Successful treatment of actinic prurigo with baricitinib in an 8-year-old child: A case report.

Actinic prurigo is a rare photodermatosis characterized by pruritic papulonodular lesions. Treatment is challenging, especially in children, as sun protection strategies need to be rigorously implemented and symptoms often persist throughout the year. Herein, we present a case of actinic prurigo in an 8-year-old patient with rapid and successful relief with baricitinib.

Assessment of Photosensitizer Concentration Effects on the Efficacy of Photodynamic Therapy.

Introduction: Photodynamic therapy (PDT) is an attractive approach in medicine. Due to its noninvasive nature and low side effects, PDT has been developed quickly. In the present study, the gene expression profiles of the human cell line that was treated via PDT in the sub-lethal concentration (LC50) and super-lethal concentration (LC90) of a photosensitizer (PS) from Gene Expression Omnibus (GEO) were extracted and the common differentially expressed genes (DEGs) were investigated. Methods: The gene expression profiles of the treated cells were compared with a control, and the common DEGs were determined. The common DEGs were assessed via protein-protein interaction (PPI) network analysis, and gene ontology enrichment was evaluated. The related biological terms for the common genes were identified. Results: Ninety-four common DEGs were selected to be analyzed. It appeared that the activation and increment of gene expression were prominent processes. Jun, Dusp1, Atf4, and Atf3 as four critical genes were highlighted. "Chromosomal and microsatellite instability in colorectal cancer" was identified as the main class of biological terms related to the assessed DEGs. Conclusion: The major molecular events which happened in both analyses indicated that PDT, independent from the concentration of PS, induced gross molecular changes such as the upregulation of Jun and Dusp1.

Conjunctival Melanoma: A Case Presentation.

Conjunctival melanoma is an uncommon tumor that is likely to recur and carries an overall mortality rate of approximately 30%. Melanoma arises from melanocytes, most often in sun-exposed skin. Less commonly, melanoma originates from other tissues such as the uvea, rectum, mouth, respiratory tract, and conjunctiva. Conjunctival melanoma represents only 1.6% of all noncutaneous melanoma. Herein, we reported a case of conjunctival melanoma followed by reviewing the literature to provide an optimal diagnostic approach.

Extraskeletal mesenchymal chondrosarcoma arising from soft tissues: A rare case report.

BACKGROUND: Chondrosarcomas are an exceedingly rare form of cancer, impacting only a few individuals per million. Among chondrosarcomas, a small fraction belongs to the mesenchymal sub-type. Furthermore, only one-third of mesenchymal chondrosarcomas manifest in extraskeletal locations. CASE: A 38-year-old woman was referred by a midwife after experiencing pain in the right upper quadrant of her right breast for 2 months. The mass had been palpable for 1 week before the initial assessment. According to radiological evaluations, the tumor is outside breast tissue and not connected to the bones. Hence, a biopsy of the mass is done. The biphasic morphology of the tumor during pathological evaluation, in addition to immunohistochemistry testing, confirms the diagnosis of extraskeletal mesenchymal chondrosarcoma (EMCS). Finally, the mass was surgically removed, and 6 months of chemotherapy were administered to the patient. CONCLUSION: Given the tumor's rarity and the lack of established guidelines, diagnosing EMCS can be challenging and prone to errors. As such, meticulous sampling, along with precise pathological and imaging investigations, is imperative to accurately establish the diagnosis of these tumors.

The uterine adenosarcoma with postoperative residual in a woman treated by total abdominal hysterectomy/bilateral salpingo-oophorectomy: A case report and review of literature.

BACKGROUND: In patients with uterine adenosarcoma, a total abdominal hysterectomy (TAH) with bilateral salpingo-oophorectomy (BSO) is typically recommended as an initial treatment. There is no consensus on adjuvant therapies. CASE: We report the case of a patient with uterine adenosarcoma with postoperative residual disease. We performed four courses of adjuvant chemotherapy, including Ifosfamide, Mesna, and Adriamycin, and whole pelvic radiation with a dose of 50.4 Gy/28 Fr. CONCLUSION: A combination of chemotherapy and radiotherapy may be a promising treatment option for uterine adenosarcoma with postoperative residual disease.

