Triple negative breast cancer: A clinico-epidemiological and histopronostic study of 90 cases.

PURPOSE: The aim of this study was to describe the clinico-epidemiological and histopronostic characteristics of triple negative breast cancer (TNBC) and to evaluate the therapeutic results in tunisian women. METHODS: We reported the results of a retrospective study including 90 patients treated for TNBC between Junuary 2008 and December 2009 in the Salah Azaiz Institute of Tunis. RESULTS: TNBCoccured in 14% of diagnosed breast cancers. The mean age at diagnosis was 53.67 years. Family history of breast cancer was reported in 10% of cases.The majority of tumors were classified as T2 (41%) and associated with invasive ductal carcinoma histological type (99%) and SBR grade-II (54%). Tumor lymph node metastases were detected in 44% of patients.Among operated patients, 46% of patients underwent conservative surgery and 54% radical surgery. Chemotherapy and postoperative radiotherapy were given in97% and 80%of patients, respectively. After a median follow-up of 33.51 months, 61% of patients remained free of disease, 12% hadloco-regional recurrence, 9% had disease progression during chemotherapy and 21% developed systemic disease. CONCLUSION: TNBC diagnosis is often made in the advanced stage and has a tendency to recur after treatment. The variable responseto chemotherapy is due to the molecular tumor heterogeneity. The development of targeted therapies is necessary to improve outcome of chemoresistant TNBC.

Comparative study of two complementary proliferation markers in 200 breast carcinomas: Ki67 and mitotic index.

BACKGROUND: The evaluation of the proliferation in the mammary carcinomas provides useful prognostic and predictive information for subsequent management. The purely morphological evaluation of proliferative activity was represented by the evaluation of mitotic index. New analytical methods were gradually developed and performed. Among these methods, evaluation of Ki67 by immunohistochemistry is particularly interesting. Its expression is significantly increased in the cell cycle. AIM: To correlate the mitotic index as a classic method of assessing cell proliferation and Ki 67 proliferation index detected by immunohistochemistry to identify the most reliable proliferative marker. METHODS: We studied 200 patients with invasive ductal carcinoma breast over a period of 12 months of 2014. We identified in each case the SBR grade, Ki67 proliferation index and the mitotic index. Correlation between the two parameters was identified using the Spearman test. A result is considered significant when p < 0.01. The distribution of these markers by SBR gradewas studied using the ANOVA method. RESULTS: Ki67 is significantly correlated to the mitotic index. Although these two methods are dependent, Ki67 is the most sensitive and bonded to SBR grade. Determination of Ki67 provides interesting information that could replace the mitotic account. It provides reliable and reproducible data that can be incorporated into a prognostic score. CONCLUSION: Ki67 is a more efficient marker mitotic index, reflecting the cell proliferation.

Mucinous breast carcinoma a rare entity to be known: clinico-pathological study of 48 cases.

BACKGROUND: Mucinous carcinoma is a particular type of breast cancer characterized by the presence of extracellular mucin and is linked with a more favorable prognosis than invasive breast carcinoma of no special type. It accounts for 1 to 7% of all breast cancers. We propose in this work to study at first the clinic-pathological characteristics and the evolution of 48 cases of mucinous carcinomas. Secondly, we propose to identify through a review of recent literature, the therapeutic management of these carcinomas. METHODS: This is a retrospective study, conducted in Salah Azaiez carcinological institute, interesting 48 cases of mucinous carcinoma collected over 19 years. Clinical, radiological and pathological information were collected from medical records. RESULTS: The mean age of our patients was 57 years. The tumor was single in 41 cases and in 7 cases bifocal. Mammographic aspects were favor of malignancy in 33 cases (75%). It was mixed subtype in 14 cases and pure in 34 cases. Lymph node involvement was noted in 14 cases. The number of metastatic lymph nodes ranged from 1 to 11 with an average of 3. Hormone receptors were positive in 35 tumors (73%). The HER2 showed overexpression in 5 cases. Surgery consisted of a radical treatment for thirty-two patients (66%). Overall survival at 5 years was 75.3% and 59.3% at 10 years. Disease-free survival was 74% at 5 years and 58% at 10 years. CONCLUSION: Mucinous carcinoma consists of two distinct subtypes: pure and mixed with different prognosis. Larger data samples with longer follow-up are necessary to achieve an improved understanding of this particular tumor.

Comparative study of two complementary proliferation markers in 200 breast carcinomas: Ki67 and mitotic index.

