An 83-year-old woman presented with a nodule in the upper lobe of her left lung, discovered incidentally on a standard chest X-ray. Chest computed tomography (CT) revealed a peripheral, subpleural nodule with spiculated margins and some calcifications, features highly suggestive of malignancy. A wedge resection of the nodule was performed. Macroscopically, the surgical specimen consisted of a firm, grayish subpleural nodule measuring 6 cm in greatest diameter. Histologically, the lung tissue was replaced by an amorphous eosinophilic acellular deposit that stained brick red with Congo red and exhibited an apple-green birefringence under polarized light. This appearance was consistent with an amyloid deposit. No associated neoplastic lesion was identified. A comprehensive clinical work-up was undertaken to exclude systemic amyloidosis, which yielded negative results. Consequently, a diagnosis of localized nodular pulmonary amyloidosis (NPA) was established. NPA is an exceedingly rare entity, often discovered incidentally, and manifests as a single or multiple subpleural nodules of varying sizes. The radiological appearance is non-specific, leading to misdiagnosis of pulmonary cancer. The definitive diagnosis is made by histopathological examination. Therefore, localized NPA should be considered in the differential diagnosis of a pulmonary nodule. Awareness of this rare condition is crucial to avoid misdiagnosis and unnecessary extensive surgical procedures.

Introduction: Liver cystic metastases (LCM) from squamous cell carcinoma (SCC) are exceedingly rare. Case presentation: This case report presents a 42-year-old man with a solitary liver cystic lesion, initially mimicking benign or infectious etiologies. Despite extensive radiological workup, the diagnosis remained elusive. Ultimately, a percutaneous biopsy revealed metastatic, non-keratinizing SCC, with the primary tumor subsequently identified in the pterygopalatine fossa. Conclusion: This case highlights the diagnostic challenges posed by solitary LCM, emphasizing the importance of considering rare malignancies in the differential diagnosis. Although imaging modalities such as magnetic resonance imaging are valuable, definitive diagnosis often requires histopathological confirmation. This case underscores the need for a high index of suspicion for SCC as a potential primary tumor in patients with unexplained liver cystic lesions.

Purpose:This study aimed to characterize the clinical and molecular features of a Tunisian family suspected of Lynch syndrome (LS) and identify the segregating pathogenic variant(s). Methods:A three-generation consanguineous family from the south of Tunisia with six members was recruited. Clinical diagnosis of LS was suspected according to the criteria of Amsterdam. A comprehensive molecular analysis was conducted, including immunohistochemical staining for mismatch repair (MMR) proteins, microsatellite instability (MSI) testing, targeted next-generation sequencing (NGS), and confirmatory Sanger sequencing. Iterative Threading ASSEmbly Refinement (I-TASSER) was used to analyze changes in the functional domains of mutant proteins. Results:Five members of the family developed cancer before the age of 45, including four cases of colorectal cancer and one case of glioblastoma. Immunohistochemical analysis of the proband showed complete loss of MSH2 and MSH6 protein expression, consistent with a high MSI (MSI-H) phenotype. Germline testing identified a pathogenic frameshift variant in MSH2 (NM_000251: c.687delA, p.Ala230LeuTer16) in the proband, her father, and two of her brothers, whereas her healthy sister did not carry the variant. An additional germline pathogenic variant in MUTYH (NM_001048171: c.1143_1144dupG, p.Glu382GlyTer43) was detected only in the proband's father and one of her brothers and was absent in the proband. Moreover, the proband later developed an extracolonic malignancy, a right ovarian tumor. NGS analysis of the tumor tissue revealed a pathogenic BRCA2 variant (c.1813delA, p.Ile605TyrTer9), which provides a potential target for personalized therapy. This case report highlights the co-segregation of a rare pathogenic MSH2 variant in a Tunisian family and underscores its clinical implications for improving the management and surveillance of patients with Lynch syndrome.

