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We have studied morphofunctional state of esophageal mucosa in 57 patients with gastroesophageal reflux disease (GERD) with normal (body mass index (BMI) — 18.5–24.9 kg/m2) and excessive (BMI over 25 kg/m2) body weight. A histologic and morphometric study of esophageal mucosa, immunohistochemical analysis of the expression of apoptosis marker CD95 and inflammatory marker cyclooxygenase-2 (COX-2) were carried out. In reflux esophagitis, most characteristic are changes in multilayered epithelium — hyperkeratosis, parakeratosis, proliferation of basal cells and acanthosis. At that, significant differences in morphometric characteristics of patients with normal BMI and overweight were not found. The development of reflux esophagitis was associated with violations of pro-apoptotic ability of esophageal mucosa cells and increased expression of COX-2, most significant in patients with high BMI. Detected disorders may determine the mechanisms of complicated course of GERD in these patients.

The article deals with a case from clinical practice: a patient complained of itching in the area of a previously performed tattoo, a change in appearance: pronounced skin thickening, peeling. As a result of clinical and morphological examination, lichen planus was diagnosed in the area of red pigment injection as a complication of tattooing.

Psoriasis is a chronic multifactorial inflammatory disease that affects 3% of people worldwide. Ustekinumab is a selective anti-IL-12/23 biologic that alleviates psoriasis, and curcumin is a natural, effective dietary turmeric extract applied to treat numerous diseases through its antioxidant and anti-inflammatory effects.The current study evaluated the therapeutic effects of curcumin and ustekinumab cotherapy (CUC) on imiquimod (IQ)-induced psoriasis in a rat model.Twenty rats were divided into four groups, G1 (control group), G2 (IQ-treated group), G3 (IQ + ustekinumab), and G4 (IQ + CUC). Clinical, histopathological (HP), immunohistochemical (IHC), antioxidant, and biochemical investigations evaluated the efficacy of these drugs for treating IQ induced-psoriasis.Rats of G2 exhibited clinical signs of psoriatic skin lesions (erythema, scaling, and skin thickening) with epidermal changes (acanthosis and parakeratosis). Additionally, the biochemical analysis revealed significant (Ustekinumab inhibits the inflammatory cytokines IL-12P40 and IL-23, while curcumin has antioxidant effects (increasing SOD, GPx, and CAT levels) with anti-inflammatory effects (decreasing the proinflammatory cytokine TNF-α and IL-17). Therefore, CUC could be an excellent cost-effective regimen that can improve the treatment of psoriasis by the synergistic effects of CUC.HighlightsIQ-induces psoriasis by elevating TNF-α, IL-17A, IL-12, and IL-23 and decreasing GPx, SOD, and CATUstekinumab exhibits anti-inflammatory effects by inhibiting IL-12 and IL-23Curcumin inhibits TNF-α and IL-17A, and increases GPx, SOD, and CAT levelsCUC mitigates psoriasis by synergistic antioxidant and anti-inflammatory effectsCUC inhibits TNF-α, IL-17A, IL-12, and IL-23 and increases GPx, SOD, and CAT levels.

Las queratosis actínicas son lesiones cutáneas preneoplásicas frecuentes causadas por una exposición crónica a las radiaciones solares. La obtención de modelos animales que contribuyan a comprender los mecanismos implicados en esta patología y a evaluar nuevas terapias farmacológicas resulta de gran interés para la comunidad científica. Se desarrolló un biomodelo de queratosis actínica en ratones Balb/c, empleando como inductor la radiación UVA. Se aplicaron dos esquemas de irradiación: Grupo I, expuesto a tres sesiones diarias de radiación de 2 h y Grupo II, dos sesiones diarias de 4 h, con igual tiempo de receso entre sesiones y durante un período de 14 días. Se evaluaron parámetros macroscópicos y microscópicos, y la frecuencia de aparición de micronúcleos en sangre periférica. Los animales correspondientes al Grupo I no mostraron lesiones mascroscópicas y microscópicamente evidenciaron una leve acantosis con ausencia de displasia; mientras que en los animales del Grupo II se observaron lesiones macroscópicas que se correlacionan histopatológicamente con la presencia de una queratosis actínica. La frecuencia de micronúcleos obtenida en el Grupo II fue significativamente superior a la formación de micronúcleos espontáneos en el Grupo Control. El biomodelo experimental de queratosis actínica obtenido reproduce el efecto de las radiaciones ultravioletas sobre la piel. Actinic keratoses are frequent preneoplastic skin lesions caused by chronic exposure to solar radiation. Obtaining animal models that contribute to understanding the mechanisms involved in this pathology and evaluating new pharmacological therapies is of great interest to the scientific community. A biomodel of actinic keratosis was developed in Balb/c mice, using UVA radiation as an inducer. Two irradiation schemes were applied: Group I, exposed to three daily radiation sessions of 2 h and Group II, two daily sessions of 4 h, with the same break time between sessions and for a period of 14 days. Macroscopic and microscopic parameters were evaluated, as well as the frequency of appearance of micronuclei in peripheral blood. The animals corresponding to Group I did not show mascroscopic lesions and microscopically they showed a slight acanthosis with the absence of dysplasia; while in Group II animals macroscopic lesions were observed that histopathologically correlate with the presence of an actinic keratosis. The frequency of micronuclei obtained in Group II was significantly higher than the formation of spontaneous micronuclei in the Control Group. The experimental biomodel of actinic keratosis obtained reproduces the effect of ultraviolet radiation on the skin. Ciencias Experimentales

