Sclerosing Extramedullary Hematopoietic Tumor (SEHT) Mimicking a Malignant Bile Duct Tumor-Case Report and Literature Review

Introduction: Sclerosing Extramedullary Hematopoietic Tumor (SEHT) is a very rare lesion associated with chronic myeloproliferative disorders (CMPD). SEHT can mimic morphologically, both macroscopically and microscopically, a wide variety of tumors/lesions. Case presentation: We present the case of a female patient diagnosed with gallstones for which surgery was decided. Intraoperatively, a malignant tumor of extrahepatic bile ducts was suspected. A frozen section examination raised the suspicion of a mesenchymal tumor or an inflammatory pseudotumor. The histological evaluation of the permanent sections, supplemented with an immunohistochemical investigation (IHC), was the one that established the diagnosis of SEHT, based on the presence of areas of sclerosis, atypical CD31+ megakaryocytes, myeloid and erythroid elements. Conclusions: The authors present the difficulties of a morphological diagnosis on the frozen section and on permanent sections in the absence of relevant clinical information and make a review of the literature data dedicated to the subject

Postmenopausal Breast Cancer in Women, Clinical and Epidemiological Factors Related to the Molecular Subtype: A Retrospective Cohort Study in a Single Institution for 13 Years. Follow-Up Data

This study focused on the characteristics of postmenopausal breast cancer in the population of southeastern Europe. This retrospective study explored the clinical, epidemiological, and molecular characteristics of women with postmenopausal breast cancer. Material and methods: A retrospective cohort study was performed on 721 postmenopausal breast cancer patients selected from the database of our institution. The data collected consisted of age, living environment, location of the breast tumor, stage of the disease, and molecular sub-type. Patient characteristics were collected based on a systematic chart audit from medical records. The data were analyzed using SPSS 20.0 and Pearson analysis. Results: The most frequent age range for breast cancer diagnosis was 51 to 70 years old. Most of the patients (80.7%) came from an urban environment. The vast majority of patients were initially diagnosed in stage II (40.3%) and III (30.3%). The most frequent molecular sub-types were luminal B (39%) and luminal A (35.4%). Almost half of the breast tumors were located in the upper outer quadrant (48.8%). Conclusions: The results of this study describe the profile of patients in southeastern Europe within our institution diagnosed with postmenopausal breast cancer. In our study, patients were first diagnosed with more advanced stages of breast cancer compared with other European countries

A Retrospective Analysis from Western Romania Comparing the Treatment and Survivability of p16-Positive versus p16-Negative Oropharyngeal Cancer

Background: Oropharyngeal cancer is a global health concern due to its multifaceted nature. Recent molecular studies have linked p16 overexpression, associated with the human papillomavirus, to oropharyngeal cancer and its prognostic implications. Materials and Methods: This retrospective study in Western Romania examined 60 patients, categorizing them based on p16 biomarker status: 28 were p16 positive, and 32 were p16 negative. Statistical tests, including Fisher’s exact and chi2, were used for analysis. Results: Patients with p16-positive oropharyngeal cancer exhibited a better prognosis (3-year survival, p = 0.0477; midtreatment, p = 0.0349) and reported lower alcohol (p = 0.0046) and tobacco (p < 0.0001) use. Conclusions: The study highlights the importance of p16 testing in oropharyngeal carcinoma diagnosis. It suggests modifying treatment approaches based on p16 status and underscores the differing prognoses associated with p16-positive and p16-negative cases

The Impact of SARS-CoV-2 Pandemic on Patients Undergoing Radiation Therapy for Advanced Cervical Cancer at a Romanian Academic Center: A Four-Year Retrospective Analysis

