Review: A Contemporary, Multifaced Insight into Psoriasis Pathogenesis.

Psoriasis is a chronic recurrent inflammatory autoimmune pathology with a significant genetic component and several interferences of immunological cells and their cytokines. The complex orchestration of psoriasis pathogenesis is related to the synergic effect of immune cells, polygenic alterations, autoantigens, and several other external factors. The major act of the IL-23/IL-17 axis, strongly influencing the inflammatory pattern established during the disease activity, is visible as a continuous perpetuation of the pro-inflammatory response and keratinocyte activation and proliferation, leading to the development of psoriatic lesions. Genome-wide association studies (GWASs) offer a better view of psoriasis pathogenic pathways, with approximately one-third of psoriasis's genetic impact on psoriasis development associated with the MHC region, with genetic loci located on chromosome 6. The most eloquent genetic factor of psoriasis, PSORS1, was identified in the MHC I site. Among the several factors involved in its complex etiology, dysbiosis, due to genetic or external stimulus, induces a burst of pro-inflammatory consequences; both the cutaneous and gut microbiome get involved in the psoriasis pathogenic process. Cutting-edge research studies and comprehensive insights into psoriasis pathogenesis, fostering novel genetic, epigenetic, and immunological factors, have generated a spectacular improvement over the past decades, securing the path toward a specific and targeted immunotherapeutic approach and delayed progression to inflammatory arthritis. This review aimed to offer insight into various domains that underline the pathogenesis of psoriasis and how they influence disease development and evolution. The pathogenesis mechanism of psoriasis is multifaceted and involves an interplay of cellular and humoral immunity, which affects susceptible microbiota and the genetic background. An in-depth understanding of the role of pathogenic factors forms the basis for developing novel and individualized therapeutic targets that can improve disease management.

Immunoexpression of Ki67, P16 and Beta-catenin in precursor lesions of cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma (CSCC) is the second most common type of skin cancer, after basal cell carcinoma, representing about 10-20% of all malignant skin tumors. The mortality rates of CSCC approach those of renal and oropharyngeal carcinomas, as well as melanoma, with the increasing of the risk once metastases and perineural invasion occur. Both actinic keratosis (AK) and Bowen's disease (BD) are direct precursors with the potential for progression to CSCC. In this study, we analyzed the expression of Ki67, P16 and Beta-catenin in the precursor lesions of CSCC in relation to histological prognostic parameters, respectively between them, with the aim of identifying possible correlations with a role in prognosis. Ki67 and P16 presented higher scores in advanced precancerous lesions, such as keratinocyte intraepithelial neoplasia (KIN) III and BD and low scores in seborrheic keratosis (SK). The immunoreactivity to the investigated markers confirms the multistage skin carcinogenesis, and their involvement starting from the initiation phase of the cancer process. The importance of the studied markers in the evolution and prognosis of precancerous lesions of CSCC is also supported by the linear correlations revealed between the immunoexpressions of P16, Ki67 and the membranous immunoexpression of Beta-catenin in AK.

Cutaneous Malignant Melanoma Metastatic to the Larynx and Trachea: A Case Report and Review of the Literature.

Malignant melanoma rarely develops in mucous membranes. Statistical data show that approximately 0.6-9.3% of patients with cutaneous malignant melanoma will develop metastases in the upper aerodigestive tract mucosa, and within these metastatic sites, the least common are the laryngeal and tracheobronchial ones. This exceedingly rare clinical entity has no clear treatment recommendations; radical surgery does not seem to benefit the patient in term of life expectancy. We present the case of a 56-year-old male patient diagnosed with laryngeal and tracheobronchial melanoma metastases. Prior to admission to our clinic the patient had a personal history of malignant melanoma of the nuchal region operated on 7 years ago, malignant melanoma of the gallbladder and metastatic left axillary polyadenopathy for which he underwent surgical treatment 3 months prior. Histopathological and immunohistochemical reports established the diagnosis of laryngeal metastasis of malignant melanoma. Genetic molecular analysis was positive for B-Raf (BRAF) gene and hence Vemurafenib was administered, with a favorable outcome at the one-year follow-up. Nevertheless, there are currently no clear universally accepted guidelines for the treatment of laryngeal melanoma, mainly due to the rarity of this clinical entity. We conducted a review of similar cases reported in the literature. Interestingly, reviewing the cases reported in the literature, it appears that laryngeal metastases of a primary cutaneous melanoma are more common in men, with an average time to metastasis of 4.3 years.

