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Beyond the Syndrome: Extensive Congenital Abnormalities in an Infant With Trisomy 21 超越症候群:21三体婴儿的广泛先天性异常
IF 1.3 Q3 PATHOLOGY Pub Date : 2022-04-01 DOI: 10.1177/2632010X221088966
Jeremy D. Ward, Mahesh S Sharma, M. Pizzuto, V. Moylan, F. Askin, D. Kaufman
Herein we discuss the clinical course and subsequent autopsy of a female infant with trisomy 21 with balanced Rastelli Type “C” complete atrioventricular septal defect (AVSD), tetralogy of Fallot and right aortic arch with mirror image branching pattern who underwent a palliative right modified Blalock-Taussig-Thomas shunt (mBTTS) for hypoxemia from progressive right ventricular outflow tract obstruction. The baby was found to have multiple concomitant pathologic findings not typically seen with this constellation of cardiac anatomy. Autopsy revealed significant abdominal adhesions with near-complete stenosis of the transverse colon. In addition, the infant was found to have significantly elongated villi within the small and large bowel and a relatively large collagenous polyp in the small bowel. The decedent also had an abnormal tracheal bronchus, characterized by an additional superior right-sided bronchus, which is an extremely rare abnormality. Her clinical course was complicated by severe pulmonary hypertensive arteriolar changes out of proportion to what would be typical for her age, trisomy 21 status, and degree of left to right intracardiac shunting. Furthermore, she had refractory anasarca and recurrent chylous pleural effusions without gross lymphatic abnormalities that may have been secondary to systemic capillary leak syndrome (SCLS) versus severe pulmonary hypertension. Due to the aforementioned findings, the family elected for comfort care and the baby expired shortly after extubation. Overall, the infant had multiple, rare coexisting congenital abnormalities that likely represents an extreme phenotype of trisomy 21 that has not been described in the literature to date.
在此,我们讨论了一例21三体女婴的临床过程和随后的尸检,该女婴患有平衡型Rastelli“C”型完全性房室间隔缺损(AVSD),法洛四联症和具有镜像分支模式的右主动脉弓,因进行性右心室流出道梗阻引起的低氧血症接受了姑息性右改良Blalock-Taussig-Thomas分流(mBTTS)。婴儿被发现有多种伴随的病理学发现,这在心脏解剖结构中是不常见的。尸检显示有明显的腹部粘连,横结肠几乎完全狭窄。此外,婴儿的小肠和大肠绒毛明显拉长,小肠有相对较大的胶原息肉。死者还有一个异常的气管支气管,其特征是额外的右上支气管,这是一种极为罕见的异常。她的临床过程因严重的肺动脉高压小动脉变化而变得复杂,这些变化与她的年龄、21三体状态和左向右心内分流的程度不相称。此外,她有难治性肛门积液和复发性乳糜性胸腔积液,无明显淋巴异常,可能继发于系统性毛细血管渗漏综合征(SCLS)和严重肺动脉高压。由于上述发现,这家人选择了舒适护理,婴儿在拔管后不久就过期了。总的来说,婴儿有多种罕见的并存先天性异常,这可能代表了21三体的极端表型,迄今为止文献中尚未描述。
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引用次数: 0
Co-Relation of Hormonal Profile and BRCA1 in Sporadic Breast Carcinoma: A Single Institutional Experience of 303 Patients. 散发性乳腺癌中激素谱与BRCA1的相关性:303例患者的单一机构经验
IF 1.3 Q3 PATHOLOGY Pub Date : 2022-02-14 eCollection Date: 2022-01-01 DOI: 10.1177/2632010X221076379
Preeti Agarwal, Fatima Khan, Sameer Gupta, Shalini Bhalla, Ann Thomas, Akshay Anand, Kulranjan Singh, Abhinav Arun Sonkar

Introduction: Invasive Breast carcinoma-No special type (NST) is the most common breast malignancy accounting for 95% of breast cancers. Study of predictive and prognostic immunohistochemical markers estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (Her2neu) expression are crucial for treatment planning.