Background and Objectives: Throughout the COVID-19 pandemic, health systems worldwide adapted to support COVID-19 patients while continuing to provide assistance to patients with other potentially fatal illnesses. While patients with cancer may be at an elevated risk of severe COVID-19-related complications, their oncologic therapies generally cannot be postponed indefinitely without a negative effect on outcomes. Taking this into account, a thorough examination of the therapy management of various cancers is necessary, such as cervical cancer. Therefore, we aimed to develop a retrospective cohort study to measure the impact of the COVID-19 pandemic on the delivery of cancer care services for women diagnosed with cervical cancer staged IB2-IVA, necessitating chemo- and radiotherapy in Romania, as well as determine the difference in cervical cancer staging between the pandemic and pre-pandemic period. Materials and Methods: Using a multicentric hospital database, we designed a retrospective study to compare the last 24 months of the pre-pandemic period to the first 24 months of the SARS-CoV-2 pandemic to evaluate the variation in the proportion of women diagnosed with cervical cancer and the percentage of inoperable cases requiring chemotherapy and radiotherapy, as well as to detail their clinical presentation and other findings. Results: We observed that the likelihood of cervical cancer patients requiring radiation therapy at a later stage than before the pandemic increased by about 20% during the COVID-19 pandemic. Patients at an advanced FIGO stage of cervical cancer had a 3.39 higher likelihood of disease progression after radiotherapy (CI [2.06&ndash;4.21], p-value &lt; 0.001), followed by tumor size at diagnosis with a hazard ratio (HR) of 3.12 (CI [2.24&ndash;4.00], p-value &lt; 0.001). The factors related to the COVID-19 pandemic, postponed treatment and missed appointments, were also identified as significant risk factors for cervical cancer progression (HR = 2.51 and HR = 2.24, respectively). Conclusions We predict that there will be a considerable rise in cervical cancer cases over the next several years based on existing data and that expanding screening and treatment capacity will attenuate this with a minimal increase in morbidity and fatality

Challenges in Diagnosis and Prevention of Iatrogenic Endometriosis as a Long-Term Surgical Complication after C-Section

Endometriosis is a gynecological condition caused by the development of endometrial tissue outside the uterine cavity. Naturally, it commonly occurs at locations such as the ovaries and pelvic peritoneum. However, ectopic endometrial tissue may be discovered outside of the typical sites, suggesting the possibility of iatrogenic seeding after gynecological operations. Based on this hypothesis, we developed a study aiming to establish the root cause of atypical implantation of endometrial foci, as the main end point, and to determine diagnostic features and risk factors for this condition, as a secondary target. The research followed a retrospective design, including a total of 126 patients with endometriosis who met the inclusion criteria. A group of 71 patients with a history of c-section was compared with a control group of patients with endometriosis and no history of c-section. Endometriosis that developed inside or in close proximity to surgical incisions of asymptomatic patients before surgical intervention was defined as iatrogenic endometriosis. Compared with patients who did not have a c-section, the c-section group had significantly more minimally invasive pelvic procedures and multiple adhesions and endometriosis foci at intraoperative look (52.1% vs. 34.5%, respectively 52.1% vs. 29.1%). The most common location for endometriosis lesions in patients with prior c-section was the abdominal wall (42.2% vs. 5.4%), although the size of foci was significantly smaller by size and weight (32.2 mm vs. 34.8 mm, respectively 48.6 g vs. 53.1 g). The abdominal wall endometriosis was significantly associated with minimally invasive pelvic procedures (correlation coefficient = 0.469, p-value = 0.001) and c-section (correlation coefficient = 0.523, p-value = 0.001). A multivariate regression analysis identified prior c-section as an independent risk factor for abdominal wall endometriosis (OR = 1.85, p-value &lt; 0.001). We advocate for strict protocols to be implemented and followed during c-section and minimally invasive procedures involving the pelvic region to ensure minimum spillage of endometrial cells. Further research should be developed to determine the method of abdominal and surgical site irrigation that can significantly reduce the risk of implantation of viable endometrial cells. Understanding all details of iatrogenic endometriosis will lead to the development of non-invasive disease diagnosis and minimally invasive procedures that have the potential to reduce postoperative complications

Clinical and genetic landscape of treatment naive cervical cancer: Alterations in PIK3CA and in epigenetic modulators associated with sub-optimal outcome

