Neoplastic Skin Research Articles

Exploring the potential of 7,4′-di(diethylamino)flavylium as a novel photosensitizer for topical photodynamic therapy of skin cancer

Photodynamic therapy (PDT) is a minimally invasive therapeutic approach that has shown promising results in recent years, particularly in the dermatological clinical treatment of several pathologies, including neoplastic skin diseases. In light of the recent discovery of the photosensitizing properties of a water-soluble group of amino-based flavylium dyes, research efforts have led to the development of a novel synthetic dye with two diethylamino moieties in its structure, 7,4’-di(diethylamino)flavylium (7,4′diN(Et)2). This dye was tested as a potential photosensitizer for PDT of skin cancer. A single light dose of 22.5 J/cm2 efficiently killed SCC-25 (squamous cell carcinoma) and A375 (melanoma) cells, reducing cellular viability by more than 80% in the presence of the flavylium at 0.75 µM. Meanwhile, the negligible cellular toxicity of the dye in the absence of light stimulus points out a wide and safe therapeutic window. Interestingly, significant light-induced toxicity effects were still observed after washing out the compound before cell irradiation. Moreover, out of the three prototype flavylium-loaded hydrogels, each one based on a different polymer (Carbomer, Caesalpinia Spinosa Gum and Hydroxypropyl methyl cellulose), carbomer-based formulation stood out for its substantial absorbance and fluorescence increment and enhanced1O2 photogeneration activity compared to the flavylium in aqueous solution. The findings of this study provide valuable insights concerning the potential of this flavylium dye as a candidate for photodynamic therapy of skin cancer and strongly support the need for further testing in more advanced biological settings to fully assess its efficacy and safety.

Skin as a Reflection of Gut Health: An Overview of Dermatological Manifestations in Primary Neoplastic and Autoimmune Gastrointestinal Disorders.

Gastrointestinal (GI) diseases can present with several extraintestinal manifestations, and cutaneous signs and symptoms are most frequent. Although conventionally GI and skin are considered two entirely separate organ systems, they are closely correlated in origin. An increasing amount of data highlights the complex relationship between GI and dermatological conditions. This review article aims to particularly explore the clinical correlation between neoplastic and autoimmune GI disorders and skin manifestations, which serve as clinical indicators of these diseases. Neoplastic diseases including pancreatic cancer, gastric adenocarcinoma, Muir-Torre syndrome, carcinoid syndrome, and malignant and benign colorectal polyposis syndromes can be accompanied by skin conditions like pancreatic panniculitis, acanthosis nigricans, keratoacanthomas, necrolytic migratory erythema, melanotic macules, oral papillomas and osteomas, respectively. Autoimmune diseases including celiac disease, autoimmune liver conditions and inflammatory bowel disease (IBD) have been linked to dermatological manifestations such as xanthomas, morphea, psoriasis, dermatitis herpetiformis, erythema nodosum and epidermolysis bullosa acquisita. The skin manifestations can precede the GI symptoms and indicate the severity of the underlying condition, serving as a significant diagnostic marker earlier in the disease. Resolution of skin findings can also indicate the efficacy of treatment strategies and provide prognostic utility. Further research is essential to outline the underlying mechanisms linking dermatological and GI diseases and there is an immediate need for collaborative efforts between dermatologists and gastroenterologists.

