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The widespread use of pesticides, particularly in combinations, has resulted in enhanced hazardous health effects. However, little is known about their molecular mechanism of interactions. The aim of this study was to assess the neurotoxicity effect of pesticides in mixtures by adopting a 3D in vitro developed neurospheroid model, followed by treatment by increased concentrations of pesticides for 24 h and analysis by a shotgun proteomic-based approach with high-resolution tandem mass spectrometry. Three proteins, namely, glyceraldehyde-3-phosphate-dehydrogenase (GAPDH), α-enolase, and phosphoglycerate-kinase-1, were selected as key targets in the metabolic process. Only high doses of pesticides mitigated cell-density proliferation with the occurrence of apoptotic cells, which unlikely makes any neurological alterations in environmental regulatory exposures. The proteomic analysis showed that majority of altered proteins were implicated in cell metabolism. De novo peptide sequencing revealed ion losses and adduct formation, namely, a trityl-post-translational modification in the active site of 201-GAPDH protein. The study also highlights the plausible role of pyrethroids to be implicated in the deleterious effects of pesticides in a mixture. To the best of our knowledge, our finding is the first in toxicoproteomics to deeply elucidate pesticides' molecular interactions and their ability to adduct proteins as a pivotal role in the neurotoxicity mechanism.

Many inherited conditions cause hepatocellular cholestasis in infancy, including progressive familial intrahepatic cholestasis (PFIC), a heterogeneous group of diseases with highly overlapping symptoms. In our study, six unrelated Tunisian infants with PFIC suspicion were the subject of a panel-target sequencing followed by an exhaustive bioinformatic and modeling investigations. Results revealed five disease-causative variants including known ones: (the p.Asp482Gly and p.Tyr354 * in the ABCB11 gene and the p.Arg446 * in the ABCC2 gene), a novel p.Ala98Cys variant in the ATP-binding cassette subfamily G member 5 (ABCG5) gene and a first homozygous description of the p.Gln312His in the ABCB11 gene. The p.Gln312His disrupts the interaction pattern of the bile salt export pump as well as the flexibility of the second intracellular loop domain harboring this residue. As for the p.Ala98Cys, it modulates both the interactions within the first nucleotide-binding domain of the bile transporter and its accessibility. Two additional potentially modifier variants in cholestasis-associated genes were retained based on their pathogenicity (p.Gly758Val in the ABCC2 gene) and functionality (p.Asp19His in the ABCG8 gene). Molecular findings allowed a PFIC2 diagnosis in five patients and an unexpected diagnosis of sisterolemia in one case. The absence of genotype/phenotype correlation suggests the implication of environmental and epigenetic factors as well as modifier variants involved directly or indirectly in the bile composition, which could explain the cholestasis phenotypic variability., (© 2023 University College London (UCL) and John Wiley & Sons Ltd.)

Introduction: Castleman's 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 13 cases (72%). Clinically, peripheral adenopathy was present in 77.7% of patients and deep adenopathy in 72.2%. Systemic signs were found in 13 patients, 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 12 cases (66%), with anemia in 11 cases, thrombocytosis in 3 cases, and hypereosinophilia in 3 cases. Cutaneous Kaposi's sarcoma was associated with Castleman's disease in 2 cases, Hodgkin's lymphoma, angioimmunoblastic T-cell lymphoma, and lymph node T-cell lymphoma were found in 1 case respectively. 3 of the patients had associated connective tissue diseases such as Sjögren's syndrome in 2 cases and rheumatoid arthritis in 1 case. 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 1 case due to transformation into Hodgkin's lymphoma, and biotherapy (rituximab) was used in 2 cases in the multicentric form. Surgical removal of superficial adenopathy was performed in 2 patients 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., (© 2024 Imen Chabchoub et al., published by Sciendo.)

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.

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.

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., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

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., Competing Interests: Conflict of interest The authors have no conflicts of interest to disclose., (Published by Elsevier Inc.)

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.