Materials and methods: In the present study we studied the hormonal profile in 303 sporadic breast cancers and BRCA1 protein expression in these patients along with its clinico-pathological correlation.

Results: In our patient population, Triple negative Breast carcinoma (TNBC) (104/303; 34.3%) was the most common luminal subtype followed by Luminal A 74/303; 24.4%), Her2 enriched (65/303; 21.5%), and Luminal B (60/303; 19.8%) respectively. This contrasts with many western studies which commonly report Luminal A being the largest subgroup. BRCA1 protein loss was more prominently seen in TNBC (64/104;61.5%) highlighting the possibility that high grade tumors are more susceptible to some epigenetic modifications leading to higher likelihood of loss of BRCA1 protein.

Conclusion: Hence, we conclude that like hereditary cases of breast carcinoma with BRCA1 mutation; BRCA1 loss is also more likely in sporadic TNBC cases.

浸润性乳腺癌-无特殊类型(NST)是最常见的乳腺恶性肿瘤,占乳腺癌的95%。研究预测和预后的免疫组织化学标志物雌激素受体(ER)、孕激素受体(PR)和人表皮生长因子受体2 (Her2neu)的表达对治疗计划至关重要。材料与方法:本研究对303例散发性乳腺癌患者的激素谱、BRCA1蛋白表达及其临床病理相关性进行了研究。结果:在我们的患者群体中,三阴性乳腺癌(TNBC) (104/303;34.3%)是最常见的luminal亚型,其次是luminal A 74/303;24.4%), Her2富集(65/303;21.5%), Luminal B (60/303;分别为19.8%)。这与许多西方研究形成对比,这些研究通常报告Luminal A是最大的亚群。BRCA1蛋白丢失在TNBC中更为明显(64/104;61.5%),这表明高级别肿瘤更容易受到一些表观遗传修饰的影响,从而导致BRCA1蛋白丢失的可能性更高。结论:BRCA1基因突变的遗传性乳腺癌病例;BRCA1基因缺失也更可能发生在散发性TNBC病例中。
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引用次数: 2
Red Cell Distribution Width as a Predictor of Mortality in Patients With Clinical Sepsis: Experience From a Single Rural Center in Central India. 红细胞分布宽度作为临床败血症患者死亡率的预测因子:来自印度中部单一农村中心的经验。
IF 1.3 Q3 PATHOLOGY Pub Date : 2022-02-03 eCollection Date: 2022-01-01 DOI: 10.1177/2632010X221075592
Kavita Jain, Darshita Sharma, Mala Patidar, Shirish Nandedkar, Ashish Pathak, Manju Purohit

Introduction: Early diagnosis of sepsis and its severity is essential for appropriate treatment to improve patient survival, especially in resource-limited settings. The aim of the present study was to study the role of red blood cell distribution (RDW) as a biomarker for the early detection of severe sepsis defined clinically and also in the prediction of mortality from sepsis.

Methods: The cross-sectional study included a total of 175 subjects who met the inclusion criteria for the diagnosis of severe sepsis. After a thorough clinical examination, blood samples were taken from all patients within 3 hours of presenting the disease. The RDW values and other investigations were studied on the day of admission compared to other severity markers with the mortality index of 30 days.

Result: The RDW value was significantly higher in patients with severe sepsis and in non-survivor patients than in survivors (P < .0001). There was a strong correlation between the SOFA score and RDW in predicting the disease outcome with the Pearson correlation coefficient of r = .46. The area under the receiver operating characteristic curve was found to be 0.852 at a CI of 95% (0.796-0.909) with RDW 17.15, sensitivity was 88.6% and specificity was 63.5%. There was a positive correlation with Pearson's correlation coefficient of r = .46 between RDW and the SOFA score.

Conclusions: RDW can be used as a potential marker for the early detection of severe sepsis and in the prediction of the outcome. Large multicenter prospective studies can confirm the utility of this routinely available marker for patients with sepsis.