BACKGROUND: The evaluation of the proliferation in the mammary carcinomas provides useful prognostic and predictive information for subsequent management. The purely morphological evaluation of proliferative activity was represented by the evaluation of mitotic index. New analytical methods were gradually developed and performed. Among these methods, evaluation of Ki67 by immunohistochemistry is particularly interesting. Its expression is significantly increased in the cell cycle. AIM: To correlate the mitotic index as a classic method of assessing cell proliferation and Ki 67 proliferation index detected by immunohistochemistry to identify the most reliable proliferative marker. METHODS: We studied 200 patients with invasive ductal carcinoma breast over a period of 12 months of 2014. We identified in each case the SBR grade, Ki67 proliferation index and the mitotic index. Correlation between the two parameters was identified using the Spearman test. A result is considered significant when p < 0.01. The distribution of these markers by SBR gradewas studied using the ANOVA method. RESULTS: Ki67 is significantly correlated to the mitotic index. Although these two methods are dependent, Ki67 is the most sensitive and bonded to SBR grade. Determination of Ki67 provides interesting information that could replace the mitotic account. It provides reliable and reproducible data that can be incorporated into a prognostic score. CONCLUSION: Ki67 is a more efficient marker mitotic index, reflecting the cell proliferation.

Complementary determination of Epstein-Barr virus DNA load and serum markers for nasopharyngeal carcinoma screening and early detection in individuals at risk in Tunisia.

Because nasopharyngeal carcinoma (NPC) has a close association with Epstein-Barr virus (EBV), measuring serum EBV DNA and anti-EBV serum marker concentrations could be a feasible method for NPC diagnosis, monitoring and probably screening especially in a community at risk. The aim of this study was to determine the EBV pattern in sporadic NPC and in high risk NPC Tunisian families in order to evaluate their risk factors and help for NPC screening. The rates of anti-EBV antibodies and EBV DNA were determined in the serum of 47 healthy members randomly selected from 23 NPC multiplex families with two or more affected members, 93 healthy Tunisian community controls chosen with the same age, sex and geographic origin as unaffected individuals and 66 EBV positive sporadic NPC patients whose serum was available before and after treatment. Unexpectedly, significant lower concentrations of anti-EA (Early Antigen) IgG and anti-VCA (Viral Capsid Antigen) IgG were found in unaffected members from NPC families than in healthy controls while viral loads were negative in all the tested sera. For sporadic NPC patients, anti-EA IgG and anti-VCA IgA concentrations were significantly higher than in healthy controls and these rates decreased after treatment. The level of EBV DNA load varied according to the condition of the tumour. This study suggests that in the Tunisian NPC families, screening for malignancy is based on serum concentrations but not on EBV DNA load while in the sporadic NPC group, serologic markers and EBV DNA load are complementary for diagnosis and follow-up.

[Inflammatory myofibroblastic tumor of the larynx: a case report]. / Tumeur myofibroblastique inflammatoire du larynx: a propos d'un cas.

BACKGROUND: Inflammatory myofibroblatic tumor is a recently caracterized solid mesenchymal tumor. They are frequently localised in the lung. However, the head and neck forms are uncommon. AIM: To report a new case of inflammatory myofibroblastic tumor of the larynx. CASE REPORT: This 47-year old man presented with dysphonia without dyspnea. Laryngoscopy showed a tumor of anterior vocal cord. CT scan of larynx confirmed diagnosis. The patient had a cordectomy. Histology concluded to the diagnosis of inflammatory myofibroblastic tumor. No relapses have been noted after 4 months. CONCLUSION: Only a few cases of laryngeal inflammatory myofibroblastic tumor have been reported in the literature. Clinical presentation depends of tumor location. Radiological images are not specific and diagnosis is based on histology. The expected course is essentially marked by the risk of local recurrences. Surgical excision seems to be the treatment of choice.

Prevalence and Prognostic Value of HPV among Tunisian Patients with Laryngeal Cancer and Relationship between DNA HPV and p16, IGF-1R, Survivin, p53 Expressions.

