Comparative study of the effect of oleuropein and hydroxytyrosol rich extracts on the reproductive toxicity induced by bisphenol A in male rats: biochemical, histopathological, and molecular analyses.

Bisphenol A, or BPA, goes into the composition of a large number of products including sunglasses, infant's feeding bottles, receipts, or food packaging. Nowadays, there is a growing evidence that BPA may be at the origin of several physiological malignancies. Oleuropein and hydroxytyrosol extracted from olive leaves are highly investigated for numerous health benefits. The present work investigates the potential protective proprieties of olive leaf extracts against BPA-induced testicular damage in Wistar rats. Thirty-two animals were randomly divided into 4 groups: control, BPA-treated (10 mg/kg), BPA and oleuropein rich extract (16 mg/kg) treatment, and the last group treated with BPA and hydroxytyrosol rich extract (16 mg/kg). Biochemical parameters and histological and molecular analyses were evaluated. Our data demonstrated that BPA treatment caused significant alteration in biochemical parameters, disorganization of germinal epithelium, an up-regulation of p53 and Bax, and a reduction of Bcl-2 protein levels. The ingestion of oleuropein- and hydroxytyrosol-rich extracts attenuated BPA-induced biochemical and histological changes. In fact, olive leaf extracts enhanced the enzymatic antioxidant system and the level of Bcl-2, and reduced the expression of p53 and Bax. Fairly, our findings propose that olive leaf extracts may compete with BPA-induced reprotoxicity in vivo.

Papillary thyroid carcinoma associated with glioblastoma in a neurofibromatosis 1 patient: An unusual and rare combination of multiple primary malignancies.

Introduction: and importance: Papillary Thyroid carcinoma (PTC) is the most common endocrine malignancy and accounts for 1-2% of all cancer cases. Second malignancies in women diagnosed with thyroid cancer are of concern given the young average age at diagnosis. The concurrent occurrence of thyroid cancer and malignant brain tumor such as glioblastoma (GBM) was rarely seen and reported. However, the simultaneous association of these 2 conditions, namely PTC and GBM, in a neurofibromatosis type 1 (NF1) patient, has never been reported before in the literature. Case presentation: The authors report the first case of an extremely rare association combining papillary thyroid carcinoma, glioblastoma, and a neurofibromatosis 1 in a 34-year-old female patient with primary generalized tonic-clonic seizures. Clinical discussion: NF1 can be associated with PTC and GBM independently. In this current case, NF1 was accompanied by both PTC and GBM. With the exception of the present case, to our knowledge, there has been no previous case report in the literature in which these 3 entities were associated. The reason for the rarity of this combination of these neoplasms in patients with NF1 remains not clear, but it may be explained by the low incidence of combined occurrence of PTC and GBM. Conclusion: This is the first reported extremely rare coexistence of GBM and PTC in a female NF1 patient. Further genetic investigations could improve our understanding of this combination and change our therapeutic approaches.

Slow-growing pedunculated nodule.

There have been limited reported cases of pedunculated basal cell carcinoma(BCC). Our case is original, and it combines two rare aspects of CBC: Pedunculated and giant. This uncommon aspect is rarely encountered.

Prognostic Value of Natural Killer Cells Besides Tumor-Infiltrating Lymphocytes in Breast Cancer Tissues.

BACKGROUND: Each subgroup of immune cells has a different prognostic role in breast cancer; however, the prognostic impact of tumor-infiltrating natural killer cells (TINKs) is still not well established. Our aim was to assess the prognostic impact of natural killer (NK) cells in breast carcinomas. MATERIALS AND METHODS: NK cells infiltration were assessed by immunohistochemistry (IHC). Statistical analyses were performed to evaluate the correlation of NK cells with clinical-pathological features and outcome. RESULTS: CD56 IHC was realized in 126 patients. NK cells infiltration showed significant and positive association with tumor high Scarff-Bloom-Richardson (SBR) grade. NK cells were significantly associated with HER2-positive breast cancer and triple-negative breast cancer subtypes. Analyses showed significant and inverse correlation with progesterone and estrogen receptors expression status. High NK cells were significantly related to high Ki-67 labeling index. Our data showed that high NK cells infiltrate was significantly associated with tumor-infiltrating lymphocytes in breast cancer tissues. At a median follow-up of 5.5 years, high CD56 expression (≥ 5 cells/10 high power field) was associated significantly with a good overall survival and with good disease-free survival. CONCLUSION: In this study, we assessed the important prognostic role of TINKs in breast carcinomas, which seems to be evident despite its association with aggressive pathological features. Thus evaluation of NK cells can be standardized and integrated in daily routine.