Metastasis to the nasopharynx is a rare clinical entity. Breast carcinoma is one of the primary tumors that can be responsible for a nasopharyngeal metastasis, which is an extremely rare occurrence. We report the case of a 50-year-old woman with a history of a confirmed breast carcinoma under chemotherapy who presented to our department with a unilateral hearing loss and tinnitus. Nasal endoscopy revealed a small bulging mass at the posterior wall of the nasopharynx. The biopsy of the lesion showed an infiltration of the nasopharyngeal mucosa by a mammary adenocarcinoma that was positive for estrogen and progesterone receptors and negative for human epidermal growth factor receptor 2. Computed tomography scan revealed a thickening of the nasopharyngeal mucosa, a pleural and pericardial effusion and diffused secondary bone lesions. The patient received chemotherapy. Control revealed a partial regression of the nasopharyngeal mass. The patient is still under chemotherapy., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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., Competing Interests: The authors declare no competing interest., (Copyright: Mouna Zghal et al.)

Low phospholipid-associated cholelithiasis (LPAC) is characterized by the association of ABCB4 mutations and low biliary phospholipid concentration with symptomatic and recurring cholelithiasis. In the present study, we reported a case of a 63-year-old woman, who presented a biliary pain beginning at the age of 30, recurrent after cholecystectomy, along with "comet-tail shadows" revealed by ultrasonography thus, fulfilling the diagnosis of LPAC. This disease evolved into a cholangiocarcinoma. To understand the molecular basis of this phenotype, we performed the ABCB4 gene sequencing, followed by in silico analysis and Q-RT-PCR assay. The results displayed a homozygous missense sequence variation (c.140G > A, p.Arg47Gln), predicted as pathogenic according to MutPred. Accordingly, this gave rise to a decreased hepatic ABCB4 mRNA level and structural alterations of the mutated protein. Eventually, we reported, here, the first description of an ABCB4 missense mutation (p.Arg47Gln) at homozygous state in a Tunisian LPAC syndrome. An elucidation of its functional consequences was performed. Besides, this case suggests that the delayed diagnosis of LPAC syndrome and the lack of UDCA treatment may contribute in the development of complications, such as cholangiocarcinoma., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: The histopathological examination of cholecystectomy specimens has not been standardized with a debate concerning the routine and the selective approach. The aim of this study was to assess the information obtained from routine histopathological examination of cholecystectomy specimens., Methods: All histopathological reports of cholecystectomy specimens between January 2003 and December 2016 were analyzed, including a clinical diagnosis of benign gallstone disease or cholecystitis., Results: A total of 20,584 reports were examined. The mean age of patients was 54.2 years. Patients aged more than 60 years represent 37.6% of the study population. Of all patients, 15,973 (77.6%) were females. Incidental gallbladder cancers (GBC) were present in 155 cholecystectomies specimens (0.8%). 67.1% of GBC are at T2 and T3 stage. Granulomatous cholecystitis was diagnosed in only 19 cases (0.1%). GBC were more prevalent in older patients (P < 10 -6 ) and cholesterolosis was more prevalent in young patients (P < 10 -6 ). There was no gender predilection for GBC (P = 0.739)., Conclusions: The rate of incidental gallbladder carcinoma in our study is low, yet, we found a higher proportion of T2 and T3 carcinomas stage. Granulomatous cholecystitis may need further investigations and treatments. When a selective approch of histopathological examination of cholecystectomy specimens is used, it is important to take into account that clinical parameters are significantly associated with gallbladder cancer., (Copyright © 2018 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.)

Microcystic urothelial carcinoma is a rare variant of invasive transitional cell carcinoma recognized by the WHO classification. It is characterized by its deceptively benign appearance. The clinical course of this uncommon variety of carcinoma is not well known and their histological and immunohistological features are not well defined. We report a case of a 37-year-old man with a microcystic transitional cell carcinoma of the urinary bladder. He was diagnosed 4 years ago with cystitis glandularis lesions and nephrogenic adenoma. Through this observation we will try to define the clinical and pathological features of this uncommon tumor which must be differentiated from a number of proliferative lesions of the urothelium. The poor prognosis and aggressiveness of this tumor seems to be related to a higher stage and grade at diagnosis., (© Copyright Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology.)

