The diagnostic value of core needle biopsy in cervical cancer: A retrospective analysis

Cervical carcinoma is a major cause of morbidity and mortality among women worldwide. Histological subtype, lymphovascular space invasion and tumor grade could have a prognostic and predictive value for patients’ outcome and the knowledge of these histologic characteristics may influence clinical decision making. However, studies evaluating the diagnostic value of various biopsy techniques regarding these parameters of cervical cancer are scarce. We reviewed 318 cases of cervical carcinoma with available pathology reports from preoperative core needle biopsy (CNB) assessment and from final postoperative evaluation of the hysterectomy specimen. Setting the postoperative comprehensive pathological evaluation as reference, we analysed CNB assessment of histological tumor characteristics. In addition, we performed multivariable logistic regression to identify factors influencing the accuracy in identifying LVSI and tumor grade. CNB was highly accurate in discriminating histological subtype. Sensitivity and specificity were 98.8% and 89% for squamous cell carcinoma, 92.9% and 96.6% for adenocarcinoma, 33.3% and 100% in adenosquamous carcinoma respectively. Neuroendocrine carcinoma was always recognized correctly. The accuracy of the prediction of LVSI was 61.9% and was positively influenced by tumor size in preoperative magnetic resonance imaging and negatively influenced by strong peritumoral inflammation. High tumor grade (G3) was diagnosed accurately in 73.9% of cases and was influenced by histological tumor type. In conclusion, CNB is an accurate sampling technique for histological classification of cervical cancer and represents a reasonable alternative to other biopsy techniques.

Basal cell carcinoma trends in Thailand: a 10-year retrospective study of demographic, clinical and histopathological features

Background: Basal cell carcinoma (BCC) is the most common skin cancer with globally increasing incidence. To date, the information regarding BCC in Thailand is limited.Objective: To evaluate the demographic, clinical, histopathological trends of BCC and other contributing factors.Methods: We retrospectively reviewed the demographic, clinical and histological data of all BCC outpatients from January 2009 to December 2018.Results: From 278 BCC patients recruited to this study, most of them (71.6%) were older than 60 years old. The most common histological subtype was nodular BCC (63.3%). A statistically significant association was observed between histological variant and location of the tumor; H and M area were associated with nodular BCC, L area was related to superficial subtype (p-value < 0.001). Misdiagnosis of BCC was observed in 53 cases, mostly as melanocytic nevus (30.2%), and about quarter (26.4%) was made by board-certified dermatologists.Conclusions: Nodular BCC is significantly associated with H and M area, while superficial subtype is related to L location. Quarter of the patients already have large tumors at their first presentation. Misdiagnosis of BCC is not uncommon.

The Advance and Correlation of KRAS Mutation With the Fertility-Preservation Treatment of Endometrial Cancer in the Background of Molecular Classification Application

The annually increasing incidence of endometrial cancer in younger women has created a growing demand for fertility preservation. However, the diverse therapeutic efficacy among patients under the same histological subtype and the same tumor grade suggests the potential interference of the innate molecular characteristics. The molecular classification has now been applied in clinical practice and might help to stratify the endometrial cancer patients and individualize the therapy, but the candidates for the fertility-spared treatment are most likely to be subdivided in the subgroup lacking the specific signature. KRAS mutation has been linked to the malignant transition of the endometrium, while its role in molecular classification and fertility preservation is vague. Here, we mainly review the advance of molecular classification and the role of KRAS in endometrial cancer, as well as their correlation with fertility-preservation treatment.

Low level of interobserver concordance in assessing histological subtype and tumor grade in patients with penile cancer may impair patient care

Differentiation between penile squamous cell carcinoma patients who can benefit from limited organ-sparing surgery and those at significant risk of lymph node metastasis is based on histopathological prognostic factors including histological grade and tumor histological subtype. We examined levels of interobserver and intraobserver agreement in assessment of histological subtype and grade in 207 patients with penile squamous cell carcinoma. The cases were assessed by seven pathologists from three hospitals located in Sweden and Italy. There was poor to moderate concordance in assessing both histological subtype and grade, with Fleiss kappas of 0.25 (range: 0.02–0.48) and 0.23 (range: 0.07–0.55), respectively. When choosing HPV-associated and non-HPV-associated subtypes, interobserver concordance ranged from poor to good, with a Fleiss kappa value of 0.36 (range: 0.02–0.79). A re-review of the slides by two of the pathologists showed very good intraobserver concordance in assessing histological grade and subtype, with Cohen’s kappa values of 0.94 and 0.91 for grade and 0.95 and 0.84 for subtype. Low interobserver concordance could lead to undertreatment and overtreatment of many patients with penile cancer, and brings into question the utility of tumor histological subtype and tumor grade in determining patient treatment in pT1 tumors.