简介:早期诊断败血症及其严重程度对于适当治疗以提高患者生存率至关重要,特别是在资源有限的情况下。本研究的目的是研究红细胞分布(RDW)作为临床定义的严重脓毒症早期检测和脓毒症死亡率预测的生物标志物的作用。方法:横断面研究共纳入175名符合严重脓毒症诊断标准的受试者。经过彻底的临床检查,在发病后3小时内采集了所有患者的血样。入院当天的RDW值及其他调查与其他严重程度指标比较,死亡率指数为30天。结果:严重脓毒症患者和非存活患者的RDW值显著高于存活患者(P r = 0.46)。受试者工作特征曲线下面积为0.852,CI为95% (0.796 ~ 0.909),RDW为17.15,敏感性为88.6%,特异性为63.5%。与Pearson相关系数r =呈正相关。RDW与SOFA评分之间的差距为46。结论:RDW可作为早期发现严重脓毒症和预测预后的潜在标志物。大型多中心前瞻性研究可以证实这种常规可用标志物对脓毒症患者的效用。
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引用次数: 2
Rare but Potentially Fatal Presentations of Diffuse Large B-cell Lymphoma: Leukemic Phase or Hemophagocytic Syndrome in Bone Marrow. 弥漫性大b细胞淋巴瘤罕见但可能致命的表现:骨髓白血病期或噬血细胞综合征。
IF 1.3 Q3 PATHOLOGY Pub Date : 2022-01-09 eCollection Date: 2022-01-01 DOI: 10.1177/2632010X211070774
Wan Awatif Wan Mohd Zohdi, Ahmad Zulhimi Ismail, Nurasyikin Yusof, Azlin Ithnin, Salwati Shuib, Noraidah Masir, Sivakumar Palaniappan, Nor Rafeah Tumian

Diffuse large B-cell lymphoma (DLBCL) is a type of non-Hodgkin Lymphoma commonly presenting as a solid tumor either by nodal or extra-nodal manifestations. Here we describe two atypical presentations of lymphoma, finally resulting in the diagnosis of DLBCL. Case 1: A 53-year-old man with a previous history of nasopharyngeal carcinoma presented with a two-week history of B-symptoms and hyperleukocytosis. Peripheral blood film showed 78% abnormal mononuclear cells. Immunohistochemical stain showing Ki-67 of 90%, negative c-myc, BCL2 and BCL6, and negative c-MYC with fluorescence in-situ hybridization studies on the trephine biopsy, concluded the diagnosis of CD5+ DLBCL of ABC subtype. He received intravenous cyclophosphamide and oral prednisolone for cytoreduction, followed by 6 cycles of chemo-immunotherapy. However, he succumbed due to severe sepsis after the completion of therapy. Case 2: A 56-year-old lady who was initially investigated for pyrexia of unknown origin was noted to have hemophagocytosis upon bone marrow aspirate examination. The bone marrow trephine biopsy revealed some atypical clusters of B-cells positive for CD20 which was inconclusive. PET-CT scan noted an enlarged hypermetabolic spleen without lymphadenopathy. Splenic biopsy with immunohistochemical studies revealed DLBCL of ABC subtype. The diagnosis was consistent with primary splenic DLBCL. She became unwell post splenic biopsy and was admitted to the intensive care unit where she passed away 2 weeks later from Candida and Sternotrophomonas septicemia. These cases highlight the atypical presentations of a common subtype of NHL in our center. Arriving at the definitive diagnosis can be difficult especially when patients are acutely ill, hampering the necessary invasive procedures for diagnosis. The outcomes of both cases are briefly discussed hoping to spread awareness among clinicians on the rare and acutely critical presentations of DLBCL.