The present study investigates the toxic effects of acrylamide (ACR) administered to rats at two doses on (i) oxidative stress and disruption of pro-oxidant/antioxidant balance in hepatic cells and (ii) its correlation with metallothioneins (MTs) genes expression, DNA damage and histomorphological changes. Treated rats with 20 and 40 mg/kg body weight of ACR led to an increase in malondialdehyde, hydrogen peroxide, advanced oxidation protein products, protein carbonyl levels as well as an alteration in the antioxidant status. Total MT content in the liver and MT I and MT II genes induction were increased. Plasma transaminases activities, albumin, total protein and glucose levels were also increased, while alkaline phosphatase activity was decreased. Moreover, total cholesterol (TC), triglyceride, low-density lipoprotein cholesterol (LDL-C) levels, TC/high-density lipoprotein cholesterol (HDL-C) and LDL-C/HDL-C ratios were increased, while HDL-C decreased in a dose-dependent manner. A random DNA degradation was observed only in the liver of ACR-treated rats with the highest dose. These changes were confirmed by histopathological observations.

Tubulo-papillary apocrine adenoma (TAA) is a very rare sweat gland tumor. TAA in association with syringocystadenoma papilliferum (SCP) is exceptional. A 2-year-old Tunisian child developed a mixed tumor on the scalp: TAA in association with SCP. Histologically, the tumor consisted of dilated duct-like areas with some apocrine gland-like areas. The superficial part of the tumor was connected to the epidermis and showed the characteristics of SCP. The characteristics and differences in histopathologic and immunohistochemical findings in this mixed tumor are described., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Background: Breast cancer is the most frequent malignant neoplasm affecting Tunisian women. It represents 25 to 35% of all female cancers. There is no published study about the features of Her-2 overexpressing breast carcinomas in North African women., Objective: The aim of this study is to assess the prognostic significance of pathological features in a cohort of a Her-2 overexpressing breast carcinoma originating from the region of south Tunisia., Methods: This study investigated a series of 100 patients followed from January 2006 to December 2011 for a Her-2 positive invasive breast carcinoma. Pathological features included in this study were: histological type, histological grade, tumor size, vascular invasion, perineural invasion, mitotic index, lymph nodes stage, positive lymph node capsular effraction, inflammatory infiltrates, nipple involvement and hormone receptors status., Results: Multivariate analysis showed that pT stage, pN stage, capsular effraction, vascular invasion, perineural invasion and Nipple involvement were independent prognostic factors for overall survival and disease free survival in patients free from distant metastasis at diagnosis. For patients with synchronous metastasis, there is no independent pathologic prognostic factor for survival., Conclusions: Our study demonstrates that pathological features are important prognostic factors for non metastatic Her-2 overexpressing breast carcinomas. This supports the idea that HER2-positive disease is a heterogeneous entity. We believe that these findings reinforce the need to identify molecular predictors of benefit and resistance to anti-Her-2 based therapies.

Purpose: Appendicitis is by far the commonest major emergency general surgical operation. Histopathological examination of the appendix is routinely performed., Methods: This study is a retrospective analysis of 24,697 appendectomies performed from January 2003 to December 2011. Pathological reports were analyzed for the following parameters: age, gender, and pathological diagnosis., Results: Appendectomy specimens represent 17 % of all pathological reports. Acute appendicitis was present in 19,637 (79.5 %) patients. The perforation rate was 6.3 % and was significantly higher in adult patients. The negative appendectomy rate was 15 % and was significantly higher in female and adult patients. The incidence of negative appendectomies had clearly decreased over the 9-year period distribution. Incidental unexpected pathological diagnoses were noted in 226 (0.9 %) appendectomy specimens. Neoplastic lesions were present in 171 cases (0.7 %); they include carcinoid, adenocarcinoma, and mucinous neoplasms., Conclusions: Routine pathological examination of appendectomy specimens is expensive. With advances in technology and imaging modalities, the diagnosis of acute appendicitis has improved, with a subsequent significant reduction in negative appendectomy. There are still a number of unusual diagnoses found in appendicectomy specimens supporting the continued use of routine histology.