International variation in oesophageal and gastric cancer survival 2012–2014: differences by histological subtype and stage at diagnosis (an ICBP SURVMARK-2 population-based study)

ObjectiveTo provide the first international comparison of oesophageal and gastric cancer survival by stage at diagnosis and histological subtype across high-income countries with similar access to healthcare.MethodsAs part of the ICBP SURVMARK-2 project, data from 28 923 patients with oesophageal cancer and 25 946 patients with gastric cancer diagnosed during 2012–2014 from 14 cancer registries in seven countries (Australia, Canada, Denmark, Ireland, New Zealand, Norway and the UK) were included. 1-year and 3-year age-standardised net survival were estimated by stage at diagnosis, histological subtype (oesophageal adenocarcinoma (OAC) and oesophageal squamous cell carcinoma (OSCC)) and country.ResultsOesophageal cancer survival was highest in Ireland and lowest in Canada at 1 (50.3% vs 41.3%, respectively) and 3 years (27.0% vs 19.2%) postdiagnosis. Survival from gastric cancer was highest in Australia and lowest in the UK, for both 1-year (55.2% vs 44.8%, respectively) and 3-year survival (33.7% vs 22.3%). Most patients with oesophageal and gastric cancer had regional or distant disease, with proportions ranging between 56% and 90% across countries. Stage-specific analyses showed that variation between countries was greatest for localised disease, where survival ranged between 66.6% in Australia and 83.2% in the UK for oesophageal cancer and between 75.5% in Australia and 94.3% in New Zealand for gastric cancer at 1-year postdiagnosis. While survival for OAC was generally higher than that for OSCC, disparities across countries were similar for both histological subtypes.ConclusionSurvival from oesophageal and gastric cancer varies across high-income countries including within stage groups, particularly for localised disease. Disparities can partly be explained by earlier diagnosis resulting in more favourable stage distributions, and distributions of histological subtypes of oesophageal cancer across countries. Yet, differences in treatment, and also in cancer registration practice and the use of different staging methods and systems, across countries may have impacted the comparisons. While primary prevention remains key, advancements in early detection research are promising and will likely allow for additional risk stratification and survival improvements in the future.

Breast Implant Associated-Anaplastic Large-Cell Lymphoma (BIA-ALCL): Data Based on the Lymphoma Study Association (LYSA) Registry. Promising Results of Brentuximab Vedotin Combined with Cyclophosphamide, Doxorubicin and Prednisone (BV-CHP) As First Line Treatment for Patient Requiring Chemotherapy

