Flavie Arbion

Pivotal role of the lipid raft SK3-Orai1 complex in human cancer cell migration and bone metastases

The SK3 channel, a potassium channel, was recently shown to control cancer cell migration, a critical step in metastasis outgrowth. Here, we report that expression of the SK3 channel was markedly associated with bone metastasis. The SK3 channel was shown to control constitutive Ca(2+) entry and cancer cell migration through an interaction with the Ca(2+) channel Orai1. We found that the SK3 channel triggers an association with the Orai1 channel within lipid rafts. This localization of an SK3-Orai1 complex seemed essential to control cancer cell migration. This suggests that the formation of this complex in lipid rafts is a gain-of-function, because we showed that none of the individual proteins were able to promote the complete phenotype. We identified the alkyl-lipid Ohmline as a disrupting agent for SK3-Orai1 lipid raft localization. Upon Ohmline treatment, the SK3-Orai1 complex moved away from lipid rafts, and SK3-dependent Ca(2+) entry, migration, and bone metastases were subsequently impaired. The colocalization of SK3 and Orai1 in primary human tumors and bone metastases further emphasized the clinical relevance of our observations. Targeting SK3-Orai1 in lipid rafts may inaugurate innovative approaches to inhibit bone metastases.

Angioimmunoblastic T-cell lymphoma is the most common T-cell lymphoma in two distinct French information data sets

Reliable information regarding the current prevalence of peripheral T-cell lymphoma (PTCL) entities is missing. Herein we report on the frequency of PTCL entities in France between 2010 and 2013. Using Lymphopath , a national lymphoma network established by the French National Cancer Agency, which

Risk of Incidental Finding of Endometrial Cancer at the Time of Hysterectomy for Benign Condition

STUDY OBJECTIVE To assess the risk of unanticipated endometrial carcinoma during hysterectomy to treat a presumed benign condition. DESIGN Retrospective analysis (Canadian Task Force classification II-2). SETTING Tertiary referral center, university hospital. PATIENTS All women who underwent hysterectomy to treat presumed benign indications at our center from January 2000 to December 2011 were identified. We analyzed all pathologic reports and identified cases of unexpected endometrial carcinoma. INTERVENTIONS Hysterectomy by any approach to treat presumed benign indications. MEASUREMENTS AND MAIN RESULTS At our institution, 2179 hysterectomies were performed to treat presumed benign indications. Nine (0.4%) revealed unexpected endometrial carcinoma (95% confidence interval, 0.2-0.7). CONCLUSION Our data suggest that the rate of unanticipated endometrial carcinoma during hysterectomy to treat benign conditions is low.

Bartholin's gland carcinoma: Epidemiology and therapeutic management

Primary carcinoma of the Bartholins gland is a very rare malignancy of the vulva. Of the utmost importance in the management of these tumors is the management by specialized gynecological oncologist at referral centres. Gynecologists should always consider these unusual neoplasms as a differential diagnosis of potentially benigns lesions of Bartholins gland. Treatment modality must be tailored to each patient: each histological type of these unusual neoplasms has their natural history and may require a different level of operative aggressiveness to obtain the optimal outcome. Given the rarity of this disease, there have been no prospective randomized trials to evaluate optimal treatment. Therapeutic principles in the management of median vulvar cancer are applicable for Bartholins gland carcinoma. In this review, we aim to update the current knowledge on the treatment of Bartholins gland carcinoma.

Impact of Expert Pathologic Review of Lymphoma Diagnosis: Study of Patients From the French Lymphopath Network

Purpose To prospectively assess the clinical impact of expert review of lymphoma diagnosis in France. Materials and Methods From January 2010 to December 2013, 42,145 samples from patients with newly diagnosed or suspected lymphomas were reviewed, according to the 2008 WHO classification, in real time by experts through the Lymphopath Network. Changes in diagnosis between referral and expert review were classified as major or minor according to their potential impact on patient care. Results The 42,145 reviewed samples comprised 36,920 newly diagnosed mature lymphomas, 321 precursor lymphoid neoplasms, 314 myeloid disorders, and 200 nonhematopoietic neoplasms, with 4,390 benign lesions. There were 4,352 cutaneous and 32,568 noncutaneous lymphomas. The most common mature noncutaneous lymphomas were diffuse large B-cell lymphomas (32.4%), follicular lymphomas (15.3%), classic Hodgkin lymphomas (13%), peripheral T-cell lymphomas (6.3%) of which angioimmunoblastic T-cell lymphomas (2.3%) were the most frequent, and mucosa-associated lymphoid tissue lymphomas (5.8%). A diagnostic change between referral and expert review occurred in 19.7% of patients, with an estimated impact on patient care for 17.4% of patients. This rate was significantly higher for patients sent with a provisional diagnosis seeking expert second opinion (37.8%) than for patients sent with a formal diagnosis (3.7%). The most frequent discrepancies were misclassifications in lymphoma subtype (41.3%), with 12.3% being misclassifications among small B-cell lymphoma entities. Fewer than 2% of changes were between benign and malignant lymphoid conditions. Minor changes (2.3%) mostly consisted of follicular lymphoma misgrading and diffuse large B-cell lymphoma subtype misclassification. Conclusion To our knowledge, this study provides the largest ever description of the distribution of lymphoma entities in a western country and highlights how expert review significantly contributes to a precise lymphoma diagnosis and optimal clinical management in a proportion of patients.