Lafora body disease is a common and severe form of progressive myoclonic epilepsy. It is an autosomal recessive disorder with a gene locus recently mapped to chromosome 6q23-27. The disease presents between the age of 10 and 18 years with generalised seizures followed by myoclunus. Intellectual deterioration occurs early and progresses to dementia. The diagnosis must be usually confirmed by demonstrating Lafora bodies. The practical procedure is the axillary skin biopsy that shows PAS positive inclusion in the cells of the sweet ducts. We present a case of Lafora disease discovered in a 26-year-old man. Moreover, we emphasize on the diagnosis difficulties of this disease., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Acromegaly is usually the result of a pituitary growth hormone cell-adenoma or is more rarely due to ectopic secretion of growth hormone releasing hormone (GHRH).We report the case of a 60-year-old woman with acromegaly due to a GH-RH-secreting pancreatic tumor. Laboratory evaluation confirmed the diagnosis of acromegaly. Magnetic resonance imaging revealed a partial empty sella with no signs of adenoma. Ultrasound sonography performed for abdominal pains showed a calcified large heterogeneous infrahepatic mass. Computed tomography scan discovered a heterogeneous pancreatic head mass with a diameter of 10cm. Measurement of fasting plasma GHRH was performed showing a high concentration of 604ng/L (normal 10-60). We therefore concluded that the acromegaly was caused by ectopic overproduction of GHRH likely due to the pancreatic tumor. The patient underwent a cephalic duodenopancreatectomy. Histology revealed a well-circumscribed tumor with organoid architecture. Immunohistochemistry demonstrated diffuse positivity for chromogranin A, neuronal specific enolase and synaptophysin and negative immunoreactivity for prolactin, GH and serotonin. These features were concordant with a well-differentiated neuroendocrine tumor of the pancreas. Surgical resection of this pancreatic tumor was followed by significant amelioration of acromegalic signs and normalization of GHRH and GH levels., (Published by Elsevier Masson SAS.)

RéSUMé: Nous rapportons ici un nouveau cas de cette entité afin de souligner les caractéristiques anatomocliniques utiles à son identification et ceci, en vue de la distinguer des corticosurrénalomes, qui sont de pronostic nettement plus sombre.

Uterine leiomyoma with massive lymphoid infiltration is a rare and unusual pathological finding; only 20 cases have been reported in the literature. We report a case of this unusual lesion in a 35-year-old woman who underwent a myomectomy. On gross examination, the tumor was of white color and firm consistency. Histological sections showed interlacing bundles of spindle shaped cells of low density with moderate to severe lymphocytic infiltrate associated to lymphoid follicles and few plasma cells. Immunohistochemically, the diffusely infiltrating lymphoid cells were predominantly of T cell phenotype. The interspersed spindle shaped cells were positive with alpha smooth muscle actin, desmin and h-caldesmon. The cause of this unusual lesion is not clear, but the recognition of its distinct histological features is important to avoid possible confusion with differential diagnosis including malignant lymphoma, inflammatory pseudotumor and pyomyoma., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Desmoplastic fibromas are uncommon osseous tumors that seldom involve the skull. These tumors are histologically benign but locally aggressive with a propensity for recurrence if resection is partial. To our knowledge, only 16 cases have been reported in the literature, seven of which concerned children. We report a further case of a desmoplastic fibroma of the skull in a 3-year-old boy who presented with a right parietal mass. The CT scan showed a lytic mass with brain compression and cortical destruction. The patient underwent a craniectomy and complete mass resection. Histological diagnosis was desmoplastic fibroma. Postoperative progress was normal without recurrence 6 months later., (Copyright © 2010. Published by Elsevier Masson SAS.)