弥漫性大b细胞淋巴瘤(DLBCL)是一种非霍奇金淋巴瘤,通常表现为实体瘤,有淋巴结或结外表现。这里我们描述了两个非典型的淋巴瘤表现,最终导致DLBCL的诊断。病例1:53岁男性,既往鼻咽癌病史,有两周b症状和白细胞增多史。外周血膜显示78%的单核细胞异常。免疫组化染色显示Ki-67为90%,c-myc、BCL2、BCL6阴性,环甲活检c-myc荧光原位杂交阴性,诊断为ABC亚型CD5+ DLBCL。静脉注射环磷酰胺和口服强的松龙减少细胞,随后化疗免疫治疗6个周期。然而,在治疗完成后,他因严重的败血症而死亡。病例2:一位56岁的女士,她最初因不明原因的发热而接受调查,在骨髓抽吸检查时发现有噬血细胞症。骨髓穿刺活检显示一些不典型的CD20阳性b细胞簇,这是不确定的。PET-CT扫描显示脾脏高代谢肿大,无淋巴结病变。脾活检和免疫组化研究显示为ABC亚型DLBCL。诊断符合原发性脾大细胞淋巴瘤。她在脾活检后感到不适,并被送进重症监护室,2周后因念珠菌和胸养单胞菌败血症去世。这些病例突出了我们中心NHL常见亚型的非典型表现。达到明确的诊断可能是困难的,特别是当病人是急性疾病,阻碍了必要的侵入性诊断程序。本文简要讨论了这两个病例的结果,希望能在临床医生中传播对罕见和急性关键的DLBCL表现的认识。
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引用次数: 0
Proptosis Revealing a Rare Lacrimal Gland Tumor: A Case of Chondroid Syringoma in a 35-year-old Patient. 突出显示罕见泪腺肿瘤:35岁软骨样性腺瘤1例。
IF 1.3 Q3 PATHOLOGY Pub Date : 2022-01-09 eCollection Date: 2022-01-01 DOI: 10.1177/2632010X211070777
Boubacar Efared, Kadre Ousmane Kadre Alio, Boubacar Idrissa, Aïchatou Balaraba Abani Bako, Habiba Salifou Boureima, Ali Salèye, Nouhou Hassan

Lacrimal gland chondroid syringoma is a very rare tumor with classic clinico-radiological symptoms that should be familiar to clinicians for appropriate patients' management as the tumor has potential for recurrence and malignant transformation. We report herein a case of chondroid syringoma in a 35-year-old patient presenting with progressive painless proptosis for 2 years. He underwent complete surgical removal of the tumor, with subsequent clinical improvement of his symptoms.