Evaluation of LGR5 Cancer Stem Cell Marker Expression in Breast Cancer and Its Relationship with Hormonal Profile and Clinical Pathological Features.

BACKGROUND: Due to the high prevalence of breast cancer and the importance of evaluating new prognostic criteria for effective treatment of these patients, this study was performed to investigate the role of LGR5 in breast cancer and its relationship with hormonal and clinicalopathological features of the disease. METHODS: This cross-sectional study was performed on breast cancer tissue samples in the archives of the pathology department of Firoozabadi Hospital in Tehran between 2019 and 2021. Inclusion criteria included invasive ductal carcinoma and exclusion criteria were preoperative chemotherapy. Blocks were examined for LGR5 marker expression by IHC method using LGR5 monoclonal antibody kits (Abcam). The expression pattern of LGR5 marker was cytoplasmic and cells presenting brown staining in the cytoplasm were considered positive for this marker and in terms of distribution and severity of staining were divided into three groups: mild, moderate and severe. RESULTS: This study was performed on 60 patients with breast cancer with a mean age of 55.5±9.7. Most of the patients (55%) were in grade II. The KI67 marker was positive in 45 cases (75%) and the HER2 marker in 14 cases (23.3%) and 8 cases (13.3%) were triple-negative. The expression severity of staining of LGR5 marker in 41 cases (68.3%) was moderate and the distribution of marker expression in 31 cases (51.7%) was moderate. No significant relationship was observed between LGR5 expression severity and tumor characteristics. CONCLUSION: LGR5 marker is expressed in a remarkable percentage of breast cancer patients and has no significant relationship with tumor characteristics.

New insights into extracellular and intracellular redox status in COVID-19 patients.

BACKGROUND: The imbalance of redox homeostasis induces hyper-inflammation in viral infections. In this study, we explored the redox system signature in response to SARS-COV-2 infection and examined the status of these extracellular and intracellular signatures in COVID-19 patients. METHOD: The multi-level network was constructed using multi-level data of oxidative stress-related biological processes, protein-protein interactions, transcription factors, and co-expression coefficients obtained from GSE164805, which included gene expression profiles of peripheral blood mononuclear cells (PBMCs) from COVID-19 patients and healthy controls. Top genes were designated based on the degree and closeness centralities. The expression of high-ranked genes was evaluated in PBMCs and nasopharyngeal (NP) samples of 30 COVID-19 patients and 30 healthy controls. The intracellular levels of GSH and ROS/O2• - and extracellular oxidative stress markers were assayed in PBMCs and plasma samples by flow cytometry and ELISA. ELISA results were applied to construct a classification model using logistic regression to differentiate COVID-19 patients from healthy controls. RESULTS: CAT, NFE2L2, SOD1, SOD2 and CYBB were 5 top genes in the network analysis. The expression of these genes and intracellular levels of ROS/O2• - were increased in PBMCs of COVID-19 patients while the GSH level decreased. The expression of high-ranked genes was lower in NP samples of COVID-19 patients compared to control group. The activity of extracellular enzymes CAT and SOD, and the total oxidant status (TOS) level were increased in plasma samples of COVID-19 patients. Also, the 2-marker panel of CAT and TOS and 3-marker panel showed the best performance. CONCLUSION: SARS-COV-2 disrupts the redox equilibrium in immune cells and the upper respiratory tract, leading to exacerbated inflammation and increased replication and entrance of SARS-COV-2 into host cells. Furthermore, utilizing markers of oxidative stress as a complementary validation to discriminate COVID-19 from healthy controls, seems promising.

Histopathologic Changes of Appendicitis Stage During the COVID-19 Pandemic.

