[Reversed polarity high-cell carcinoma of the breast: A case report]. / Carcinome à cellules hautes et à polarité inversée du sein : à propos d'un cas.

Reverse polarity high-cell carcinoma of the breast, formerly known as reverse polarity solid papillary carcinoma, is a rare entity recently introduced into the latest edition of the WHO classification of breast tumors. Its phenotype is triple-negative, and its diagnosis difficult. Although few cases have been reported in the literature, knowledge of this breast tumor is essential to distinguish it from other triple-negative carcinomas, which have a poorer prognosis. We report a case of high-cell, inverted-polarity carcinoma of the breast in a 43-year-old female patient with no history of breast neoplasia and no palpable mass on clinical examination. The tumour was discovered following a screening echomammogram, which revealed a lesion classified ACR 4b. A microbiopsy of this lesion concluded that it was a papillary proliferation that should be removed. A lumpectomy was performed. Histopathological and immunohistochemical studies of the surgical specimen confirmed the diagnosis of high-cell, reverse-polarity carcinoma expressing calretinin and IDH1. Given the rarity of this entity, there is no standard treatment. In our case, a mastectomy without lymph node curage was performed. The extension work-up was negative and the patient received no adjuvant treatment. After 12 months, the patient is in complete remission. In this case report, we describe the histopathological, immunohistochemical and molecular features of this rare entity.

Expression Profile of Survivin and p16 in Laryngeal Squamous Cell Carcinoma: Contribution of Tunisian Patients.

The objective of this study was to evaluate the expression of survivin and p16 in laryngeal squamous cell carcinoma (LSCC) in order to analyze their pathogenesis and prognostic significance in Tunisian patients. A total of 70 patients with LSCC collected at the Salah Azaiez Cancer Institute of Tunis were retrospectively evaluated. Expression of survivin and p16 was examined using immunohistochemistry, and the correlations with clinicopathological parameters, overall survival (OS), and disease-free survival (DFS) were statistically evaluated. The positive expression of survivin and p16 were found in 58.6% and 51.43% of LSCC cases, respectively. The p16 expression was not associated with either clinical parameters or patient survival, whereas there was a strong correlation of survivin expression and lymph node metastases (P = .002), alcohol consumption (P = .024), and therapeutic protocol (with or without chemotherapy; P = .001). Kaplan-Meier survival curves showed that patients with LSCC having positive survivin expression have shorter OS (P = .026) and shorter DFS (P = .01) than those with negative expression. Positive survivin expression was also correlated with high recurrence rate (P = .014). Therefore, survivin is a poor prognostic marker for LSCC but the therapeutic protocol remains, in multivariate study, the most decisive for the OS and DFS of our patients with P < .01. Our data indicated that, in Tunisian laryngeal squamous cell carcinoma, survivin expression is associated with unfavorable outcomes and represents a predictor marker of recurrence and chemoresistance. However, p16 expression has no prognosis value.

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 Prognostic Significance of IGF-1R and the Predictive Risk Value of Circulating IGF-1 in Tunisian Patients with Laryngeal Carcinoma.

The aim was to evaluate the clinical impact of IGF-1/IGF-1R in Tunisian laryngeal carcinoma. A high IGF-1R immunohistochemical expression was found in our series (81.43%). A tendency toward an association between IGF-1R expression and lymph node metastasis was found (p = 0.068). Patients with positive IGF-1R expression showed a short disease free survival (p = 0.053) and a high recurrence rate. Furthermore, circulating IGF-1 levels sera, detected by ELISA, were higher among patients compared to controls (p < 0.001). IGF-1R might have a prognostic significance and could be a factor of tumor recurrence. However, high levels of IGF-1 increase the risk of developing of LSCC disease.

MARCKS protein overexpression is associated with poor prognosis in male breast cancer.