Prognostic significance of E-cadherin and Cox 2 expression in Tunisian patients with colorectal mucinous adenocarcinoma.

INTRODUCTION: Mucinous colorectal carcinoma (MC) is a rare subtype of colorectal adenocarcinoma known to be associated with bad prognosis. Lately, research has turned to identify new prognostic markers allowing the use of targeted therapy. The aim of our study is to evaluate the prognostic impact of E-cadherin and Cox-2expression in MC. MATERIALS AND METHOD: A total of 40 formalin-fixed, paraffin-embedded MC specimens were collected within a period of 13 years and were studied for the expression of the two proteins. We used SPSS 22 software to study associations with clinicopathological parameters and overall survival (OS). RESULTS: A reduced or absent E-cadherin expression was noted in 52.5% of cases. It was associated with distant metastases (p = 0.049) and venous invasion (p = 0.049). Cox-2 was overexpressed in 17.5% of cases. It was associated with negative lymph node status (p = 0.020) and with early stage tumor (p = 0.020). A significant association between the two proteins was also noted (p = 0.04). No significant association with OS was found; However, there was an improvement in the survival of patients overexpressing Cox-2 (p = 0.16). CONCLUSION: Our findings link the loss of E-cadherin expression with spread and aggressiveness in MC and Cox-2 overexpression with better prognosis and survival. Because MC has a distinct genetic pathway we encourage the analysis of MSI and Cox-2 expression in all MC. Cox-2 inhibitors may not be effective chemopreventative agents in the setting of defective DNA mismatch repair. More molecular studies are needed to better understand the role of these markers and their prognostic significance in MC.

Hemophagocytic Lymphohistiocytosis: A Rare Complication of an Ultrarare Lysosomal Storage Disease.

Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening hyperinflammatory condition that may be triggered by infections, autoimmune and immunologic disorders, malignancies, and metabolic diseases. Early and accurate diagnosis of HLH and its underlying cause is of paramount importance for proper management and prognosis. We report the case of a Tunisian 21-month-old girl who initially presented clinical features of HLH related to a lysosomal acid lipase deficiency. The genetic sequence analysis of the LIPA gene revealed a never described homozygous mutation c.966G>C (p.Gln322His). The parents were heterozygous for this mutation. Enzyme replacement therapy was not provided for the patient. She received etoposide, corticosteroids, and cyclosporine for the HLH. She is waiting for hematopoietic stem cell transplantation. To the best of our knowledge, this is the second Tunisian case of secondary HLH complicating lysosomal acid lipase deficiency related to a new homozygous mutation: c.966G>C (p.Gln322His).

Fine needle non-aspiration cytology for the diagnosis of cervical lymph node tuberculosis: a single center experience / Punção não aspirativa com agulha fina para o diagnóstico de tuberculose linfonodal cervical: experiência de centro único