Recurrent primary cutaneous mucinous carcinoma with neuroendocrine differentiation: case report and review of the literature

We report the case of a 60‐year‐old woman presenting with primary cutaneous mucinous carcinoma (PCMC) with neuroendocrine differentiation, revealed by neuroendocrine tumor lymph node metastasis 7 years before identification of the skin tumor. Only five cases of PCMC with neuroendocrine differentiation have been reported to date. The frequency of this neuroendocrine component may be underestimated, as it can require immunohistochemistry for identification, rather than being obvious on initial histopathologic examination. In the case presented here, the prominent neuroendocrine component displayed the morphological features of a well‐differentiated neuroendocrine tumor with expression of common neuroendocrine markers, strong expression of estrogen and progesterone receptors and low Ki67 proliferation index (5%). This case shows that not all primary cutaneous neuroendocrine carcinomas are Merkel cell carcinomas (MCCs). In addition to rare primary cutaneous carcinoid tumors, the diagnosis of PCMC with neuroendocrine differentiation must be considered, particularly when confronted by a mucinous tumor or lymph node metastases of neuroendocrine carcinoma of unknown origin. On the basis of this case, identification of a neuroendocrine component in a PCMC might be an adverse prognostic indicator of recurrence or of lymph node metastasis and should support wider excision margins of the tumor.

N-3 Polyunsaturated Fatty Acids of Marine Origin and Multifocality in Human Breast Cancer

Objective The microenvironment of breast epithelial tissue may contribute to the clinical expression of breast cancer. Breast epithelial tissue, whether healthy or tumoral, is directly in contact with fat cells, which in turn could influence tumor multifocality. In this pilot study we investigated whether the fatty acid composition of breast adipose tissue differed according to breast cancer focality. Methods Twenty-three consecutive women presenting with non-metastatic breast cancer underwent breast-imaging procedures including Magnetic Resonance Imaging prior to treatment. Breast adipose tissue specimens were collected during breast surgery. We established a biochemical profile of adipose tissue fatty acids by gas chromatography. We assessed whether there were differences according to breast cancer focality. Results We found that decreased levels in breast adipose tissue of docosahexaenoic and eicosapentaenoic acids, the two main polyunsaturated n-3 fatty acids of marine origin, were associated with multifocality. Discussion These differences in lipid content may contribute to mechanisms through which peritumoral adipose tissue fuels breast cancer multifocality.

Is there a justification for hysterectomy in patients with borderline ovarian tumors

OBJECTIVE To determine the frequency of uterine involvement in patients with borderline ovarian tumors (BOT) and to evaluate the recurrence risk and survival after hysterectomy. MATERIALS AND METHODS In two French hospitals: A tertiary referral centre (University hospital centre of Tours, France) and the Alliance community hospital of Tours (France), we reviewed data of consecutive women undergoing surgery for presumed stage I BOT between January 1997 and December 2012. Patients were divided into two groups: patients treated with fertility sparing surgery (group 1) and those treated with radical surgery (group 2). RESULTS A total of 135 patients were evaluated. 35 had fertility sparing surgery, 81 had radical surgery with hysterectomy and 19 had previous hysterectomy for other reasons. There were more recurrent borderline ovarian disease and more ovarian invasive disease developed in group 1 (p = 0.02, p = 0.04, respectively). Hysterectomy affected favorably borderline disease-free survival, OR = 0.09 95%CI (0.005-0.69), p = 0.04, but perceived benefits may be related to bilateral salpingo-oophorectomy and not hysterectomy directly.

What should be the width of radiological margin to optimize resection of non-palpable invasive or in situ ductal carcinoma?

PURPOSE the aim of our study was to investigate whether there is radiological margin that optimize resection of non-palpable invasive or in situ ductal carcinoma. MATERIALS AND METHODS Data were collected for all patients undergoing wire localization prior to therapeutic surgical excision between January 2010 and December 2013 at our institution. A 5 and 10-mm radiological margins were considered adequate for invasive ductal carcinoma (IDC) and in situ ductal carcinoma (DCIS) respectively. Clear histological margins were defined as no ink on the tumor for IDC and ≥2 mm for DCIS. Data were analyzed both in order to assess accuracy of the technique and in order to determine what radiological threshold should be taken. RESULTS Three hundred seventy seven women were included to the study. The radiological thresholds permitted negative histological margins in 94.7%, 60.9% and 80.9% in the pure invasive ductal carcinoma group (IDC, n = 133), the pure ductal carcinoma in situ group (DCIS, n = 92) and the mixed group (both IDC and DCIS, n = 152) respectively. In an ROC analysis evaluating the ability of radiological thresholds to obtain free pathological margins: the AUC was 0.79 (0.71-0.87, 95% confident interval, p = .0007) for Pure IDC group, 0.67 (0.57-0.87, 95% confident interval, p = .0005) for pure DCIS group, and 0.72 (0.62-0.80, 95% confident interval, p < .0001) for the mixed group. CONCLUSION We found that a radiological margin of 10 mm is needed in presence of an in situ component and 5-mm radiological margin seems enough in case of pure IDC tumors.

Lymphome intravasculaire : à propos de deux observations autopsiques et revue de la littérature

Intravacular large B-cell lymphoma (LIV) is a rare entity individualized in the WHO classification since 2001 as a subtype of extranodal diffuse large B-cell lymphoma. We report two autopsic cases of LIV: a 77-year-old woman presenting with fever, dyspnea, antehypophyseal failure and a 54-year-old man presenting with fever, weight-loss, night-sweats and encephalopathy. They died respectively 10 and 7 months after the beginning of symptoms, without diagnosis. Neither infectious disease nor lymphomatous proliferation had been identified. From these two cases and our literature review, we insist on the importance of histopathological diagnosis on biopsy for this rare pathology which clinical diagnosis remains difficult.