Photogallery. HIV infection and neoplastic skin diseases

Malignant neoplasms constitute a group of the most important secondary diseases that develop in people infected with the human immunodeficiency virus (HIV). The first neoplastic disease described in HIV-infected patients is Kaposi's sarcoma. In contrast to other types of Kaposi's sarcoma, its epidemic (AIDS-associated) type is more common in young and middle-aged HIV-positive individuals, especially among men who have same-sex sex. Epidemic Kaposi's sarcoma does not have a favourite localisation. However, there is a tendency to lesions of the scalp (face, ear flaps), upper extremities, anogenital area, oral mucosa. On the trunk, the pathological process spreads along the Langer lines. Skin rashes are represented by spotty, papular, nodular elements of red-brown or purple colour. The aggressive course is characteristic: rapid dissemination and generalisation of rashes. Plasmoblastic lymphoma is associated with immunodeficiency states and is rare. The tumour lesion is usually located in the oral cavity. Few cases of plasmoblastic lymphoma with skin and soft tissue involvement have been described in the literature. Squamous cell skin cancer in the context of HIV infection is a dangerous disease. In people living with HIV, it manifests at a significantly earlier age and is associated with a high risk of local recurrence. The extent of invasion and the likelihood of metastasis are influenced by HIV-associated immunodeficiency. In the vast majority of cases, risk factors and clinical manifestations of basal cell skin cancer do not differ from those in immunocompetent individuals. Basal cell carcinomas rarely metastasise. Nevertheless, metastatic forms lead to unfavourable outcome. Here is a photo gallery of cases of neoplastic skin lesions developed in HIV-positive patients.

Histopathological and Ultrastructural Study of a Canine Langerhans Cell Tumour (Canine Cutaneous Histiocytoma).

Canine cutaneous histiocytoma (CCH) represents a significant proportion of dog skin tumours, often manifesting as the most common neoplastic skin condition in young animals. Predominantly affecting dogs under four, these tumours appear primarily as solitary lesions that may regress spontaneously. This study, conducted over five years at the University of Trás-os-Montes e Alto Douro, involved a detailed histopathological and ultrastructural examination of 93 CCH cases. Histologically, these tumours showed distinct patterns of lymphoid infiltration, which contributed to their classification into four groups based on the inflammatory response and histological architecture. Most tumours displayed signs of epidermal invasion and frequent mitotic figures, with necrosis present in over half of the cases. Ultrastructurally, the neoplastic cells were characterised by pleomorphism, abundant organelles, and adherens-type junctions. This study offers significant insights into the pathophysiology and morphological characteristics of CCH, underscoring the importance of detailed histological and ultrastructural analysis in accurately diagnosing and understanding this common canine tumour.

Features of the skin diseases with pathological examination at Hue University of Medicine and Pharmacy Hospital

Background: Dermatopathology is an important tool that aids dermatologists in diagnosing skin disease. In order to provide useful information on the features of skin disease that needs to support a diagnosis by histopathology, the study was carried out with the objectives: (1) To make statistics on the skin disease with pathological exams and (2) To analyze the relationship between clinical diagnosis and dermatopathologic results. Methods: Cross-sectional study, 52 patients with pathological examination in Dermatologic Clinic at Hue University of Medicine and Pharmacy Hospital from May 2022 to March 2023 participated in the study. Results: The most common skin lesions were plaques (65.4%), followed by pigment lesions (44.2%), and papules/nodules (32.7%). Most of the disease duration is more than 6 months (53.8%). The number of initial clinical diagnoses was mainly one diagnosis (71.2%). The highest proportion of pathologic exams was 36.5%, belong to neoplastic skin diseases, followed by inflammatory skin diseases (34.6%). The match between the initial clinical diagnosis and histopathology reached 71.2%. The usefulness of histopathology for the final diagnosis was 86.5%. 25% of cases have yet to reach the final conclusion, mainly in the inflammatory skin diseases group. Conclusion: The highest proportion of pathologic exams was 36.5%, belong to neoplastic skin diseases, followed by inflammatory skin diseases. Key words: dermatopathology, skin biopsy, neoplastic skin disease, inflammatory skin disease.

Guide to shave procedures in general practice.

General practitioners manage a significant proportion of inflammatory and neoplastic skin conditions on a daily basis. Various surgical techniques can be employed to aid in diagnosis, including punch biopsies, shave biopsy, shave excision, incisional biopsy, curettage and formal excision with closure. Requiring minimal equipment, shave procedures are quick to perform, produce good cosmetic outcomes and minimise costs. Our aim is to discuss shave procedures indetail and highlight the difference between shave biopsies and shave excisions, as well as the role they each have in diagnosing an array of benign, inflammatory and malignant skin conditions, including melanocytic lesions. Shave procedures performed on suitable lesions by trained practitioners can be used for sampling or removing suspect lesions. Where the intent is complete removal, margin involvement is rare given good lesion selection and technique.