Background Inverse psoriasis represents a less commonly described form of psoriasis in intertriginous areas. The pathologic findings of inverse psoriasis are typically grouped in with those of plaque psoriasis, as the histopathological features specific to inverse psoriasis have not received significant investigation. Methods A single institution, retrospective cohort study was performed to review biopsy slides for psoriasis occurring in typical intertriginous areas. Patient's charts were reviewed and only those where the clinical diagnosis of inverse psoriasis was also favored were included. Results 12 patients met inclusion criteria - 58% male and 42% female, 18-86 years of age. Classic features of psoriasis such as hypogranulosis, confluent parakeratosis, and thinning of the suprapapillary plate were seen in 100%. Regular psoriasiform acanthosis and dilated tortuous dermal vessels were seen in 92%. Neutrophils were present in the scale in 83% and in the dermis in 100%. Features considered atypical for psoriasis included spongiosis in 83%, eosinophils in 67%, and focal serum in the scale in 42%. Conclusions While inverse psoriasis commonly exhibits features considered to be classic for psoriasis, it is not unusual for inverse psoriasis to show features considered atypical for plaque psoriasis such as dermal eosinophils, epidermal spongiosis, and focal serum in the scale. This article is protected by copyright. All rights reserved.

BACKGROUND Extramammary Paget's disease (EMPD) is a rare neoplasm that commonly affects post-menopausal women. It usually presents in the anogenital area where apocrine sweat glands are abundant, most commonly in the vulva. The disease is characterised by slow growth and high local recurrence rates. Clinically, EMPD presents as well-demarcated erythematous lesions or plaques that may be ulcerated. Microscopically, it shows a group of atypical cells with abundant clear cytoplasm and nuclear pleomorphism. METHODS We present the case of a 58-year-old female with a history of poorly differentiated squamous cell carcinoma of the cervix, status post-radical-hysterectomy with bilateral salpingo-oophorectomy, and chemoradiation in 2016. The patient also had a long-standing history of vulvar pain, skin changes on her left labia, and itching. RESULTS Punch biopsies of the vulva revealed acanthosis and acantholysis of the epidermis with an intraepidermal scattering of single, or clusters of, large cells with round/oval nuclei and abundant clear cytoplasm. The cells were positive for p16, CK19, CK7, and PAX8, supporting the diagnosis of EMPD without evidence of dysplasia. The concurrent Papanicolaou smear showed a hypercellular specimen composed of hyperchromatic tissue fragments with high nuclear-to-cytoplasmic ratios and apoptotic bodies. The presence of intracytoplasmic mucin and the tridimensionality of the fragments supported the diagnosis of adenocarcinoma. CONCLUSIONS This study compares the histological and cytomorphological features of EMPD with high-grade squamous intraepithelial lesions, since the pathogenesis, precursor lesions, etiological associations, staging, clinical treatment, and prognosis differ substantially and may have a significant clinical impact on the patient's treatment.

Periodontal disease is a chronic inflammatory, multifactorial condition, that, in the absence of an early and adequate treatment, may lead to a progressive damaging of the alveolar tissues that support the teeth (periodontal ligament, cement and alveolar bone) followed by teeth mobility and, subsequently, their loss. Periodontal disease is one of the most common inflammatory disease affecting adult individuals all over the world, being considered a real worldwide pandemic. This disease may influence the progression of certain systemic diseases: diabetes mellitus, cardiovascular diseases, ischemic cardiomyopathy, myocardial infarction, stroke, neurodegenerative diseases, chronic kidney diseases, cancer, etc. The association between smoking and periodontal disease was described in numerous clinical and epidemiological studies, suggesting that products derived from tobacco burning may change the clinical aspects and the disease progression. The present study analyzed microscopically and immunohistochemically 58 periodontal fragments, from 50 patients, chronic smokers, clinically diagnosed with severe periodontitis. There were highlighted major changes in the gingival epithelium (epithelium thickening, acanthosis, intraepithelial edema, infiltrates of neutrophils or lymphocytes, epithelial necrosis), in the periodontal conjunctive tissue (more or less intense inflammatory infiltrates, microhemorrhages, vascular congestion, intense immunohistochemical expression for some matrix metalloproteinases). The periodontal changes may be the expression of both toxic factors present in tobacco smoke and due to the changes caused by tobacco in the microbial flora of the oral cavity.

Turner syndrome (TS) is characterized by partial or complete loss of a sexual chromosome, resulting in an incomplete development of the body, gonadic failure, cardiac and renal abnormalities, oro-dental changes, etc. In our study, we proposed to perform a histological and immunohistochemical (IHC) study of the periodontium changes in patients with TS. The biological material under study was represented by fragments of gingival mucosa harvested from 18 patients with TS who presented advanced periodontal lesions and required dental extractions. The fragments of gingival mucosa were processed by the classical histological technique of paraffin inclusion, subsequently the obtained sections being stained by the Hematoxylin–Eosin (HE) and examined under the optical microscope. For the IHC study, there were performed serial sections incubated with anti-cluster of differentiation (CD) 3, anti-CD20 and anti-CD68 antibodies for highlighting immune cells, as well as with anti-matrix metalloproteinase (MMP) 2 and anti-MMP8 antibodies for highlighting MMPs (MMP2 and MMP8) involved in the periodontal tissue lesions. In the present study, during the histological examination, there were observed morphological changes, both in the epithelium and in the gingival mucosa chorion. Epithelial changes consisted in the onset of acanthosis processes, in the thickening of the epithelium due to the increase of the spinous layer, as well as in the parakeratosis phenomenon. In the chorion, there was observed the presence of inflammatory infiltrates in various stages, presence of fibrosis (extended in some cases) and the presence of an important vascularization in some cases, with a high number of immunocompetent cells involved in the inborn immune response, but also in the adaptive one, as well as a more or less intense immunoexpression of MMP2 and MMP8. Our study suggests that TS may contribute to the development of some inflammatory processes in the marginal periodontium.