BACKGROUND: Male breast cancer (MBC) is a rare and aggressive disease. Thus, identification of new therapeutic targets is crucial. OBJECTIVE: Our objective was to evaluate the protein expression of MARCKS (Myristoylated Alanine-Rich C-Kinase Substrate) in MBC and to investigate its prognostic value. MATERIALS AND METHODS: MARCKS protein expression in tumor and stromal cells was analyzed by immunohistochemistry (IHC) in a retrospective series of 96 pre-chemotherapy MBC samples and 80 normal breast samples, from Tunisian patients treated at Salah Azaiez Institute. Correlations were searched between MARCKS expression and clinicopathological features including overall survival (OS). RESULTS: MARCKS was overexpressed in epithelial tumor cells in 66% of the MBC samples versus 26% of normal samples (p= 1.40 × 10-7). Such positive MARCKS expression in epithelial tumor cells was associated with positive HER2 status (p= 4.0 × 10-3). It was associated with shorter OS in uni-and multivariate analysis. By contrast, stromal IHC MARCKS expression was correlated only with tumor grade. CONCLUSION: MARCKS tumor cell overexpression might in part explain the aggressiveness and the poor prognosis of MBC. MARCKS can represent a potential therapeutic target for MBC.

Submandibular lipoblastoma: Case report of a rare tumor in childhood.

Lipoblastoma is a rare, benign tumor usually occurring in childhood. It is essentially localized in the extremities and trunk, with few cases reported in the neck. We report the case of a 2-year-old girl with a rapidly enlarging, painless neck mass. Magnetic resonance imaging (MRI) revealed a 3-cm mass in the right submandibular region. Review of literature, diagnostic methods, and genetics of lipomatous tumors are discussed. Complete surgical excision via a lateral cervical approach demonstrated a white soft tissue with an adherent ganglion. Histology and immunohistochemistry confirmed the diagnosis of lipoblastoma. Cervical lipoblastoma is rare, and typically asymptomatic, rarely causing nerve compression or airway obstruction. MRI can help identifying the lipomatous nature of the mass, but the findings can be inconsistent due to variable maturity of fat cells and the mesenchymal content of the tumor. Diagnosis is always based on pathological examination. Further chromosomal analysis is useful in differentiating lipoblastoma from liposarcoma. Complete surgical excision is the recommended treatment.

Forkhead box M1 (FOXM1) expression predicts disease free survival and may mediate resistance to chemotherapy and hormonotherapy in male breast cancer.

BACKGROUND: Male breast cancer (MBC) is a rare and neglected disease. Prognostic and predictive factors in MBC are extrapoled from trials conducted on its female counterpart. OBJECTIVE: Since the relationship between the transcription factor Forkhead box M1 (FOXM1) expression and the clinical response to chemotherapy and hormonotherapy in MBC remains unknown, we sought to investigate the predictive value of FOXM1 in MBC. METHODS: FOXM1 expression was assessed in 130 MBC cases. Clinical significance was analyzed by Kaplan Meier curves, log-rank test and multivariate Cox regression analyses. RESULTS: Patients with high FOXM1 expression had a significantly lower response rate to chemotherapy (P = 0.045) and hormonotherapy (P = 0.029) than those with low FOXM1 expression. Multivariate analyses indicated that FOXM1 was an independent prognostic factor for disease free survival in MBC patients (P < 0.001). CONCLUSIONS: FOXM1 may have a reliable predictive significance in male breast cancer and thus may become an important target for male breast cancer therapy in the near future.

Prognostic implications of the intrinsic molecular subtypes in male breast cancer.

PURPOSE: Intrinsic molecular subtyping has been widely used in female breast cancer, and it has proven its significance. In this article, we aimed to study the intrinsic subtypes of male breast cancer (MBC) in correlation with clinicopathological features. METHODS: We retrospectively identified 130 MBC cases from 2004 to 2013. Intrinsic molecular subtypes were determined by immunohistochemistry (IHC). RESULTS: From a total of 130 MBC cases, 45.4% of tumors were luminal A subtype, 44.6% were luminal B, 5% were HER2 positive and 5% were triple negative tumors. There were statistically significant differences between different IHC intrinsic subtypes regarding tumor size (p=0.001), estrogen receptor (ER) status (p=0.001), progesterone receptor (PR) status (p=0.001), HER2 status (p=0.001) and Ki67 proliferation index (p=0.001). CONCLUSION: The distribution of breast cancer intrinsic subtypes in males is different compared to its female counterpart; however, they don't seem to give the same prognostic value.