A rare subcutaneous periorbital zoonotic infection in a 42-year-old female patient.

Human dirofilariasis represents a zoonotic infectious disorder caused by parasites belonging to the Dirofilaria genus, which includes numerous species with a large variability regarding the host specificity, life cycle, and clinical manifestations. This disease appears to be a vector-borne parasitosis that is spread through insects - intermediate hosts (usually mosquitos) - and affects several carnivores as definitive hosts. Humans represent an unsuitable host for the parasite to complete its life cycle, being unable to release microfilariae in the blood as the inoculated larvae fail to reach sexual maturity. Therefore, humans are unable to transmit the infection to other humans, neither directly nor through an intermediate host. The current case report indicates a rare encounter of a Dirofilaria repens infection in a 42-year-old female patient living in an urban area (Craiova, Romania), who developed intermittent right periorbital edema after a previous trip to Greece. Over the course of one month, the right periorbital edema gradually remitted, and a firm, round lump developed in the external inferior right periorbital region. There were no similar clinical manifestations among other family members. Her medical history showed no other complaints or any serious general health problems. Also, the patient denied having any pets at home. The blood tests did not reveal any abnormalities. The exact source of infection could not be identified, but the chances for this infection to be related to the history of traveling to Greece are high, given that this region is one of the most important endemic areas in Europe.

Atopic Dermatitis with Multiple Comorbidities Treated with Dupilumab. A Case Report and Review of the Literature Regarding the Safety of Dupilumab.

Dupilumab is the only available biological treatment for moderate-to-severe atopic dermatitis (AD). Even so, limited clinical data regarding its safety profile are available. Interactions with other drugs and the adverse effects of Dupilumab on patients with multiple comorbidities, such as chronic heart disease, diabetes, chronic kidney disease, etc., are not known yet. Moreover, there have been described cases of cutaneous lymphomas induced by Dupilumab. Therefore, the clinician that wants to start treatment for moderate-to-severe atopic dermatitis, which does not respond to conventional drugs, might be reluctant to choose biologic agents such as Dupilumab. In this paper, we reported a case of severe atopic dermatitis with multiple comorbidities in which the patient was successfully treated with Dupilumab despite numerous underlying conditions. We also conducted a review of the current literature on the safety profile of Dupilumab in special categories of patients with comorbidities, such as heart, kidney, and liver disease, oncologic conditions, and during pregnancy.

New Approach to Addison Disease: Oral Manifestations Due to Endocrine Dysfunction and Comorbidity Burden.