泪腺软骨样淋巴瘤是一种非常罕见的肿瘤,具有典型的临床放射学症状,临床医生应该熟悉这些症状,以便对患者进行适当的治疗,因为肿瘤有复发和恶性转化的可能性。我们在此报告一个35岁的软骨样淋巴瘤患者,表现为进展性无痛性突起2年。他接受了完全切除肿瘤的手术,随后他的临床症状有所改善。
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引用次数: 0
Molecular Classification of Gastric Cancer With Emphasis on PDL-1 Expression: The First Report From Iran 以PDL-1表达为重点的癌症分子分类:伊朗首次报道
IF 1.3 Q3 PATHOLOGY Pub Date : 2022-01-01 DOI: 10.1177/2632010X221096378
F. Amirmoezi, B. Geramizadeh
Background: Gastric cancer is one of the lethal cancers and there is no effective treatment for these patients and still, 5-year survival rate is about 25% to 30%. Finding reliable biomarkers for early-stage diagnosis, targeted therapy, and survival prediction is a priority in this cancer. Objectives: In this study we were trying to know about the molecular classification of gastric cancers in a group of patients from the South of Iran. Patients and Methods: In a cross sectional study, 50 specimens of gastric cancer were selected that have enough tissue to be stained by immunohistochemistry (IHC). IHC was performed for Her-2, mismatch repair genes (MLH-1, MSH-2, MSH-6, and PMS-2), and PDL-1. Frequency of positive makers was compared with survival and outcome. Results and Conclusion: In our study, deficient MMR (dMMR) was detected in 4 patients (8.0%). PD-L1 expression in tumor cells (TC) was observed in 1 of 4 cases (25%) with PMS2 loss. However, PD-L1 in TCs and TILs (tumor infiltrating lymphocytes) was negative in 1 case with MLH1 loss and in 3 of 4 cases with PMS2 loss, which was not statistically significant. All of our 50 cases were positive for MSH2 and MSH6, 24% of which showed TCs with PDL-1 expression and 32% of them in TIL. HER2 was positive in 2 (2/50, 4.0%) cases, among which all of the cases were positive for PD-L1 expression in TCs and TILs, respectively. However, in HER2-negative group, 26.2% (11/42) and 28.6% (12/42) of tumors were positive for PD-L1 in TCs and TILs, respectively. The expression rate of PD-L1 in HER2 negative TCs was significantly higher than that in HER2 positive TCs (P = .033). Immunohistochemistry for Her-2 was equivocal in 6 cases (12.0%) none of which expressed PD-L1 in tumor cells. In our study minimum and maximum survival times from detection of gastric cancer were 1 and 87 months, respectively. The mean ± SD and median ± SD of overall survival time were 30.69 ± 4.88 and 18 ± 1.45 months, respectively. One and 3-year survival rates of 40% and 24%, respectively. PD-L1 expression was not associated with survival, but its expression was associated with intestinal type Lauren classification and negative HER-2. PD-L1 positivity in tumor cells or tumor infiltrating lymphocytes was not an independent prognostic factor in gastric cancer.
背景:癌症是恶性肿瘤之一,目前尚无有效的治疗方法,5年生存率约为25%-30%。寻找用于早期诊断、靶向治疗和生存预测的可靠生物标志物是这种癌症的优先事项。目的:在这项研究中,我们试图了解来自伊朗南部的一组患者胃癌的分子分类。患者和方法:在一项横断面研究中,选择50例癌症标本,这些标本具有足够的组织进行免疫组织化学(IHC)染色。对Her-2、错配修复基因(MLH-1、MSH-2、MSH-6和PMS-2)和PDL-1进行IHC。将阳性标记的频率与生存率和结果进行比较。结果与结论:在我们的研究中,4例(8.0%)患者检测到MMR缺陷,4例PMS2缺失患者中有1例(25%)肿瘤细胞中PD-L1表达。然而,在MLH1缺失的1例和PMS2缺失的4例中,TC和TIL(肿瘤浸润淋巴细胞)中的PD-L1为阴性,这在统计学上没有显著性。在我们的50例病例中,MSH2和MSH6均呈阳性,其中24%的TCs表达PDL-1,32%的TCs在TIL中表达。HER2阳性2例(2/50,4.0%),其中所有病例分别在TC和TIL中表达PD-L1。然而,在HER2阴性组中,TCs和TIL中分别有26.2%(11/42)和28.6%(12/42)的肿瘤PD-L1阳性。PD-L1在HER2阴性TC中的表达率显著高于HER2阳性TC(P=0.033)。Her-2的免疫组化在6例(12.0%)中不明确,其中没有一例在肿瘤细胞中表达PD-L1。在我们的研究中,癌症检测的最小和最大存活时间分别为1个月和87个月。总生存时间的平均值±SD和中位数±SD分别为30.69±4.88和18±1.45个月。一年和三年生存率分别为40%和24%。PD-L1的表达与生存率无关,但其表达与肠型Lauren分类和阴性HER-2有关。肿瘤细胞或肿瘤浸润性淋巴细胞中PD-L1阳性不是癌症的独立预后因素。