International audienceBACKGROUND: There is a lack of information as to which molecular processes, present at diagnosis, favor tumour escape from standard-of-care treatments in cervical cancer (CC). RAIDs consortium (www.raids-fp7.eu), conducted a prospectively monitored trial, [BioRAIDs (NCT02428842)] with the objectives to generate high quality samples and molecular assessments to stratify patient populations and to identify molecular patterns associated with poor outcome.METHODS: Between 2013 and 2017, RAIDs collected a prospective CC sample and clinical dataset involving 419 participant patients from 18 centers in seven EU countries. Next Generation Sequencing has so far been carried out on a total of 182 samples from 377 evaluable (48%) patients, allowing to define dominant genetic alterations. Reverse phase protein expression arrays (RPPA) was applied to group patients into clusters. Activation of key genetic pathways and protein expression signatures were tested for associations with outcome.FINDINGS: At a median follow up (FU) of 22 months, progression-free survival rates of this FIGO stage IB1-IV population, treated predominantly (87%) by chemoradiation, were65•4% [CI95%: 60•2-71.1]. Dominant oncogenic alterations were seen in PIK3CA (40%), while dominant suppressor gene alterations were seen in KMT2D (15%) and KMT2C (16%). Cumulative frequency of loss-of-function (LOF) mutations in any epigenetic modulator gene alteration was 47% and it was associated with PIK3CA gene alterations in 32%. Patients with tumours harboring alterations in both pathways had a significantly poorer PFS. A new finding was the detection of a high frequency of gains of TLR4 gene amplifications (10%), as well as amplifications, mutations, and non-frame-shift deletions of Androgen receptor (AR) gene in 7% of patients. Finally, RPPA protein expression analysis defined three expression clusters.INTERPRETATION: Our data suggests that patient population may be stratified into four different treatment strategies based on molecular markers at the outset. FUND: European Union's Seventh Program grant agreement No 304810

Human papilloma virus (HPV) integration signature in Cervical Cancer: identification of MACROD2 gene as HPV hot spot integration site

Background: Cervical cancer (CC) remains a leading cause of gynaecological cancer-related mortality with infection by human papilloma virus (HPV) being the most important risk factor. We analysed the association between different viral integration signatures, clinical parameters and outcome in pre-treated CCs. Methods: Different integration signatures were identified using HPV double capture followed by next-generation sequencing (NGS) in 272 CC patients from the BioRAIDs study [NCT02428842]. Correlations between HPV integration signatures and clinical, biological and molecular features were assessed. Results: Episomal HPV was much less frequent in CC as compared to anal carcinoma (p 300 different HPV-chromosomal junctions (inter- or intra-genic). The most frequent integration site in CC was in MACROD2 gene followed by MIPOL1/TTC6 and TP63. HPV integration signatures were not associated with histological subtype, FIGO staging, treatment or PFS. HPVs were more frequently episomal in PIK3CA mutated tumours (p = 0.023). Viral integration type was dependent on HPV genotype (p < 0.0001); HPV18 and HPV45 being always integrated. High HPV copy number was associated with longer PFS (p = 0.011). Conclusions: This is to our knowledge the first study assessing the prognostic value of HPV integration in a prospectively annotated CC cohort, which detects a hotspot of HPV integration at MACROD2; involved in impaired PARP1 activity and chromosome instability

Corrigendum to ‘clinical and genetic landscape of treatment naive cervical cancer: Alterations in PIK3CA and in epigenetic modulators associated with sub-optimal outcome’ (EBioMedicine (2019) 43 (253–260), (S2352396419302142), (10.1016/j.ebiom.2019.03.069))

The authors wish to clarify that the authors Aljosa Mandic, Katarina Koprivsek, and Goran Malenkovic are also affiliated with Faculty of Medicine Novi Sad, University of Novi Sad, Serbia, as well as Gynecologic Oncology Department Clinic for Operative Oncology, Institute of Oncology of Vojvodina, Serbia