This review highlights oral anomalies with major clinical impact in Addison disease (AD), including dental health and dermatologic features, through a dual perspective: pigmentation issues and AD comorbidities with oral manifestations. Affecting 92% of AD patients, cutaneomucosal hyperpigmentation is synchronous with or precedes general manifestations by up to a decade, underlying melanocytic infiltration of the basal epidermal layer; melanophages in the superficial dermis; and, rarely, acanthosis, perivascular lymphocytic infiltrate, and hyperkeratosis. Intraoral pigmentation might be the only sign of AD; thus, early recognition is mandatory, and biopsy is helpful in selected cases. The buccal area is the most affected location; other sites are palatine arches, lips, gums, and tongue. Pigmented oral lesions are patchy or diffuse; mostly asymptomatic; and occasionally accompanied by pain, itchiness, and burn-like lesions. Pigmented lingual patches are isolated or multiple, located on dorsal and lateral areas; fungiform pigmented papillae are also reported in AD individuals. Dermoscopy examination is particularly indicated for fungal etiology; yet, it is not routinely performed. AD's comorbidity burden includes the cluster of autoimmune polyglandular syndrome (APS) type 1 underlying AIRE gene malfunction. Chronic cutaneomucosal candidiasis (CMC), including oral CMC, represents the first sign of APS1 in 70-80% of cases, displaying autoantibodies against interleukin (IL)-17A, IL-17F ± IL-22, and probably a high mucosal concentration of interferon (IFN)-γ. CMC is prone to systemic candidiasis, representing a procarcinogenic status due to Th17 cell anomalies. In APS1, the first cause of mortality is infections (24%), followed by oral and esophageal cancers (15%). Autoimmune hypoparathyroidism (HyP) is the earliest endocrine element in APS1; a combination of CMC by the age of 5 years and dental enamel hypoplasia (the most frequent dental complication of pediatric HyP) by the age of 15 is an indication for HyP assessment. Children with HyP might experience short dental roots, enamel opacities, hypodontia, and eruption dysfunctions. Copresence of APS-related type 1 diabetes mellitus (DM) enhances the risk of CMC, as well as periodontal disease (PD). Anemia-related mucosal pallor is related to DM, hypothyroidism, hypogonadism, corresponding gastroenterological diseases (Crohn's disease also presents oral ulceration (OU), mucogingivitis, and a 2-3 times higher risk of PD; Biermer anemia might cause hyperpigmentation by itself), and rheumatologic diseases (lupus induces OU, honeycomb plaques, keratotic plaques, angular cheilitis, buccal petechial lesions, and PD). In more than half of the patients, associated vitiligo involves depigmentation of oral mucosa at different levels (palatal, gingival, alveolar, buccal mucosa, and lips). Celiac disease may manifest xerostomia, dry lips, OU, sialadenitis, recurrent aphthous stomatitis and dental enamel defects in children, a higher prevalence of caries and dentin sensitivity, and gingival bleeding. Oral pigmented lesions might provide a useful index of suspicion for AD in apparently healthy individuals, and thus an adrenocorticotropic hormone (ACTH) stimulation is useful. The spectrum of autoimmune AD comorbidities massively complicates the overall picture of oral manifestations.

Electrochemical monitoring of bronchial inflammation in pediatric athletes: A prospective study.

The assessment of inflammation by accessible, reproducible and especially non-invasive methods is one of the main goals for numerous medical specialties. One variable for assessment is the fraction of nitric oxide in exhaled air (FeNO), which correlates with the inflammatory syndrome of the airways. The objective of the present study was the biochemical evaluation of FeNO in children practicing sports in Oltenia, Romania. Between January and December 2018, children practicing sports (football, track and field, judo, fencing, handball, volleyball and basketball) were enrolled in the study. The FeNO values were compared with the asthma history and with the spirometric evaluation. A total of 23 children without a previous asthma diagnosis exhibited positive spirometry results. The prevalence of the disease was 3.6% in the cohort, and FeNO dosing showed higher values in the group at risk in children diagnosed with asthma, compared with that in children without this diagnosis. The children who performed outdoor sports (soccer, and track and field) had higher electrochemical levels of nitric oxide compared with those who performed indoor sports (mean, 29.70 vs. 20.56; P<0.0005), which led to the hypothesis that these children had an increased risk of developing bronchospasm. FeNO dosing can thus be a useful and easy-to-use tool in practice for assessing bronchial inflammation in children practicing various types of sports. The spirometric data of undiagnosed asthma patients from the present study may indicate that the disease is still underdiagnosed within Romania.

Histopathological and immunohistochemical changes of the marginal periodontium in patients with Turner syndrome.

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.