A 67-year-old man with non-small-cell lung carcinoma was referred to our department because of a pruritic rash on his head and upper extremities. Prior to the development of the rash, he had received 4 cycles of combination therapy with pemetrexed, carboplatin, and pembrolizumab, followed by 2 cycles of pembrolizumab monotherapy. On physical examination, violaceous scaly erythema grouped on his scalp and upper extremities. Histologically, the scalp lesions demonstrated irregular acanthosis that formed a characteristic saw-tooth appearance with hypergranulosis and typical lichenoid tissue reaction. These findings suggested that the scalp lesions were lichen planus. Two-week administration of topical corticosteroid dramatically improved the rash. Immunotherapy with pembrolizumab, an anti-PD-1 antibody, can induce T-cell activation that results in various immune-related adverse effects such as lichenoid tissue reaction. However, lichen planus is generally found on the extremities and/or oral mucosa, and unlike in this case, the scalp is rarely affected. Although the exact mechanism underlying predominant scalp involvement is unknown, the present case indicates that anti-PD-1 therapy-induced lichen planus can develop not only on the extremities and oral mucosa but also on the scalp. Interestingly, the lesions were not induced by the combination of chemotherapy and pembrolizumab; rather, they occurred soon after initiation of pembrolizumab monotherapy. In the present case, pembrolizumab-induced T-cell activation which triggered lichenoid tissue reaction may have been suppressed by chemotherapy-induced immunosuppression. Dermatologists should have a thorough knowledge of the cutaneous lesions that manifest as irAEs of anti-PD-1 therapy.

AIMS Most vulvar squamous cell carcinomas are human papillomavirus (HPV)-associated or TP53-mutant. A third category of HPV-independent TP53-wild-type lesions is uncommon and not fully understood. Differentiated exophytic vulvar intraepithelial lesion (DEVIL) has been characterised as a precursor of this latter category. The reproducibility of the diagnosis of DEVIL and its distinction from lesions with overlapping morphology has not been studied. Our aim was to establish the interobserver agreement in the diagnosis of DEVIL and its distinction from neoplastic and reactive conditions of the vulva on haematoxylin and eosin evaluation. METHODS AND RESULTS A set of 35 slides was evaluated by eight reviewers (two trainees and six practising gynaecological pathologists). The set included DEVIL, condyloma, established vulvar precursors [high-grade squamous intraepithelial lesion (HSIL) and differentiated vulvar intraepithelial neoplasia (dVIN)] with superimposed acanthosis or verruciform growth, lichen simplex chronicus (LSC), and psoriasis. Kappa (κ) values were calculated. Overall, interobserver agreement was moderate (κ = 0.56), improving to substantial (κ = 0.7) when evaluation was performed by practising pathologists. Agreement was strong for the diagnosis of HSIL (κ = 0.88), and substantial for the diagnosis of DEVIL (κ = 0.61), condyloma (κ = 0.79), and LSC (κ = 0.72). Agreement was moderate for the diagnosis of dVIN (κ = 0.59) and psoriasis (κ = 0.53). Perfect agreement (6/6) among practising pathologists was observed in 43% of cases, and majority agreement (5/6 or 4/6) was observed in 48% of cases. CONCLUSIONS Reproducibility in the diagnosis of verruciform vulvar lesions, including the novel DEVIL, is acceptable overall. Reproducibility is higher for well-known lesions such as HSIL and condyloma than for more challenging diagnoses such as DEVIL, dVIN, and psoriasis. Agreement is higher among practising gynaecological pathologists, suggesting that training and experience improve reproducibility. Our findings support the inclusion of DEVIL as a diagnostic entity in the classification of vulvar squamous lesions.

Aim to evaluate the correctness of the diagnosis of lichen sclerosus with an evaluation of complications in the form of urethral strictures and to ensure long-term monitoring of patient management in order to avoid recurrence of fibrous complications and ascending infection in case of lower urinary tract obstruction. Material and methods a total of 55 men aged from 17 to 85 years with lichen sclerosus complicated by urethral stricture who were treated from 2005 to 2020 were included in the study. All patients underwent a comprehensive urological examination. From them, 18 (32.7%) patients had previously undergone various types of urethral procedures and were admitted with recurrent urethral stricture for repeated surgery. Results an examination of patients with lichen sclerosus complicated by urethral strictures is presented, including a morphological assessment of the resected tissue and analysis of etiopathogenetic factors. In addition, the results of complex treatment of patients with urethral strictures associated with sclerosus were evaluated. An increase in the maximum urine flow rate and a decrease in post-void residual volume by almost three times was noted 1-3 months after urethroplasty. After 6 months, a recovery of an adequate micturition and complete absence of residual urine were revealed. The morphological picture in patients with urethral strictures associated with lichen sclerosus is characterized by focal atrophy of the epidermis, replacement of the columnar epithelium with a stratified epithelium with signs of hyperkeratosis and acanthosis, histiolymphocytic infiltration, and the formation of microcalcifications under the basement membrane. Conclusion the correctness of the diagnosis verification and the choice of the treatment strategy in patients with urethral strictures caused by lichen sclerosus significantly contributes to the favorable outcomes. Based on comparative analysis, we can conclude than complex approach to the treatment of patients with urethral strictures associated with lichen sclerosus is highly effective.