Proteomic analysis of pleomorphic dermal sarcoma reveals a fibroblastic cell of origin and distinct immune evasion mechanisms

Pleomorphic dermal sarcomas are infrequent neoplastic skin tumors, manifesting in regions of the skin exposed to ultraviolet radiation. Diagnosing the entity can be challenging and therapeutic options are limited. We analyzed 20 samples of normal healthy skin tissue (SNT), 27 malignant melanomas (MM), 20 cutaneous squamous cell carcinomas (cSCC), and 24 pleomorphic dermal sarcomas (PDS) using mass spectrometry. We explored a potential cell of origin in PDS and validated our findings using publicly available single-cell sequencing data. By correlating tumor purity (TP), inferred by both RNA- and DNA-sequencing, to protein abundance, we found that fibroblasts shared most of the proteins correlating to TP. This observation could also be made using publicly available SNT single cell sequencing data. Moreover, we studied relevant pathways of receptor/ligand (R/L) interactions. Analysis of R/L interactions revealed distinct pathways in cSCC, MM and PDS, with a prominent role of PDGFRB-PDGFD R/L interactions and upregulation of PI3K/AKT signaling pathway. By studying differentially expressed proteins between cSCC and PDS, markers such as MAP1B could differentiate between these two entities. To this end, we studied proteins associated with immunosuppression in PDS, uncovering that immunologically cold PDS cases shared a “negative regulation of interferon-gamma signaling” according to overrepresentation analysis.

Dermoscopy to differentiate clinically similar inflammatory and neoplastic skin lesions.

Over the few last decades, dermoscopy has become an invaluable and popular imaging technique that complements the diagnostic armamentarium of dermatologists, being employed for both tumors and inflammatory diseases. Whereas distinction between neoplastic and inflammatory lesions is often straightforward based on clinical data, there are some scenarios that may be troublesome, e.g., solitary inflammatory lesions or tumors superimposed to a widespread inflammatory condition that may share macroscopic morphological findings. We reviewed the literature to identify dermoscopic clues to support the differential diagnosis of clinically similar inflammatory and neoplastic skin lesions, also providing the histological background of such dermoscopic points of differentiation. Dermoscopic differentiating features were identified for 12 relatively common challenging scenarios, including Bowen's disease and basal cell carcinoma vs. psoriasis and dermatitis, erythroplasia of Queyrat vs. inflammatory balanitis, mammary and extramammary Paget's disease vs. inflammatory mimickers, actinic keratoses vs. discoid lupus erythematosus, squamous cell carcinoma vs. hypertrophic lichen planus and lichen simplex chronicus, actinic cheilitis vs. inflammatory cheilitis, keratoacanthomas vs. prurigo nodularis, nodular lymphomas vs. pseudolymphomas and inflammatory mimickers, mycosis fungoides vs. parapsoriasis and inflammatory mimickers, angiosarcoma vs granuloma faciale, and Kaposi sarcoma vs pseudo-Kaposi. Dermoscopy may be of aid in differentiating clinically similar inflammatory and neoplastic skin lesions.

Reduction of photodynamic damage of blood vessels in the protected region by (–)-epigallocatechin gallate

Photodynamic therapy (PDT) has been increasingly used in the clinical treatment of neoplastic, inflammatory and infectious skin diseases. However, the generation of reactive oxygen species (ROS) may induce undesired side effects in normal tissue surrounding the treatment lesion, which is a big challenge for the clinical application of PDT. To date, (–)-Epigallocatechin gallate (EGCG) has been widely proposed as an antiangiogenic and antitumor agent for the protection of normal tissue from ROS-mediated oxidative damage. This study evaluates the regulation ability of EGCG for photodynamic damage of blood vessels during hematoporphyrin monomethyl ether (Hemoporfin)-mediated PDT. The quenching rate constants of EGCG for the triplet-state Hemoporfin and photosensitized 1O2 generation are determined to be [Formula: see text] M−1S−1 and [Formula: see text] M−1S−1, respectively. The vasoconstriction of blood vessels in the protected region treated with EGCG hydrogel after PDT is lower than that of the control region treated with pure hydrogel, suggesting an efficiently reduced photodamage of Hemoporfin for blood vessels treated with EGCG. This study indicates that EGCG is an efficient quencher for triplet-state Hemoporfin and 1O2, and EGCG could be potentially used to reduce the undesired photodamage of normal tissue in clinical PDT.