Clinical, histopathological and immunohistochemical study of keratoacanthoma.

Keratoacanthoma (KA) is an epithelial tumor of the skin, classically considered as having a malignant transformation risk of 15%; however, many authors and the new World Health Organization (WHO) Classification of skin tumors consider KA as an incipient variant of the cutaneous squamous cell carcinoma (SCC). The aims of the study were to assess the clinical, histopathological (HP) and immunohistochemical (IHC) aspects of the KA and the role of these factors in malignancy occurrence. The studied group comprises 194 patients diagnosed with KA or malignant KA, hospitalized in the Clinic of Dermatology, Emergency County Hospital, Craiova, Romania, between 2006 and 2019. There were 83 males and 111 females, aged 34 to 90 years, 57.21% of the patients being from the rural environment. The histopathology diagnosed 51 KAs and 143 malignant KAs (SCCs). Clinical diagnosis had a limited value in detecting the absence or presence of malignancy in the KA lesion, due to a low accuracy (36.08% and 29.89%, respectively) and specificity (23.07% and 27.02%, respectively); therefore, the HP exam of the surgical excision specimen has a paramount importance in establishing the diagnosis. IHC analysis revealed that the immunostainings for apoptosis-associated proteins and keratinocyte proliferative activity [p53, B-cell lymphoma-2 (Bcl-2), Ki-67 and proliferating cell nuclear antigen (PCNA)] provide some arguments to differentiate between KA and SCC in the studied cases. The correlation of clinical, HP and IHC data lead to an accurate diagnosis of KA; moreover, the clinical, HP and IHC data sustain the idea that KA is a particular form of well-differentiated SCC, which require an active therapeutic attitude.

Vulvar Verrucous Carcinoma and Genital Condylomatosis.

Verrucous carcinoma is a histopathological type of well-differentiated squamous cell carcinoma, clinically characterized by slow and continuous growth, having a local destructive character, but low metastasis potential. Condyloma acuminatum is a sexually transmitted infection caused mainly by subtypes 6 and 11 of HPV, with subtypes 16, 18 being involved in malignant transformation. We present the case of a 70-year-old woman, hospitalized for a vulvar and perineal vegetative, ulcerated, bleeding tumor, with onset 20 years ago. The therapeutic option was surgical excision of the lesions and long-term oncological monitoring.

Complex regional pain syndrome as a paraneoplastic disorder associated with metatypical basal cell carcinoma.

Metatypical basal cell carcinoma (MTBCC) is a rare form of tumor, which associates the clinical and histopathological (HP) characteristics of both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), with a 5% chance for the development of metastases. The reference diagnosis remains the HP confirmation from the lesional tissue. The current report illustrates the case of a 74-year-old patient, diagnosed with MTBCC consequently to the biopsy from the clinically malignant lesion with HP and immunohistochemical examination, currently in clinical remission following surgical treatment. The musculoskeletal symptoms represent the patient's admission reason to the Clinic of Rheumatology, where he was diagnosed with paraneoplastic type I complex regional pain syndrome (CRPS-I). The onset was six weeks prior with intense pain in the upper limb, burning sensation and nondermatomal distribution, exacerbated by lowering the position of the upper limb. The clinical evaluation revealed vasomotor disorders: color changes on the skin of the upper limb, venous turgescence on the back of the hands, and local increased temperature. Also, there were evident sudomotor modifications with hyperspiration and fluffy edema. The presence of clinical manifestations associated with the HP confirmation of MTBCC and the information provided by the imaging tests regarding the evaluation of tumor extension advocates for the diagnosis of paraneoplastic CRPS, consequently to both the primary tumor and the pulmonary metastasis. Diagnosis of CRPS-I is generally established on the basis of clinical criteria after excluding other conditions that may explain the degree of pain and the existing dysfunction. The therapist should be aware of the clinical manifestation of CRPS, as early recognition and aggressive treatment often leads to the best response.

