Sternal tail: A new entity; A case report.

INTRODUCTION AND IMPORTANCE: Supernumerary ribs are very rare. They may occur at any level of the spine. We present here a case of an unusual localization of an extra rib that has not been previously described in the literature. CASE PRESENTATION: A 4-year-old girl, with no medical history, presented with a congenital deformity in the sternal region mimicking a tail. The tail-like structure had a bony axis and was covered by normal skin and hairs. A computed tomography of the chest demonstrated that this structure was an abnormal bone articulated with the the sternum. For cosmetic purposes, we have decided to resect the malformation. On histopathological examination, it was a supernumerary rib. CLINICAL DISCUSSION: A review of the literature reveals a global incidence of cervical ribs ranging from 0.04 % up to 4.5 %, intrathoracic ribs in about 50 cases to date and very few reports on supernumerary ribs in the lumbar and sacral region. We were unable to find any similar cases of supernumerary ribs in the sternum. CONCLUSION: Supernumerary ribs are rare and benign congenital anomalies. This case report describes an unusual localization of an extra rib in the sternum mimicking a tail.

Strategies for diagnosis and management of CMMRD in low-resource countries: report of a Tunisian family.

Constitutional Mismatch Repair Deficiency (CMMRD) is a rare childhood cancer predisposition syndrome, caused by biallelic pathogenic germline variants in the mismatch repair genes. Diagnosis and management of this syndrome is challenging, especially in low-resource settings. This study describes a patient diagnosed with colorectal cancer and grade 3 astrocytoma at the age of 11 and 12 respectively. Immunohistochemistry analysis showed a loss of MSH2 and MSH6 protein expression in CRC tissues of the patient. We identified by Targeted Exome Sequencing a homozygous pathogenic germline variant in exon 9 of the MSH6 gene (c.3991 C > T; p.Ala1268Glyfs*6). Genetic investigation of the family showed that the father was heterozygous for the identified pathogenic variant while the brother was wild type for this variant. Our study highlights the importance of a correct and timely diagnosis of CMMRD which can have implications for treatment. It also underlines the imperative need to enhance awareness, diagnostic standards, and surveillance that are crucial for patients and their families.

Impact of the COVID-19 pandemic on breast cancer pathological stage at diagnosis in Tunisian patients.

BACKGROUND: Breast cancer (BC) patients' diagnosis and management was affected by a global reorganization after the Coronavirus disease 2019 (COVID-19). Our study aimed to assess the impact of the pandemic on the pathological stage of newly diagnosed patients with BC compared to pre-pandemic and to identify predictive factors of tumor advanced stage. METHODS: Pathological records of all consecutive newly operated BC patients between March 2020 and December 2021 were reviewed retrospectively. Clinical and pathological prognostic factors of BC were collected and compared between pre-pandemic and pandemic periods. Then, predictive factors of tumor advanced stage were identified. RESULTS: Of the 225 cases included in the analysis, 98.7% were females and 1.3% were males. The median time from first histological diagnosis to first surgical treatment was enlarged by 42 days with a significant difference between the two periods (p = 0.002). Newly diagnosed BC patients during the COVID-19 pandemic were operated at a more advanced stage (54.1% vs 36.2%, p = 0.007), had a greater lymphovascular invasion (p = 0.002), lymph node metastasis (p = 0.015) and are more commonly of IBC NST histological type (p = 0.005). Moreover, multivariate analyses showed that the pandemic period (AOR = 2.28; p = 0.016) and the lympho-vascular invasion (p < 0.001) were independently associated with advanced stage of tumors. CONCLUSION: Our findings proved an increase in alarming rates of advanced stage BC associated with the COVID-19 crisis. These findings support recommendations for a quick restoration of BC screening at full capacity, with adequate prioritization strategies to mitigate harm.

Colorectal Cancer Archaeome: A Metagenomic Exploration, Tunisia.

