Pleomorphic carcinoma of the lung revealed by uncommon colonic metastasis: An exceptional case report with literature review.

Lung pleomorphic carcinoma is a rare and aggressive cancer that uncommonly metastasizes to the colon and only a few case reports have been published thus far. We present an exceptional case of colon metastasis from lung pleomorphic carcinoma in a 68-year-old man which was revealed by large bowel perforation, and we review the previous three published cases. Metastasis to the bowel from primary lung malignancy often lacks specific symptoms which result in delayed diagnosis. Bowel metastasis is a poor prognostic factor in patients with lung pleomorphic carcinoma, regardless of management strategy.

Clinical features and outcomes in patients with human immunodeficiency virus-negative, Castleman disease: a single medical center study in Tunisia.

Introduction: Castleman disease (CD), known as angiofollicular lymph node hyperplasia, is an uncommon condition. The two most common histological subtypes are hyaline vascular and plasma cell. We performed a retrospective analysis to define the clinic-pathological features and survival of CD, which is quite rare focusing on the particularities of our series with a review of the recent literature. Methods: This is a retrospective study conducted in the department of internal medicine of Hedi Chaker hospital in Sfax, Tunisia over 25 years. The disease was histologically confirmed in all patients. For each file, we collected a set of data by filling in a pre-designed form. Results: 18 patients were included. There were 8 men and 10 women with a mean age of 42.8 years. CD was monocentric in 5 cases (28%) and multicentric in 13cases (72%). Clinically, peripheral adenopathy was present in 77.7% of patients and deep adenopathy in 72.2%. Systemic signs were found in 13patients, including general condition (4.4%), fever (16.6%), serositis (27.7%), and skin involvement (33.3%). A biological inflammatory syndrome accompanied the clinical picture in 66% of patients. Abnormalities in the blood count were found in 12cases (66%), with anemia in 11cases, thrombocytosis in 3cases, and hypereosinophilia in 3cases. Cutaneous Kaposi's sarcoma was associated with Castleman's disease in 2cases, Hodgkin's lymphoma, angioimmunoblastic T-cell lymphoma, and lymph node T-cell lymphoma were found in 1case respectively. 3 of the patients had associated connective tissue diseases such as Sjögren's syndrome in 2 cases and rheumatoid arthritis in 1case. HHV8 serology was positive in 1 case with a multicentric plasma cell form. Histologically, the plasma cell form represented 50% of cases, hyaline-vascular (39% of cases), and mixed (11% of cases). Therapeutically, high-dose corticosteroid therapy was initiated in 13 cases. As a second-line treatment, MOPP chemotherapy was used in 1case due to transformation into Hodgkin's lymphoma, and biotherapy (rituximab) was used in 2cases in the multicentric form. Surgical removal of superficial adenopathy was performed in 2patients with monocentric CD. Conclusion : Castleman's disease (CD) is a non-malignant lymphoproliferation of localized or multicentric form with a wide and heterogeneous clinical spectrum. Diagnosis can be difficult due to the lack of clinical and radiological specificity. Management depends on the clinical form involving surgical and/or medical management.

Shotgun Proteomic-Based Approach with a Q-Exactive Hybrid Quadrupole-Orbitrap High-Resolution Mass Spectrometer for Protein Adductomics on a 3D Human Brain Tumor Neurospheroid Culture Model: The Identification of Adduct Formation in Calmodulin-Dependent Protein Kinase-2 and Annexin-A1 Induced by Pesticide Mixture.