The skin is the largest organ of the body that has many functions. Canine dermatology remain a challenging field that requires a variety of knowledge as dermatological problems are reported to be the most common health problem in small animal practice. Blood, skin and biopsy samples were collected from 50 dogs of different breeds and sexes. The present study is designed for identification of the different etiological agents causing skin diseases in dogs, evaluation of some hematological and biochemical parameters in diseased dogs and histopathological examination of selected cases using skin biopsy. These dogs were grouped into two groups, the first one was the control group (n=10) apparently healthy dogs and the second group (n=40) diseased dogs presented with different skin ailments where 12 out of 40 dogs were suffered from demodicosis, dermatophytosis (6 cases), pyoderma (8 cases) , mixed infection (10 cases) and canine atopic dermatitis (4 cases). Evaluation of the hematological parameters revealed presence of anemia and leukocytosis with apparent neutrophilia in dogs with pyoderma and eosinophilia in the other groups. Biochemical parameters lied within the reference range in all diseased groups. Staphylococcus spp. was the most common bacterial isolate in canine pyoderma. With respect to histopathological picture, results indicated presence of large focal area of epidermal liquefactive necrosis associated with dense neutrophils infiltration. Severe dermatitis, folliculitis, perifollicular and perivascular inflammatory cells infiltration, all these changes associated with cases of pyoderma. Demodicosis cases demonstrated as heavy mite infestation in different developmental stages in the stratum conium of the epidermis and in the follicles. Laminar orthokeratotic hyperkeratosis, vacuolated epidermal prickle cells, acanthosis and vaculation of keratinocytes of the infundibula. Dermatitis characterized by moderate to marked inflammatory infiltration. Necrosis of adnexa, folliculitis and perifollicultis were also recorded in demodecosis infected dogs. Fungal dermatosis showed pronounced laminar orthokeratotic hyperkeratosis and acanthosis. Vacuolar degeneration of keratinocytes and fungal Hyphae were seen in dermatophytosis infected dog. Ulcerative dermatitis in form of focal extensive area of epidermal necrosis and ulceration associated with inflammatory cells infiltration, acanthosis and spongiosis of prickle cell layer were noticed in mixed infection infected dogs. The most common infectious skin problems during our study were pyoderma, red mange and dermatophytosis. The predominant pathogen in pyoderma affected dogs was Staphylococcus spp. Histopathological examination was very useful in our study as they provide accurate diagnosis in a short period of time and help in clear visualization of the clinical picture.

Psoriasis, an immune-mediated inflammatory disease, is characterized by keratinocyte hyperproliferation. Tumor necrosis factor (TNF)-alpha, interleukin (IL)-23, and IL-17A play critical roles in the pathogenesis of psoriasis. IL-17A secreted by T-helper 17 acts more directly against keratinocytes than TNF-alpha or IL-23 do. Regarding the receptors of cytokines, fibroblasts also express receptors against IL-17A and TNF-alpha, and induce the production of growth factors. Epiregulin (EREG), an epidermal growth factor receptor ligand, is produced by both keratinocytes and fibroblasts. EREG enhances keratinocyte proliferation and differentiation. We hypothesized that fibroblasts stimulated with IL-17A and/or TNF-alpha may play a role in epidermal hyperproliferation through the production of epidermal growth factors in psoriasis. The mRNA expression of EREG was found to be significantly upregulated by co-stimulation with IL-17A and TNF-alpha (mean, 49.2-fold). Furthermore, the stimulation with TNF-alpha alone, but not IL-17A alone, induced significant increases. Immunofluorescent staining demonstrated that the protein expression level of EREG was also increased in fibroblasts stimulated with these cytokines. Stimulation with EREG significantly enhanced keratinocyte proliferation in vitro. In human psoriatic patients' skin, immunofluorescence staining of EREG showed significantly high intensity in the dermis of lesional skin. In conclusion, cytokine stimulation with TNF-alpha and IL-17A induces the overexpression of EREG from dermal fibroblasts in the lesional skin of psoriasis, and plays a role in epidermal hyperproliferation.

Annually recurring erythema annulare centrifugum (AR-EAC) is a rare variant, characterized by typical annular plaques recurring in the same period of the year. We describe 5 new cases and present a review of the literature. Patients were 3 females and 2 males with an age range of 25–55 years. Multiple annular plaques were located at the thighs in 4 patients and the neck in one patient. In 1 patient, a single lesion was present. Plaques were recurring in summer in 3 cases; in 1 case, in spring; and another patient, in winter since 3–4 years. Lesions were self-healing in few days or weeks. Histologically, the epidermis presented mild acanthosis with patchy spongiosis, slight parakeratosis, and mild exocytosis. There was a perivascular lympho-histiocytic infiltrate of variable intensity in the superficial dermis, with occasional eosinophils. In 1 case, the inflammatory infiltrate reached the deep dermis. Mucin deposition was absent. Phenotyping studies in 1 case revealed a predominance of T cells, with a small B-cell component. Moreover, a moderate number of CD123+ plasmacytoid dendritic cells and CD1a+ dendritic cells were noted. Fourteen cases of AR-EAC have been published previously. Collectively, patients’ age ranged from 16 to 83 years, with a mean age of 47 years and a disease duration of 1–30 years. Lesions affected more frequently extremities and recurred most commonly in summer. Patients were all in good general health. Topical corticosteroids were the mainstay of treatment. AR-EAC is a benign disorder, the nature of which remains enigmatic.