OBJECTIVES: Tobacco and alcohol are the main etiological factors common to laryngeal cancers. However, the Human Papilloma Virus (HPV) constitutes an alternative risk factor according to several studies. In Tunisia, despite the annual increasing incidence of laryngeal squamous cell carcinoma (LSCC), the prevalence and prognostic significance of HPV have never been explored.In this study, we sought to highlight HPV DNA in 70 biopsies of laryngeal cancer, and to analyze the status of HPV infection in association with p53, p16, survivin, and IGF-1R expressions. METHODS: HPV high risk (HPV HR) DNA was detected in tumors by in situ hybridization. However, the expression of p53, p16, survivin and IGF-1R were stained by immunohistochemistry test. The correlations of HPV status with clinicopathological parameters, overall survival, disease-free survival and proteins expressions were statistically evaluated. RESULTS: HPV HR DNA was detected in 39 out of 70 (55.71%) laryngeal tumors. HPV+ patients have a better overall survival (P = .081) and long disease-free-survival (P = .016) with a low rate of recurrence (P = .006) than HPV- patients. No significant correlations were found between HPV HR status and clinicopathological parameters (all P > .005). Moreover, HPV+ tumors were not associated with expression of p53, p16 and survivin. However, HPV HR status correlates with weak to moderate IGF-1R expression (P = .043). CONCLUSION: The substantial detection of HPV HR in LSCC tumors suggest that this virus plays an important part in laryngeal cancer in Tunisia. It is a good prognostic factor. In addition, HPV infection could act to block the pathway of IGF-1R expression.

The inhibitory effects on adult male reproductive functions of crude garlic (Allium sativum) feeding.

AIM: to investigate the effects of crude garlic on adult male rat reproductive functions. METHODS: Thirty male rats were divided into five groups: group 1 (untreated) and groups 2, 3, 4 and 5 were fed for 30 days with 5%, 10%, 15% and 30% crude garlic, respectively. Testes and accessory organs were weighed and some markers were assessed. Light and electron microscopy observations were also performed. RESULTS: A significant decrease was observed in the body weight of groups 4 (14%; P < 0.01) and 5 (20%; P < 0.01); of the prostate weight in group 5 (29.1%; P < 0.05) and of seminal vesicle weight in groups 3 (14.4%; P < 0.01), 4 (18.3%; P < 0.01) and 5 (27.3%; P < 0.01). In contrast, testis and epididymis weights were unchanged. In epididymis tissue, the alpha glucosidase activity and the spermatozoa density were unchanged. The treatment resulted in a significant decrease in testosterone serum levels in groups 3 (77.3%; P < 0.01), 4 (77.3%; P < 0.01) and 5 (90.9%; P < 0.01), associated with a significant increase in LH serum levels (P < 0.01). Testicular histology showed a dose-dependent increase in the percentage of empty seminiferous tubules. Moreover, testicular function was affected; a significant decrease in phosphatase acid activity (P < 0.01) and testosterone (P < 0.05) contents were observed. CONCLUSION: Crude garlic consumption during 1 month reduced testosterone secretion and altered spermatogenesis at 10%, 15% and 30% doses.

46 XY pure gonadal dysgenesis with gonadoblastoma and dysgerminoma.

BACKGROUND: Swyer syndrome is a distinct type of pure gonadal dysgenesis characterized by a 46 XY karyotype in female phenotypic patients. It shows an abnormality in testicular differentiation. It is usually revealed by primary amenorrhea. The tumor that usually develops in Swyer syndrome is gonadoblastoma. Although gonadoblastoma is considered benign, the risk of malignant germ cell tumor development is high. OBJECTIVE: The aim of this report is to stress on the risk of occurrence of malignant germ cell tumors on these dysgenesic gonads. CASE REPORT: We present the clinical, sonographic and endocrine findings in the case of a 13 year-old phenotypic young girl with a 46 XY karyotype and gonadal dysgenesis. The patient underwent surgery for adnexal torsion. An examination of the gonads revealed gonadoblastoma associated to dysgerminoma. The treatment and the follow up are detailed. CONCLUSION: The presence of Y chromosome in the karyotype of a patient presenting a gonadal dysgenesis must lead to prophylactic bilateral gonadectomy in order to avoid a malignant transformation. Gonadectomy must be followed by a hormone replacement therapy.

Effect of Hypericum humifusum aqueous and methanolic leaf extracts on biochemical and histological parameters in adult rats.