Pesticides are increasingly used in combinations in crop protection, resulting in enhanced toxicities for various organisms. Although protein adductomics is challenging, it remains a powerful bioanalytical tool to check environmental exposure and characterize xenobiotic adducts as putative toxicity biomarkers with high accuracy, facilitated by recent advances in proteomic methodologies and a mass spectrometry high-throughput technique. The present study aims to predict the potential neurotoxicity effect of imidacloprid and λ-cyhalothrin insecticides on human neural cells. Our protocol consisted first of 3D in vitro developing neurospheroids derived from human brain tumors and then treatment by pesticide mixture. Furthermore, we adopted a bottom-up proteomic-based approach using nanoflow ultraperformance liquid chromatography coupled with a high-resolution mass spectrometer for protein-adduct analysis with prediction of altered sites. Two proteins were selected, namely, calcium-calmodulin-dependent protein kinase-II (CaMK2) and annexin-A1 (ANXA1), as key targets endowed with primordial roles. De novo sequencing revealed several adduct formations in the active site of 82-ANXA1 and 228-CaMK2 as a result of neurotoxicity, predicted by the added mass shifts for the structure of electrophilic precursors. To the best of our knowledge, our study is the first to adopt a proteomic-based approach to investigate in depth pesticide molecular interactions and their potential to adduct proteins which play a crucial role in the neurotoxicity mechanism.

Research of Pesticide Metabolites in Human Brain Tumor Tissues by Chemometrics-Based Gas Chromatography-Mass Spectrometry Analysis for a Hypothetical Correlation between Pesticide Exposure and Risk Factor of Central Nervous System Tumors.

Pesticides are widely used, resulting in continuing human exposure with potential health impacts. Some exposures related to agricultural works have been associated with neurological disorders. Since the 2000s, the hypothesis of the role of pesticides in the occurrence of central nervous system (CNS) tumors has been better documented in the literature. However, the etiology of childhood brain cancers still remains largely unknown. The major objective of this work was to assess the potential role of pesticide exposure as a risk factor for CNS tumors based on questionnaires and statistical analysis of information collected from patients hospitalized in the Neurosurgery Department of the Habib Bourguiba Hospital Medium in Sfax, Tunisia, during the period from January 1, 2022, to May 31, 2023. It also aimed to develop a simple and rapid analytical method by the gas chromatography-mass spectrometry technique for the research traces of pesticide metabolites in some collected human brain tumor tissues in order to more emphasize our hypothesis for such a correlation between pesticide exposure and brain tumor development. Patients with a history of high-risk exposure were selected to conduct further analysis. Chemometric methods were adapted to discern intrinsic variation between pathological and control groups and ascertain effective separation with the identification of differentially expressed metabolites accountable for such variations. Three samples revealed traces of pesticide metabolites that were mostly detected at an early age. The histopathological diagnosis was medulloblastoma for a 10-year-old child and high-grade gliomas for 27- and 35-year-old adults. The bivariate analyses (odds ratio >1 and P value <5%) confirmed the great probability of developing cancer by an exposure case. The Cox proportional hazards model revealed the risk of carcinogenicity beyond the age of 50 as a long-term effect of pesticide toxicity. Our study supports the correlation between pesticide exposure and the risk of development of human brain tumors, suggesting that preconception pesticide exposure, and possibly exposure during pregnancy, is associated with an increased childhood brain tumor risk. This hypothesis was enhanced in identifying traces of metabolites from the carbamate insecticide class known for their neurotoxicity and others from pyridazinone, organochlorines (OCs), triazole fungicide, and N-nitroso compounds known for their carcinogenicity. The 2D-OXYBLOT analysis confirmed the neurotoxicity effect of insecticides to induce oxidative damage in CNS cells. Aldicarb was implicated in brain carcinogenicity confirmed by the identification of oxime metabolites in a stress degradation study. Revealing "aziridine" metabolites from the OC class may better emphasize the theory of detecting traces of pesticide metabolites at an early age. Overall, our findings lead to the recommendation of limiting the residential use of pesticides and the support of public health policies serving this objective that we need to be vigilant in the postmarketing surveillance of human health impacts.

Differential Proteome Profiling Analysis under Pesticide Stress by the Use of a Nano-UHPLC-MS/MS Untargeted Proteomic-Based Approach on a 3D-Developed Neurospheroid Model: Identification of Protein Interactions, Prognostic Biomarkers, and Potential Therapeutic Targets in Human IDH Mutant High-Grade Gliomas.