Background: We decided to compare the pathology stage of appendicitis in patients referred to Firoozabadi Medical Center before and after the official announcement of the coronavirus outbreak in Iran because we believe that people's fears of COVID-19 are keeping them away from hospitals and it likely causes them to come in later stages of the disease. Therefore, this study aims at investigating the effect of the COVID-19 pandemic on the stage of appendicitis at presentation. Methods: In this retrospective study, histopathology records of all acute appendicitis patients who underwent an emergency appendectomy in the surgical unit in our institute between December 2019 and April 2020 were reviewed retrospectively. The study period was designed to include 2 months before and 2 months after the officially announced onset of the COVID-19 outbreak in Iran on February 20, 2020. All cases of complicated appendicitis (perforated appendicitis, phlegmonous appendix, itis or abscess) were excluded. Descriptive statistics were used to describe our study variables. Furthermore, ordinal logistic regression was used to investigate the effect of the COVID-19 pandemic and demographic variables on the stage of appendicitis at presentation. Data were analyzed using SPSS Statistics Version 22. Results: The study was conducted on 170 clinically diagnosed acute appendicitis patients. The odds ratio for gender was equal to 0.45 (0.23, 0.86), which means that women presented at an earlier pathological stage than men ( p = 0.016). Also, patients who had health insurance were 50% less likely to present in later pathological stages than those who did not ( p = 0.024). The COVID-19 outback did not have a significant role in the pathological stage at presentation ( p = 0.235). Conclusion: The number of appendicitis patients was down by about 50% following the outbreak announcement in Iran. Surprisingly, we did not find any significant changes in the distribution pattern of appendicitis pathological staging after the outbreak. Being uninsured and male sex were found to have the most significant roles in delayed hospital presentation and higher pathological stages in patients with acute appendicitis.

Primary cutaneous B-Cell lymphoblastic lymphoma presenting with solitary scalp mass in a female child: A case report and review of the literature.

Lymphoblastic lymphoma is a group of non-Hodgkin lymphomas that account for approximately 2% of all lymphomas. This is a report of a case of a young girl presenting with a solitary scalp mass which was resected. Histopathological examination of the mass along with bone marrow analysis revealed primary cutaneous B-cell lymphoblastic lymphoma. A nine-year-old girl presenting with an asymptomatic erythematous, non-tender scalp mass present for 12 months was admitted. Skull and brain were intact and devoid of any pathological findings on computed tomography imaging. Systemic examination also showed no evidence of mass lesion in other parts of the body. The lesion was resected and referred for pathological analysis. Microscopic study revealed heavy diffuse dermal and subcutaneous infiltration of monomorphous medium-sized mononuclear cells, with fine chromatin, scant cytoplasm, and variable nucleoli along with intact epidermis and presence of grenz zone. Tumor cells dissect through the collagen fibers. Extensive mitotic figures and focal infiltration of the skin adnexa are seen. IHC study revealed that TdT, CD79a, CD99, CD45, CD20, and Ki67 markers were positive. According to these findings, a definitive diagnosis of primary cutaneous lymphoblastic lymphoma of B cell type was concluded. The 1-year follow up after necessary treatment revealed normal findings without traces of recurrence. Lymphoblastic lymphomas (LBL) are a neoplasm of immature B cells belonging to the B-(B-LBL) or T-cell lineage (T-LBL) that accounts for approximately 2% of all lymphomas. Lymphoblastic lymphoma (LBL) is similar to acute lymphoblastic leukemia (ALL) and the differentiation between these neoplasms is based upon proportion of involvement of lymphoblasts in bone marrow. It has a higher male to female predominance, higher incidence in older children and younger adults, and a relatively higher frequency of CNS and gonadal involvement. The differential diagnosis is based on immunohistochemistry study of B-cell linage tumor markers. Cutaneous involvement is present in about one third of patients with B-LBL but rarely in patients with ALL.

A pure Cutaneous Rosai-Dorfman disease: case report and a review of the literature.