Background: Ovarian cancer is the leading cause of death from gynaecological malignancies. Newer biological prognostic factors and predictors of response to therapy are needed. Our study was designed to evaluate the expression of p53, Bcl-2, Estrogen receptor (ER) and Progesterone receptor (PR) in ovarian carcinoma and to compare it with other prognostic parameters such as age, FIGO stage, size of residual tumor, histological type and grade., Methods: This is a retrospective study conducted in the department of pathology at Sfax University Hospital. Confirmed 57 cases of ovarian carcinoma were reviewed in the period between January 1995 and December 2006. We used immunohistochemistry to evaluate the expression of p53, Bcl-2, ER and PR receptors and Chi-Square and Student test to correlate immunohistochemical findings with some prognostic parameters of ovarian carcinoma., Results: The percentage of expression of p53, Bcl-2, ER and PR was 73,7; 47,4; 35,1 and 33,3 % respectively. p53 overexpression correlated with an advanced FIGO stage (p = 0,026) and presence of ascitis (p < 10 -4 ). The expression of PR was associated with an early stage (FIGO I and II), a non serous histologic type and a low tumour grade (p = 0,045; 0,010 and 0,036 respectively). No correlation was found between Bcl-2 and ER and prognostic parameters. Survival analysis revealed that Bcl-2 status, FIGO stage, presence of ascites, peritoneal cytology, and residual disease were significant predictive factors of survival., Conclusion: p53 expression correlates with a worse prognosis in epithelial ovarian cancer, whereas Bcl-2 expression is related to a better outcome. For hormonal status, expression of PR is found to be an independent indicator of favourable prognosis. These results should be supported by more and larger studies., Competing Interests: The authors declare that they have no competing interests.

HER2 has been thought to play a critical role in both breast cancer development and progression. Any functional polymorphisms can potentially affect breast cancer risk as well as cancer phenotype and outcome. In our study, we analyzed three polymorphisms in the HER2 gene: the single-nucleotide polymorphism (SNP) HER2 Ile(655)Val as well as another SNP (rs903506) close to it and a new screened dinucleotide repeat H(AC)I4 in intron 4, in a sample of 148 cases and 290 controls from the Tunisian population and investigated their association with breast cancer risk. For the HER2 Ile(655)Val, we found similar allele frequencies between cases and controls (frequency of I allele was 0.92 and 0.91, respectively). The same was observed for the noncoding SNP (rs903506). These two SNPs also showed no association with any clinical parameters, except the association of HER2 Ile(655)Val with tumor size (p = 0.002). But, a significant association was found between the short tandem repeat (STR) [H(AC)I4] and breast cancer risk at both genotypic and allelic levels (p = 0.0004 and p = 0.0001, respectively). Multivariate analysis with binary logistic regression of disease status on genotypes of the three polymorphisms confirmed the association of STR with breast cancer risk (p = 0.016). Therefore, this STR seems to be a promising biomarker in breast cancer and deserves further investigation.

Introduction: Congenital epulis (CE) of the newborn also known as congenital granular cell tumor or Neumann tumor is an uncommun benign tumour occuring in the anterior alveolar ridge of the jaws. It may interfer with breathing and feeding. In our study, we discuss the clinicopathologic and evolutive caracteristics and the diagnosis problems of this entity., Observation: A newborn girl, two months old, presented at birth a nodular mass in the upper alveolar crete of the maxilla. The mass measured 1.5 cm and exhibited a smooth surface. Histologically, it was composed of diffuse sheets and clusters of granular cells with abundant coarsely granular cytoplasm. The evolution was good without recurrence after five months., Discussion: CE is a rare tumor; its etiopathogenesis is still unclear. The diagnosis suspected clinically is confirmed by the histopathological study. The prognosis is exellent without recurrence.