Colorectal cancer (CRC) is a serious public health problem known to have a multifactorial etiology. The association between gut microbiota and CRC has been widely studied; however, the link between archaea and CRC has not been sufficiently studied. To investigate the involvement of archaea in colorectal carcinogenesis, we performed a metagenomic analysis of 68 formalin-embedded paraffin fixed tissues from tumoral (n = 33) and healthy mucosa (n = 35) collected from 35 CRC Tunisian patients. We used two DNA extraction methods: Generead DNA FFPE kit (Qiagen, Germantown, MD, USA) and Chelex. We then sequenced the samples using Illumina Miseq. Interestingly, DNA extraction exclusively using Chelex generated enough DNA for sequencing of all samples. After data filtering and processing, we reported the presence of archaeal sequences, which represented 0.33% of all the reads generated. In terms of abundance, we highlighted a depletion in methanogens and an enrichment in Halobacteria in the tumor tissues, while the correlation analysis revealed a significant association between the Halobacteria and the tumor mucosa (p < 0.05). We reported a strong correlation between Natrialba magadii, Sulfolobus acidocaldarius, and tumor tissues, and a weak correlation between Methanococcus voltae and healthy adjacent mucosa. Here, we demonstrated the feasibility of archaeome analysis from formol fixed paraffin-embedded (FFPE) tissues using simple protocols ranging from sampling to data analysis, and reported a significant association between Halobacteria and tumor tissues in Tunisian patients with CRC. The importance of our study is that it represents the first metagenomic analysis of Tunisian CRC patients' gut microbiome, which consists of sequencing DNA extracted from paired tumor-adjacent FFPE tissues collected from CRC patients. The detection of archaeal sequences in our samples confirms the feasibility of carrying out an archaeome analysis from FFPE tissues using a simple DNA extraction protocol. Our analysis revealed the enrichment of Halobacteria, especially Natrialba magadii, in tumor mucosa compared to the normal mucosa in CRC Tunisian patients. Other species were also associated with CRC, including Sulfolobus acidocaldarius and Methanococcus voltae, which is a methanogenic archaea; both species were found to be correlated with adjacent healthy tissues.

Tetraploidization Increases the Motility and Invasiveness of Cancer Cells.

Polyploidy and metastasis are associated with a low probability of disease-free survival in cancer patients. Polyploid cells are known to facilitate tumorigenesis. However, few data associate polyploidization with metastasis. Here, by generating and using diploid (2n) and tetraploid (4n) clones from malignant fibrous histiocytoma (MFH) and colon carcinoma (RKO), we demonstrate the migration and invasion advantage of tetraploid cells in vitro using several assays, including the wound healing, the OrisTM two-dimensional cell migration, single-cell migration tracking by video microscopy, the Boyden chamber, and the xCELLigence RTCA real-time cell migration. Motility advantage was observed despite tetraploid cell proliferation weakness. We could also demonstrate preferential metastatic potential in vivo for the tetraploid clone using the tail vein injection in mice and tracking metastatic tumors in the lung. Using the Mitelman Database of Chromosome Aberrations in Cancer, we found an accumulation of polyploid karyotypes in metastatic tumors compared to primary ones. This work reveals the clinical relevance of the polyploid subpopulation and the strategic need to highlight polyploidy in preclinical studies as a therapeutic target for metastasis.

Warthin-like papillary thyroid carcinoma: a case report and comprehensive review of the literature.