High-grade gliomas represent the most common group of infiltrative primary brain tumors in adults associated with high invasiveness, agressivity, and resistance to therapy, which highlights the need to develop potent drugs with novel mechanisms of action. The aim of this study is to reveal changes in proteome profiles under stressful conditions to identify prognostic biomarkers and altered apoptogenic pathways involved in the anticancer action of human isocitrate dehydrogenase (IDH) mutant high-grade gliomas. Our protocol consists first of a 3D in vitro developing neurospheroid model and then treatment by a pesticide mixture at relevant concentrations. Furthermore, we adopted an untargeted proteomic-based approach with high-resolution mass spectrometry for a comparative analysis of the differentially expressed proteins between treated and nontreated spheroids. Our analysis revealed that the majority of altered proteins were key members in glioma pathogenesis, implicated in the cellular metabolism, biological regulation, binding, and catalytic and structural activity and linked to many cascading regulatory pathways. Our finding revealed that grade-IV astrocytomas promote the downstream of the mitogen-activated-protein-kinases/extracellular-signal-regulated kinase (MAPK1/ERK2) pathway involving massive calcium influx. The gonadotrophin-releasing-hormone signaling enhances MAKP activity and may serve as a negative feedback compensating regulator. Thus, our study can pave the way for effective new therapeutic and diagnostic strategies to improve the overall survival.

A Case of Intra-Amniotic Umbilical Vein Varices Misdiagnosed as an Omphalocele.

Background: Intra-amniotic umbilical vein varices are characterized by a focal dilatation of the extra abdominal umbilical vein. Case report: We report a full-term baby female with extra-abdominal umbilical vein varices misdiagnosed clinically as an omphalocele. The umbilical vein was ligated and excised near the level of the liver. The infant died one day after surgery due to extrinsic compression of the renal pedicle by a massive thrombus, resulting in severe renal failure and life-threatening hyperkalemia despite intensive resuscitation. Conclusion: Large intra-amniotic umbilical vein varices can be clinically misdiagnosed as an omphalocele. Their resection near the level of the fascia, as with normal umbilical veins, could be a better management with a better prognosis.

Bioactivity of Falkenbergia rufolanosa Methanolic Extract: Assessment of Its Effect on Methyl-Thiophanate Induced Bone and Blood Disorders.

This study aimed to evaluate the potentiality of a mineral and antioxidant-rich methanolic extract of the red marine alga Falkenbergia rufolanosa (FRE) against methyl-thiophanate (MT)-induced toxicity in adult rats. The animals were allocated into four groups: controls, MT (300 mg/kg), MT + FRE, and FRE-treated group for 7 days. Our results demonstrated severe mineral perturbations due to MT treatment, especially in calcium and phosphorus levels in plasma, urine, and bone. Similarly, the hematological analysis revealed increased red blood cells, platelets, and white blood cells associated with striking genotoxicity. Interestingly, a significant rise in lipid peroxidation and advanced oxidation protein products level in erythrocytes and bone were noted. Meanwhile, a depletion of the antioxidant status in both tissues occurred. These biochemical alterations were in harmony with DNA degradation and histological variation in bone and blood. In the other trend, data showed that treatment with alga improved MT-induced hematotoxicity, genotoxicity, and oxidative stress in the blood and bone. Osteo-mineral metabolism and bone histo-architecture were also noted. In conclusion, these findings demonstrated that the red alga Falkenbergia rufolanosa is a potent source of antioxidant and antibacterial agents, as revealed by the in vitro analysis.

Complete remission in metastatic hepatocellular carcinoma.

Bone metastases from hepatocellular carcinoma (HCC) are unusual. Optimal treatment strategies are not well defined. The prognosis of this entity is very poor with a survival that does not exceed 1 year. We report here a new case of metastatic HCC with longer overall survival of more than 5 years in a 67-year-old man.

Spontaneous perforation of primary gastric diffuse large B-cell lymphoma.