Inhibition of Upf2-Dependent Nonsense-Mediated Decay Leads to Behavioral and Neurophysiological Abnormalities by Activating the Immune Response.

In humans, disruption of nonsense-mediated decay (NMD) has been associated with neurodevelopmental disorders (NDDs) such as autism spectrum disorder and intellectual disability. However, the mechanism by which deficient NMD leads to neurodevelopmental dysfunction remains unknown, preventing development of targeted therapies. Here we identified novel protein-coding UPF2 (UP-Frameshift 2) variants in humans with NDD, including speech and language deficits. In parallel, we found that mice lacking Upf2 in the forebrain (Upf2 fb-KO mice) show impaired NMD, memory deficits, abnormal long-term potentiation (LTP), and social and communication deficits. Surprisingly, Upf2 fb-KO mice exhibit elevated expression of immune genes and brain inflammation. More importantly, treatment with two FDA-approved anti-inflammatory drugs reduced brain inflammation, restored LTP and long-term memory, and reversed social and communication deficits. Collectively, our findings indicate that impaired UPF2-dependent NMD leads to neurodevelopmental dysfunction and suggest that anti-inflammatory agents may prove effective for treatment of disorders with impaired NMD.

Therapeutic inhibition of mTORC2 rescues the behavioral and neurophysiological abnormalities associated with Pten-deficiency.

Dysregulation of the mammalian target of rapamycin (mTOR) signaling, which is mediated by two structurally and functionally distinct complexes, mTORC1 and mTORC2, has been implicated in several neurological disorders1-3. Individuals carrying loss-of-function mutations in the phosphatase and tensin homolog (PTEN) gene, a negative regulator of mTOR signaling, are prone to developing macrocephaly, autism spectrum disorder (ASD), seizures and intellectual disability2,4,5. It is generally believed that the neurological symptoms associated with loss of PTEN and other mTORopathies (for example, mutations in the tuberous sclerosis genes TSC1 or TSC2) are due to hyperactivation of mTORC1-mediated protein synthesis1,2,4,6,7. Using molecular genetics, we unexpectedly found that genetic deletion of mTORC2 (but not mTORC1) activity prolonged lifespan, suppressed seizures, rescued ASD-like behaviors and long-term memory, and normalized metabolic changes in the brain of mice lacking Pten. In a more therapeutically oriented approach, we found that administration of an antisense oligonucleotide (ASO) targeting mTORC2's defining component Rictor specifically inhibits mTORC2 activity and reverses the behavioral and neurophysiological abnormalities in adolescent Pten-deficient mice. Collectively, our findings indicate that mTORC2 is the major driver underlying the neuropathophysiology associated with Pten-deficiency, and its therapeutic reduction could represent a promising and broadly effective translational therapy for neurological disorders where mTOR signaling is dysregulated.

Correlations between clinical and placental histopathological and immunohistochemical features in women with and without hereditary thrombophilia.

