particular- diagnosis of pigmented NMSC (pNMSC) located in the genital region, emphasizing the features assessed by dermoscopy and reflectance confocal microscopy. As an implementation, we included data on pNMSC from the Dermatology Unit of the University of Campania Vanvitelli. BCC in the genital region represents only 1% of all BCC cases. It has been supposed that the mutation of patched 1 may lead to the development of BCC even without concomitant UV exposure. Pigmented variants on genitals have seldom been described. More prominent dermoscopic features seem to be blue-gray ovoid nests and arborizing vessels associated with whitish structureless areas. SCC and Bowen's disease (BD) - a variant of in situ SCC - may be encountered in the genital area and are sometimes associated with human papillomavirus (HPV) infection. Pigmented SCC is very rare, and most of the literature is focused on pigmented BD (pBD), which is mainly characterized by gray-brown dots in a linear fashion and glomerular vessels without evident scales. In conclusion, pNMSC is rarely encountered on genitals; evaluation with dermoscopy or other ancillary devices like RCM is important both to exclude benign lesions like seborrheic keratosis and lentigo and to rule out melanoma.

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

AimsCutaneous 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...

Tumor-Infiltrating T Cells in Skin Basal Cell Carcinomas and Squamous Cell Carcinomas: Global Th1 Preponderance with Th17 Enrichment-A Cross-Sectional Study.

Basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) are high-incidence, non-melanoma skin cancers (NMSCs). The success of immune-targeted therapies in advanced NMSCs led us to anticipate that NMSCs harbored significant populations of tumor-infiltrating lymphocytes with potential anti-tumor activity. The main aim of this study was to characterize T cells infiltrating NMSCs. Flow cytometry and immunohistochemistry were used to assess, respectively, the proportions and densities of T cell subpopulations in BCCs (n = 118), SCCs (n = 33), and normal skin (NS, n = 30). CD8+ T cells, CD4+ T cell subsets, namely, Th1, Th2, Th17, Th9, and regulatory T cells (Tregs), CD8+ and CD4+ memory T cells, and γδ T cells were compared between NMSCs and NS samples. Remarkably, both BCCs and SCCs featured a significantly higher Th1/Th2 ratio (~four-fold) and an enrichment for Th17 cells. NMSCs also showed a significant enrichment for IFN-γ-producing CD8+T cells, and a depletion of γδ T cells. Using immunohistochemistry, NMSCs featured denser T cell infiltrates (CD4+, CD8+, and Tregs) than NS. Overall, these data favor a Th1-predominant response in BCCs and SCCs, providing support for immune-based treatments in NMSCs. Th17-mediated inflammation may play a role in the progression of NMSCs and thus become a potential therapeutic target in NMSCs.

Advanced Squamous Cell Carcinoma of the Skin Induced by Long-Term Hydroxyurea Treatment in a Patient with Essential Thrombocythemia

Abstract Background and Objective SCCs represents 20-30% of the non-melanocytic skin cancers. It is the second most common skin cancer in the U.S. The main risk factors for SCCs development are: skin phototype l-ll, excessive UV-exposure, chronic inflammatory skin diseases, radiation exposure and drug usage. Hydroxyurea is a drug used for the treatment of chronic myeloid leukemia, polycythemia vera and essential thrombocythemia. The therapy is associated with development of actinic keratoses, Bowen's disease, squamous cell carcinoma and basal cell carcinoma. Patients and methods We present a 70-year-old female patient suffering from essential thrombocythemia, undergoing treatment with hydroxyurea since 2005, who developed advanced squamous cell carcinoma of the skin of the face and wrists. Results The patient was diagnosed with advanced moderately differentiated SCCs (Grade 2), stage III (T4 N0 M0). Immunotherapy with cemiplimab 350 mg i.v. every 21 days was initiated. After 6 therapeutic cycles decrease of erythema and desquamation was registered. In 2022 the patient had an ischemie stroke, decompensated heart failure and acute kidney insufficiency. Unfortunately the patient died. Conclusions Patients undergoing long-term hydroxyurea treatment are prone to develop multiple squamous cell carcinomas of the skin and are subject to regular dermatological examinations.

Effect of DeltaRex-G ± DeltaRex-G Plus (an FDA-approved drug) on advanced chemoresistant pancreatic cancer, sarcoma, and breast cancer.

e15086 Background: Expanded access for DeltaRex-G, a tumor targeted retrovector encoding a CCNG1 inhibitor, is being studied for advanced cancers. Methods: 137 archived tumor specimens were analyzed with AI RNA sequencing to identify CCNG1 expression levels, reported as: Low = 17%, Medium-low = 17%-49%, Medium-high = 50%-83%, High = 83%. Nine patients with advanced solid malignancies, whose CCNG1 levels were identified, received DeltaRex-G (2-3 x 10e11 cfu/dose one to three times a week), either without an FDA-approved drug, or with an FDA-approved drug (“DeltaRex-G Plus”). Overall survival, duration of treatment, and responses were evaluated. Results: All analyzed tumors showed enhanced CCNG1 expression. Thirty (22%) tumors exhibited High CCNG1 expression, 48 (35%) showed Medium-High CCNG1 expression, 53 (39%) displayed Medium-Low CCNG1 expression, and six (4%) had Low CCNG1 expression. One hundred (73%) patients had metastatic disease, and 37 (27%) had localized disease. There was no correlation between CCNG1 expression and disease stage. Four patients with advanced pancreatic cancer (n = 1), Stage 1 HR+Her2+ invasive breast cancer (n = 1), Stage 1 triple negative breast cancer (n = 1), and squamous cell carcinoma of skin (n = 1), received DeltaRex-G alone or DeltaRex-G Plus between 2008 and 2021 and are alive 15, 3, 2.5, and 2.5 years since treatment initiation, respectively. Retrospective analysis of their respective tumors showed CCNG1 expression levels of 24%, 23%, 74%, and 40%. Three of the patients are in sustained remission and the patient with squamous cell carcinoma had a partial response. Of the five patients currently being treated with DeltaRex-G Plus: one patient with advanced breast cancer had a partial response (n = 1), one patient with advanced pancreatic cancer (n = 1) and three patients with soft tissue sarcoma (n = 3) had stable disease. Four of five patients had previously progressed with standard doses of chemotherapy. All patients are alive from 11 to 22 weeks since treatment initiation. No serious treatment-related adverse events have been reported. Conclusions: Taken together, the data shows that (1) 100% of 137 tumors tested have enhanced CCNG1 expression, further reinforcing the 2021 FDA-CBER authorization for use of DeltaRex-Plus, and (2) DeltaRex-G Plus is a promising therapy for advanced pancreatic cancer, sarcoma, and breast cancer. Randomized Phase 2/3 studies are warranted to confirm the efficacy and safety of DeltaRex-G Plus. Clinical trial information: NCT04091295 .