Primary gastric malignant lymphoma is a rare tumor. The complications associated with lymphoma are perforation, bleeding, or upper gastrointestinal stricture. While it is well known that perforations in gastric lymphoma often occurs during chemotherapy, spontaneous perforation is extremely rare in patients who did not receive chemotherapy. This complication requires a surgical treatment.

Mixed Hepatocellular-Neuroendocrine Carcinoma: A Case Report and Literature Review.

Mixed hepatocellular-neuroendocrine carcinoma (HCC-NEC) is a rare entity with a poor prognosis. We report a case of a 44-yearold Tunisian man who was admitted for diffuse abdominal pain. Body computed tomography showed multinodular hepatomegaly. Pathologic findings concluded to HCC-NEC. Clinicians should be aware about this entity. Further collection of case reports is needed to standardize the optimal treatment.

The Prognostic Significance of CD10 Expression in Invasive Breast Carcinoma in Tunisian Patients.

BACKGROUND: Breast cancer is the first female cancer worldwide. Its prognosis depends mainly on pathological stage and histological grade. These classical prognostic factors are essential but may be insufficient to predict the outcome of the disease. Research focuses on identifying new prognostic factors such as CD10, which is a cell surface metalloproteinase. OBJECTIVE: This study aims to evaluate CD10 expression on stromal and tumor cells in invasive breast carcinomas and its correlations with other clinicopathological factors and survival. METHODS: A series of 100 cases of breast carcinoma of no special type diagnosed from 2009 to 2011, was investigated in this study. CD10 expression was detected by immunohistochemistry. Stromal CD10 expression (=10% stromal positivity was considered positive) and tumor cells expression (=1% stained carcinomatous cells) were noted. Statistical correlations were analyzed with different known prognostic parameters; survival analysis were performed using SPSS 22.0. RESULTS: Stromal CD10 expression was seen in 60% of the cases. It showed positive correlation with high tumor grade (p=0,012) and distant metastasis (p=0,02). CD10 expression on tumor cells was observed in 10% of the cases. It was associated with high tumor grade (p=0,009), hormone receptor negativity (estrogen receptor: p<0,0001), progesterone receptor: p=0,005), triplenegative phenotype (p=0,001), and Ki67 overexpression (p=0,046). Stromal CD10 expression was significantly associated to a shorter overall survival (p=0,029) and disease-free survival (p=0,05) in univariate analysis. CONCLUSION: Given these results, it can be concluded that CD10 expression predict an aggressive behavior of breast cancer. This marker can be introduced as a determinant prognostic factor.

Discordance in receptor status between primary and metastatic breast cancer and overall survival: A single-center analysis.

BACKGROUND: The tumor phenotype may change between primary and metastatic breast cancer. We compared the expression of estrogen receptor (ER), progesterone receptor (PR), and HER2 in a series of primary breast carcinomas (PBC) with their metastatic relapses and analyzed the impact of any changes on survival. MATERIALS AND METHODS: It was a single-center retrospective study, collecting consecutive cases of metastatic breast carcinoma diagnosed in the pathology and medical oncology departments at Habib Bourguiba University Hospital in Sfax, Tunisia. An immunohistochemical study was used to assess ER, PR, and HER2 expression. Overall survival (OS) and post-metastasis survival (PMS) were evaluated using multivariable Cox regression analysis. RESULTS: Our study included 68 patients. ER and PR status changed in 29.4 % and 39.7 % of cases, respectively. Conversions were mainly from positive to negative status (22 % and 23.5 % for ER and PR, respectively). Differences in HER2 status were observed in 19.6 % of cases, with loss of overexpression in 6 patients (10.7 %). Adjuvant trastuzumab therapy and PBC molecular subtype (HR-, HER2+) were associated with HER2 status discordance (p = 0.02 and 0.03, respectively). On multivariable analysis, HR-negative conversion tumors were significantly associated with a worse OS (p = 0.042) and PMS (p < 0.001), compared to HR-concordant positive tumors. CONCLUSION: This study establishes that HR and HER2 status discordance between primary and metastatic breast carcinoma has a prognostic impact on patient outcome. Analyzing these receptors' status in all newly diagnosed cases of metastatic breast carcinoma is strongly recommended and would provide information for changing treatment strategies.

