Implication of VDR Rs7975232 and FCGR2A Rs1801274 Gene Polymorphisms in the Risk and the Prognosis of autoimmune Thyroid Diseases in the Tunisian Population.

Hashimoto's thyroiditis (HT) and Graves' disease (GD) are autoimmune thyroid diseases (AITD) that cause hypothyroidism and hyperthyroidism, respectively. The vitamin D receptor (VDR) and the Fey receptor IIA (FcγRIIA), are implicated in the etiology of AITD. This study was conducted to examine the implication of VDR rs7975232 and FCGR2A rs 1801274 variations in the susceptibility and the prognosis of AITD in the Tunisian population. The rs7975232 and rs1801274 (R131H) polymorphisms were analyzed in 162 controls and 162 AITD patients (106 HT and 56 GD) by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and amplification of refractory mutation system-PCR (ARMS-PCR), respectively. No significant difference was demonstrated for the rs7975232 between patients and controls. However, a significant association was shown between the rs1801274 polymorphism and AITD or HT in the dominant (p = 0.03 or p = 0.01), codominant (p = 0.019 or p = 0.026) and allelic (p = 0.011 or p = 0.012) models. The rs7975232 was associated with the absence or the presence of anti-thyroglobulin antibody, with the age of AITD and GD patients during the first diagnosis (p = 0.01 and p = 0.009, respectively) and with a high T4 level at the beginning of HT disease. However, the FCGR2A gene polymorphism was associated with a low T4 level at the beginning of GD disease. In conclusion, this study indicates that only the FCGR2A variation could be related to AITD and HT susceptibility and that VDR and FCGR2A gene variations constitute factors to prognosticate the severity of AITD, HT and GD.

Polymorphisms in TSHR gene and the risk and prognosis of autoimmune thyroid disease in Tunisian population.

BACKGROUND: Autoimmune thyroid diseases (AITD) including Graves' disease (GD) and Hashimoto's thyroiditis (HT) are complex genetic diseases. TSHR is considered as candidate gene in GD. This finding prompted us to investigate the association of TSHR gene polymorphism with the risk and the prognosis of AITD in Tunisia. METHODS: A total of 84 healthy controls and 91 patients with AITD (69HT and 22 GD) were genotyped for TSHR rs74067403A>G polymorphism and 134 healthy controls and 149 patients with AITD (98 HT and 51 GD) were genotyped for TSHR rs1054708 T>C polymorphism. RESULTS: For rs1054708, we found an association between HT, AITD and the heterozygous genotype TC, the mutated genotype CC and the genotypes presented the mutated allele C (TC+CC) and with mutated allele C. The heterozygous genotype TC and the genotypes that presented the mutated allele C of rs1054708 are associated with male patients with AITD evenly the heterozygous genotype TC is associated with age of onset of disease. CONCLUSIONS: These preliminary results suggest that TSHR rs1054708 polymorphism may be a protective factor against HT and AITD. This polymorphism can affect the etiology of AITD between men and women and also by age.

Epstein-Barr virus infection in gliomas.

PURPOSE OF THE STUDY: Epstein-Barr virus (EBV) has been involved in the development of some tumors, including Burkitt's lymphoma and Hodgkin's lymphoma. However, its potential role in glioma tumorigenesis remains debated. In this study, we investigated the EBV infection in gliomas from Tunisian patients. PATIENTS AND METHODS: We conducted a retrospective study of 112 gliomas on archival material. The EBV DNA sequence was analyzed by polymerase chain reaction (PCR). Latent membrane protein 1 (LMP1) was detected by immunohistochemistry. In situ hybridization was used to detect EBV encoded small RNA (EBER). Clinicopathological features were recorded. Survival analysis was carried out using the Kaplan-Meier method and the Log-Rank test to compare EBV-positive and EBV-negative patients. RESULTS: Overall, there were twenty-four EBV-positive gliomas (21.4%). EBV DNA was identified in 24 cases. LMP1 and EBER were detected in four EBV DNA-positive cases. All EBV-positive cases were glioblastomas multiforme (GBM). Median overall survival and recurrence-free survival of EBV-negative patients were better than those of EBV-positive patients (Log Rank p = 0.006). CONCLUSION: Altogether, these findings support the occurrence of EBV infection in Tunisian GBM. Furthermore, when compared to EBV-negative tumors, EBV infection seems to be associated with the worst patient prognosis. Advanced molecular studies are recommended to confirm these results and to shed further light on the potential role of EBV in these devastating tumors.