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引用次数: 1
Neutrophil Lymphocyte Ratio as a Marker of In-Hospital Deterioration in COVID-19: Observations From a Resource Constraint Setting 中性粒细胞淋巴细胞比率作为新冠肺炎住院病情恶化的标志:资源限制条件下的观察
IF 1.3 Q3 PATHOLOGY Pub Date : 2022-01-01 DOI: 10.1177/2632010X221090898
Nilanka Perera, A. D. de Silva, M. Kumbukage, Roshan Rambukwella, J. Indrakumar
Introduction and Objectives: The study was conducted to assess the association of neutrophil lymphocyte ratio (NLR) in COVID-19 and to identify the cut-off value that predicts mortality, need of respiratory support and admission to high-dependency or intensive care. Methods: A retrospective observational study was conducted to collect demographic data, clinical variables, the neutrophil-lymphocyte ratio on-admission and the outcome of confirmed COVID-19 patients admitted to a tertiary care center in Sri Lanka. Results: There were 208 patients with a median age of 56 years (IQR 43-67) and 98 (47.1%) males. The median neutrophil count was 4.07 × 103/µL (IQR 2.97-6.79) and the median lymphocyte count was 1.74 × 103/µL (IQR 1.36-4.75). The calculated NLR ranged from 0.12 to 48.28 with a median value of 2.32 (IQR 1.37-4.76). A NLR value >3.6 predicted development of severe disease requiring respiratory support, transfer to a high-dependency or an intensive care unit and/or succumbing to the illness with a sensitivity 80% and specificity 80% (area under the curve 0.8, 95% CI 0.72-0.88, P < .0001). The adjusted odds ratio of NLR > 3.6 on predicting severe disease was 11.1, 95% CI 4.5- 27.0, P < .0001. Conclusions: A NLR > 3.6 is a useful variable to be included in risk prediction scores in Sri Lanka.
前言和目的:本研究旨在评估中性粒细胞淋巴细胞比率(NLR)与COVID-19的相关性,并确定预测死亡率、呼吸支持需求和进入高依赖性或重症监护的临界值。方法:采用回顾性观察性研究,收集斯里兰卡某三级医疗中心收治的COVID-19确诊患者的人口学资料、临床变量、入院时中性粒细胞淋巴细胞比率和转归。结果:208例患者中位年龄56岁(IQR 43 ~ 67),男性98例(47.1%)。中性粒细胞计数中位数为4.07 × 103/µL (IQR 2.97 ~ 6.79),淋巴细胞计数中位数为1.74 × 103/µL (IQR 1.36 ~ 4.75)。NLR为0.12 ~ 48.28,中位数为2.32 (IQR为1.37 ~ 4.76)。NLR值b> 3.6预测需要呼吸支持的严重疾病的发展,转移到高依赖性或重症监护病房和/或因疾病而死亡的敏感性为80%,特异性为80%(曲线下面积0.8,95% CI 0.72-0.88,预测严重疾病的p3.6为11.1,95% CI 4.5- 27.0, p3.6是一个有用的变量,可纳入斯里兰卡的风险预测评分。
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引用次数: 2
COVID-19 Pulmonary Pathology, Ventilator-Induced Lung Injury (VILI), or Sepsis-Induced Acute Respiratory Distress Syndrome (ARDS)? Healthcare Considerations Arising From an Autopsy Case and Miny-Review COVID-19肺部病理,呼吸机诱导的肺损伤(VILI),还是败血症诱导的急性呼吸窘迫综合征(ARDS)?一例尸体解剖病例的医疗保健问题及综述
IF 1.3 Q3 PATHOLOGY Pub Date : 2022-01-01 DOI: 10.1177/2632010X221083223
Roberto Scendoni, Diego Gattari, M. Cingolani