Background: Breast implant-associated anaplastic large-cell lymphoma (BI-ALCL) is a rare form of T-cell lymphoma arising adjacent to a breast implant, recently recognized as a provisional entity in the 2017 revised World Health Organization (WHO) lymphoma classification. The pathogenesis of this entity remains elusive even if gene alterations in epigenetic modifiers and JAK-STAT signaling are frequent. ECHELON 2 trial (Horwitz S et al. The Lancet 2019) has set BV-CHP as a new standard of treatment for CD30-positive peripheral T-cell lymphoma, mainly in systemic ALCL patients (pts) but not in BIA-ALCL. Our objective is to describe a series of pts with BIA-ALCL included in the LYSA registry focusing on the use of BV CHP as front-line chemotherapy for patient requiring chemotherapy. Methods: since 2016, a national multidisciplinary meeting has been implemented by the French Cancer Agency to better define therapeutic strategies for newly diagnosed cases after histologic confirmation. Meanwhile, BIA-ALCL registry was funded by the LYSA to collect ambispectively, in France and more recently in Belgium, patient clinical data including reasons for breast implantation, implant manufacturer, treatment and outcome. Results: from 2009 to 2021 , 85 pts (73 in France and 12 in Belgium) gave their informed consent to participate to the registry. Median age was 57 years (range 29-82) at diagnosis. In 39 out of 85 pts (45.9%) the first implant followed a mastectomy for breast cancer. In this analysis, only implants in the breast(s) where the lymphoma occurred have been considered. Five pts (5.9%) had bilateral lymphoma and 80 pts had unilateral lymphoma (35 left side and 45 right side), 35 pts were implanted once (41.2%), 35 twice (41.2%) and 15 pts (17.6%) 3 times or more. The median period between first implant and BIA-ALCL diagnosis was 12.2 years (range 4.1-40.5), and 7 years (range 0.2-25.4) from last implant to diagnosis. The clinical presentation was seroma in 64 pts (75.3%), breast tumor mass with or without seroma in 18 pts (21.1%) and 3 pts were diagnosed without any mass or seroma (1 contiguous lymph node involvement, 2 in the context of systematic implant removal). The two main clinical presentation (i.e. seroma and tumor mass) were most often correlated with the two distinct histological subtypes (in "situ/mixed" (n=62) or "infiltrative" (n=21)). For 2 pts, histological subtype was not available. The majority of pts were Ann Arbor stage I-II (n=65, 76.5%), and 18 (21.2%) pts were stage IV. Stage was unknown in 2 pts. Considering available information, almost all patients had at least one silicone-filled (n=76) and at least one textured implant (n=85) with Biocell texturation (n=61, 71.8%). No patient had only smooth implant. Implant removal with total capsulectomy was performed in 66 patients and 25 underwent chemotherapy based on CHOP or CHOP-like (4 to 6 cycles) chemotherapy regimens (n=13), BV-CHP (6 cycles) (n=10) and others (n=2). Among the patients receiving chemotherapy, CR was obtained in 21 pts (84%) and in 2 pts failed to respond (8%). Among the patients treated with BV-CHP, 8 pts achieved CR (80%) and 2 pts were not yet evaluated at the time of analysis. No limiting toxicity was noted. After a median follow-up of 28.6 months, 78 pts are alive and free of evolutive disease and 8 are lost to follow up. Seven pts died, either from lymphoma progression alone (n=2) or associated with concomitant active breast cancer (n=2), one from breast cancer alone, one from lung epidermoid cancer and one due to myocardial infarction. Patients with an "infiltrative" histological subtype have a significantly worse outcome with a 2y-PFS of 73.8% vs 96.7% for other subtypes ("in situ/mixed subtypes") (p=0.0039, HR=5.3) and a 2y-OS of 78.7% vs 100% (p=0.0022, HR=8.5). With a median follow-up of one year, the 10 patients treated with BV-CHP are alive and free of evolutive disease at the time of analysis. Conclusions: We report on the basis of a limited series of patients that 6 cycles of BV-CHP provide an excellent disease control in patients with BIA-ALCL requiring chemotherapy. Confirmation of these results on a larger series of patients with a longer follow-up is needed. Such observation provides basis for a prospective trial in order to determine if treatment with BV-CHP could be installed as a standard of care for higher risk patients with BIA-ALCL, as those presenting with tumor mass and /or infiltrative subtype. Disclosures Le Bras: Novartis: Honoraria; Celgene BMS: Research Funding; Takeda: Honoraria, Research Funding; Kite Gilead: Honoraria. Bachy: Kite, a Gilead Company: Honoraria; Novartis: Honoraria; Daiishi: Research Funding; Roche: Consultancy; Takeda: Consultancy; Incyte: Consultancy. Bonnet: Roche: Consultancy. André: AbbVie: Other: Travel/accomodation/expenses; Roche: Other: Travel/accomodation/expenses, Research Funding; Johnson & Johnson: Research Funding; Celgene: Other: Travel/accomodation/expenses; Bristol-Myers-Squibb: Consultancy, Other: Travel/Accommodations/Expenses; Karyopharm: Consultancy; Gilead: Consultancy, Other: Travel/Accommodations/Expenses; Incyte: Consultancy; Takeda: Consultancy, Research Funding. Haioun: Amgen: Honoraria, Research Funding; Servier: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Gilead: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; F. Hoffmann-La Roche Ltd: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Miltenyi: Honoraria, Research Funding.