Background: Papillary Thyroid Carcinoma (PTC) is the most frequent endocrine malignancy with a variety of histological presentations. Warthin-like Papillary Thyroid Carcinoma (WLPTC) is an uncommon neoplasm that is recognized as a distinct subtype of PTC in the WHO classification of thyroid tumors. In this report, we present a novel case of WLPTC in a female patient and provide an in-depth review of the available literature on its clinical, pathological, and therapeutic characteristics. Case presentation: A 27-year-old female patient was referred for neck swelling. Ultrasound showed two suspicious thyroid nodules leading to a thyroidectomy. She was diagnosed with intermediate-risk bifocal foci of classic PTC and WLPTC, arising from a background of chronic lymphocytic thyroiditis (CLT). This pT1b(m) N1b M0 malignancy was treated with adjuvant isotopic ablation and suppressive thyroxine therapy. The 1-year outcomes were favorable. Literature review: It covered articles published from 1995 to 2022, by searching PubMed and Google Scholar using specific terms. Out of 148 articles reviewed by two authors, 25 relevant articles were selected, including 13 case reports and 12 case series. The study included 150 cases of WLPTC. Data related to clinical presentation, imaging, histological features, management, and outcomes, were extracted. The mean age of diagnosis was 39 years, with a female predominance. The most common clinical presentation was neck swelling. Thyroid autoimmunity was positive in 71.6% of patients. Lymph node metastases were present in 28% of cases, with no reported distant metastases. Overall, the outcomes were favorable. Conclusion: WLPTC shares similar clinical and radiological presentations as classic PTC. The hallmark histological features of WLPTC are papillae lined with oncocytic tumor cells with papillary nuclear changes and lymphoid stroma. WLPTC is almost constantly associated with CLT. The management of WLPTC aligns with that of classic PTC with comparable stage and risk category, often resulting in favorable outcomes.

Phyllodes Tumor of the Bladder in a 2-Year-Old Boy - An Exceptional Finding.

Background: Breast phyllodes tumor has a distinct histologic appearance. There are no pediatric phyllodes tumors of the bladder in English literature reported. Case report: A 2-year-old boy presented with a urinary infection and obstructive urinary symptoms. A 3-cm slow-growing bladder mass revealed by repeated transabdominal ultrasonography was initially considered a ureterocele. Cystoscopic and laparoscopic exploration using pneumovesicum confirmed the diagnosis of a bladder neck tumor. Histologically, the features were of a benign phyllodes tumor, morphologically similar to those seen in breast tissue. The patient received no further treatment and showed no recurrence or metastasis. Conclusion: Phyllodes tumor can cause a pediatric bladder tumor.

Congenital Epulis Diagnosed Antenatally.

Background: Congenital epulis is a benign gingival tumor whose differential diagnosis includes other oral-facial masses such as teratoma, hemangioma, lymphatic malformation and dermoid cysts. This tumor can cause obstruction of the airway or feeding problems in the newborn. Surgical excision is the treatment of choice. Case Report: We present a case of congenital epulis, diagnosed prenatally with ultrasonography. Conclusion: Although difficult, a defined prenatal image of congenital epulis is possible by means of accurate high-resolution ultrasonography. It facilitates the narrowing down of differential diagnosis. The confirmatory final diagnosis relies on histopathological examination.

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.

Atypical spindle cell lipomatous tumor of the tongue: A rare entity arising in an unusual location.

Atypical spindle cell/pleomorphic lipomatous tumor (ASCPT) constitutes an emerging entity of lipomatous tumors. It is a benign tumor. It occurs typically in limbs and limb girdles. The occurrence in oral cavity is unusual. The diagnosis of this neoplasm is challenging. Herein, we report a case of ASCPT arising in the tongue.

Predominance of the Rare EGFR Mutation p.L861Q in Tunisian Patients with Non-Small Cell Lung Carcinoma.