Objective: Choroid plexus carcinomas are rare and occur more frequently in children than in adults. The differential diagnosis includes choroid plexus papilloma and papillary ependymoma. The prognosis is generally poor. The objective of this paper is to discuss the epidemiological characteristics, diagnosis, treatment, and prognosis of this rare childhood tumor., Case Report: A three-year-old child was hospitalized with a history of partial epilepsy and intracranial hypertension. A computed tomography scan showed an intracranial mass measuring 11cm in diameter, extending to the ventricle system with heterogeneous contrast enhancement. He was urgently operated for loss of consciousness. During the operation, the patient developed an abundant hemorrhage and died. The histopathological examination of the excised tumor identified a choroid plexus carcinoma., Conclusion: Choroid plexus carcinomas are rare and treatment is currently controversial. Radical excision is quite difficult and associated with excessive blood loss.

Introduction: Small cell osteosarcoma (SCO) is a rare bone tumour representing 1.3% of all osteosarcomas. This rare variety of osteosarcoma tends to arise in the metaphysis of long bones and may extend secondary to epiphysis. By histopathology, the tumour is composed of small round cells with a variable degree of osteoid production. We report a new case of SCO in the distal femur with epiphyseal involvement. We also present the clinical, radiologic and therapeutic features of SCO with particular emphasis on the pathologic features that allow differentiation of this neoplasm from other small round cell tumours., Observation: A 14-year-old girl presented with a 6-month history of a painful tumefaction of the left knee with motor deficit. Imaging analysis of the knee demonstrated a lytic lesion of the metaphysis in addition to epiphysis of the distal femur with cortical destruction and invasion of soft tissues. Histological examination of a biopsy specimen showed sheets of neoplastic small round cells simulating Ewing's sarcoma. Osteoid was focally present. A diagnosis of SCO was made. The patient received 2 cycles of adjuvant chemotherapy with ifosfamide, adriamycin and cisplatin. MRI showed no change in tumour size. An en bloc, wide-margin resection of the lesion was performed. Histological examination showed a viable tumour with few necrotic foci. The patient received adjuvant chemotherapy with Holoxan and VP16. The clinical response was favourable., Conclusion: SCO is a rare clinical entity with a high grade of malignancy that must be distinguished from other round cell tumours, particularly Ewing's sarcoma, in order to optimise treatment protocols.

Purpose: Breast mucinous carcinoma is a particular histological form characterized by the extracellular production of mucus. The pure form is rarely reported and its prognostic is better than the other types of the breast cancer. The aim of the present study was to discuss the various anatomoclinical, therapeutic aspects and the prognostic factors of the pure mucinous carcinoma of the breast., Patients and Methods: We report seven cases diagnosed over a period of 11 years (1993-2003) in the laboratory of anatomy and pathological cytology of the university hospital of Sfax. A review of the clinical files with immunohistochemistry study (hormonal receptor, synaptophysine, chromogranine, Bcl2, Ki67, P53 and Her-2/neu (C-erbB-2)) were carried out for all the cases., Results: pure colloid carcinoma of the breast accounted for 0,5% of the whole of the breast cancers. The average age of patients was 69 years. At the time of the diagnosis, four tumours were classified T4, one T3, two T2, two N1 and one N3; no patient had presented metastasis (M0) according to pTNM classification. The echomammography showed regular contours mass in four cases. The anatomopathological study showed that the neuroendocrine differentiation was found in two cases, all the tumours had presented positivity for the hormonal receptors (oestrogen and progesterone) and negativity for the other antibodies, two cases exhibited the Bcl2 positivity and negativity for the other antibodies. An adjuvant radiotherapy was carried out for all the patients. The average duration of follow-up was of 33 months; the evolution was marked by the occurrence of metastases in two cases., Conclusion: The pure colloid carcinoma of the breast constitutes a particular morphological entity which deserves to be individualized; neuroendocrine differentiation of these tumours must be required. Their forecast is relatively favourable.

Mucinous tumors of the kidney are rare. The pathogenesis of these lesions is controversial. We report the observation of a 31-year-old woman presented with right-flank pain and hematuria. Abdominal ultrasonography and computed tomography revealed a multicystic mass of the right kidney. A total nephrectomy was performed. The pathological exam concluded on a mucinous cystadenoma of the right kidney. Mucinous cystadenoma of the kidney with a multicystic presentation has not been previously reported. In this work, we present the different pathogenic hypothesis and the means of treatment of this rare entity.