Introduction The onset of sarcoidosis is likely the result of a complex genetic-environment-immunological interaction. This systematic review and meta-analysis aimed to identify occupational toxic particles associated with an increased risk of developing pulmonary sarcoidosis.Methods Publications in English, published from January 2000 to January 2025, were searched in PubMed, Scopus and JSTOR. The risk of bias was assessed for all included studies. Sensitivity analyses stratified by study quality were conducted to evaluate the robustness of the findings and potential bias. To assess publication bias, a funnel plot was used when more than six studies were included in the analysis.Results Five categories of toxic particles were identified to be associated with increased risk of the onset of sarcoidosis: chemicals, inorganic dusts, metals, mixed dusts and fumes and organic dusts. The quantitative analysis includes data from 13 studies. The results suggested that occupational silica, pesticides, mould/mildew and World Trade Center ((WTC) dust exposures were associated with increased odds of pulmonary sarcoidosis. Sensitivity analysis confirmed the robustness of the association for WTC dust and mould, whereas the risk associated with silica appeared attenuated in high-quality studies. However, gold exposure was identified as a protective factor.Conclusion Pulmonary sarcoidosis is associated with occupational silica, pesticides, WTC dust and mould. Future research should prioritise gene-environment interactions and granuloma mineralogy to refine preventive strategies and disease management.

Epidermal Growth Factor Receptor (EGFR) mutations play a central role in the management of non-small cell lung cancer (NSCLC) by identifying patients who may benefit from targeted therapies. While the global distribution of EGFR mutations has been widely described, data from North African populations remain sparse. This gap limits the understanding of regional molecular profiles and underscores the need for population-specific evidence to inform precision oncology in North Africa. We analysed EGFR mutations in a cohort of 385 Tunisian patients with histologically confirmed NSCLC. Real-time PCR was used to screen for mutations in exons 18–21 of the EGFR gene. Associations between mutational status and clinical or demographic characteristics were assessed using appropriate statistical methods. EGFR mutations were detected in 77 among 385 patients (20

BACKGROUND:Ovarian cancer is one of the leading causes of death from gynecological cancer worldwide. Genetic mutations in genes involved in key cellular functions such as BRCA1/2 play a central role in tumorigenesis and have major implications for targeted therapeutic strategies, especially the use of poly (ADP-ribose) polymerase (PARP) inhibitors. CASE:Herein, we described a case of a 50-year-old woman diagnosed with severe anemia secondary to heavy menometrorrhagia. Initial gynecological evaluation, including transvaginal ultrasound, was unremarkable, and endometrial biopsy was not indicated. Imaging revealed no ovarian abnormalities; however, exploratory laparotomy identified a peritoneal nodule, leading to further investigation. Targeted NGS was performed on somatic and germline DNA samples and showed a frame shift deletion of 10 bp (c.1256_1265del: p.R419Ter) in the BRCA1 gene. This variant, identified only in tumor tissues, is novel and classified as pathogenic in ClinVar and ACMG databases. Additional somatic alterations were detected in TP53 and MSH6, while germline testing revealed only a variant of uncertain significance in BARD1. After first-line chemotherapy, the patient benefited from olaparib and achieved a progression-free survival of 23 months with good tolerance and no evidence of disease recurrence. CONCLUSION:This finding highlights the importance of integrating tumor-based genomic profiling with germline testing to identify actionable mutations and guide precision oncology. The identification of a novel somatic BRCA1 mutation expands the mutational spectrum of HGSOC and underscores the need to include underrepresented populations, such as those from North Africa, in genomic studies.

Pemphigus foliaceus (PF) is a multifactorial skin disease. Substantial evidence for microbiota dysbiosis in skin disorders was gradually revealed. In PF patients' skin lesions, we characterized the profile of microbial communities and the expression of microbial peptides. Using real-time reverse transcriptase PCR and immunohistochemistry, skin lesions were analyzed for gene and protein expression of human β-defensin (hBD) 1, 2, and 3, cathelicidin (LL-37), RNAse-7, and psoriasin. Bacterial 16S rRNA gene sequencing was used for assessing skin microbial communities in 15 samples from PF patients' lesioned skin and 11 PF patients' non-lesioned skin. Gene expression of hBD 2 and 3 and psoriasin were significantly downregulated in skin samples from remittent patients compared to chronic or de novo diagnosed patients. Protein expression of hBD 2, Psoriasin, and LL-37 was increased in skin from de novo patients compared to skin from healthy donors showing markedly different distribution patterns. The skin microbial analysis revealed a substantial difference in microbiome diversity between lesioned and non-lesioned skin of de novo PF patients and, non-lesioned skin of remittent patients. In addition, microbiome diversity within samples of lesioned skin from de novo PF patients showed lower diversity with a lower abundance of specific bacterial genera, namely Dermabacter, Psychrobacter, and Bradyrhizobium. Thus, there is a noticeable over-representation of Staphylococcus and decreased richness in the bacterial communities of PF-active skin lesions. Our data supports the hypothesis that active skin lesions in PF patients exhibit alterations in skin bacterial diversity interlinked with increased expression of AMPs.