Immunohistochemical Overexpression of Cyclin D1 in Tunisian Invasive Breast Carcinoma Women.

BACKGROUND: Breast cancer represents the most frequent cancer and cause of death in women worldwide and in Tunisia. Cyclin D1 is a gene of cell cycle regulation. It represents a potential oncogene in invasive breast cancer; however; the results are conflicting. We performed a retrospective study aiming to analyze the prognostic impact of cyclin D1 expression in patients with invasive breast carcinoma of no special type and its relation with clinical-pathological features. METHODS: One hundred cases of invasive breast carcinoma of no special type diagnosed between 2009 and 2011 were included in this study. Immunohistochemical (IHC) staining was performed for cyclin D1 in all cases. Results were analyzed statistically. RESULTS: Cyclin D1 positivity was seen in 74 cases (74%), of which 32 cases (32%) showed strong immunoreactivity. Cyclin D1 staining was statistically significantly associated with estrogen receptor (ER) and progesterone receptor (PR) positivity (P<0.0001) and with low grade SBR (P=0.007). None of the clinical data and other pathological features had any association with cyclin D1 expression (P>0.05). Univariate analysis revealed that expression of cyclin D1 was not statistically associated with overall survival (OS) and disease-free survival (DFS) (P=0.459 and P=0.564, respectively). CONCLUSION: These results confirm that cyclin D1 overexpression can be employed as a beneficial prognostic marker and suggest that anti-cyclin D1 therapy may be efficient, especially for ER positive tumors.

Ectopic Cervical Thymic Hyperplasia In A Patient Treated For Hodgkin Lymphoma.

True thymic hyperplasia results from stressful situations such as chemotherapy. It commonly presents as an anterior mediastinal mass; cervical location is exceptional. Here we report a case of a cervical true thymic hyperplasia in a 12-year-old girl who had a Hodgkin lymphoma treated by radiotherapy and chemotherapy. She was referred to our department for a left cervical mass. The PET scan showed a hypermetabolic adenopathy. Mediastinal MRI was unremarkable. The patient underwent resection of the cervical mass under general anesthesia. Pathological examination confirmed the diagnosis of a true thymic hyperplasia. The aim of this paper is to illustrate a case of an incidental ectopic cervical thymic hyperplasia in a patient treated for Hodgkin lymphoma.

Liver injury in COVID-19: pathological findings.

Hepatic injuries have been reported in patients with Coronavirus disease 2019 infection, particularly in those with moderate to severe illness. To date, pathological changes caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in liver tissue are unclear. Moreover, the mechanisms involved in liver injury in Coronavirus disease 2019 infection are not yet established. In this paper, we summarize the spectrum of pathologic findings of liver injury in patients infected by SARS-CoV-2 and we discuss the clinicopathological correlation and the mechanisms of liver damage in Coronavirus disease 2019 infection.

Laryngeal Myxoma: A rare localization.

INTRODUCTION: Myxomas are benign mesenchymal neoplasms which arise mainly in the heart. The laryngeal localization is very rare. We aim to describe the clinical, histological and therapeutic features of this condition. CASE REPORT: We report two cases of laryngeal myxomas occurred in male and female patients, presenting with a history of prolonged hoarseness. Laryngoscopy revealed a polypoid mass on the true vocal folds. The lesions were excised with cold instruments. One patient presented a recurrence 4 years after the first surgery. CONCLUSIONS: Laryngeal myxoma should be considered in case of a benign looking vocal fold lesion, especially a vocal cord polyp. Histologic exam is the only tool to confirm the diagnosis. It is treated by surgical resection. In the literature, recurrence is rare in laryngeal site, but patients need to be kept on close follow-up.

Alveolar Adenoma: A Rare Benign Tumour of the Lung with A Challenging Diagnosis.