BACKGROUND Angiofibromas are common benign skin lesions that are diagnosed clinically and histopathologically. Fibrous papule (FP) is one of the clinical types of angiofibromas located primarily on the nose. METHODS The cases with the confirmed diagnosis of angiofibroma were enrolled. Demographic features of the patients and clinical characteristics of the lesions were extracted. Moreover, histopathological features of the available slides were microscopically reviewed. RESULTS From 83 cases of cutaneous angiofibromas, 57 (69%) had lesions consistent with FP. The mean age at diagnosis was 37.7 ± 16.3 years and the most common site of involvement was the nose (53% of cases). Regarding the histopathological evaluation of 71 slides, most cases represented vascular changes (97%) and dermal fibroplasia (87%). Melanin incontinence (41%), acanthosis (31%), and lichenoid features (25%) were other common histopathological findings. Moreover, a sparse inflammatory cell infiltrate was present in 68% of cases. The most prevalent inflammatory cells were lymphocytes (61%) and histiocytes (34%). CONCLUSION This study presented the histopathological findings of a series of cutaneous angiofibromas. Dermatopathologists should be aware of these features, especially those that are less common, to better diagnose and differentiate them from malignant neoplasms.

Lichen planus is a traumatic (koebner positive), chronic, inflammatory and autoimmune disease affecting the oral and genital mucosa, scalp and nails. The Food and Drug Administration approved the use of medical leeches for therapeutic purposes (hirudotherapy) in 2004 to ensure flap nutrition in plastic surgery. A 34-year-old male patient was admitted to our dermatology outpatient clinic with a swollen, itchy and purple-coloured rash on legs and back for a month, and white and reticulated plaques in the mouth. It was learned that a week earlier, eight leeches was applied to both knees and ankles to alleviate knee and leg pain. The patient had no history of drug use. A punch biopsy was taken from the patient with a preliminary diagnosis of lichen planus and lichenoid drug reaction. The histopathological examination showed hyperkeratosis, irregular acanthosis and hypergranulosis. Systemic methylprednisolone, levocetrizine and topical methylprednisolone aceponate were planned for the therapy. To the best of our knowledge, the appearance of lichen planus after hirudotherapy was never reported in literature. Hence, physicians should keep in mind that lichen planus and similar dermatoses could be triggered due to hirudotherapy. The fact that lichen planus appeared a week after hirudotherapy does not necessarily mean that leeches were the cause of this phenomenon. Accordingly, it could be deduced that lichen planus was probably developed as a result of leech therapy.Liken planus oral ve genital mukoza, saçlı deri ve tırnakları ekileyen travma ile tetiklenen (koebner pozitif) kronik, enflamatuvar, otoimmün bir hastalıktır. Tıbbi sülüklerin iyileşme amaçlı kullanımı (hirudoterapi) plastik cerrahide flep beslenmesini sağlamak için 2004 yılında Gıda ve İlaç İdaresi tarafından onaylanmıştır. Otuz dört yaşında erkek hasta, bir ay boyunca bacaklarda ve sırtında kabarık, kaşıntılı, mor renkli döküntü ve ağızda beyaz ağsı plaklarla dermatoloji polikliniğimize başvurdu. Başka ilaç kullanım öyküsü yoktu. Liken planus ve likenoid ilaç reaksiyonu ön tanısı alan hastadan punch biyopsisi alındı. Histopatolojik incelemede hiperkeratoz düzensiz akantoz ve hipergranüloz görüldü. Tedavi için sistemik metlprednizolon, levosetrizin ve topical metilprednizolon aseponoat planlandı. Bildiğimiz kadarıyla hirudoterapi sonrası liken planus literatürde daha önce bildirilmemiştir. Hirudoterapiye bağlı olarak liken planus ve benzeri dermatozların tetiklenebileceği daima akılda tutulmalıdır. Liken planusun hirudoterapiden bir hafta sonra ortaya çıkması, sülüklerin bu fenomenin mutlak nedeni olduğu anlamına gelmez. Buna göre liken planusun muhtemelen sülük tedavisinin bir sonucu olarak geliştiği söylenebilir.