Introduction and importance: Tall cell carcinoma with reverse polarity (TCCRP) is a rare and newly recognized subtype of invasive breast carcinoma, first described in 2003. It shares histological similarities with tall cell papillary thyroid carcinoma, characterized by papillary structures with reverse cellular polarity. Due to its rarity, TCCRP has been poorly understood, and fewer than 100 cases have been reported globally. This report presents the first case of TCCRP in South Tunisia, contributing to the growing body of knowledge regarding this rare tumor. Case presentation: A 34-year-old woman with no significant personal or family history of breast cancer presented with an incidental finding of a 1 cm breast mass. Imaging studies revealed an atypical mass classified as ACR 4a. Histological analysis following lumpectomy showed circumscribed nests of epithelial cells with delicate fibrovascular cores, resembling papillary structures. Immunohistochemical staining revealed diffuse positivity for cytokeratin 5/6 and calretinin, and negativity for estrogen, progesterone, HER-2, and TTF1. The diagnosis of TCCRP was confirmed. The tumor was classified as SBR grade I, with no lymphovascular invasion or carcinoma in situ. No metastasis was observed in the 31 axillary lymph nodes. Clinical discussion: TCCRP primarily affects women over 60, with a low incidence in younger individuals. It typically presents as a small, palpable breast mass. Histologically, TCCRP exhibits a solid-papillary architecture with tall cells, reverse polarity, and rare foamy histiocytes. Immunohistochemical findings include negative estrogen, progesterone, HER-2, and TTF1 markers, along with positive staining for calretinin. Molecular studies have revealed IDH2 and PIK3CA mutations in the majority of cases. Despite being triple-negative, TCCRP has a favorable prognosis, with low rates of metastasis or recurrence. Conclusion: TCCRP is a rare subtype of invasive breast carcinoma with distinct histological and immunohistochemical features. It is characterized by an indolent clinical course and an excellent prognosis. Conservative surgical management with clear margins is the optimal treatment approach, with no clear indications for lymph node dissection, chemotherapy, or radiotherapy.

Background and objectives: The fifth edition of the WHO Classification of Tumors of the Central Nervous System divides grade 4 diffuse glioma based on IDH1 mutation in grade 4 astrocytoma, IDH-mutant and glioblastoma, IDH-wild type tumors. This study aimed to evaluate the IDH1 status in grade 4 diffuse glioma as well as its correlation with clinicopathological features and patient survival. To our knowledge, no Tunisian studies on the molecular profile of diffuse glioma have yet been published. Methods: This is a retrospective study including all cases of adult, grade 4 diffuse glioma collected in the pathology department of Habib Bourguiba hospital. Results: A total of 67 patients were included in the final analysis. The expression of IDH1 was positive in 22 cases (32%). IDH1-positive tumors were classified as grade 4 astrocytoma, IDH1-mutant while, 45 IDH1-negative tumors were classified as glioblastoma, IDH1-wild type tumors (68%). IDH1 expression was correlated with younger age (≤ 40 years old), frontal location, complete surgical resection and well-defined borders. IDH1-positive tumors were associated significantly with better prognosis. The 1-year overall survival (OS) for grade 4 astrocytoma, IDH1-mutant was 86% compared with 8% in glioblastoma, IDH1-wild type (p=0.008). Conclusion: Our study investigated IDH1 expression in grade 4 diffuse glioma and proved that grade 4 astrocytoma, IDH1 positive tumors displayed different characteristics with a more favorable outcome compared to glioblastoma, IDH1 negative. Thus, evaluation of IDH1 mutation should be standardized routinely not only as diagnostic marker but also to refine the prognostic classification of these tumors.