Background: Cutaneous Rosai-Dorfman disease (CRDD) is a rare variant of benign histiocytic proliferative disorder limited to the skin. The underlying etiology is still unclear, but it had been claimed that infections, immunodeficiencies, and autoimmune disorders might have a role in the etiology of this disorder. The characteristic presentation of RDD is lymphadenopathy due to abnormal production and accumulation of histiocytes in lymph nodes; however, the extra-nodal areas could also be affected, such as cutaneous. Herein, we presented a 45-year-old Iranian woman presented with an atypical pure cutaneous Rosai Dorfman disease, in addition to a summarized list of atypical cases of RDD that are reported as pure cutaneous RDD with atypical presentation. Case presentation: Herein, we presented a 45-year-old woman who referred to us with an ulcerative nodule with a size of 5×5 cm on her buttock, gradually growing over one year. After the primary evaluations, a biopsy specimen was obtained, and histologic studies revealed a dense cellular infiltrate involving the dermis and the subcutis, which was composed of abundant sheets of large histiocytes with admixtures of lymphocytes, plasma cells, neutrophils, and eosinophils within their cytoplasm -known as the emperipolesis phenomenon. The immunohistochemistry staining was positive for S100 and CD68 and negative for CD1a. Conclusion: The diagnosis of CRDD was confirmed based on these histopathological findings.

Foamy Cell Angiosarcoma in a Patient with Xeroderma Pigmentosum: A Case Report and Comprehensive Review of the Literature.

Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder characterized by a DNA repair defect caused by ultraviolet light and cutaneous manifestations, including solar lentigines, xerosis, actinic damage, and cutaneous neoplasms (e.g., basal cell carcinoma, squamous cell carcinoma, and melanoma). Cutaneous angiosarcoma (AS) is a rare group of aggressive skin tumors that infrequently occur in patients with XP, usually involving the scalp or face. The AS has three subtypes: idiopathic, complicating lymphedema, and post-irradiation. The AS has diverse histopathological types, and the uncommon variants are clear cell, epithelioid, granular cell, pseudo lymphomatous, verrucous, and signet-ring cell variants. Although the foamy cell variant of AS is the rarest type, its diagnosis would be really challenging due to the wide variety of differential diagnoses, especially for poorly differentiated ones. Therefore, definitive diagnosis and effective management in the early stages are crucial, and immunohistochemical (IHC) tests are essential. Here we report a 50-year-old Iranian man with AS complicating XP who presented with an ulcerative erythematous and progressive plaque. Histopathologic studies revealed foamy cells and vascular markers (i.e., CD 31 and CD 34) were positive, immunohistochemically which was found unusual features. In addition,, we review previously reported cases in the literature to provide some information on the diagnosis and management of such cases.

Therapeutic effects, immunogenicity and cytotoxicity of a cell penetrating peptide-peptide nucleic acid conjugate against cagA of Helicobacter pylori in cell culture and animal model.

BACKGROUND AND OBJECTIVES: Helicobacter pylori causes several gastrointestinal diseases, including asymptomatic gastritis, chronic peptic ulcer, duodenal ulcer, lymphoma of the mucosa-associated lymphoid tissue (MALT), and gastric adenocarcinoma. In recent years, failure to eradicate H. pylori infections has become an alarming problem for physicians. It is now clear that the current treatment strategies may become ineffective, necessitating the development of innovative antimicrobial compounds as alternative treatments. MATERIALS AND METHODS: In this experimental study, a cell-penetrating peptide-conjugated peptide nucleic acid (CPP-PNA) was used to target the cagA expression. cagA expression was evaluated using RT-qPCR assay after treatment by the CPPPNA in cell culture and animal model. Additionally, immunogenicity and toxicity of the CPP-PNA were assessed in both cell culture and animal models. RESULTS: Our analysis showed that cagA mRNA levels reduced in H. pylori-infected HT29 cells after treatment with CPPPNA in a dose-dependent manner. Also, cagA expression in bacterial RNA extracted from stomach tissue of mice treated with PNA was reduced compared to that of untreated mice. The expression of inflammatory cytokines also decreased in cells and tissue of H. pylori-infected mice after PNA treatment. The tested CPP-PNA showed no significant adverse effects on cell proliferation of cultured cells and no detectable toxicity and immunogenicity were observed in mice. CONCLUSION: These results suggest the effectiveness of CPP-PNA in targeting CagA for various research and therapeutic purposes, offering a potential antisense therapy against H. pylori infections.