AIM: The primary objective of this study was to correlate hereditary thrombophilia (high- or low-risk) with specific placental histopathological (HP) and∕or immunohistochemical (IHC) changes, for confirming∕ruling out a possible linkage between these two biological parameters. PATIENTS, MATERIALS AND METHODS: We present a 3-year prospective study conducted between 2016 and 2019 that enrolled 90 women registered in two Clinics of Obstetrics and Gynecology in Craiova, Romania, with personal thrombotic and/or pathological obstetrical history. The HP and IHC analysis of the placenta was performed using monoclonal anti-cluster of differentiation 34 (CD34) antibody, anti-hypoxia-inducible factor-1 alpha (HIF-1α) and anti-endothelial nitric oxide synthase (eNOS) antibody. RESULTS: There was a high incidence of all thrombophilia (TPh) mutations in Caucasian women with thrombotic and obstetrical complications. Among them, both HP and IHC examination revealed significant changes. These were more severe in the placentas of patients with homozygous Factor V Leiden (FVL) gene mutation and double heterozygous FVL∕PII gene mutation. Multiple placental infarctions with massive fibrinoid necrosis and an increase in syncytial knots are common findings. In the same group, we found by means of IHC examination - intense positive HIF-1α and eNOS immunoexpression, and low positive CD34 expression, especially in fibrinoid necrosis and thrombosis areas. We found no correlation between clinical, HP and IHC changes in patients with low-risk TPh or without TPh. CONCLUSIONS: Among patients with obstetric and thrombotic complications, there is a high prevalence of TPh. It appears that hypercoagulability reported in high-risk thrombophilia (HR-TPh) has major effects on placental tissue (fibrinoid necrosis, multiple thromboses, hypoxia and oxidative stress). Significant placental changes were found predominantly in women with HR-TPh. Strategies for TPh screening based on HP/IHC pattern would be, most probably, more cost-effective compared with the extended TPh testing offered in large populations. This way, a smaller number of patients will be tested and in this group a higher proportion of patients will be found as having HR-TPh mutations.

Giant basal cell carcinoma of the nasal pyramid - case report.

Basal cell carcinoma (BCC) is a frequent form of skin cancer, which usually affects people that have been exposed to the sunlight for longer periods of time. The cells of the lower part of the epidermis are called the basal cell layer. These cells constantly divide to form new cells to replace the squamous cells that wear off the skin's surface. As these cells move up in the epidermis, they get flatter, eventually becoming squamous cells. Therefore, the BCC develops from these cells. Most BCCs have indolent behavior, with cure rates very high after low-complexity treatment. However, some lesions are very aggressive and there are only a few papers focusing on the subtype of this skin cancer known with the name ulcus rodens or giant BCC. In this study, we evaluate a case of ulcus rodens or giant BCC, subtype of the BCC skin cancer located in the area of the nasal pyramid, stage III, TxNxMx, with lymphatic and vascular invasion present.

ATP6AP2 variant impairs CNS development and neuronal survival to cause fulminant neurodegeneration.

Vacuolar H+-ATPase-dependent (V-ATPase-dependent) functions are critical for neural proteostasis and are involved in neurodegeneration and brain tumorigenesis. We identified a patient with fulminant neurodegeneration of the developing brain carrying a de novo splice site variant in ATP6AP2 encoding an accessory protein of the V-ATPase. Functional studies of induced pluripotent stem cell-derived (iPSC-derived) neurons from this patient revealed reduced spontaneous activity and severe deficiency in lysosomal acidification and protein degradation leading to neuronal cell death. These deficiencies could be rescued by expression of full-length ATP6AP2. Conditional deletion of Atp6ap2 in developing mouse brain impaired V-ATPase-dependent functions, causing impaired neural stem cell self-renewal, premature neuronal differentiation, and apoptosis resulting in degeneration of nearly the entire cortex. In vitro studies revealed that ATP6AP2 deficiency decreases V-ATPase membrane assembly and increases endosomal-lysosomal fusion. We conclude that ATP6AP2 is a key mediator of V-ATPase-dependent signaling and protein degradation in the developing human central nervous system.

Diabetic foot - epidemiological and histopathological aspects.

Our study included a total of 259 patients with diabetes, who were admitted to the Department of Plastic Surgery and Reconstructive Microsurgery of the Emergency County Hospital of Pitesti, Romania, in 2016, with the diagnosis of "diabetic foot". Of the 259 patients, 55 (21.23%) were diagnosed with type 1 diabetes, and the remaining 204 (78.77%) were diagnosed with type 2 diabetes; the ratio of type 1∕type 2 diabetes was 1∕3.7. The injuries presented by the patients were osteitis (27.81%), moist gangrene (21.62%), abscesses (18.92%), cellulitis (11.19%), various forms of fasciitis (8.88%), perforating strand (6.18%), and dry gangrene (5.4%). The disease was most commonly diagnosed in males in the rural environment. Most of the patients were in the age group of 61-70 years old. All patients were surgically treated, but 142 (54.82%) patients needed amputations of foot segments (fingers, metatarsal or tarsal bones). The histopathological and immunohistochemical study on excised fragments revealed the existence of a chronic inflammatory process formed mainly from macrophages, mast cells and CD4+ T-lymphocytes.

mTORC2, but not mTORC1, is required for hippocampal mGluR-LTD and associated behaviors.