Malignant degeneration of a branchial cyst: A case report.

INTRODUCTION: Malignant degeneration of a branchial cyst is rare (Thompson, 1997). It varies from 4% to 22% (Unal et al., 2005). CASE REPORT: A74-year-old man presented to our department with a left painless upper neck mass which was excised and histopathology revealed squamous cell carcinoma in a cystic lesion. The appropriate clinical tests and imaging were performed to determine the possible presence of a primary tumor. No primary carcinoma was found. This finding suggests that this was a malignant degeneration of a branchial cyst. The patient was treated with adjuvant radiotherapy and followed up over a 2-year-period and no recurrence was found. DISCUSSION: The development of an epidermoid carcinoma in situ in the amygdaloid cyst wall is a very rare entity. The challenge is to be able to distinguish between cystic metastasis of squamous cell carcinoma of the aerodigestive tract and a primary epidermoid carcinoma developed in the wall of an amygdaloid cyst. Martin and Khafif proposed some criteria to confirm the diagnosis of branchiogenic carcinoma.

Molecular genotyping of Echinococcus granulosus using formalin-fixed paraffin-embedded preparations from human isolates in unusual tissue sites.

Cystic echinococcosis (CE) caused by Echinococcus granulosus remains a serious problem worldwide for issues relating to public health and the economy. The most predominantly affected sites are the liver and the lungs, but other organs such as the heart, the spleen and the peritoneum can also be infected. Access to cysts from uncommon sites has limited genomic and molecular investigations. In the present study, genotypes of E. granulosus sensu lato were identified from formalin-fixed paraffin-embedded tissues (FF-PETs) implicated in human CE. Tissue samples were obtained from 57 patients with histologically confirmed CE. DNA samples were analysed using Egss 1 polymerase chain reaction (PCR) specific to the mitochondrial 12S rRNA gene of E. granulosus sensu stricto. All cysts were typed as E. granulosus sensu stricto with up to 35% of the liver and 16.6% of lungs being the most frequently infected, and up to 48.4% of samples being from rare sites. No correlation was found between cyst site and either the gender or the age of patients. This study demonstrates the possibility of exploiting atypical cysts using FF-PET samples and highlights the predominance of E. granulosus sensu stricto species in the Tunisian population, even in unusual infection sites.

Juvenile hyaline fibromatosis: a case report.

Juvenile hyaline fibromatosis is a rare, hereditary disease with distinct clinical and histopathological features. Clinically, it presents with gingival hypertrophy, pappulonodular skin lesions and joint contractures. Bone involvement is usually an uncommon finding. We report a case of a 2-year-old patient, daughter of consanguineous parents, who presented since the age of 2 months with impairment of mental development, multiple joint contractures, motion limitation and nodules on the scalp. The calvarian lesions were surgically removed, and histopathological examination concluded to juvenile hyaline fibromatosis.

Metastasizing pleomorphic adenoma of the submandibular gland: a case report.

Pleomorphic adenoma (PA), originally called mixed tumour, is the most common neoplasm of the salivary glands. It is usually a benign, slow-growing and well-circumscribed tumour. However, PA may occasionally give rise to metastases that usually occur after a previous recurrence. These tumours display benign histological features in both primary tumours and metastases. Such tumours have been termed metastatic PA or metastatic mixed tumours. We report a case of metastatic PA of the submandibular gland with metastasis to the cervical lymph nodes.

Eosinophilic cystitis with eosinophilic cholecystitis: a rare association.

We describe a rare case of eosinophilic cystitis associated with eosinophilic cholecystitis in a 30-year-old patient who underwent bladder biopsy for irritative voiding symptoms and routine elective cholecystectomy for gallstones. Diagnosis was confirmed by histopathological examination. The rarity of this condition prompted us to report this entity in which no specific cause could be found.

Immunodetection of SV40 T/t-antigens in human osteosrcoma in a series of Tunisian patients.