Alveolar adenoma is a rare lung benign tumour originating from type II pneumocytes. It presents as a well-defined nodule. In some cases, it is difficult to differentiate from lung cancer. Few cases of this tumour have been reported. We describe here a case of alveolar adenoma in a 63-year-old man discovered incidentally on chest X-ray. The lesion was reported as lepidic adenocarcinoma in bronchoscopic biopsy. The patient underwent a thoracoscopic left lower lobectomy. The histopathological and immunohistochemical examinations resulted in a diagnosis of alveolar adenoma. We report this case to describe its morphological and immunohistochemical characteristics and to emphasize its diagnostic difficulties.

Development and Evaluation of the Wound Healing Effect of a Novel Topical Cream Formula Based on Ginkgo biloba Extract on Wounds in Diabetic Rats.

Despite advances in diabetes care, impaired diabetic wound healing remains a significant clinical problem. The present study was aimed at developing a novel cream based on Ginkgo biloba extract and investigating its wound healing effect on full-thickness wounds in diabetic rats. The topical formulated oil-in-water emulsion-based cream contains Ginkgo biloba aqueous extract in an amount of about 1% to 5% as an active agent. The prepared formula was subjected to physicochemical assessment and pharmacotechnical characterization. Eighteen alloxan-induced diabetic rats completing full-thickness excisional skin wounds were randomly divided into three groups topically treated with either a normal saline (control group), the reference drug ("Cytol Centella cream®"), and cream based on the Ginkgo biloba extract. The response to treatment was assessed by macroscopic, qualitative, and quantitative histopathological analysis. The prepared formula showed good physicochemical properties. The rheological behavior of the prepared cream followed a non-Newtonian pseudoplastic pattern at different storage temperatures. The cream, which is a macroemulsion with uniform size distribution, remained stable for 6 months. Skin tolerance studies confirmed the compatibility of the cream with the skin. During the experimental trial, the cream based on the Ginkgo biloba-treated group showed significant improvements over the control and reference groups for both general wound appearance and healing dynamics. This increased rate of closure of wounds in diabetic rats was associated with increased collagen synthesis. Our findings showed that the cream could be a promising and innovative topical treatment with Ginkgo biloba extract for the management of acute diabetic wounds.

Bilateral multifocal nodular oncocytic hyperplasia of the parotid gland: a rare entity.

Multifocal nodular oncocytic hyperplasia is an uncommon oncocytic lesion that rarely occurs in the parotid gland. Here, we report a case of a 43-years-old woman who presented with isolated gradual swelling in the 2 parotid regions. She underwent exofacial right parotidectomy. Histologic exam confirmed the diagnosis of oncocytoma arising in a background of multifocal nodular oncocytic hyperplasia with a histological variant of clear cells. Since the lesion was diagnosed as a benign lesion, surgery of the left side was not done. Our case is characterized by: early onset, the histological variant of clear cells and the presence of synchronous oncocytoma. We describe the clinical, histological and therapeutic features of this entity.

Antioxidant and hepatopreventive effects of Cassia angustifolia extract against carbon tetrachloride-induced hepatotoxicity in rats.

The present study aimed to investigate the preventive effects of methanol fraction from Cassia angustifolia leaf extract (MECA), associated with its phytochemical content, on CCl4-induced hepatic toxicity in adult rats. In the controls, CCl4 induced an increase of serum biochemical parameters and triggered oxidative stress in the liver. MECA caused significant reductions in CCl4-elevated levels of hepatic markers, total cholesterol, triglycerides, and low-density lipoprotein and increased the level of high-density lipoprotein compared to the CCl4 group. Moreover, pretreatment with the MECA produced significant reductions in lipid peroxidation (thiobarbituric acid reactive substances) and protein carbonyl level in liver tissues as compared with the untreated group. The formation of pathological hepatic lesions was strongly prevented by MECA. Overall, this study suggests that administration of MECA has a high potential to quench free radicals and alleviate CCl4-induced hepatotoxicity in rats.