Design of a decellularized fish skin as a biological scaffold for skin tissue regeneration.

The use of decellularized natural skin as an extracellular matrix (ECM) may be a great candidate to regenerate damaged tissues. In this study, decellularized scaffolds from fish skin were designed by different techniques (physical, chemical, and enzymatic methods) and investigated by analyses such as Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy (SEM), Tensile strength, Degradability, Histological studies, Toxicity test, and Determination of DNA content. Results showed that the best sample is related to the decellularized skin by hypertonic & hypotonic technique and Triton X100 solutions. Structural and mechanical results were demonstrated that samples have similar properties to human skin to regenerate it. The cytotoxicity results showed that decellularized skin by hypertonic & hypotonic method and Triton solution is non-toxic with minimal amount of genetic materials. Cellular results with epithelial cells indicated good adhesion on decellularized matrix, so it can be a suitable candidate for skin tissue regeneration.

C-reactive protein as a possible marker for severity and mortality of COVID-19 infection.

AIM: The present study aimed to introduce a possible biomarker to differentiate between severe and fatal conditions of COVID-19. BACKGROUND: The COVID-19 pandemic, appearing as a complicated health problem, has changed the lifestyle of people in recent years. Clinical findings indicate mild, severe, and fatal conditions of this disease. Prediction of disease severity is a significant point in managing COVID-19 infection. METHODS: In this study, 195 differentially expressed genes (DEGs) that discriminate between fatal and severe conditions in patients were extracted from the literature and screened to determine the significant ones. The significant DEGs plus the 90 first neighbors added from the STRING database were included in the interactome using Cytoscape software v 3.7.2. The central nodes of the analyzed network were identified and assessed. RESULTS: Ten significant DEGs were candidates for assessment, of which 9 were recognized by the STRING database. IL6, ALB, TNF, CRP, INS, MPO, C3, CXCL8, TTR, and TLR4 were determined as central nodes; IL6, CRP, and TTR were highlighted as the critical genes related to the severity of COVID-19 infection. CONCLUSION: CRP was identified as the best possible biomarker with levels related to the severity and fatality of COVID-19 infection.

A first case of fixed drug eruption due to Tamsulosin.

BACKGROUND: Fixed Drug Eruption (FDE) is a drug reaction involving the skin and less commonly the mucosal membranes. Tamsulosin is an alpha-1 adrenergic receptor blocker used to treat benign prostatic hyperplasia. Dizziness and headache are among its most common side effects (Singapore Med J, 2018;59:336). Although cutaneous drug eruption has been reported with other alpha-1 adrenergic receptor blockers. AIMS: Drug rash due to Tamsulosin is relatively uncommon (Singapore Med J, 2018;59:336). In this case we report an incidence of fixed drug eruption due to Tamsulosin. PATIENTS: A 54 year old male, with benign prostatic hyperplasia was referred to our office for evaluation of certain eruptions, having developed his hyper-pigmented patches after 2 weeks of using oral 0.4 mg Tamsulosin per day. Based on the clinical course and the skin biopsy we diagnosed the condition as Tamsulosin associated fixed drug eruption. The most important therapeutic measure was discontinuing Tamsulosin medication. Following this, his eruptions improved remarkably in a few days without complications. RESULTS: According to previous findings, there has been no case report on fixed drug eruption caused by Tamsulosin. CONCLUSION: Our case is a relatively mild form of fixed drug eruption. Therefore it should be kept in mind that a severe cutaneous drug eruption might occur after Tamsulosin administration.

Overexpression of cancer stem cell marker Lgr5 in colorectal cancer patients and association with clinicopathological findings.