Osteosarcoma is a primary bone malignancy that typically occurs during adolescence but also has a second incidence peak in the elderly. The etiology of osteosarcoma is not well understood. Recent investigations have identified SV40 DNA sequences in osteosarcomas, suggesting that SV40 may contribute to tumor development. However, these studies also demonstrated geographical differences in SV40-positive osteosarcomas. The purpose of this study was to determine the prevalence and clinicopathological characteristics of SV40 positive osteosarcoma in Tunisian patients. Fifty-six formalin-fixed paraffin-embedded specimens of osteosarcomas were retrospectively investigated. Samples investigated were clinical cases examined between 1990 and 2004 in the Laboratory of Pathology at the University Hospital Farhat-Hached of Sousse (Tunisia). The search for SV40 was performed by immunohistochemistry using the Pab108 antibody for the detection of the viral oncoproteins: large T antigen and small t antigen (T/t-ag). SV40 status was correlated with clinico-pathological data. T/t-ag immunostaning was detected in the tumor cells in 31/56 (55.4%) osteosarcoma cases. SV40 positivity was more frequent (83%) in patients older than 40 years (5/6 cases) than in patients under 40 years (52%, 26/50), but the difference does not reach statistical significance (p = 0.33). Moreover, the time between the onset of clinical symptoms and diagnosis was shorter for SV40 positive than SV40 negative cases (p = 0.08). However, the viral status did not differ significantly according to gender, tumor size, histological subtype, tumor location, or metastases. This study documents the presence SV40 T/t-antigens in a proportion of osteosarcomas in Tunisian patients. The expression of these viral oncoproteins supports the hypothesis that SV40 may have a role in the pathogenesis of this tumor.

[Extra-nodal T lymphomas of the nasal cavities and sinuses]. / Les lymphomes T des fosses nasales et des sinus.

INTRODUCTION: Extra-nodal T lymphomas of the ear, nose, and throat (ENT) are unusual in Western countries, with differential diagnosis from other destructive and necrotizing lesions of the sino-nasal tract often difficult. MATERIAL AND METHODS: Eleven cases of extra-nodal lymphomas of the upper aerodigestive tract tract managed in the ENT department of F. Hached hospital in Sousse, Tunisia, were retrieved over a 10-year period (1995-2004). The aim of our study was to report the clinical and pathological data and the outcome for each patient. RESULTS: The median age of patients was 41-years. The most frequent site of involvement was the nasal cavity. Clinically, the symptoms were not specific. Histological examination identified two cases of T/NK lymphoma and nine cases of T-lymphoma not otherwise specified. Immunohistochemistry and in situ hybridization techniques positively detected Epstein-Barr virus in tumoral cells, in seven cases. Tumor staging, in 10 patients, found distant metastasis in three. Nine patients underwent the following treatment: exclusive radiotherapy (one patient), radiochemotherapy (three patients), and exclusive polychemotherapy (five patients). The two remaining patients had no treatment because of a rapidly unfavorable progression. After a median follow-up of 11-months, clinical outcome consisted in death in seven patients and remission in three patients; one patient was lost of follow-up. CONCLUSION: Extra-nodal lymphomas of the ORL tract are rare in Tunisia. Clinical presentation is not specific, depending on the lymphoma location. Diagnosis relies on clinical presentation and immunophenotypic and molecular characteristics; morphological features are not specific. These are aggressive lymphomas, often requiring multidisciplinary management.

Collision epithelial and stromal tumours of the stomach: a case report.

Collision epithelial and stromal tumours of the stomach are uncommon, and only a few cases have been reported in the literature. We describe a new case of a 54-year-old man who presented with bloody emesis. An oesophagogastroduodenoscopy revealed a stomach induration, and preoperative histological diagnosis was signet ring carcinoma. Total gastrectomy was performed and histological examination revealed a gastric collision tumour composed of gastrointestinal stromal tumour intermixed with a primary signet ring carcinoma. The neoplastic cells of the gastrointestinal stromal tumour were diffusely positive for CD117, while the signet ring cells were positive for cytokeratin. There was no transition between the two components.

A history of partial complex seizures in a 30-year-old woman.

Dysembryoplastic neuroepithelial tumour is an uncommon lesion of the brain characterised by a heterogeneous population of neurons, astrocytes and oligodendroglia-like cells. Most patients are young adults with a long history of drug-resistant seizures. We report a case of a 31 year-old woman with a history of severe epileptic attacks. Cerebral imaging showed a left temporal tumour measuring 4 cm in its greater dimension. After surgical intervention, histopathological examination showed a tumoural proliferation with both glial and neuronal components that was confirmed by immunohistochemistry. We also describe the spectrum of dysembryoplastic neuroepithelial tumours and their histological features.

