An update in pathologic diagnosis of uterine mesenchymal tumours

Recent discovery of new disease-defining molecular alterations and development of novel targeted therapies has dramatically changed the classification and management of uterine mesenchymal neoplasms. This review discusses diagnostic updates in endometrial stromal sarcoma, PEComa, uterine tumor resembling ovarian sex cord tumor (UTROSCT), inflammatory myofibroblastic tumor, NTRK fusion uterine sarcoma, COL1A1-PDGFB fusion sarcoma, and SMARC-deficient uterine sarcoma. Key clinical, morphologic, immunophenotypic, and molecular features are reviewed, with emphasis on common differential diagnoses and pitfalls, and their impact on prognosis or management. Where applicable, the role of novel targeted therapies is discussed. A stepwise approach to uterine mesenchymal neoplasms can achieve a proper diagnosis and guide appropriate clinical management in most cases. Nonetheless, given the rarity of these tumors, their overlapping pathologic features, and rapid evolution in their classification and management, we advocate a low threshold for diagnostic consultation.     

Renal Neoplasia in Tuberous Sclerosis: A Study of 41 Patients

ObjectiveTo study the clinical features and identify unique renal neoplasia subtypes and their prognostic implications in individuals with tuberous sclerosis complex (TSC).Patients and MethodsThe Mayo Clinic nephrectomy registry included 37 patients with TSC diagnosed between 1970 and 2018. Four additional patients were identified from the pathology consultation and autopsy files. All available renal tumors were further characterized using immunohistochemistry and fluorescence in situ hybridization. Clinicopathologic features and follow-up were obtained from the medical record. The American Association for Cancer Research Project GENIE registry was accessed using cBioPortal for molecular profiling of angiomyolipoma (AML).ResultsA total of 276 renal tumors from 41 patients were analyzed. Renal tumors were classified into 9 distinct morphological subtypes, with AML predominating (238 [86%]). Interestingly, all these tumors acted in a benign fashion except one renal cell carcinoma with clear cells and fibromyomatous stroma and one epithelioid AML that metastasized. Molecular profiling studies revealed that epithelioid AMLs were enriched for alterations of TP53, RB1, and ATRX. Eight patients died of direct complications of TSC, including 3 of end-stage renal disease. To date, none have died of a renal epithelial neoplasm.ConclusionThe identification of unique renal neoplasia subtypes may provide important clues to establish a diagnosis of TSC, and in the somatic setting, this finding has important implications for accurate prognostication. These tumors tend to be indolent, and only 2 of 276 tumors in our study exhibited metastatic behavior. Our results support multidisciplinary management with a focus on preservation of renal function.     

Factors accelerating recurrences and secondary tumors in cutaneous squamous cell carcinoma

To investigate factors that affect and also decrease the duration for recurrences and secondary tumors in cSCC.A retrospective study was conducted for all patients who were treated for a cSCC of the head and neck between 2009 and 2016. Anamnestic as well as epidemiological and histological data were noted and correlated with the occurrence of recurrences and secondary cancers. The duration between surgery and these events was used to determine if histological factors accelerate their occurrence.The highest risk for recurrences was seen in patients with previous skin cancers (RR 3.23). Histological ulceration (p = 0.003) and grading (p = 0.031) of the tumor were found as significant factors accelerating the time to relapse. Surrounding chronic precancerotic lesions (p < 0.001) and poor tumor grading (p = 0.035) were found as significant factors accelerating the time until a secondary cSCC was observed.Known risk factors increase not only the risk for a cSCC but also for recurrences. Specific histologic findings can help to adjust follow-up intervals to identify recurrences and secondary tumors at an early stage as these were shown to decrease the duration for a further event.     

Imaging Features of Pulmonary Immune-related Adverse Events

Pulmonary immune-related adverse events represent rare but potentially severe side effects of immunotherapies. Diagnosis is often challenging, as symptoms and imaging features are not specific and may mimic other lung diseases, thus potentially delaying appropriate patient management. In this setting, an accurate imaging evaluation is essential for a prompt detection and correct management of these drug-induced lung diseases. The purpose of this article is to review the different types of pulmonary immune-related adverse events, describe their imaging characteristics on both high-resolution computed tomography and positron emission tomography/computed tomography and stress their underlying diagnostic challenge by presenting the mimickers.     

Ten years psychosocial outcomes among adolescents following suicide attempts – early recurrence and psychosocial outcomes

ObjectivesA suicide attempt (SA) is a major risk factor of recurrent SA in adolescence and may be associated with psychological or social problems in the future. REPEATERS is a longitudinal study which examines the long-term psychosocial outcome of adolescents following attempted suicide. It focuses on the impact of early recurrence (i.e., within the first year of the index SA) – data which is, in fact, poorly documented.MethodsTen years after the index SA, a self-reporting questionnaire was sent to all adolescents who had attempted suicide and were followed up by the CHRU (Regional University Hospital Centre) de Nancy, France, between 1994 and 2003 and their parents. The purpose of this questionnaire was to assess psychosocial outcomes. Data concerning SA were collected retrospectively.ResultsAfter ten years, 146 of the 309 adolescents who had attempted suicide and were participating in the study had responded: 90% lived with a partner and 41% had children. The mean (SD) current emotional life of suicide attempt survivors scored 7.3 (2.3) on a scale of 0 to 10. Compared to the general population of the same age, responders felt more depressed than their peers (29% vs. less than 8% of males and 20% of females), had more suicidal thoughts (14% vs. 5%), and had more SAs (27% vs. 0.3%). Moreover, the risk of recurrence over the ten year period was associated with suicide recurrence in the first year after the index SA (odds ratio [OR] = 2.3; 95% confidence interval [CI] = 1.1–4.9) and with a lower level of education at ten years (OR = 0.37; 95% CI = 0.19–0.45).ConclusionsAlthough a favorable outcome was reported ten years after the event for the majority of adolescents who had attempted suicide, some with a lower level of education were nevertheless at increased risk of recurrence and depression. Post-intervention strategies are therefore essential in order to evaluate risk factors which may persist if not taken into consideration.     