Natural Compounds in Non-Melanoma Skin Cancer: Prevention and Treatment.

The elevated occurrence of non-melanoma skin cancer (NMSC) and the adverse effects associated with available treatments adversely impact the quality of life in multiple dimensions. In connection with this, there is a necessity for alternative approaches characterized by increased tolerance and lower side effects. Natural compounds could be employed due to their safety profile and effectiveness for inflammatory and neoplastic skin diseases. These anti-cancer drugs are often derived from natural sources such as marine, zoonotic, and botanical origins. Natural compounds should exhibit anti-carcinogenic actions through various pathways, influencing apoptosis potentiation, cell proliferation inhibition, and metastasis suppression. This review provides an overview of natural compounds used in cancer chemotherapies, chemoprevention, and promotion of skin regeneration, including polyphenolic compounds, flavonoids, vitamins, alkaloids, terpenoids, isothiocyanates, cannabinoids, carotenoids, and ceramides.

Pseudocereal Oils, Authenticated by Fourier Transform Infrared Spectroscopy, and their Chemopreventive Properties.

Amaranth, quinoa, and buckwheat are the representatives of pseudocereals, different parts and by-products of which are used in daily nutrition and food processing industry. However, only scarce information exists on the bioactivity of their oils. Thus, oils obtained from amaranth, buckwheat, and red, yellow, and white quinoa seeds were evaluated in terms of their nutritional (fatty acid profile, squalene), cytotoxic (against normal and neoplastic gastrointestinal, prostate, and skin cells), anti-inflammatory and antiradical (interleukin 6, TNF-alpha, nitric oxide, DPPH, Total phenolics, and superoxide dismutase) potential in the in vitro model. Linoleic (42.9-52.5%) and oleic (22.5-31.1%) acids were the two main unsaturated, while palmitic acid (4.9-18.6%) was the major saturated fatty acid in all evaluated oils. Squalene was identified in all evaluated oils with the highest content in amaranth oil (7.6g/100g), and the lowest in buckwheat oil (2.1g/100g). The evaluated oils exerted a high direct cytotoxic impact on cancer cells of different origins, but also revealed anti-inflammatory and antiradical potentials. Yellow quinoa oil was the most active, especially toward skin (A375; IC50 6.3µg/mL), gastrointestinal (HT29 IC50 4.9µg/mL), and prostate cancer cells (LNCaP IC50 7.6µg/mL). The observed differences in the activity between the oils from the tested quinoa varieties deserve further studies. High selectivity of the oils was noted, which indicates their safety to normal cells. The obtained results indicate that the oils are good candidates for functional foods with perspective chemopreventive potential.

Assessment of specificity of dermatopathologic criteria for IgG4-related skin disease.