Primary aortic tumours are very rare. To our knowledge, only 120 cases had been reported in the world literature. Their clinical presentation is not specific. They are usually diagnosed at aortic surgery or by post-mortem examination. Intimal sarcoma is the most frequent histological type. We report a case of intimal sarcoma of the thoracic aorta diagnosed on autopsy of a 48-year-old man victim of sudden death. The main problem raised by intimal sarcoma lies in its poor differentiation or lack of differentiation. Thus, the pathologist must perform a phenotypic analysis as complete as possible of this tumor.

Purpose: To determine the level and prognostic significance of c-kit expression in the two age groups of North African nasopharyngeal carcinomas., Patients and Methods: A retrospective study of 99 NPC specimens from Tunisian patients was investigated by immunohistochemistry. Immunohistochemical data were correlated with Epstein-Barr virus LMP1 expression and pathological, clinical and survival parameters., Results: c-kit was detected in 79% of the cases for patients under 30 years of age (juvenile form) but in only 56% of specimens in patients over 30 years (P=0.039) and was significantly over-expressed for patients with lymph node involvement (P=0.015). LMP1 score was 5.78 (+/-1.84) for c-kit negative tumors compared to 8,23 (+/-2.39) for c-kit positive tumors (P=0.002). Multivariate analysis including age, lymph nodes involvement and LMP1 expression as co-variables, showed that only age (P=0.027) and LMP1 expression (P=0.005) were significantly correlated to the c-kit expression., Conclusion: c-kit is highly expressed in the juvenile form of North African nasopharyngeal carcinomas. There is a significant association between LMP1 and c-kit expression. The contrasted levels of C-kit expression in the two age groups strengthen the hypothesis that these clinical forms result from distinct oncogenic mechanisms.

Metastatic carcinoma of the iris is rare and accounts for 5-10% of uveal metastasis and 3% of all iris lesions. Breast and lung carcinoma are the primary sites in 90% of patients. We report here the case of a 66-year-old man treated in 1992 for follicular thyroid carcinoma and hospitalized in 1995 for a pink vascularized mass in the iris. At that time, neither local recurrence nor metastasis in other organs was observed. Histopathologic findings were typical of follicular thyroid metastasis carcinoma. The patient had refused adjuvant treatment but was followed up for 23 months after the diagnosis of the iris metastasis. Through this observation and a literature review, we discuss clinicopathological and prognosis aspects of this exceptional location.

Purpose: The rhabdoid cerebral tumors were first identified by Briner et al. in 1985. Their frequency was estimated to be 2.1% of those affecting children under 18 months. Such tumors are equally characterized by a critically and speedly mortal development. Their historical genesis is still of a controversial issue. The aim of the present study was to discuss the various anatomicoclinical and therapeutic aspects of these rare tumors., Patients and Methods: We report five cases diagnosed over a period of eight years (1997-2004) in the Laboratory of Anatomy and Pathological Cytology of the University Hospital of Sfax., Results: The average age of patients was 20 years old, there were children under 14 years and 4 patients were male. Clinical symptomatology showed the predominance of intra-cranial hypertension syndrome. Radiography through magnetic resonance revealed a heterogeneous tumor process localized respectively on the spine (one case), the insula (one case), the temporofrontal lobes (two cases) and the medulla (one case). Histological examination of the tumors also showed a proliferation of giant cells with a hyaline-based cytoplasmic inclusion. These inclusions were positive for vimentin and keratin. An adjuvant radiotherapy treatment was prescribed for two patients. A recurrence of rhabdoid tumors occurred in two cases. All five patients died within eighteen months., Conclusion: The cerebral rhabdoid malignant tumor constitutes one of the most aggressive and life-threatening intracranial tumors. The optimal management of such tumors remains unknown.