Abstract Introduction: The fine-needle cytology is being used as a first line of investigation in the diagnosis of head and neck swellings, as it is simple, cost effective and less invasive as compared to biopsy. Objective: The aims of this study were to evaluate the results of the fine-needle non-aspiration cytology of cervical lymphadenopathy and to study the factors influencing the rate of non-diagnosis results. Methods: This retrospective study was conducted on selected patients with cervical lymphadenopathy that had undergone a fine-needle non-aspiration cytology followed by a histological biopsy. The sensitivity, specificity, positive predictive value and negative predictive value of fine-needle non-aspiration cytology for diagnosing tuberculosis were estimated. The risk factors of non-diagnosis results were evaluated. Results: The sensitivity, specificity, positive predictive value rates of fine-needle non-aspiration cytology for tuberculosis were 83.3%, 83.3%, 78.9% and 86.9% respectively. In total, 47 out of the 131 samples (35.8%) were considered non-diagnosis. Of the non-diagnosis samples, 84.2% (38 out of 47) were benign mostly due to tuberculosis (30 cases). Among the studied factors, only tuberculosis (confirmed by histopathological examination) was significantly associated with non-diagnosis cytology (p = 0.02, Odds-Ratio = 2.35). Conclusion: Tuberculosis is currently the commonest cause of cervical lymphadenopathy in North Africa. Fine-needle non-aspiration cytology is safe and accurate in the diagnosis of cervical tuberculous lymph node that is associated with the risk of non-diagnosis cytology.

Resumo Introdução: A punção não aspirativa com agulha fina tem sido utilizada como primeira linha de investigação no diagnóstico de tumores de cabeça e pescoço, por ser uma técnica simples, custo-efetiva e menos invasiva quando comparada à biópsia. Objetivo: Os objetivos deste estudo foram avaliar os resultados de citologia por punção não-aspirativa com agulha fina de linfadenopatias cervicais e estudar os fatores que influenciam a taxa de falha diagnóstica. Método: Este estudo retrospectivo foi realizado em pacientes selecionados com linfadenopatia cervical submetidos a punção não aspirativa com agulha fina, seguida por biópsia histológica. Foram estimadas a sensibilidade, especificidade, o valor preditivo positivo e valor preditivo negativo da punção não aspirativa com agulha fina para o diagnóstico de tuberculose. Os fatores de risco dos resultados com falha diagnóstica foram avaliados. Resultados: As taxas de sensibilidade, especificidade, valor preditivo positivo e valor preditivo negativo da punção não aspirativa com agulha fina para tuberculose foram de 83,3%, 83,3%, 78,9% e 86,9%, respectivamente. Das 131 amostras, 47 (35,8%) foram consideradas como falha diagnóstica. Das amostras não diagnosticadas, 84,2% (38 de 47) eram benignas, principalmente devido à tuberculose (30 casos). Entre os fatores estudados, apenas a tuberculose (confirmada pelo exame histopatológico) estava significativamente associada à citologia com falha diagnóstica (p = 0,02, odds ratio = 2,35). Conclusão: A tuberculose é atualmente a causa mais comum de linfadenopatia cervical no norte da África. A punção não aspirativa com agulha fina é uma técnica segura e precisa no diagnóstico de linfonodos cervicais associados ao risco de citologia com falha diagnóstica.

Fine needle non-aspiration cytology for the diagnosis of cervical lymph node tuberculosis: a single center experience.

INTRODUCTION: The fine-needle cytology is being used as a first line of investigation in the diagnosis of head and neck swellings, as it is simple, cost effective and less invasive as compared to biopsy. OBJECTIVE: The aims of this study were to evaluate the results of the fine-needle non-aspiration cytology of cervical lymphadenopathy and to study the factors influencing the rate of non-diagnosis results. METHODS: This retrospective study was conducted on selected patients with cervical lymphadenopathy that had undergone a fine-needle non-aspiration cytology followed by a histological biopsy. The sensitivity, specificity, positive predictive value and negative predictive value of fine-needle non-aspiration cytology for diagnosing tuberculosis were estimated. The risk factors of non-diagnosis results were evaluated. RESULTS: The sensitivity, specificity, positive predictive value rates of fine-needle non-aspiration cytology for tuberculosis were 83.3%, 83.3%, 78.9% and 86.9% respectively. In total, 47 out of the 131 samples (35.8%) were considered non-diagnosis. Of the non-diagnosis samples, 84.2% (38 out of 47) were benign mostly due to tuberculosis (30 cases). Among the studied factors, only tuberculosis (confirmed by histopathological examination) was significantly associated with non-diagnosis cytology (p=0.02, Odds-Ratio=2.35). CONCLUSION: Tuberculosis is currently the commonest cause of cervical lymphadenopathy in North Africa. Fine-needle non-aspiration cytology is safe and accurate in the diagnosis of cervical tuberculous lymph node that is associated with the risk of non-diagnosis cytology.