IgG4-related disease (IgG4-RD) represents a recently characterized multisystemic fibroinflammatory condition that can manifest a spectrum of skin findings (IgG4-related skin disease; IgG4-RSD). Histopathologic and immunohistochemical criteria have been proposed; however, the specificity of these criteria merits scrutiny given the potential histopathologic overlap of IgG4-RSD and both neoplastic and inflammatory skin conditions featuring lymphoplasmacytic infiltrates (IgG4-RSD mimics). This study sought to assess the specificity of the criteria by quantifying the frequency by which an expanded spectrum of IgG4-RSD mimics meet proposed thresholds. Following IRB approval, a total of 69 cases of IgG4-RD mimics, representing 14 different diagnoses featuring plasma cells, were reviewed and analyzed for the following histopathologic and immunohistochemical features: (i) maximum IgG4+ count/high-powered field (hpf) >200; (ii) IgG4/IgG ratio >0.4 averaged over 3 hpfs; (iii) IgG4+ count >10 per hpf. Screening for IgG4-RSD by histopathologic criteria demonstrated the high frequency of lymphoplasmacytic infiltrates, contrasted with the rarity of storiform fibrosis (only one case of erythema elevatum diutinum [EED]) and obliterative phlebitis (0 cases). By immunohistochemical criteria, the analysis revealed that no cases exceeded 200 IgG4+ cells; 13% (9/69) cases demonstrated an IgG4/IgG ratio of >0.4 averaged over 3 hpfs; and 23% (16/69) cases demonstrated a mean IgG4+ count of >10 per hpf. Application of proposed IgG4-RSD histopathologic criteria to an expanded spectrum of potential IgG4-RSD mimics (to include cutaneous marginal zone lymphoma, syphilis, necrobiosis lipoidica, lichen sclerosus, ALHE, psoriasis, lymphoplasmacytic plaque, EED, and erosive pustular dermatosis), highlights the relative nonspecificity of lymphoplasmacytic infiltrates contrasted with the stringency of storiform fibrosis and obliterative fibrosis. Furthermore, an IgG4+ cell count of >10 per hpf and an IgG4/IgG ratio of >0.4 are not specific to IgG4-RSD alone. In the appropriate clinical context for IgG4-RSD, histopathologic features still represent the entry threshold for diagnosis consideration, which then allows for further screening by immunohistochemical criteria.

High-resolution full-field optical coherence tomography microscope for the evaluation of freshly excised skin specimens during Mohs surgery: A feasibility study.

Histopathology for tumor margin assessment is time-consuming and expensive. High-resolution full-field optical coherence tomography (FF-OCT) images fresh tissues rapidly at cellular resolution and potentially facilitates evaluation. Here, we define FF-OCT features of normal and neoplastic skin lesions in fresh ex vivo tissues and assess its diagnostic accuracy for malignancies. For this, normal and neoplastic tissues were obtained from Mohs surgery, imaged using FF-OCT, and their features were described. Two expert OCT readers conducted a blinded analysis to evaluate their diagnostic accuracies, using histopathology as the ground truth. A convolutional neural network was built to distinguish and outline normal structures and tumors. Of the 113 tissues imaged, 95 (84%) had a tumor (75 basal cell carcinomas [BCCs] and 17 squamous cell carcinomas [SCCs]). The average reader diagnostic accuracy was 88.1%, with a sensitivity of 93.7%, and a specificity of 58.3%. The artificial intelligence (AI) model achieved a diagnostic accuracy of 87.6 ± 5.9%, sensitivity of 93.2 ± 2.1%, and specificity of 81.2 ± 9.2%. A mean intersection-over-union of 60.3 ± 10.1% was achieved when delineating the nodular BCC from normal structures. Limitation of the study was the small sample size for all tumors, especially SCCs. However, based on our preliminary results, we envision FF-OCT to rapidly image fresh tissues, facilitating surgical margin assessment. AI algorithms can aid in automated tumor detection, enabling widespread adoption of this technique.

Autophagy critically controls skin inflammation and apoptosis-induced stem cell activation