Wilson's disease is an autosomal recessive disorder related to genetic defects in ATP7B gene and characterized by a hepatic and/or neurological impairment. This disease is often misdiagnosed on due to its phenotypic heterogeneity, supporting the importance of the genetic testing. In our study, we reported two brothers presenting with a chronic hepatopathy, classified as intrahepatic cholestasis with unknown etiology based on clinical explorations. A molecular screening through Whole-exome-sequencing was conducted, followed by sanger sequencing and co-segregation analysis in the family's members. Generated data were the subject of in silico analysis. Results revealed two pathogenic heterozygous variants in ATP7B gene (p.Met665Ile/ p.Gly869Arg) in compound heterozygous state in the analyzed proband and his brother. Predictive data supported their effect on the stability at the RNA and protein levels. In line of these data, additional clinical explorations were ensured and the Leipzig score was assessed to establish the WD diagnosis. Moreover, we identified two additional heterozygous variants shared by both siblings in CFTR (p.Thr351Ser) and PEX26 (p.Leu153Val), which may act as phenotype modifiers. Notably, both patients exhibited exocrine pancreatic insufficiency, raising the possibility of a contributory role for the CFTR variant in this atypical presentation. In conclusion, our study reveals a complex genetic background involving ATP7B, CFTR, and PEX26. While the ATP7B variants are responsible for WD, the additional variants may influence the age of onset and severity of the clinical phenotype. These findings underscore the value of high-throughput sequencing technologies in uncovering the molecular basis and phenotypic complexity of inherited diseases.

AA amyloidosis is a rare complication of systemic lupus erythematosus (SLE). We report a 39-year-old woman with well-controlled SLE who developed nephrotic syndrome and progressive multi-organ involvement. Evaluation revealed elevated serum amyloid A levels, proteinuria, and increased cardiac biomarkers. Echocardiography suggested cardiac infiltration. Renal and labial salivary gland biopsies confirmed AA amyloid deposition by Congo red staining and immunohistochemistry. High-dose corticosteroid therapy led to partial clinical and biological improvement; however, the patient later developed gastrointestinal involvement and rapidly progressive clinical deterioration, resulting in death. This case highlights the diagnostic challenges of AA amyloidosis in SLE and emphasizes the importance of early recognition, systematic histological confirmation, and multidisciplinary management due to its poor prognosis.

Introduction and importance Congenital lung malformations (CLMs) are rare congenital abnormalities resulting from abnormal development of the foregut and tracheobronchial tree. Pulmonary sequestration (PS) and bronchogenic cysts (BC) are two such anomalies, and while they can occasionally coexist, the combination of intralobar pulmonary sequestration (ILS) and BC is exceptionally rare. Only a limited number of cases have been reported in the literature. This case presents a unique occurrence of ILS and BC in the left lower lobe of an elderly woman, contributing to the understanding of these anomalies' shared origin. Case presentation A 57-year-old woman with no significant medical history presented with left-sided chest pain and cough lasting for one month. Chest CT revealed a well-circumscribed cystic lesion in the left lower lobe, initially suspected to be a hydatid cyst. During surgery, a feeding artery originating from the descending thoracic aorta was found, confirming ILS. The cyst contained a thick chocolate-like fluid, suggesting a BC. Pathological analysis confirmed the presence of a unilocular cyst lined by respiratory epithelium, with features consistent with BC and ILS. The postoperative recovery was uncomplicated. Clinical discussion CLMs include various malformations such as foregut duplication cysts, PS, and congenital pulmonary airway malformations. BCs arise from the ventral foregut and are usually asymptomatic but may present with symptoms due to infection or complications. PS is characterized by non-functioning lung tissue supplied by an aberrant systemic artery. CT features of PS vary, and angiography remains the gold standard for diagnosis. Two types of sequestration exist: extralobar and intralobar. ILS, typically considered acquired, has been occasionally linked to congenital anomalies, suggesting an embryological origin. The coexistence of BC and ILS is extremely rare, with only 10 cases reported in the literature. Conclusion The coexistence of Bronchogenic Cyst (BC) and Intralobar Pulmonary Sequestration (ILS) is a rare condition, with only a few cases documented. This case highlights the complexity of diagnosing these pulmonary malformations and suggests a potential shared congenital origin, challenging previous theories that ILS arises from chronic inflammation. Further studies are needed to elucidate the embryological link between these malformations and their clinical implications.