Hypericum genus is traditionally known for its medicinal use and its therapeutic and antioxidant effects. However, the toxic effect of this plant has not been much explored. Our study aimed at investigating the effect of Hypericum humifusum (Hh) leaf extracts on oxidative stress parameters in male rats. For it, we first focused on the phytochemical analysis of the aqueous and methanolic extracts of Hh leaves. Hence, Wistar rats were treated per gavage for 30 days and divided into Control (1 mL/rat, distilled water), A200 group (200 mg/kg body weight (bw) aqueous extract), A400 group (400 mg/kg bw aqueous extract), M10 group (10 mg/kg bw methanolic extract), M20 group (20 mg/kg bw methanolic extract). The phytochemical analysis revealed the presence of tannins, flavonoids, steroids, carbohydrates, and phenolic compounds. Biochemical and histological investigations were performed in plasma and liver tissue. Liver tissue homogenates were used for the measurement of malondialdehyde (MDA), catalase (CAT) and superoxide dismutase (SOD) levels. At the same time, alanine transaminase (ALT), aspartate transaminase (AST) and lactate dehydrogenase (LDH) were assayed in plasma samples. Histological study was also conducted in liver. We showed that Hh extracts reduced relative liver weight and increased ALT, AST, LDH activities in treated groups compared to control group. These results were associated with an increase of MDA levels and a decrease of antioxidant enzyme activities (CAT and SOD) in liver tissues of treated rats. Histology of liver demonstrated several alterations showing necrosis, altered hepatocytes and lymphocyte migration mainly in A200 group and dilated sinusoids, foamy appearance of hepatocytes and lymphocyte accumulation in the other treated groups. This original work indicated that chronic consumption of Hh leaf extracts has no antioxidant effect but instead it induces oxidative stress and enhances markers of cell damage which was confirmed by histological study of liver rats.

[Squamous cell carcinoma arising in a papillary carcinoma of the thyroid: a case report]. / Coexistence d'un carcinome epidermoïde et papillaire de la thyroïde: a propos d'un cas.

BACKGROUND: primary squamous cell carcinoma (scc) of the thyroid is a rare malignant tumor that needs to be distinguished from other neoplasms. Cases of papillary carcinoma merging in association with squamous cell carcinoma are extremely rare. AIM: the characteristics of such association will be studied herein through a review of literature. CASE REPORT: we report a case of an 87-year-old patient presented with an enlarged right lobe of the thyroid. Thyroid scintigraphy revealed a cold nodule. Clinically, malignancy was suspected. Histopathologic diagnosis was a well-differentiated scc associated with areas of papillary carcinoma. Exhaustive clinical, endoscopic and radiological examinations did not reveal any primary site of scc or any contiguous spread from neighboring structures. Surgery was followed by radiotherapy, but the patient died 6 months later. CONCLUSION: the coexistence of epidermoide and papillary carcinomas in the thyroid gland must be known because of its prognostic impact.

Correlation between P53 expression and CD34 angiogenic factor in Tunisian breast cancer.

BACKGROUND: Angiogenesis is a significant prognostic factor in breast cancer, but the factors that control angiogenesis in vivo are not well defined. AIM: The purpose of this study was to investigate P53 expression in breast cancer and to examine the relationship between P53 overexpression and the degree of angiogenesis. METHODS: A total of 52 paraffin-embedded tumors were evaluated immunohistochemically for expression of P53 and CD34 angiogenesis factor. RESULTS: The majority of P53 positive cases (82%) demonstrated high level of microvessel density (MVD); 18% demonstrated no CD 34 expression. In contrast there was no variation of CD34 expression among P53 negative tumors. CONCLUSION: This data suggests that microvessel density is promoted by P53 overexpression in breast cancer, and is correlated with high histologic grade.

Chronic consumption of Hypericum humifusum leaf extracts impairs epididymis spermatozoa characters in association with oxidative stress in adult male Wistar rats.

Recently, there has been increasing interest in Hypericum (Hypericaceae) genus. The first part of the present study focused on the phytochemical analysis of the methanolic and aqueous extracts of Hypericum humifusum leaves. The second part of the study investigated the effect of Hypericum humifusum leaf extracts on male reproductive parameters. 30 male rats were grouped into control (1mL/rat, distilled water), treated by 200mg/kg body weight (bw) aqueous extract (A200), 400mg/kg bw aqueous extract (A400), 10mg/kg bw methanolic extract (M10) and 20mg/kg bw methanolic extract (M20) groups. The phytochemical analysis revealed the presence of tannins, flavonoids, steroids, carbohydrates, and phenolic compounds. After thirty-day treatment, body and reproductive organs were weighed. Testes in all rat groups were processed for biochemical assays and histopathological examinations. Epididymis sperm analyses were also performed. Testicular tissue homogenate samples were used for Malondialdehyde (MDA), catalase and superoxide dismutase (SOD) measurements. We showed that Hh extracts induced a severe seminiferous tubular damage with an increase in the percentage of empty seminiferous tubules. Epididymis sperm analysis revealed a significant reduction in density and viability of sperm with alteration of spermatozoa morphology. Also, we found that Hh leaf extracts decreased plasma total cholesterol, HDL-cholesterol and triglycerides levels. These results were associated with an increase of MDA levels and a decrease of catalase and SOD activities in testis tissues. Our finding revealed that chronic consumption of Hh extracts induces disruption of normal spermatogenesis by alteration of sperm density, viability, and morphology. This action may be due to an inhibition of the antioxidant-defense system.