ABSTRACT Macroautophagy/autophagy is a cellular recycling program regulating cell survival and controlling inflammatory responses in a context-dependent manner. Here, we demonstrate that keratinocyte-selective ablation of Atg16l1, an essential autophagy mediator, results in exacerbated inflammatory and neoplastic skin responses. In addition, mice lacking keratinocyte autophagy exhibit precocious onset of hair follicle growth, indicating altered activation kinetics of hair follicle stem cells (HFSCs). These HFSCs also exhibit expanded potencies in an autophagy-deficient context as shown by de novo hair follicle formation and improved healing of abrasion wounds. ATG16L1-deficient keratinocytes are markedly sensitized to apoptosis. Compound deletion of RIPK3-dependent necroptotic and CASP8-dependent apoptotic responses or of TNFRSF1A/TNFR1 reveals that the enhanced sensitivity of autophagy-deficient keratinocytes to TNF-dependent cell death is driving altered activation of HFSCs. Together, our data demonstrate that keratinocyte autophagy dampens skin inflammation and tumorigenesis but curtails HFSC activation by restraining apoptotic responses. Abbreviations: ATG16L1: autophagy related 16 like 1; DMBA: 2,4-dimethoxybenzaldehyde; DP: dermal papilla; EpdSCs: epidermal stem cells; Gas6: growth arrest specific 6; HF: hair follicle; HFSC: hair follicle stem cell; IFE: interfollicular epidermis; KRT5: keratin 5; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; PMK: primary mouse keratinocyte; RIPK3: receptor-interacting serine-threonine kinase 3; scRNAseq: single-cell RNA-sequencing; SG: sebaceous gland; TEWL: transepidermal water loss; TPA: 12-O-tetradecanoylphorbol-13-acetate; TNF: tumor necrosis factor; TNFRSF1A/TNFR1: tumor necrosis factor receptor superfamily, member 1a; UMAP: uniform manifold approximation and projection

A clinicopathological analysis of forkhead box A1 (FOXA1) and estrogen receptor alpha expression in extramammary Paget's disease.

Extramammary Paget's disease (EMPD) is a neoplastic skin disease of unknown etiology. EMPD is frequently associated with forkhead box A1 (FOXA1) expression, which correlates with the expression of estrogen receptor alpha (ER). FOXA1 regulates the transcriptional activity of ER and may function cooperatively in the tumorigenesis of breast cancer. We performed immunohistochemical staining for FOXA1 and ER using tissue samples from 16 patients with EMPD. The nuclei of Paget cells isolated from each of the 16 patients with EMPD (100%) were strongly FOXA1-positive, and the FOXA1 staining intensity was similar across all samples. ER staining was detected in the nuclei of Paget cells originating from seven patients with EMPD (44%), and the ER staining intensity varied between these patients. In the present study, we confirmed that EMPD was frequently associated with FOXA1 expression. However, ER expression varied between patients and did not always coincide with FOXA1 expression. No clear relationship was observed between ER expression, the intensity of ER staining, or EMPD metastasis and prognosis. However, the results indicate that hormone-dependent cancer therapy may be effective in patients with ER-positive EMPD.

FINE NEEDLE ASPIRATION CYTOLOGY: A VALUABLE DIAGNOSTIC TOOL FOR NEOPLASTIC CUTANEOUS NODULAR SKIN LESIONS - INSIGHTS FROM A TERTIARY CARE INSTITUTE

This study aimed to evaluate the diagnostic utility of Fine Needle Aspiration Cytology (FNAC) in the evaluation of neoplastic cutaneous nodular skin lesions and to provide insights from a tertiary care institute. A total of 150 patients with cutaneous nodular skin lesions were included in the study, and FNAC was performed using a 23-gauge needle attached to a 10-ml syringe. The study found that FNAC is a valuable diagnostic tool for the evaluation of neoplastic cutaneous nodular skin lesions. It had a sensitivity of 88% and a specificity of 100% for diagnosing malignant lesions. The high sensitivity and specificity of FNAC for diagnosing malignant lesions indicate its usefulness as a diagnostic tool, and it can also help to guide appropriate management and treatment decisions. Therefore, FNAC should be considered as an initial diagnostic tool for evaluating cutaneous nodular skin lesions.

The Role of Mast Cells in the Induction and Maintenance of Inflammation in Selected Skin Diseases.

Under physiological conditions, skin mast cells play an important role as guardians that quickly react to stimuli that disturb homeostasis. These cells efficiently support, fight infection, and heal the injured tissue. The substances secreted by mast cells allow for communication inside the body, including the immune, nervous, and blood systems. Pathologically non-cancerous mast cells participate in allergic processes but also may promote the development of autoinflammatory or neoplastic disease. In this article, we review the current literature regarding the role of mast cells in autoinflammatory, allergic, neoplastic skin disease, as well as the importance of these cells in systemic diseases with a pronounced course with skin symptoms.