Actinomycosis is a rare chronic granulomatous infection caused by Actinomyces species. We report the case of a 47-year-old man with no previous medical history, who presented with a slowly growing abdominal mass extending to the abdominal wall, initially mimicking a malignant tumor. A diagnosis of an Actinomyces abscess was confirmed through surgical resection and histopathological examination. This case is presented to highlight the morphological characteristics and emphasize the diagnostic difficulties of this disease.

Bartholin gland abscesses are typically caused by bacterial agents. Abscesses induced by Enterobius vermicularis are exceptional. We report, here, the case of a 27-year-old woman, whose histopathological examination of the Bartholin gland cyst confirmed the presence of E. vermicularis eggs in the lumen of the cyst.

Scorzonera undulata Vahl. roots are used for their nutraceutical and medicinal properties. In this work, GC-MS revealed that polysaccharides (P) and the methanolic extract (MB) of S. undulata roots contained 8 and 7 different components, respectively. They also potently inhibited the Free DPPH radical (IC50% equals 103 ± 0.01 and 105 ± 0.01 µg/ml, respectively) and the viability of Hela cancer cell line (IC50 of 2.074 ± 0.05 mg/ml and 2.208 ± 0.05 mg/ml respectively). Furthermore, polysaccharides showed a relevant anti-inflammatory effect, as assayed by on carrageenan-induced paw edoema model. S. undulata contains several active molecules such as derivatives of gluconic acid, hexapyranosids, arabinofuranoside, and xylofuranose that might be useful in preventing and treating cancer and inflammation. It merits further investigations to pinpoint their mechanisms of action and their properties as a functional food.

Intramedullary spinal cord metastasis (ISCM) is very rare. Symptoms from ISCM metastasis being the initial presentation are extremely rare. We present a case of a 42-year-old woman without previous medical history who presented with complaints of progressive lower limb weakness of three weeks evolution. Neurological examination elicited a medullary syndrome, and physical examination showed a palpable mass on her right breast. A spinal MRI revealed a dorsal intramedullary tumor mass. A biopsy sample from the breast mass revealed the diagnosis of carcinoma. The diagnosis of an Intramedullary breast cancer metastasis (IMBCM) was made according to positron emission tomography. The patient received treatment with corticosteroids and radiation therapy without improvement, and she died, 3 months after the diagnosis. As far as we know, this is the first reported case of IMBCM revealing a breast carcinoma. Although extremely rare, ISCM should be considered as a differential diagnosis of a spinal intramedullary lesion.

OBJECTIVE:Colorectal cancer (CRC) is among the most commonly diagnosed cancers worldwide, with 2% to 5% of cases being linked to inherited syndromes. MATERIAL AND METHODS:A cohort of 30 Tunisian patients was selected and divided into two groups based on clinical features and family history: Group 1 included patients clinically diagnosed with hereditary polyposis syndromes, including MUTYH-Associated Polyposis (MAP: 15 cases) and Familial Adenomatous Polyposis (FAP: 5 cases). Group 2 consisted of patients clinically diagnosed with non-polyposis syndromes, including Lynch Syndrome (LS: 7 cases) and other rare syndromes (OS: 3 cases). Genetic testing was performed using either Sanger sequencing or targeted next-generation sequencing (NGS) with a cancer panel including 31 cancer-related genes. RESULTS:In Group 1, MAP was confirmed in 13 patients who were homozygous carriers of the pathogenic variant (c.1143_1144dup p.Glu382fs) in the MUTYH gene. For patients suspected of having FAP, pathogenic variants in the APC gene were identified in only two patients (c.3183_3187del p.Lys1061_Gln1062insTer, and c.2016_2017del p.His672Ter), while another patient carried a frameshift variant (c.502_503del, p.Ile168SerTer11) in the PTEN gene, indicating Cowden Syndrome. In Group 2, genetic testing confirmed Peutz-Jeghers Syndrome in a young girl who had a large deletion in the STK11 gene. For patients suspected to have LS, only variants of unknown significance (VUS) were identified in MMR. Further genetic investigations are required to identify the pathogenic variant in these patients. CONCLUSION:Overall, our results highlight the importance of genetic testing to better understand hereditary CRC syndromes in Tunisian families, and to improve the management of patients and their relatives.