BACKGROUND: To determine the expression of cancer stem cell marker Leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) in colorectal carcinoma samples compared to normal adjacent tissue and any possible association with clinicopathological findings. METHODS: This study was performed on forty samples of cancerous colorectal tissues (case group) and their adjacent normal mucosa (control group) in Imam Khomeini Hospital (Sari, Mazandaran, Iran). Expression of Lgr5 in tissue sections was done by immunohistochemistry. Statistical analysis was carried out using SPSS software. RESULTS: Forty colorectal cancer patients including 21 males (57.8±11.6 years) and 19 females (58.4±12.77 years) were enrolled. Lgr5 was overexpressed in tumoral samples than normal adjacent tissues (77.5% vs 27.5%, p<0.001). Also, no association was found between primary tumor, regional lymph nodes, invasion, histological type, grade, distant metastasis and IHC results. Patients with low Lgr5 expression had a better survival rate than patients with high expression but this was not statistically significant (p=0.121). CONCLUSION: The higher immunoreactivity of Lgr5 in colorectal cancer tissues may indicate its role as a cancer stem cell marker in tumor carcinogenesis and patient's survival however; Lgr5 is not associated with pathological prognostic variables.

Neurofolicullar hamartoma presenting as a rare adnexal neoplasm in association with basal cell carcinoma.

BACKGROUND: Neurofollicular hamartoma (NFH) is characterized histopathologically by fascicles of spindle cells that laterally delimited by hyperplastic folliculosebaceous units. It usually appears on face, near the nose or nasolabial fold. It does not manifest true neural differentiation and recently the term spindle cell predominant trichodiscoma (SCPT) has been used instead. CASE PRESENTATION: We present a case of a 40-year-old male with co-incidence of NFH and basal cell carcinoma (BCC) that the mesenchymal components of NFH were similar to SCPT but these components highly expressed S-100 protein. We also discuss about the histological aspect of the neoplasia in this report and consider the findings of other reports in association with classification of NFH by means of cellular markers and morphological resemblance to other skin hamartomas. CONCLUSION: Neurofollicular hamartoma is a rare benign tumor that thought to represent the cellular end of a morphological spectrum with trichodiscoma. The morphological features and expression of S100 protein in neural element helped us to achieve the diagnosis of neurofollicular hamartoma. However, variable reports of S-100 protein expression in NFH are available and further studies are needed to determine the classification of this tumor.

Serum and tissue angiotensin-converting enzyme in patients with alopecia areata.

BACKGROUND: Alopecia areata is an immune-dependent disorder characterized by the interaction of T-lymphocytes with follicular antigens. Recent studies have shown the existence of a local renin-angiotensin system in the skin, where angiotensin-converting enzyme (ACE) plays a role in autoimmunity and inflammation. AIM: The objective of this study was to evaluate serum and tissue ACE activity in patients with alopecia areata. METHODS: This case-control study was conducted on patients with alopecia areata and healthy controls. Serum and tissue ACE activity were assessed and compared between the two groups. RESULTS: Twenty-five alopecia areata patients (60% male, mean age 32.1 ± 9.9 years) and 24 controls (50% male, mean age 37.4 ± 8.8 years) were included. Mean serum ACE activity was 52.1 ± 9 U/L in cases and 55.3 ± 14.7 U/L in controls (P = 0.37). Tissue ACE activity was significantly lower in cases in all parts of the skin i.e. epidermis (P = 0.016), follicular epithelium (P = 0.004), and endothelium (P = 0.037). Among cases, serum ACE activity was significantly higher in patients with more severe disease (P = 0.030), nonpatchy alopecia areata (alopecia universalis; ophiasis, patchy and ophiasis, diffuse) (P = 0.029), and with nail involvement (P = 0.027). LIMITATIONS: The sample size was too small to draw definite conclusions. Further, most of the patients had only mild or moderate alopecia areata. CONCLUSION: Unlike in some other inflammatory diseases, the tissue level of ACE seems to be significantly lower in alopecia areata compared to normal controls. Serum ACE was significantly higher in patients with more severe disease.