Microsporіа affect different species of animals and humans. The high contagiousness of the pathogen determines the relevance of research into this disease. Microsporum canis is the pathogen that most often causes microsporia. Weakened functions of the immune system and violation of the epithelial barrier of the skin are a favourable factor that causes microspores. The main source of infection is cats, which are involved in the storage and transmission of the pathogen. To clarify the dynamics of morphological, immunological and histological changes in microsporia, blood and skin studies of guinea pigs infected with M. canis were carried out. The animals were divided into two groups of 6 guinea pigs (healthy and sick). Test material (blood and skin) was taken from clinically healthy and sick animals 21 and 42 days after infection. The number of erythrocytes and leukocytes was determined by counting them in the Goryaev chamber, the hemoglobin content – by the method of cyanide hemoglobin. The leukogram was derived based on the counting and differentiation of 200 leukocyte cells in blood smears. Material for histological examination (pieces of skin) was fixed in 10–12% cooled solution of neutral formalin, followed by pouring in paraffin according to the scheme proposed by G. A. Merkulov. The obtained results demonstrated that leukocytosis developed in guinea pigs with microsporia on the 21st and 42nd days; the number of rod-shaped neutrophils increased, that of segmental neutrophils decreased, and that of ESR increased. The immune response to the course of microsporia was manifested in an increase in the percentage of T-lymphocytes, T-suppressors and a decrease in T-helper cells and an increase in T-killers compared with healthy animals. Histological examination showed that on the 21st day after infection, hyphae and spores of the fungus M. canis were localized in the skin. There is swelling of the dermis, stratification of collagen fibers and the accumulation of inflammatory infiltrates around the hair follicles. On the 42nd day, the infiltration spread and dystrophic changes in the skin occurred in the form of desquamation of the epidermis and the formation of acanthosis and hyperkeratosis on the surface of the dermis. The conducted research will allow further assessment of the course of microsporia under the action of various drugs and help establish the most effective method of treatment.

This study aimed to describe the first reports of outbreaks of hepatogenous photosensitization in cattle, sheep, and horses caused by spontaneous ingestion of Chamaecrista serpens, as well as to reproduce poisoning in sheep experimentally. Eleven photodermatitis outbreaks of unknown cause occurred in cattle, sheep and horses on nine farms in the semiarid region of Bahia, northeastern Brazil, between July 2017 and July 2020. Cutaneous lesions of photosensitization initiated until one week after the animals were introduced in paddocks invaded by the plant at the beginning of the rainy season. The photosensitive skin lesions were progressive and consisted of hyperemia, edema, ulcerative-crusted lesions with necrosis, especially in non-pigmented skin areas. The lesions in young animals were more severe. The animals avoided the sun and exhibited hyporexia, weight loss, restlessness, irritability, and severe itching. An experimental study was made using seven sheep, and resulted in photodermatitis, similar to that observed in the natural poisoning, seven days after the beginning of plant ingestion. Two sheep were reserved for the control group. Serum biochemistry changes indicated liver injury caused by the plant. Skin biopsies and liver biopsy guided by ultrasound were performed. The one sheep that had more pronounced skin lesions was euthanized and necropsied. At the necropsy, the liver was enlarged, diffusely pale, and firm, with an evident lobular pattern and an empty gallbladder. Histopathology revealed similar skin and liver lesions in samples from biopsies and the necropsy. There was a marked disorganization of the cords of hepatocytes associated with degenerative necrotic changes on the liver. The cutaneous injuries included orthokeratotic hyperkeratosis, hypergranulosis, acanthosis, and extensive areas of epidermic necrosis and ulceration. Three sheep were protected from sunlight and the lesions regressed within 45 days after the plant's consumption ceased. In conclusion, C. serpens causes hepatogenous photosensitization in ruminants and horses, and should be included in the list of differential diagnoses in cases of photosensitive dermatitis.

Background and Aim: Lichen planus (LP) is an immunological disease of skin and mucous membranes. Cutaneous and oral LP (CLP and OLP) have almost similar histopathological changes determined microscopically with symptoms such as basal cell layer degeneration, hyperkeratosis, band-like infiltration of lymphocytes, and saw tooth ridges. The present study aimed to determine the frequency and compare the histopathological features of OLP and CLP samples. Materials and Methods: This was a descriptive-analytical, and cross-sectional research performed on 91 paraffin-embedded tissue blocks (41 OLP lesions and 50 CLP lesions). The frequency of histopathological features was determined by an optical microscope, and data analysis was performed in SPSS version 21 using descriptive statistics (frequency and percentage) and Chi-square. Results: In this study, the frequency of LPs was higher in female subjects, compared to male participants. The frequency of histopathological features of hyperkeratosis, acanthosis, spongiosis, and epithelial hypertrophy was significantly higher in CLP samples, compared to OLP lesions (P

Seborrheic keratoses (SK) are benign skin tumor characterized by well-demarcated and skin-colored to pigmented papules, plaques, or nodules with stuck-on appearance. Typical SKs are normally treated for cosmetic reasons. However, total excision and histopathological examination have to be considered in SK with unusual properties. The island pedicle flap (IPF) is a method of flap for defect closure, especially on the cheek. It has the capability to maintain the vascularization, thus it is also suitable in the elderly. We report a case of an SK with atypical clinical presentation in a 69-year-old female, with a solitary enlarging, hyperpigmented, verrucous, and bleeding tumor. The dermoscopic examination did not show characteristic features of SK. Total excision was performed due to its clinical properties. The histopathological examination revealed hyperkeratosis, acanthosis, hyperplasia, and papillomatosis, along with intercellular pseudo-horn cyst which confirmed the diagnosis of SK. The patient underwent total excision of the skin lesion which left a primary defect. We performed IPF procedure to reconstruct the defect after total excision of the skin lesion. After a year of follow-up, no meaningful complication was detected. The final result of the procedure was satisfying due to its ability to restore the natural contour and texture match by utilizing cheek laxity, without interfering the nasolabial fold. In conclusion, IPF is an appropriate method for defect closure in an elderly patient after facial total tumor excision.