Oleuropein and hydroxytyrosol protect rats' pups against bisphenol A induced hypothyroidism.

Bisphenol A (BPA) can disturb the endocrine system and the organs that respond to endocrine signals in organisms, indirectly exposed during prenatal and/or early postnatal life. The present study was designed to assess the protective effect of phenolic compounds from olive leaves against BPA induced thyroid dysfunction and growth perturbation in young rats during lactation. The BPA disrupting effect on thyroid function was investigated by measuring changes in plasma levels of thyroid hormones. Free triiodothyronine (FT3) and thyroxine (FT4) were decreased in young rats breast-fed from mothers treated with bisphenol A. This effect was associated with an increase in the plasma level of thyroid-stimulating hormone (TSH). The histological and immunohistochemical study of the thyroid gland revealed a disturbance in morphological structure and thyroid cells function. Thyroid dysfunction led to a disruption in the skeletal bone growth of young rats. In fact, the infrared microspectroscopic analysis and histological examination of femoral bone showed significant changes in their histoarchitecture associated with a perturbation in the mechanism of bone tissue mineralization. The administration of oleuropein or hydroxytyrosol in BPA treated lactating mothers improved the thyroid cells function by enhancing thyroid hormone levels. Moreover, these phenolics increased the body growth characterized by an amelioration in the structure and the microstructure of femoral bone tissue. HPLC analysis of rats-breast milk indicated the presence of oleuropein and hydroxytyrosol, which could contribute to the protective effect against bisphenol A induced hypothyroidism in pups rats.

The Increased Expression of Toll-Like Receptor 4 in Renal and Skin Lesions in Lupus Erythematosus.

Toll-like receptor 4 (TLR-4), a bacterial lipopolysaccharide sensor, is an innate immunity essential modulator. It is expressed on both immune and non-immune cells and may contribute to the cutaneous and renal manifestations during lupus erythematosus (LE). Our purpose is to evaluate TLR-4 expression and analyzing its role in lupus nephritis (LN) and chronic cutaneous lupus erythematosus (CLE) pathogenesis. TLR-4 immunohistochemical staining was performed on 30 LN renal biopsies compared with 11 healthy renal tissues and 30 skin biopsies from CLE patients compared with 15 normal individuals. CLE patients' biopsies showed a strong and diffuse TLR-4 expression throughout the epidermis and labeled inflammatory infiltrate and glands in the dermis whereas controls' skin expressed weakly TLR-4 only in the epidermis basal layer. LN glomeruli and tubules showed an increased and more intense TLR-4 expression compared with normal controls where TLR-4 expression was weak and rarely detected in glomeruli, diffuse and weak in tubules. A significant difference in TLR-4 expression between LN classes, both in glomeruli and tubules, was observed. These data confirm an up-regulation of TLR-4 expression in the affected tissues of CLE and LN patients and highlight the critical role of TLR-4 in the pathogenesis of cutaneous and renal disorders in LE.

Low-Grade Sinonasal Sarcoma With Neural and Myogenic Features: A Recently Discovered Entity With Unique Features and Diagnostic Challenge.

Low-grade sinonasal sarcoma with neural and myogenic features is an entity recently described in the literature. Little is known about its etiopathogenesis, natural history, or optimal treatment. In fact, it has relatively unique findings: it has a distinctive cytogenetic signature, and it expresses both smooth muscle actin and S100 protein. However, its diagnosis is challenging on biopsies showing negative staining for these 2 markers. The differential diagnoses include fibrosarcoma, malignant peripheral nerve sheath tumors, and other benign and malignant lesions. A complete resection, with or without radiotherapy, is required because this lesion appears to be locally aggressive. However, the clinical outcome seems to be good. Low-grade sinonasal sarcoma with neural and myogenic features merits classification as an independent tumor in the next World Health Organization classification of head and neck tumors. Reports of additional cases are required to support its unique classification.