Objectives: Several new cancer therapies targeting signaling pathways involved in the growth and progression of cancer cells were developed as personalized medicine. Our study aimed to identify epidermal growth factor receptor (EGFR) mutations for TKI treatment in non-small-cell lung cancer (NSCLC) Tunisian patients. Methods: Analysis of the TKI sensitivity mutations in exons 18 to 21 of the EGFR gene and exon 15 of the B-raf gene was performed in 79 formalin fixed-paraffin embedded (FFPE) NSCLC samples using pyrosequencing. Results: EGFR mutations were detected in 34 cases among 79 (43%), with the predominance of the L861Q in exon 21 found in 35.3% of the cases (12 out of 34). Deletions in exon 19 were found in 8 cases (23.5%), and only one young male patient had the T790M mutation. Three patients harbored composite EGFR mutations (p.E746_A750del/p.L861R, p.E746_S752>V/p.S768I, and p.G719A/p.L861Q). Furthermore, the EGFR mutated status was significantly more frequent in female patients (p = 0.019), in non-smoker patients (p = 0.008), and in patients with metastasis (p = 0.044). Moreover, the B-raf V600E was identified in 5 EGFR negative patients among 39 analyzed samples (13.15%). Conclusion: The p.L861Q localized in exon 21 of the EGFR gene was the most common mutation identified in our patients (35.3%), whereas the "classic" EGFR mutations such as Del19 and p.L858R were found in 23.5% and 11.7% of the cases, respectively. Interestingly, most of p.L861X mutation-carrying patients showed good response to TKI treatment. Altogether, our findings suggest a particular distribution of the EGFR-TKIs sensitivity mutations in Tunisian NSCLC patients.

Unusual facial lesions in H syndrome.

H Syndrome is a rare genodermatosis. It may include facial involvement such as: facial telangiectasia, both hypo- and hyperpigmented lesions, hirsutism, swollen cheeks due to subcutaneous infiltration and eczematous lesions. We describe a new facial phenotype with dermoscopic and histological features in the spectrum of non-Langerhans cell histiocytosis.

Great imitator with exclusive oral manifestations.

Oral manifestations in syphilis are frequent through the different stages of the disease. Exclusive oral localization in secondary syphilis (SS) is yet uncommon. Delays in diagnosis are frequent in these patients. We describe a case of SS limited to the buccal mucosa with both serological and histological confirmation.

Multiple nodules in the scrotal wall.

Herein, we report a rare case of extensive ISC. It affects dark-colored skin men aged from 20 to 40 years old, suggesting an ethnic susceptibility. Pathogenesis of scrotal calcinosis remains controversial.

Effect of Artichoke (cynara scolymus) on cardiac markers, lipid profile and antioxidants levels in tissue of HFD-induced obesity.

Obesity plays a pivotal role in the insulin resistance disease, which is related to hypertension, hyperlipidemia, type 2 diabetes mellitus, and an increased risk of cardiovascular disease. The purpose of the present study was done to evaluate the effect of artichoke leaves extract (ALE) in the high-fat diet (HFD)-induced cellular obesity and cardiac damage in Wistar rats. Body and organ weights, serum lipid profile, cardiac markers, and antioxidants enzymes were measured. Oral administration of ALE at two doses 200 and 400 mg/kg for a period of 60 days showed a significant decrease in body and organ weights, serum total cholesterol, triglycerides, LDH, ALT accompanied by decreasing in oxidative stress biomarker (MDA, and AOPP) and increasing antioxidant enzymes (SOD, CAT, and GPx) levels as compared to HFD groups. The histological findings showed a cardioprotective effect of ALE. These findings suggest that ALE exert anti-oxidant cardiac effects in HFD- induced obese rats.

Preventive effect of Artichoke (Cynara scolymus L.) in kidney dysfunction against high fat-diet induced obesity in rats.

A high-fat diet (HFD) promotes oxidative stress, which contributes to the development of kidney dysfunction. We examined the protective effects of an ethanol extract of artichoke leaves (EEA) compared to Atorvastatin (ATOR) in the kidney of Wistar rats fed a high-fat diet. The experimental animals were divided into five groups: control (Cont), HFD, HFD treated with EEA (200 mg/kg), HFD treated with EEA (400 mg/kg), and HFD treated with ATOR. Organ weights, lipid profile, renal markers, and antioxidants enzymes were measured. Oral administration of EEA (200 and 400 mg/kg) for 60 days showed a significant decrease in organ weights and kidney markers levels accompanied by decreasing in oxidative stress biomarkers as compared to HFD groups. The histological findings showed a renoprotective effect of artichoke extract. These findings suggest that EEA exerts anti-oxidant kidney effects in HFD- induced obese rats.