Pemphigus vulgaris (PV) is an anti-cadherin autoimmune disease, characterized by the production of anti-desmoglein 3 (and to a lesser extent anti-desmoglein 1) antibodies, producing acanthosis, typically suprabasal, which clinically translates into flaccid blisters and erosions, generally starting on mucous membranes, with subsequent appearance of skin lesions. Only about 25 cases of PV of exclusively cutaneous location have been described in the literature. Treatment with potent topical steroids is usually sufficient to control the symptoms. We present the case of a 68-year-old female patient with localized PV in the scalp, presenting as alopecic and scabby plaque, with excellent response and hair regrowth with topical corticotherapy.

Human papillomavirus (HPV)-independent vulvar squamous cell carcinoma (VSCC) is an aggressive clinical entity. Current diagnostic guidelines for premalignant lesions are ambiguous, and their molecular profile and progression events are still unclear. We selected 75 samples, from 40 patients, including 33 VSCC, 8 verrucous carcinomas (VC), 13 differentiated-type vulvar intraepithelial neoplasia (dVIN), 11 suspicious for dVIN (?dVIN), 6 differentiated exophytic vulvar intraepithelial lesions (DE-VIL), 2 vulvar acanthosis with altered differentiation (VAAD), and 2 usual-type vulvar intraepithelial neoplasia (uVIN/HSIL). Invasive and precursor lesions were matched in 29 cases. Clinical information, p16 immunohistochemistry, and mutation analysis were performed on all lesions. All dVIN, ?dVIN, DE-VIL, and VAAD were p16 negative, all uVIN/HSIL were p16 positive. In the HPV-independent group, mutations were identified in 6 genes: TP53 (n = 40), PIK3CA (n = 20), HRAS (n = 12), MET (n = 5), PTEN (n = 4), and BRAF (n = 1). TP53 mutations occurred in 73% (22/30) VSCC, 85% (11/13) dVIN, 70% (7/10) ?dVIN and no VC (0/8), DE-VIL (0/6) nor VAAD (0/2). Basal atypia was the only reliable feature of TP53 mutations. ?dVIN lesions that were non-acanthotic and atypical but obscured by inflammation, all harbored TP53 mutations. In lesions without TP53 mutations, PIK3CA (50% VC, 33% DE-VIL, 100% VAAD, 40% VSCC) and HRAS (63% VC, 33% DE-VIL, 0% VAAD, 20% VSCC) mutations were found. Mutational progression from in situ to invasive was seen (7/26, 27%) and usually involved TP53 (4/26, 15%). Cases with TP53 and PIK3CA co-mutations had the worse clinical outcomes (p

Precursor lesions of vulvar squamous cell carcinoma (VSCC) can be divided into two major biologic and prognostic groups: HPV-associated and HPV-independent VSCC. These two pathways are categorized as usual vulvar intraepithelial neoplasia (uVIN) with progression to basaloid or warty VSCC and differentiated vulvar intraepithelial neoplasia (dVIN) with progression to the more common keratinizing VSCC. While the HPV-dependent pathway to squamous cell carcinoma is well-understood, the development of squamous cell carcinoma from HPV-independent lesions is less clear. The majority of HPV-independent lesions fall into the dVIN category, and mutations in TP53 have been implicated as the driver behind their development. Other less common HPV-independent precursor lesions, termed differentiated exophytic vulvar intraepithelial lesion (DEVIL) and vulvar acanthosis with altered differentiation (VAAD), have also been characterized as precursors to keratinizing and verrucous VSCC. Inflammatory conditions of the vulva such as lichen sclerosus and lichen simplex chronicus also put patients at risk for developing VSCC. We herein evaluate the available evidence and biologic basis for these VSCC precursor lesions, among other speculated entities, and discuss their clinical, diagnostic, and prognostic features.

Relevance. The relationship between endocrinopathies and the condition of the oral cavity is associated with disorders of metabolism, hemodynamics, immunological and neuroregulatory changes. Since the first line of contact with the environment of the oral cavity is the mucous membrane, changes in its properties adversely affect the functional state of other periodontal tissues. Objective: to examine the structural changes of the oral mucosa in rats with combined endocrinopathy. Materials and methods. The studies were carried on 120 rats, which were divided into three experimental (animals with iodine deficiency – ID, insulin resistance – IR, IR on the background of ID) and a control group of animals. Histological examination of the oral mucosa, computer morphometry, and densitometry of objects was performed. Results. In rats with ID, the epithelium of the mucous membrane was characterized by the development of acanthosis, expansion of the granular layer, enhanced keratin formation. The development of IR caused hyperplastic changes in the epithelium with the formation of unexpressed cords of acanthosis, epithelial basal hypercellular infiltration, which was confirmed by morphometric data. Under conditions of combined endocrinopathy, more pronounced changes in the histological structure of oral mucosa were observed. In particular, the development of mucosal edema in connective tissue, with predominantly macrophage hypercellularity at the periphery, was noted. Densitometric examination of the samples indicated a decrease in the optical density of connective tissue. At the same time, hyperplastic changes in most layers of the epithelium and pronounced changes in the vascular wall were observed. Conclusions. Combined endocrinopathy leads to pronounced changes of the oral mucosa, which can lead to disruption of the structure of periodontal tissues and the entire tooth-alveolar complex.