Overexpression of miR-10b in colorectal cancer patients: Correlation with TWIST-1 and E-cadherin expression.

MicroRNAs are emergent players of epigenetics that function as oncogenes or tumor suppressors and that have been implicated in regulating diverse cellular pathways. MiR-10b is an oncogenic microRNA involved in tumor invasion and metastasis in various cancers. Our data have shown that miR-10b is overexpressed in colorectal cancer samples in comparison with non-tumorous adjacent mucosa (p = 0.0025) and that it is associated with severe features such as tumor size >5 cm (p = 0.023), distant metastasis (p = 0.0022), non-differentiated tumors (p = 0.016), and vascular invasion (p = 0.01). Regarding the regulation of its expression, positive correlation between the loss of miR-10b and aberrant DNA methylation (p = 0.02) as well as a loss of TWIST-1 messenger RNA (p = 0.018) have been observed. Furthermore, expression analysis of the downstream miR-10b targets has shown that there are associations between low HOXD10 messenger RNA and E-cadherin protein levels (p < 0.0001, p = 0.0008, respectively) and overexpression of miR-10b. Our data suggests that overexpression of miR-10b results from high levels of TWIST-1 and may induce a decrease of E-cadherin membranous protein levels, thus contributing to the acquisition of metastatic phenotypes in colorectal cancer.

[Tubulo-papillary apocrine adenoma in association with syringocystadenoma papilliferum]. / Adénome tubulo-papillaire apocrine associé à un syringocystadénome papillifère.

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.

Expression and mutation pattern of ß-catenin and adenomatous polyposis coli in colorectal cancer patients.

BACKGROUND AND AIMS: ß-Catenin and adenomatous polyposis coli (APC) are major components of the Wnt pathway. This study aimed to investigate the expression of ß-catenin and APC in tumors and lymph nodes in colorectal cancer (CRC) patients and the mutational spectrum of the genes coding these proteins. METHODS: Expression of APC and ß-catenin was examined in 124 tumors and 41 lymph nodes. Exon 3 of CTNNB1 and the mutation cluster region (MCR) in exon 15 of the APC gene were screened for mutation by PCR-sequencing. RESULTS: Nuclear/cytoplasmic immunostaining of ß-catenin was detected in 58.1 and 48.8% in tumors and lymph nodes, respectively. In tumors, abnormal expression of ß-catenin correlated with tumor size and with those in lymph nodes. Membranous ß-catenin expression occurred in 41.9 and 14.6% of tumors and lymph nodes, respectively. In tumors, lack of membranous ß-catenin correlated with high invasiveness and metastatic potential. Positive immunostaining for APC was observed in 2 and 14% of tumors and lymph nodes, respectively. Overexpression in nucleus/cytoplasm and lack of membranous ß-catenin significantly correlated with a reduced overall survival. Among 25 tumors, four harbour mutation in Ser33 and Ser47 and overexpress the ß-catenin in the nucleus/cytoplasm. Mutations were identified in the APC gene in 13 tumors and six mutations were novel. CONCLUSIONS: Positive association between aberrant expression of ß-catenin in the nucleus/cytoplasm of tumors and lymph nodes was observed. Nucleus/cytoplasmic accumulation of ß-catenin and loss of membranous expression are related to reduced survival and could serve as a candidate prognostic predictor.

A spindle cell myoepithelioma of parotid gland : a case report.

