Jean Christophe Noël

Variable Stromal Periductular Expression of CD34 and Smooth Muscle Actin (SMA) in Intraductal Carcinoma of the Breast

In breast carcinoma, the stromal loss of CD34 expression and acquisition of SMA myofibroblastic features may constitute a prerequisite for tumor invasiveness. However, this hypothesis remains controversial, with some authors describing the loss of CD34 fibrocytes in the absence of SMA myofibroblastic-like cells in the stroma of invasive carcinoma. Others have also described the disappearance of CD34 fibrocytes from in situ carcinoma. To clarify this issue, we compared the distribution of CD34 fibrocytes and SMA reactive myofibroblasts between stromal areas of tumor-free mammary tissue, ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). In addition to 28 IDC, 300 normal duct–lobular units and 600 ducts with DCIS (158 low-grade, 266 intermediate, and 176 high-grade) were scored. The relationships between staining patterns and different histological features (grade of DCIS and presence or absence of necrosis) were compared. Loss of CD34 expression and acquisition of SMA expression were more frequent in high-grade in situ lesions than in intermediate and low-grade lesions (p<0.001). When necrosis was found in association with grade 2 or 3 DCIS, the decrease in CD34 expression was higher than in lesions without necrosis and that independently of the grade of DCIS (p<0.05). Necrosis did not appear to play a significant role in the expression of SMA (pu200a=u200a0.35). In all cases, the stroma of invasive carcinomas showed a complete loss of CD34 fibrocytes. Future research on both CD34 fibrocytes and mechanisms stromal changes are essential in the future and may potentially lead to new treatment approaches.

Myofibroblastic stromal reaction and lymph node status in invasive breast carcinoma: possible role of the TGF-β1/TGF-βR1 pathway

BackgroundThe microenvironment modulates tissue specificity in the normal breast and in breast cancer. The stromal loss of CD34 expression and acquisition of SMA myofibroblastic features may constitute a prerequisite for tumor invasiveness in breast carcinoma. The aim of the present study is to examine the stromal expression of CD34 and SMA in cases of invasive ductal carcinoma and to try to demonstrate the role played by the TGF-ß 1 et TGF-ß R1 pathway in the transformation of normal breast fibrocytes into myofibroblasts.MethodsWe carried out an immunohistochemical study of CD34, SMA, TGF-ß and TGF-ß R1 on a series of 155 patients with invasive ductal carcinoma. We also treated a breast fibrocytes cell line with TGF-ß1.ResultsWe found a loss of stromal expression of CD34 with the appearance of a myofibroblastic reaction in almost 100% cases of invasive ductal carcinoma. The strong stromal expression of SMA correlates with the presence of lymph node metastases. We were also able to show a greater expression of TGF-ß in the tumor cells as well as a higher expression of TGF- ß R1 in the tumor stroma compared to normal breast tissue. Finally, we demonstrated the transformation of breast fibrocytes into SMA positive myofibroblasts after being treated with TGF-ß1.ConclusionsOur study demonstrated that a significant tumor myofibroblastic reaction is correlated with the presence of lymph node metastasis and that this myofibroblastic reaction can be induced by TGF-ß1. Future research on fibrocytes, myofibroblasts, TGF-ß and stromal changes mechanisms is essential in the future and may potentially lead to new treatment approaches.

Evaluation of the Oncogenic Human Papillomavirus DNA Test with Liquid-Based Cytology in Primary Cervical Cancer Screening and the Importance of the ASC/SIL Ratio: A Belgian Study

Objectives. In Belgium, very few studies have focused on cervical high-risk human papillomaviruses (hrHPV) prevalence and the relationship between HPV and cervical cytological abnormalities. The aim of this study was to investigate hrHPV prevalence and its relationship with cytological screening and histological results in the French-speaking community in Belgium (Brussels and Wallonia). Methods. A total of 58,265 liquid-based cytology tests were performed during this period. All cases of ASC-US, ASC-H, LSIL, and HSIL were tested by Hybrid Capture 2 for hrHPV screening. Results. The prevalence of cytological abnormalities was 3.1% for ASC-US, 0.3% for ASC-H, 1.5% for LSIL, and 0.3% for HSIL. The frequency of hrHPV infection was 47% in ASC-US, 90% in ASC-H, 86% in LSIL, and 98.4% in HSIL. CIN 2+ lesions were found in 12.2% of smears with an ASC-US result, in 54% of smears with an ASC-H result, in 12.5% of smears with a LSIL result, and in 89.3% of smears with a HSIL result. The ASC/SIL ratio was 1.9%. Conclusions. This study provides a good representation of cytological abnormalities and HPV status in patients living in Belgiums French-speaking community. The prevalence in our study was similar to that derived from meta-analyses of European studies. Our ASC/SIL ratio was 1.9%, being within the lower and upper limits proposed in the literature, which tends to prove the good quality diagnosis of cervical smears in our laboratory.