[Mesenchymal tumors of the digestive tract, immunohistochemistry contribution]. / Les tumeurs mésenchymateuses du tube digestif, apport de l'immunohistochimie.

UNLABELLED: Mesenchymal tumors of the digestive tract are rare and display variable morphological appearances. Thanks to immunohistochemistry and molecular biology, these tumors are now better classified and dominated by stromal tumors. AIMS: the aim of this article is to study morphological characteristics of mesenchymal tumors of the digestive tract and to insist on immunohistochemistry contribution to diagnosis, especially the c-Kit. MATERIALS AND METHODS: this is a retrospective study of 40 mesenchymal tumors of the digestive tract diagnosed before the event of c-Kit, from 1985 to 1999 in the pathology laboratory of F. Hached hospital in Sousse. Immunohistochemical studies were performed on these tumors with the following antibodies: c-Kit, CD34, smooth muscle actin and S-100 protein. RESULTS: after immunostaining, the tumors were reclassified as the following: 33 stromal tumors, 4 leiomyosarcomas, 1 leiomyoma, 1 schwannoma and 1 desmoid tumor. CONCLUSION: mesenchymal tumors of the digestive tract are dominated by stromal tumors. The latter are defined usually by a spindle cell proliferation, often expressing the c-Kit protein which must be used in all mesenchymal tumors of the digestive tract.

Granuloma multiforme: first case report in Tunisia.

Granuloma multiforme is a rare granulomatous skin disease, usually reported in sub-Saharan African countries. The exact aetiology of granuloma multiforme is still unknown. We report the case of a patient who presented clinical and histopathological features of granuloma multiforme that can be considered the first described case in Tunisia.

[Salivary duct carcinoma]. / Carcinome des canaux salivaires.

INTRODUCTION: Salivary duct carcinoma is a very rare tumor of the salivary glands that has been principally reported in the parotid gland. It displays histologically a striking similarity to ductal carcinoma of the breast. OBSERVATION: We report the case of a salivary duct carcinoma arising in the parotid gland of a 62 year-old man. The fact that the tumor was confined to the parotid gland has allowed a radical treatment. After two year follow-up, there was no evidence of recurrence. DISCUSSION: This tumor is characterized clinically by local aggressiveness, frequent metastatic evolution and poor prognosis. This case report illustrates both the clinicopathological features and the prognostic factors of this entity.

[Prevalence of Epstein-Barr virus in Sjögren's syndrome in Tunisia]. / Prévalence du virus d'Epstein-Barr dans le syndrome de Sjögren en Tunisie.

PURPOSE: The cause of Sjögren's syndrome is unclear. Several studies suggested the role of Epstein-Barr virus (EBV) in the pathogenesis of this syndrome, but this always remains a subject of numerous controversies. The purpose of this study was to evaluate the prevalence of EBV in Sjögren's syndrome in Tunisia. METHODS: A series of 31 paraffin-embedded biopsies of salivary glands from patients with Sjögren's syndrome were studied in comparison with 19 control glands. EBV was investigated by PCR, EBERs in situ hybridization and by immunohistochemistry for the detection of LMP1, EBNA2 and ZEBRA. RESULTS: EBV DNA was detected by PCR in 3 of 22 PCR beta-globin positive Sjögren's syndrome cases (13.6%) and in 2 of 17 PCR beta-globin positive control glands (11.7%); in situ hybridization positivity was noted in rare lymphocytes in the 3 EBV positive cases of Sjögren's syndrome, but not in control glands; immunohistochemical study was negative in all cases. CONCLUSION: EBV infection does not appear to play a significant role in the pathogenesis of Sjögren's syndrome in Tunisia.

[Human subconjunctival dirofilariasis: two Tunisian case studies]. / La dirofilariose sous-conjonctivale humaine. A propos de deux cas tunisiens.

Two new cases of human subconjunctival dirofilariasis are reported in Tunisia. Dirofilaria immitis was identified in the first case and Dirofilaria repens in the second. Diagnosis was made by histological examination of excised nodules. We note that the patients are young (8 and 10 years, respectively) and that cases of human dirofilariasis caused by Dirofilaria immitis are present in Tunisia.