BACKGROUND: Myoepthelioma is a rare salivary gland tumor which is usually located in parotid gland and in minor salivary glands. CASE REPORT: We report a case of myoepithelioma arising in an accessory paritid gland in a 47-yearold woman who presented with a slowly expanding subcutaneous nodule on the left cheek, that was within the parotid gland at surgical resection . This tumor was composed of spindle cells. Immunophenotypical characterization demonstrated its myoepithelial nature. CONCLUSION: In the subcutaneous tissue, this unusual neoplasm may be confused with soft tissue tumors showing spindle cell features.

[Mixed breast carcinoma with melanocytic differentiation in a man]. / Carcinome mammaire mixte avec différenciation mélanocytaire chez un homme.

INTRODUCTION: Male breast cancer is rare; the lobular type is exceptional. Only one case of mixed ductal and lobular type is reported in the literature. This is the first report on a mixed ductal and lobular carcinoma with melanocytic differentiation in a man. The aim of our study is to describe the clinicopathological characteristics of this rare type of breast tumor and to discuss its histogenesis. CASE REPORT: A 63-year-old man presented with cutaneous ulceration of the left breast. Ultrasound of the breast revealed a solid hypoechoic lesion, 13 mm in diameter. Microscopic evaluation of the biopsy showed an invasive ductal carcinoma. The patient received three cycles of chemotherapy and lost of view. Then consulted for increasing of the tumor size reaching 3 cm. Histological examination of the mastectomy specimen showed a mixed ductal and lobular carcinoma with melanocytic differentiation, confirmed by the immunohistochemical study. The patient received adjuvant chemotherapy and the evolution was favorable with an average follow-up of 9 months. CONCLUSION: Breast carcinoma with melanocytic differentiation is extremely rare; only seven cases are reported in the literature and all occurs in females. Its histogenesis is unclear; tumors exhibiting this combination of cell types may occur as collision or composite tumors.

Multiple myeloma presenting as bilateral breast lumps in pregnant woman.

BACKGROUND: Multiple myeloma (MM) is a systemic disease in the elderly. Its incidence in patients younger than 40 years old and especially in pregnant women is extremely rare. MM may involve extraosseous sites, and only in rare cases it is observed in the breast. CASE REPORT: We describe the case of a 39-year-old woman diagnosed with an IgG lambda light-chain MM (Durie-Salmon stage IIIA, International Staging System II) in the 26th week of pregnancy, presenting with bilateral breast lumps. Dexamethasone (20 mg/m(2)/day on days 1-4, 9-12, and 17-20) was given as an induction agent to decrease tumor mass during pregnancy. Adverse response to dexamethasone was minor with excellent tolerance. A healthy baby was delivered at week 34 of gestation. CONCLUSION: Breast nodules revealing MM are extremely rare. Clinical and radiological features are atypical. Presentation during pregnancy is extremely rare, making anti-MM treatment potentially challenging.

High prevalence of the c.1227_1228dup (p.Glu410GlyfsX43) mutation in Tunisian families affected with MUTYH-associated-polyposis.

Germline mutations in the base excision repair gene MUTYH have been associated with recessive inheritance of multiple colorectal adenomas. Screening of the MUTYH gene was carried on index cases of 10 unrelated Tunisian families and on available DNA samples from some members. Three germline mutations: c.536A > G (p.Y179C), c.1187 G > A (p.G396D) and c.1227_1228dup (p.Glu410GlyfsX43), were identified in the homozygous or compound heterozygous state in 8 out of 10 families. The c.1227_1228dup (p.Glu410GlyfsX43) mutation was the most frequent, since it was found in biallelic homozygous in 7 probands and 2 members of family F1 and in compound heterozygous associated with the c.536 A > G (p.Y179C) or c.1187 G > A (p.G396D) in family F2. Haplotype analysis revealed that the 8 families are unrelated. Moreover, in sporadic colorectal cancer, the c.1227_1228dup (p.Glu410GlyfsX43) mutation was identified in 13 % of patients compared to the p.G396D and p.Y179C found in 1.2 and 2.12 % respectively. Our data shows the high prevalence of the p.Glu410GlyfsX43 mutation in Tunisian families affected with MUTYH associated polyposis as well as in sporadic colorectal carcinoma.