Immune checkpoint CD155 promoter methylation profiling reveals cancer-associated behaviors within breast neoplasia.

BACKGROUND: CD155 immune checkpoint has recently emerged as a compelling immunotherapeutic target. Epigenetic DNA methylation changes are recognized as key molecular mechanisms in cancer development. Hence, the identification of methylation markers that are sensitive and specific for breast cancer may improve early detection and predict prognosis. We speculate that CD155 promoter methylation can be a valuable epigenetic biomarker, based upon strong indications for its immunoregulatory functions. METHODS: Methylation analyses were conducted on 14 CpGs sites in the CD155 promoter region by bisulfite pyrosequencing. To elucidate the related gene expression changes, a transcriptional study using RT-qPCR was performed. Statistical analyses were performed to evaluate correlations of CD155 methylation profiles with mRNA expression together with clinical-pathological features, prognosis and immune infiltrate. RESULTS: CD155 promoter methylation profile was significantly associated with SBR grade, tumor size, molecular subgroups, HER2 and hormonal receptors expression status. Low CD155 methylation rates correlated with better prognosis in univariate cox proportional hazard analysis and appeared as an independent survival predictor in cox-regression multivariate analysis. Further, methylation changes at CD155 specific CpG sites were consistent with CD155 membranous mRNA isoform expression status. Statistical analyses also showed a significant association with immune Natural Killer cell infiltrate when looking at the CpG7, CpG8, CpG9 and CpG11 sites. CONCLUSION: Altogether, our results contribute to a better understanding of the impact of CD155 immune checkpoint modality expression in breast tumors, revealing for the first time that specific CpG sites from CD155 promoter may be a potential biomarker in breast cancer monitoring.

Protective effect of Urtica dioica in induced neurobehavioral changes, nephrotoxicity and hepatotoxicity after chronic exposure to potassium bromate in rats.

BACKGROUND AND PURPOSE: Chronic exposure to potassium bromate (KBrO3), a toxic halogen in the environment, has become a global problem of public health. The current study aims to elucidate for the first time the effect of Urtica dioica (UD) on behavioural changes, oxidative stress, and histopathological changes induced by KBrO3 in the cerebellum, kidney, liver and other organs of adult rats. STUDY DESIGN AND METHODS: The rats were divided into four groups: group 1 served as a control received physiological serum, Group 2 received KBrO3 (2 g/L of drinking water), group 3 received KBrO3 and Urtica dioica (100 mg/kg), and group 4 received KBrO3 and Urtica dioica (400 mg/kg). We then measured behavioural changes, oxidative stress, and biochemical and histological changes in the cerebellum, liver, kidney and others organs in these rats. After 30 days of treatment, the animals were sacrificed. RESULTS: We observed significant behavioural changes in KBrO3-exposed rats. When investigating redox homeostasis in the cerebellum, we found that mice treated with KBrO3 had increased lipid peroxidation and protein oxidation in the cerebellum. In addition, it inhibits hepatic and lipid peroxidation (malondialdehyde), advanced oxidation protein product (AOPP), attenuates KBrO3-mediated enzyme depletion, catalase, superoxide dismutase, glutathione peroxidase enzymatic and antioxidant activities in the liver and kidney. Rats that were co-managed with Urtica dioica at the high portion of 400 mg/kg indicated a higher effect than that treated with the low dose of 100 mg/kg practically in all the tests carried out. CONCLUSION: Our results demonstrate that Urtica dioica is a potential therapeutic agent for oxidative stress associated with neurodegenerative diseases.