Anti-tumor and anti-oxidant effects of Ganoderma lucidum extracts on oral squamous cell carcinoma and skin squamous cell carcinoma in vitro

Anti-tumor and anti-oxidant effects of <i>Ganoderma lucidum</i> extracts on oral squamous cell carcinoma and skin squamous cell carcinoma <i>in vitro</i>

Pagetoid Bowen Disease: A Simulator of Clonal Seborrheic Keratosis, Case Report

Seborrheic keratosis (SK) and Bowen disease (BD) are different entities in dermatopathology. Differentiating between these two is important and can sometimes be a challenge for the pathologist, who may need to rely on complementary techniques. To obtain a reliable distinction, several immunohistochemistry markers have been explored such as p16 and Ki67, being positive in Bowen disease and negative in Seborrheic keratosis. Ki-67 is a non-histone protein associated with ribosomes and a well-known marker of cellular proliferation, overexpressed in Bowen disease. In addition, it has been related to a greater expression of antigens associated with the growth and differentiation of keratinocytes. P16 is a tumor suppressor gene that inhibits cyclin-dependent kinases 4 and 6. His inactivation leads to a unregulated proliferation of the cell cycle. A greater expression was found in Bowen Disease compared to Seborrheic Keratosis. Immunohistochemistry allows the distinction between entities that may be appear similar both clinically and histopathologically. This is of utmost relevance since proper treatment depends on a precise diagnosis.

Assessing outcomes of topical 5-fluorouracil as primary and adjuvant therapy for squamous cell carcinoma in-situ.

Cutaneous squamous cell carcinoma in-situ (SCCis) is an intraepithelial tumor with a good prognosis. Standard treatment includes both surgical and non-surgical interventions. We determined the clearance rate for SCCis and residual SCCis identified on frozen section during Mohs micrographic surgery (MMS) after treatment with topical fluorouracil 5% cream (5-FU). All MMS cases were initiated for biopsy-proven invasive squamous cell carcinoma (SCC). A retrospective chart review was conducted from January 2017-February 2024 at Columbia University Irving Medical Center (CUIMC) to identify patients with SCCis who were treated with topical 5-FU as primary therapy or adjuvant therapy(AT) for residual SCCis post-MMS for invasive SCC. 41 patients were included (80% males, 70.1 ± 11.8 years). The average follow-up time for the primary therapy group was 25.4 ± 12.8 months, and for the post-MMS AT group 22.5 ± 11.1 months. In the group treated with topical 5-FU as primary therapy (n = 28), 27 patients (96.43%, 95% confidence interval: 81.65-99.91%) achieved complete clearance. One patient had recurrence at 8 months post-treatment. Of the patients in the post-MMS adjuvant treatment group (n = 13), 12 (92.3% clearance, 95% confidence interval 63.97-99.81%) achieved complete clearance. One patient had recurrence at 8 months post-treatment. This study found that topical 5-FU cream is effective as both primary therapy for SCCis and as adjuvant therapy for residual SCCis following MMS of invasive SCC.

Surface material analysis for human papillomavirus detection in nail Bowen's disease caused by HPV type 58.

Over the past few years, cases of human papillomavirus (HPV) infection in nail Bowen's disease have been reported. This disease presents diagnostic challenges due to its similarity to nail malignant melanoma, particularly with respect to the clinical manifestation of black nail streaks. While skin biopsy is usually employed for diagnosis, it is an invasive procedure. We report the case of a 52-year-old healthy Japanese male with a pigmented streak on the nail of the fourth finger of his right hand, which had extended from the central to the lateral nail fold within 4 months. Dermoscopic examination revealed a dark-brown pigmented band with splinter microhemorrhage. Clinically, nail Bowen's disease was suspected. The lesion was excised in strips under local anesthesia. Histopathological examination revealed hyperkeratosis, parakeratosis, papillomatosis, and dyskeratotic cells with atypical nuclei irregularly arranged. Immunohistochemistry using anti-HPV L1 antibody detected HPV-positive cells in the upper epidermis and stratum corneum of the nail matrix. Mucosal high-risk HPV type 58 DNA was detected from brush cytology of the keratotic surface prior to surgery, which was confirmed in formalin-fixed, paraffin-embedded excised samples using polymerase chain reaction (PCR) and subsequent direct DNA sequencing. Our case highlights HPV type 58 as a potential causative agent of nail Bowen's disease and shows that brush cytology of the surface material prior to excision may be a useful and less invasive way for mucosal high-risk HPV detection. PCR analysis of the nail surface could serve as a supplementary diagnostic tool for nail Bowen's disease.