Overexpression of FOXM1 Is a Potential Prognostic Marker in Male Breast Cancer.

BACKGROUND: Several studies have outlined biological differences between female and male breast cancer (MBC) and concluded that MBC should be considered as an entirely separate disease. Whether FOXM1 has any indication for prognosis in MBC patients remains unknown. We sought to examine the expression levels of FOXM1 in MBC and to identify the relationship between FOXM1 expression and patient survival. PATIENTS AND METHODS: FOXM1 expression was evaluated in a total of 130 MBC specimens. RESULTS: FOXM1 was overexpressed in 37% of the MBC samples. FOXM1 overexpression was significantly associated with tumor size (p = 0.045), histological grade (p = 0.048), lymph node metastasis (p = 0.012), Ki-67 proliferation index (p = 0.016), and molecular subtypes (p < 0.001). Multivariate analyses indicated that FOXM1 was an independent prognostic factor for overall survival in MBC patients (p < 0.001, hazard ratio = 0.69 (0.43-0.96)). CONCLUSIONS: Overexpression of FOXM1 was associated with well-established markers of poor prognosis; thus FOXM1 may represent a potential novel prognostic marker for MBC.

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.

Clinico-pathological and prognostic findings on 27 cases of medullary thyroid carcinoma.

INTRODUCTION: Medullary thyroid carcinoma is a rare tumor accounting for less than 10% of thyroid neoplasm. This tumor is characterized by important histological polymorphism which makes morphological diagnosis difficult and immunohistochemical study often necessary. OBJECTIVE: We aim to perform a retrospective review of clinical and pathological characteristics of medullary carcinoma. We will discuss the place of immunohistochemistry in the positive diagnosis and as a prognostic factor. METHODS: patients with thyroid medullary carcinoma diagnosed in department of pathology at carcinologic institute between 1998 and 2013 were retrospectively included. Clinic, radiologic and prognostic variables were assessed. Slides were reviewed for all the patients with confirmed tumors. RESULTS: Twenty-seven patients with CMT were identified. The average age was 55 years with predominance of males. The average consultation time was 16 months. The most common presentation symptom was a cervical lymph node. Total thyroidectomy was performed in 23 patients. Tumor was nodular and unique in 22 cases. The average size was 2.1 cm. CMT was of mixed type containing both medullary and papillary compound in four cases. Amyloid substance was present and abundant in 21cases. Positive staining for calcitonin was observed in 16 cases. Distant metastasis or metastatic lymph nodes was observed in eight cases with an average period of 42 months. Radiotherapy was performed in fifteen cases and two patients received chemotherapy. CONCLUSION: In the absence of amyloid deposits, immunohistochemical staining with calcitonin is useful to confirm the diagnosis. The prognosis of this entity is more pejorative than papillary thyroid carcinoma.

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.

Descriptive analysis of molecular subtypes in Tunisian breast cancer.

AIM: The objective is to report the correlation between pathology and molecular subtype classifications of breast cancer in Tunisian women. METHODS: This retrospective study concerned data of 966 breast cancer cases collected from 2007 to 2009 at Salah Azaiz Institute of Tunis. These cases were classified by an immunohistochemistry test for estrogen and progesterone receptors and human epidermal growth factor receptor 2 (HER2) status in the four molecular subtypes, namely luminal A, luminal B, HER2+ and triple negative. The molecular classifications were correlated with the clinicopathological characteristics of the tumors. RESULTS: Luminal A (50.7% of cases) was the most common subtype, with triple negative subtype 22.5%, luminal B 13.4% and HER2+ 13.4%. Triple negative and HER2+ subtypes were significantly associated with large tumor size (>5 cm, P < 0.001), younger age (<40 years, P < 0.03) and high grade (P < 0.001). Conversely, there was no correlation with the lymph node status. CONCLUSION: Our data demonstrated that the luminal A subtype, associated with a favorable prognosis, was the most frequent subtype in the Tunisian population; however the triple negative subtype occurred at a high incidence in Tunisia compared to Western countries. The molecular subtypes are correlated to the tumor size, histological grade and patient's age.