The mechanistic target of rapamycin complex 1 (mTORC1) has been reported to be necessary for metabotropic glutamate receptor-mediated long-term depression (mGluR-LTD). Here we found that mTORC1-deficient mice exhibit normal hippocampal mGluR-LTD and associated behaviors. Moreover, rapamycin blocks mGluR-LTD in mTORC1-deficient mice. However, both rapamycin and mGluR activation regulate mTOR complex 2 (mTORC2) activity, and mTORC2-deficient mice show impaired mGluR-LTD and associated behaviors. Thus, mTORC2 is a major regulator of mGluR-LTD.

Histopathological and clinical traps in lichen sclerosus: a case report.

Lichen sclerosus et atrophicus and limited systemic scleroderma (acrosclerosis) are inflammatory skin diseases that ultimately evolve into two distinct modes of atrophic scar formation, but which can easily be confused clinically. They are very rarely associated. The literature has reported cases in which lichen sclerosus was associated with various forms of scleroderma, but often with localized morphea. The characteristic histopathological picture of lichen sclerosus includes a thin epidermis, with orthohyperkeratosis and vascular degeneration in the basal layer, loss of elastic fibers, and band-like inflammatory infiltrate in the papillary dermis, while systemic sclerosis is characterized by excessive deposition of collagen in the dermis, accompanied by reduction in adnexal structures and their entrapment in collagen, and the presence of perivascular lymphocytic inflammatory infiltrate. We present the case of a 40-year-old female patient clinically diagnosed with systemic scleroderma and lichen sclerosus involving the genital mucosa. Physical examination in conjunction with laboratory findings (elevated antinuclear, anti-Scl-70, anti-SSA antibodies and immunogram) induced the supposition of the coexistence of lichen sclerosus and systemic scleroderma, fact confirmed by pathological examination. Systemic therapy with corticosteroids, immunosuppressive and phlebotropic drugs, peripheral vasodilators and other tropic adjuvants and topically potent topical corticosteroids was initiated. The course was favorable under therapy, the hardened skin slightly regaining elasticity, relief of itching and disappearance of lichen sclerosus lesions. Our case reaffirms the uncommon association of these two disorders. The importance of history, physical and laboratory examinations in making a diagnosis of certainty in emphasized.

Atypical Spitz Tumor - Case Report.

Atypical Spitzoid tumors represent a poorly defined and characterized category of melanocytic tumors with histologic features of both benign Spitz nevi and malignant melanomas. The group of atypical Spitz tumors represents a mixture of Spitz nevi with atypical features and Spitzoid melanomas. We report the case of an eight years old female patient, who was admitted in Dermatology Clinic Craiova for the presence of a skin tumor with 1/0.8 cm diameter, irregular edges, brown - black coloured with irregular pigment distribution. The skin tumor was located on the dorsal foot above the third metatarsal. The skin tumor appeared in the first two years of childhood and above the third metatarsal. The skin tumor appeared in the first two years of childhood and had slow increase. From about six months, the tumor had changed the colour becoming darker and had also a rapid increase in size. The patient had no comorbidities and had no family history of malignancy or other skin diseases. In our clinic we did the surgical excision of the skin tumor and sent the fragment for the histopathological examination and immunohistochenmical tests. After the clinical examination, dermoscopic evaluation, histopathological and immunohistochemical examination, our diagnosis was Atypical Spitz Tumor.