Predictors of invasive breast cancer in mammographically detected microcalcification in patients with a core biopsy diagnosis of flat epithelial atypia, atypical ductal hyperplasia or ductal carcinoma in situ and recommendations for a selective approach to sentinel lymph node biopsy

15±30% of malignancies detected through screening programs are ductal carcinoma in situ (DCIS), and the majority of DCIS cases present in the form of mammographic microcalcification. This study was performed in order to determine the value of features in predicting invasive disease in patients with mammographic calcification and to help determine which patients (with, Core Needle Biopsy-diagnosed DCIS) are the most appropriate candidates for Sentinel Lymph Node (SLN) biopsy. The original aspect of this study was to select patients with mammographic microcalcification but without an associated mass. The factor that we identified to be associated with invasive disease at final surgical excision was the presence of necrosis at core histology. SLN biopsy or complete axillary lymph node dissection was performed in 22 (40%) patients of whom only one (4.5%) had a micrometastasis. Further larger studies are needed to see if it would be interesting to propose a SLN biopsy in case of necrosis on CNB-diagnosed DCIS with microcalcifications but not associated with a mass.

Myofibroblastic reaction is a common event in metastatic disease of breast carcinoma: a descriptive study

BackgroundThe modification of stromal components with the disappearance of CD34 positive fibrocytes and by contrast the acquisition of smooth-muscle actin positive myofibroblasts is a frequent event in breast carcinomas but has been little studied in its metastatic sites. Therefore, the aim of the present study is to examine the stromal expression of CD34 and SMA in lymph node and liver metastases which are two of the most frequent metastatic breast cancer sites.MethodsThe distribution of CD34 fibrocytes and SMA myofibroblasts has been studied by immunohistochemistry in 41 lymph node and 36 liver metastases from patients with invasive carcinoma of no special type.ResultsNo CD 34 fibrocytes were noted in the stroma of metastasis. By contrast, smooth-muscle actin stromal expression was observed in 95.1% of lymph node and 97.2% of liver metastases, independently of histological features of tumours.ConclusionsMyofibroblasts represent a major and constant component in the metastatic tumoral stroma of breast carcinoma highlighting that these cells could play an active role in tumour cells proliferation and spread.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_196

Chronic lymphocytic leukemia mimicking recurrent carcinoma of the breast: Case report and review of the literature

Secondary localization of chronic lymphocytic leukemia (CLL) in breast is rare, while concurrent invasive ductal carcinoma and CLL manifesting as a collision tumor in breast is extremely rare. The observation of a CLL infiltration closely associated with a distinct breast neoplasm with the absence of any other localization for the leukemia is an indisputable argument for a relationship between the two diseases. The presence of both tumors is not simply due to chance. This association (CLL and carcinoma) has also been described in other organs. Hereafter, we report a second case of an 80 year-old woman in whom a leukemic infiltrate was confined to the region immediately surrounding poorly differentiated primary breast carcinoma, and we will discuss the association between CLL and carcinoma.

Expression of the glucocorticoid receptor in breast cancer‑associated fibroblasts

Cancer- associated fibroblasts (CAFs) are actively involved in breast carcinoma. Our previous study demonstrated that the majority of these CAFs were smooth muscle actin (SMA) positive and were therefore termed peritumoral myofibroblast (PMY). Glucocorticoid, linked or not with its receptor (GR), has been postulated to serve a major role in normal breast and breast carcinoma; however, their role in CAFs remains poorly understood. The aim of the present study was to assess the presence of GR in breast CAFs and particularly in PMY in 56 cases of invasive breast carcinoma in correlation with clinicopathological parameters, by immunohistochemistry. GR was observed in CAFs in 51 cases (91%) and were more frequent in luminal A subtype (19/19 cases; 100%). The stromal expression was statistically correlated with the tumor grade (P=0.03), the Ki-67 index (P=0.003) and the presence of GR in the epithelial component (P=0.01). The demonstration of a frequent expression of GR in breast CAFs may serve as an interesting target for future therapeutics for the regulation of the tumoral breast microenvironment.

Pure invasive micropapillary carcinoma of the male breast: Report of a rare case with C-MYC amplification

Male breast cancer is rare. The most common histological subtypes include invasive carcinoma of no special type and papillary carcinoma. Other variants, including pure micropapillary carcinoma, have been described as well but are extremely rare. Pure micropapillary carcinoma has been recently characterized by a C-MYC gene amplification in women. We report here, occurring in a 73-year-old man, the first case of pure micropapillary carcinoma with amplification of the C-MYC gene.

Detection of high-grade lesions on cell blocks from residual fluids of Pap smears diagnosed as low-grade abnormalities: a preliminary pilot study.

Objective: To investigate the feasibility of the technique of cell blocks (CBs) from residual fluids of Papanicolaou (Pap) smears diagnosed as low-grade abnormalities in the detection of high-grade lesions on biopsies. Study Design: In the present pilot study, we evaluated the sensitivity and specificity of 70 CBs from liquid-based cervicovaginal smears of women with atypical squamous cells (ASCs) of undetermined significance (ASCUS; n = 39), ASCs that cannot exclude high-grade squamous intraepithelial lesion (ASC-H; n = 17) and low-grade squamous intraepithelial lesions (LSILs; n = 14) in the detection of cervical intraepithelial neoplasia (CIN) type 2+ lesions. Results: Of the 70 CBs, 22 were diagnosed as negative, 27 as CIN1 and 21 as CIN2+. The sensitivity and specificity of CB preparation for the diagnosis of CIN2+ lesions were 50 and 100%, respectively, in ASCUS, 92 and 100%, respectively, in ASC-H, 100 and 100%, respectively, in LSILs. Conclusions: Our study confirms that CB preparation is a simple and reproducible technique with a good specificity that could be added advantageously to Pap smears to detect CIN2+ lesions in women with ASCs and LSILs.