HISTO-PATHOLOGICAL SPECTRUM OF SKIN LESIONS IN TERTIARY CARE CENTRE: A THREE YEAR STUDY

Introduction: The largest sensory organ of human body is the skin, which accounts for about 15% of total body weight. It is a complex organ having multiple functions. Primarily it acts as a barrier against various harmful environmental agents (1).Skin diseases affect all age groups and are much common in developing countries. In the field of dermatology, 2000 different skin diseases are well known(2) Objectives: The objectives of the study were as follows: (1) To estimate the prevalence of various non-neoplastic and neoplastic skin lesions in our tertiary care hospital. (2) To study the age and sex-wise distribution of non-neoplastic and neoplastic skin lesions. Methods: The present study comprised a total of 102 skin biopsies of non-neoplastic lesions and neoplastic skin lesions, relevant data like age, sex, and sites of skin lesion were obtained from request forms provided to histopathology section. Specimens received were fixed in 10% formalin. Biopsy bits were submitted as whole and processed in automated tissue processor for routine paraffin embedding. Results: Out of 102 biopsies that were analyzed, most belonged to 21- 60years with slight male predominance with a total of 85 cases being Non-Neoplastic skin lesions, of which Chronic dermatitis 18 (28.5%) was the most common histopathological diagnosis, followed by Hansens disease 21(24.7%) among granulomatous skin disease, and a total of 17 cases of neoplastic skin lesions were identified of which dermatofibroma 2(11.8%) and eccrine spiradenoma 2(11.8%) were the benign variants , and Squamous cell carcinoma 3(17.6%) was the most common malignant variant. Conclusion: Histopathological evaluation of skin biopsies holds gold standard technique for diagnosing various skin lesions and their microscopic evaluation helps in assessing variegated morphological features of different types of skin lesions.

Evaluation of Variant Lymphocyte Count in Peripheral Blood Smear of Patients with Mycosis Fungoides and Its Comparison with the Normal Population

Background and Objective: Mycosis fungoides is a neoplastic skin disorder whose underlying cause is not yet fully understood. There are hypotheses about the possible effect of viral agents on the development of mycosis fungoids that have not yet been proven. The present study aimed to evaluate the lymphocyte variant in peripheral blood smear of patients with mycosis fungoides fungoids to determine the possible role of viral agents in the development of mycosis fungoids. Materials and Methods: In this case-control study, 55 patients with a definite diagnosis of mycosis fungoides based on pathology, clinical and immunological findings (ISCL) were selected by convenience and consecutive sampling method from those referring to referred to Farshchian Hospital (Sina) in Hamadan in 2020 and compared with 55 healthy individuals regarding variant lymphocytes percent of peripheral blood smear. Results: Patients with mycosis fungoides and the control group were matched in terms of age and gender. In the study of peripheral blood smear in patients with mycosis fungoides and the control group, the mean percentage of eosinophils was 5.35±5.11 and 3.00±2.01 (P=0.043), monocytes were 8.27±4.08 and 3.17±1.57 (P<0.001), neutrophils were 53.38±12.97 and 61.64±13.00 (P=0.001), lymphocytes were 31.67±12.57 and 32.95±12.60 (P=0.597), variant lymphocytes was 24.69±15.58 and 3.60±4.66 (P<0.001), and band cells were 1.75±0.96 and 2.25±0.71 (P=0.368) respectively. Conclusion: In patients with mycosis fungoides, the percentage of variant lymphocytes was significantly higher than that in the control group, suggesting the role of infectious agents, especially EBV & CMV, in this disease.