Background Inflammatory linear verrucous epidermal nevus (ILVEN) is a rare type of epidermal nevus that occurs in infancy and develops along Blaschko's lines. Due to its rarity and clinical/histological similarities with other cutaneous disorders, correct diagnosis is sometimes difficult. In the present case, the whole exome sequencing of blood found no germline mutation, but the sequencing of the biopsy specimen revealed a novel potential pathogenic somatic mutation, C > T at rs200881715 (p.R698X) in the cspp1 gene, which may provide new insight into the mechanism of ILVEN. Patient concerns A 10-year-old girl presented with linear, pruritic, erythematous, scaly, and exophytic verrucous skin lesions on her left thigh, buttock, and hand unilaterally along Blaschko's lines from the third day after birth. Diagnosis Biopsy revealed psoriasiform acanthosis, papillary hyperplasia with orthohyperkeratosis, and parakeratosis of squamous epithelium, which are histological characteristics of ILVEN. Interventions Owing to the large lesion size and significant refractory response to previous treatments, multiple-stage surgical resections with a tissue expander were performed. Outcomes After surgical resection and defect reconstruction with a tissue expander, the outcome was satisfactory for the patient and her family. No recurrence was detected during the follow-up visits. Conclusion ILVEN is a rare type of cutaneous hyperplastic disease, and treatment is extremely challenging. Biopsy should be performed at the diagnostician's discretion or if refractory to conservative treatments. Timely diagnosis and surgical intervention could result in satisfactory outcomes.

A 29-year-old woman presented with dark-colored raised lesions on both eyelids since early childhood. Ophthalmological examination revealed pigmented verrucous lesions on her upper and lower eyelids bilaterally. The patient had a history of generalized tonic-clonic seizures. Dermatological examination revealed hyperpigmented verrucous plaques arranged along lines of Blaschko on the neck, trunk, and arms. On the basis of these findings, the diagnosis of epidermal nevus syndrome (ENS) was made. She had surgery for debulking of the lesions. Histological analysis revealed hyperkeratosis with foci of parakeratosis, acanthosis, and papillomatosis, consistent with linear verrucous epidermal nevus. Postoperative residual lesions did not respond to oral acitretin therapy (10 mg/kg/day for 2 months). Systematized ENS can rarely cause linear verrucous nevi on the upper and lower eyelids on both sides. These patients should be investigated for accompanying systemic anomalies and followed for potential malignant transformation of the skin lesions.

Background : Psoriasis is a common disease of unknown etiology, worldwide in distribution affecting men and women of all ages, races, and social strata. Psoriasis has diverse clinical variations, which mimic varied dermatological conditions and might need a histopathological confirmation of the diagnosis. Clinical and histopathological features have not been extensively studied in the Indian population. Aims : To study the clinical and histopathological features of psoriasis. Materials and Methods : This was a retrospective observational, single Centre study. 276 patients with psoriasis confirmed by biopsy were taken up for the study. Age, sex, duration, site of lesions, type of psoriasis, and individual histopathological parameters of psoriatic lesions were noted from the data and analyzed. Results : The majority of patients belonged to the fourth decade with male preponderance. Chronic plaque psoriasis was the most common type, followed by palmoplantar psoriasis. Following histopathological features were seen, hyperkeratosis (85%), parakeratosis (72%), acanthosis (81%), hypogranulosis (53%), agranulosis (17%), hypergranulosis (12.7%), normal granular layer (10%), suprapapillary thinning (42%), elongation of rete ridges (73%), Munro micro abscess (34%), spongiform pustule of Kogoj (30%), capillary dilatation (90%) and lymphocytic dermal infiltration (97.8%). Conclusion : Diagnostic features of psoriasis in histopathology are not present in all the cases. Features of psoriasis are variable clinically and even in histopathology. Hence it is the combination of histopathological features of psoriasis with the clinical correlation that helps the physician to arrive at the diagnosis in doubtful cases. Keywords: Psoriasis, Histopathology, Hypogranulosis, Capillary dilatation, Munro microabscess.

Verruciform proliferations of the vulva unrelated to HPV infection are rare. The term differentiated exophytic vulvar intraepithelial lesion (DEVIL) was recently proposed for these lesions, which harbor recurrent PIK3CA mutations. It is still unclear whether DEVIL is related to verrucous carcinoma, a neoplasm characterized by persistence and local recurrence but nil risk of distant spread. Specimens identified using the words “verruciform” and “verrucous” were reviewed. Diagnosis of DEVIL required verruciform acanthosis, hyper and/or parakeratosis, hypogranulosis, cytoplasmic pallor, and bland nuclei. Verrucous carcinoma required, in addition, discontinuous, bulbous, puzzle-like nests in the stroma. A targeted next-generation sequencing using a custom 11-gene panel was performed. Eighteen specimens corresponding to ten patients with DEVIL and/or verrucous carcinoma were included. Median age at presentation was 66 years for DEVIL and 70 years for verrucous carcinoma. A similar spectrum of prevalent mutations was found in both lesions involving HRAS, PIK3CA, and BRAF. DEVIL preceded verrucous carcinoma and/or was diagnosed concurrently or in subsequent follow-up in five patients. In four of these, the same mutation was identified in DEVIL and synchronous or metachronous carcinoma. All cases showed wild-type 53 staining and lacked pathogenic TP53 mutations. DEVIL is a rare form of squamous proliferation characterized by prevalent PIK3CA and HRAS mutations. Its temporal relationship with verrucous carcinoma and their shared mutational profile in some patients suggest that DEVIL is a precursor of verrucous carcinoma. Moreover, given their morphologic and molecular overlap and the nil risk of verrucous carcinoma for distant spread, it is conceivable that DEVIL and verrucous carcinoma represent a spectrum of the same entity.