脾脏血管性病变与淋巴瘤CT鉴别诊断

目的 运用CT区分脾脏血管性病变与淋巴瘤。方法 回顾性分析20例经手术、穿刺病理学检查证实的脾脏病变的发病年龄、性别、脾脏指数、病变大小、数目、有无液化、钙化、强化幅度、强化方式等特征,并进行统计学分析。结果 20例脾脏病变中,11例血管性病变(6例海绵状血管瘤,3例窦岸细胞血管瘤,2例硬化性血管瘤样结节性转化),9例淋巴瘤;两组间发病年龄、病变大小、数目、有无液化、钙化等差异无统计学意义;两组间脾脏指数、动脉期强化幅度差异具有统计学意义(P＜0.05)。5例海绵状血管瘤呈不均匀性强化,1例呈渐进性填充式强化,2例窦岸细胞血管瘤呈“雀斑征”,1例硬化性血管瘤样结节性转化呈“辐轮征”;9例淋巴瘤实质部分均呈均匀、轻中度强化。结论 脾脏血管性病变与淋巴瘤CT表现不同,CT有助于明确诊断。     

lncRNA-FTX与脑胶质瘤病人预后的相关性分析

目的 探讨长链非编码RNA（lncRNA）FTX表达水平与脑胶质瘤病人预后的相关性。方法 前瞻性收集2016年1月~2018年1月手术切除的脑胶质瘤88例（46例获得瘤旁组织），采用实时逆转录PCR检测lncRNA FTX表达水平，以脑胶质瘤组织lncRNA FTX表达水平均值为界分为高表达组（n=57）和低表达组（n=31）。术后随访3年，主要观察指标为无进展生存期、总生存期。结果 脑胶质瘤组织lncRNA FTX表达水平[（7.54±2.15）]明显高于瘤旁组织[（2.65±0.69）；P<0.001]。多因素Cox比例回归风险模型分析显示，lncRNA FTX高表达是脑胶质瘤生存预后不良的独立危险因素（RR=1.589；95% CI 1.004~2.515；P=0.048）。生存曲线分析显示，高表达组无进展生存期（15.10个月）和总生存期（20.24个月）较低表达组（分别为18.96和25.53个月）明显缩短（P<0.05）。结论 脑胶质瘤lncRNA FTX呈高表达，与病人不良生存预后有关。     

Predictors of survival following surgical resection of limited-stage small cell lung cancer

BackgroundAdjuvant chemotherapy, postoperative radiation (PORT), and prophylactic cranial irradiation (PCI) have been individually examined in limited-stage small cell lung cancer (SCLC). There is a paucity of data on the effectiveness of each adjuvant treatment modality when used in combination after surgical resection of SCLC.MethodsData were collected from 5 cancer centers on all patients with limited-stage SCLC who underwent surgical resection between 1986 and 2019. Univariate and multivariable models were conducted to identify predictors of long-term outcomes, focusing on freedom from recurrence and survival benefit of adjuvant chemotherapy, PORT, and PCI.ResultsA total of 164 patients were analyzed. Multivariable Cox regression analysis did not identify any adjuvant therapies to significantly influence recurrence in this cohort. Specifically, PORT was not associated with a significant influence on locoregional recurrence and PCI was not significantly associated with intracranial outcomes. Adjuvant chemotherapy improved survival in all stage I through III disease (hazard ratio, 0.49; 95% confidence interval, 0.29-0.81; P = .005) and even in pathologically node negative patients (hazard ratio, 0.49; 95% confidence interval, 0.27-0.91; P = .024). Although PCI was found to improve survival in univariate analysis, it was not significant in a multivariable model. PORT was not found to affect survival on either univariate or multivariable analysis.ConclusionsThis is among the largest multi-institutional studies on surgically resected limited-stage SCLC. Our results highlight survival benefit of adjuvant chemotherapy, but did not identify a statistically significant influence from mediastinal PORT or PCI in our cohort. Larger prospective studies are needed to determine the benefit of PORT or PCI in a surgically resected limited-stage SCLC population.     

Mechanical Hemolysis Complicating Transcatheter Interventions for Valvular Heart Disease: JACC State-of-the-Art Review

Mechanical intravascular hemolysis is frequently observed following procedures on heart valves and uncommonly observed in native valvular disease. In most cases, its severity is mild. Nevertheless, it can be clinically significant and even life threatening, requiring multiple blood transfusions and renal replacement therapy. This paper reviews the current knowledge on mechanical intravascular hemolysis in valvular disease, before and after correction, focusing on pathophysiology, approach to diagnosis, and impact of other hematological conditions on the resultant anemia. The importance of a multidisciplinary management is underscored. Laboratory data are provided about subclinical hemolysis that is commonly observed following the implantation of surgical and transcatheter valve prostheses and devices. Finally, clinical scenarios are reviewed and current medical and surgical treatments are discussed, including alternative options for inoperable patients.