A systematic review of laser therapy for vulvar skin conditions

To the Editor: While laser devices have been utilized for a variety of vulvar skin conditions, much of the literature focuses on laser use in vulvovaginal atrophy or genitourinary syndrome of menopause.1Song S. Budden A. Short A. Nesbitt-Hawes E. Deans R. Abbott J. The evidence for laser treatments to the vulvo-vagina: making sure we do not repeat past mistakes.Aust N Z J Obstet Gynaecol. 2018; 58: 148-162Google Scholar,2Pitsouni E. Grigoriadis T. Falagas M.E. Salvatore S. Athanasiou S. Laser therapy for the genitourinary syndrome of menopause. A systematic review and meta-analysis.Maturitas. 2017; 103: 78-88Google Scholar Prior reviews have also shown limited evidence for clinical efficacy and safety of laser treatments in female gynecologic and urologic conditions.3Preti M. Vieira-Baptista P. Digesu G.A. et al.The clinical role of LASER for vulvar and vaginal treatments in gynecology and female urology: an ICS/ISSVD best practice consensus document.Neurourol Urodyn. 2019; 38: 1009-1023Google Scholar Herein, we conducted a systematic review of laser devices for neoplastic and inflammatory vulvar skin conditions. A literature search was conducted using PubMed, Ovid, and CINAHL using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines with search terms “vulvar” or “vulva” and “laser”. Inclusion criteria consisted of articles published in English after 1990. Studies on rejuvenation and genitourinary syndrome of menopause were excluded. We identified 90 articles consisting of 2072 vulvar cases, comprising 23 diagnoses, treated by laser as monotherapy or in combination with other therapies (Supplementary Table I, available via Mendeley at https://doi.org/10.17632/f9sgx9nt2t.2, Supplementary Fig 1, available via Mendeley at https://doi.org/10.17632/f9sgx9nt2t.2). Of these 2072 cases, 1615 (78%) were neoplastic and 160 (7.7%) were inflammatory conditions. The remaining 297 (14%) were cases of vulvodynia. The most common neoplastic condition was vulvar intraepithelial neoplasia (VIN) (660/1615, 41%). The most common inflammatory condition was lichen sclerosus (LS) (154/160, 96%). For both VIN and LS, CO2 laser was the most common laser utilized in 79% (520/660) and 66% (102/154) of cases, respectively. Of 10 unique lasers used for vulvar conditions, CO2 lasers were most common overall (1674/2072, 81%). CO2 laser was at least partially effective for the following diagnoses: VIN (n = 468), LS (n = 100), Bartholin gland cyst/abscess (n = 689), condyloma acuminata (n = 79), extramammary Paget disease (n = 34), squamous cell hyperplasia/carcinoma (n = 27), vulvar papillomatosis (n = 16), lymphangioma/lymphangiectasia (n = 9), Buschke Lowenstein tumor (n = 3), vulvar syringoma (n = 3), vulvar tumor unspecified (n = 2), inflammatory linear verrucous epidermal nevus (n = 2), bowenoid papulosis (n = 1), vulvar adenosis (n = 1), lymphedema (n = 1), papular acantholytic dyskeratosis (n = 1), epidermoid cyst (n = 1), trichoadenoma of Nikolowski (n = 1), and vulvar pigmented follicular cyst (n = 1). While neither neoplastic or inflammatory, we found CO2 laser was also reported to be partially effective for vulvodynia (n = 96), Thirty-five (38.9%) studies reported at least 1 side effect, the most common being mild or transient pain and discomfort. Conventional treatments for vulvar inflammatory and malignant conditions include surgical excision, photodynamic therapy, and laser ablation. This review specifically highlights the use of laser therapies for vulvar conditions, with the most evidence for CO2 laser for VIN and LS. The heterogeneity of the studies precludes us from providing a standard of care in laser type and laser settings. While most studies reported minimal short-term complications, there is a paucity of data on long-term outcomes. The majority of the studies did not specify Fitzpatrick skin type of patients, limiting our ability to comment on the safety of laser-based devices across a broader range of skin types. More robust studies are needed to ultimately establish guidelines for optimal recommendations for use of lasers in vulvar inflammatory and neoplastic skin conditions. None disclosed.