Novel Single Agents Are Equivalent to Conventional Chemotherapy Inpatients with Relapsed and Refractory Mature T-Cell Lymphomas: A Meta-Analysis

Background: Patients with advanced peripheral and cutaneous T-cell lymphomas (PTCL and CTCL) have an unfavorable prognosis . Primary refractoriness to traditional chemotherapy and relapse is common. Few FDA-approved "novel" single agents (SA) are available but their effectiveness as salvage agents relative to traditional multiagent cytotoxic chemotherapy (CC) regimens remains unknown. Therefore, we conducted a systematic meta-analysis to compare the response rates of approved and experimental single agents to conventional chemotherapy for patients with relapsed and refractory (R/R) PTCL and CTCL. Methods: This systematic review is reported in accordance with the PRISMA guidelines. Briefly a Harvard University Librarian (PB) systematically searched the publication libraries of: MEDLINE (through Ovid SP), Embase, Web of Science Core Collection, and Cochrane's Central Register for adult patients with R/R PTCL and CTCL enrolled in phase I, II, and III clinical trials of novel single and cytotoxic drugs. Agents determined as novel included antifolates, histone deacetylase inhibitors (HDACi), antibody-drug conjugates, therapeutic antibodies, hypomethylating agents, cereblon modulators, inhibitors of PI3K/AKT/mTOR, JAK/STAT, aurora kinase, farnesyl transferase and proteosome pathways, and CD4 CAR T- cells. Conventional chemotherapy agents included ifosfamide-, gemcitabine-, anthracycline-, and platinum-based treatments. Three researchers (NS, RS and LB) independently reviewed eligible studies and extracted data for baseline demographics, histological subtype, treatment characteristics including response rates, duration of response, overall and progression free survival, toxicity, and risk of bias assessment. Primary outcome was overall response rate (ORR), defined as the best reported partial response (PR) or better. Meta-analyses were conducted for ORR and the scale of logarithm of odd using the generic inverse variance method. The random effects model was used to pool the effect sizes for each study assuming a normal distribution of the random effects. Preplanned subgroup by therapy type and histological subtypes of lymphoma were treated as fixed effects and compared using Wald test. The degree of statistical heterogeneity was evaluated by inconsistency index (I2). Results: Our literature search identified 1873 articles, which after filtering for inclusion and exclusion criteria, ruling in only papers including T-cell lymphoma specific response, was narrowed to 128 studies for data extraction. Of these 128 studies, 35 were phase I trials, 70 phase II, 13 phase III, and 10 were combination. First, we divided all studies into upfront (n=33) versus R/R (n=100) based on timing of their treatments. We specifically focused on patients with R/R TCLs and subdivided those studies into the novel SA (n=84) and conventional chemotherapy (n=16) categories. The ORR for novel agents was lower at 37% (95% confidence interval [CI]: 34, 41) in comparison with 55% (95% CI: 40, 69) for standard chemotherapy agents (p=0.02). When stratified by histological subtype, patients with PTCL-NOS (n=751) had comparable ORR to novel agents (31%; 95% CI: 27, 35) and conventional chemotherapy (40%; 95% CI: 31,50; p=0.08). Similar results were seen with patients with AITL (n=296) who achieved equivocal ORR to single agents (45%; 95% CI: 38, 52) when contrasted with conventional chemotherapy (55%; 95% CI: 27, 80; p=0.52). Similar efficacy was seen for patients with CTCL (n=612) across SA (34%, 95% CI:29, 40) and CC (44%; 95% CI: 33, 56; p=0.11). Conclusions: Our meta-analysis highlights that for particular histological subtypes of PTCL such as PTCL-NOS and AITL, single agents are non-inferior to cytotoxic chemotherapy regimens in the R/R setting. These findings warrant serious consideration in the design and development of clinical trials for patients with R/R PTCL and the need for tailored treatments. Our meta-analysis also informs clinicians and patients about the benefits of single agents in comparison with standard chemotherapy while making clinical decisions for specified histologies. Disclosures Foss: Mallinckrodt: Honoraria; Kyowa: Honoraria; Kura: Honoraria; Seattle Genetics: Honoraria, Speakers Bureau; Acrotech: Honoraria, Speakers Bureau; Daiichi Sankyo: Honoraria. Jain: Trillium Therapeutics, Inc: Research Funding; Acro Biotech, Inc: Research Funding; Abcuro, Inc: Research Funding.