Expression profile of biomarkers altered in papillary and anaplastic thyroid carcinoma: Contribution of Tunisian patients.

AIMS: The objective of this study was to compare the protein expression profile between well-differentiated (papillary) and undifferentiated (anaplastic) thyroid carcinoma in Tunisian patients. METHODS: This first Tunisian retrospective study concerned data of 38 thyroid cancer cases (19 papillary carcinoma PTC and 19 anaplastic carcinoma ATC) collected at Salah Azaiez Institute of Tunisia. Immunohistochemistry was used to evaluate tumor expression of different molecular markers (p53, Ki67, E-cadherin, cyclin D1, bcl2, S100 and Her-2). The molecular expression was correlated with the clinicopathological characteristics of the tumors. RESULTS: There were 6 differentially expressed markers when comparing anaplastic thyroid carcinoma ATC with papillary thyroid carcinoma PTC. Expression of p53 and Ki67 were significantly increased in 16 and 18 ATC cases respectively, the Ki67 expression was lost in PTC. Cyclin D1, E-cadherin, bcl2 and S100 were overexpressed in PTC tumors; however, they were significantly decreased in ATC. The last marker, Her-2 was expressed in one case of PTC only. CONCLUSION: Our results, similar with findings of other ethnic groups, showed alteration in expression of molecular markers associated with tumor dedifferentiation, indicating loss of cell cycle control with increased proliferative activity in ATC carcinoma. These data support the hypothesis that ATC may derive from dedifferentiation of preexisting PTC tumor.

Lymphadenopathic form of alveolar rhabdomyosarcoma: A case report.

We report the case of a special form of rhabdomyosarcoma called "lymphadenopathic" which was reported only two times in the literature. This lymphadenopathic alveolar RMS shows lymph nodes as clinical manifestation mimicking lymphoma with an unknown primary neoplasm. In the case we report, clinical examination, and radiological studies revealed superficial and deep located lymph nodes in association with bilateral pleural effusion. Conventional histological examination showed lymph node infiltration by a metastatic tumour having alveolar pattern. Some of tumour cells were round with multilobed off-centred nucleus and eosinophilic cytoplasm containing fibril material with longitudinal and transverse striation indicating a muscle nature of the tumour proliferation. The immunohistochemical study showed intense and diffuse immunoreactivity of tumour cells for vimentin and a discreet immunostaining by desmin. These findings were compatible with the diagnosis of lymph node metastasis by alveolar rhabdomyosarcoma.

[Linguinal metastasis from clear cell carcinoma of the kidney]. / Metastase linguale d'un carcinome a cellules claires du rein.

Clear cell carcinoma is the most frequent cancer of the kidney (60-80% of cases). This tumour has a great propensity to metastasis. Metastasis lesions appear 15 to 20 years after nephrectomy and differential diagnosis with can be difficult to establish. We report an exceptional case of renal cell carcinoma metastasis to the tongue in a 63-years-old male patient who had a nephrectomy 20 years previously. To our knowledge, this is the second case reported in the literature.

[Malignancy arising in seborrheic keratosis: two cases report]. / Transformation maligne d'une keratose seborrheique: a propos de deux cas.

Seborrheic keratosis are one of the most common benign epidermal tumors encountered in clinical practice. Malignant transformation is exceptional. It may occur by the involvement of human papilloma virus. We report two cases of seborrheic keratosis in respectively 58 and 60-years-old women, which, on biopsy, revealed the presence of Bowen's disease for the former and Squamous cell carcinoma for the later.

[Leiomyosarcoma of the penis: a case report and review of the literature]. / Le leiomyosarcome de la verge: a propos d'un cas et revue de la litterature.

The sarcoma of the penis is a very rare tumor more exceptional is the Leiomyosarcoma of the penis for which the diagnosis required an immunohistochemical study. The prognosis for this tumor is poor. We report a case, which arise to a 53 year-old-man in this instance we did a review of the medical literature.