Acute respiratory distress syndrome (ARDS) caused by coronavirus disease (COVID-19) is a serious complication that requires early recognition. Autopsy reports or biopsies of the lungs in patients with COVID-19 revealed diffuse alveolar damage (DAD) at different stages; the fibrotic phase is usually associated with long-standing severe disease. Care management of hospitalized patients is not easy, given that the risk of incurring a ventilator-induced lung injury (VILI) is high. Additionally, if the patient develops nosocomial infections, sepsis-induced ARDS should be considered in the study of the pathophysiological processes. We present an autopsy case of a hospitalized patient whose death was linked to COVID-19 infection, with the histopathological pattern of advanced pulmonary fibrosis. After prolonged use of non-invasive and invasive ventilation, the patient developed polymicrobial superinfection oh the lungs. After analyzing the individual’s clinical history and pulmonary anatomopathological findings, we consider healthcare issues that should lead to an improvement in diagnosis and to more adequate standards of care management among health professionals.
由冠状病毒病(COVID-19)引起的急性呼吸窘迫综合征(ARDS)是一种需要早期识别的严重并发症。COVID-19患者的尸检报告或肺活检在不同阶段显示弥漫性肺泡损伤(DAD);纤维化期通常与长期严重疾病有关。住院患者的护理管理并不容易,因为发生呼吸机诱导的肺损伤(VILI)的风险很高。此外,如果患者发生院内感染,在病理生理过程的研究中应考虑败血症引起的ARDS。我们报告了一名住院患者的尸检病例,该患者的死亡与COVID-19感染有关,其组织病理学模式为晚期肺纤维化。在长期使用无创和有创通气后,患者肺部出现多微生物重复感染。在分析了个体的临床病史和肺部解剖病理结果后,我们考虑了医疗保健问题,这些问题应该导致诊断的改善,并在卫生专业人员中建立更充分的护理管理标准。
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引用次数: 5
The First Case of Coxiella Burnetti Infection Detected Through Bone Marrow Biopsy in Vietnam 越南首例骨髓活检发现伯内蒂Coxiella感染病例
IF 1.3 Q3 PATHOLOGY Pub Date : 2022-01-01 DOI: 10.1177/2632010X221096397
Do Thi Vinh An, Bui Thi Viet Ha, Dao Xuan Co, Vu Minh Tam, Le Thi Diem Tuyet, Vu Van Truong
Coxiella burnetii is an obligate intracellular bacterium that causes the zoonotic infectious disease, Q fever. The common clinical presentation is fever, hepatitis, and pneumonia; laboratory examination could reveal pancytopenia, elevated liver enzymes. In bone marrow, many fibrin ring granulomas, also known as “Doughnut” granulomas can be seen and suggest the diagnosis of Q fever. However, these bone marrow granulomas can also be presented in infectious diseases by other pathogens such as EBV, CMV, and HBV; therefore, other serology or PCR—based tests are needed to confirm the diagnosis of Q fever. We report the first case of acute Q fever in Vietnam, presented as a fever of unknown origin with hepatitis in a 53-year-old male patient. A bone marrow biopsy was performed and showed various fibrin ring granulomas; therefore, Coxiella was suspected and the diagnosis was confirmed by PCR. Some infectious diseases can cause specific changes in the bone marrow, such as Doughnut granulomas in Q fever. These features can help direct the diagnosis and decide earlier treatment for the patient.
烧伤Coxiella burnetii是一种引起人畜共患传染病Q热的细胞内专性细菌。常见的临床表现是发烧、肝炎和肺炎;实验室检查可发现全血细胞减少,肝酶升高。骨髓中可见许多纤维蛋白环形肉芽肿,也称为“甜甜圈”肉芽肿,提示Q热的诊断。然而,这些骨髓肉芽肿也可通过其他病原体如EBV、CMV和HBV在感染性疾病中出现;因此,需要其他血清学或基于PCR的检测来确认Q热的诊断。我们报告了越南首例急性Q热病例,表现为一名53岁男性患者的不明原因发热伴肝炎。骨髓活检显示各种纤维蛋白环肉芽肿;因此,怀疑为Coxiella,并通过PCR确认诊断。一些传染病会引起骨髓的特定变化,如Q热中的甜甜圈肉芽肿病。这些特征可以帮助指导诊断并决定患者的早期治疗。
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引用次数: 1
Molecular Signatures of KRAS-Mutated Lung Adenocarcinoma: Analysis of Concomitant EGFR, ALK, STK11, and PD-L1 Status KRAS突变型肺腺癌的分子特征:EGFR、ALK、STK11和PD-L1共存状态的分析
IF 1.3 Q3 PATHOLOGY Pub Date : 2022-01-01 DOI: 10.1177/2632010X221102054
Jim Hsu, Joseph F Annunziata, E. Burns, E. Bernicker, R. Olsen, Jessica S. Thomas
Background: KRAS mutations are the most common oncogenic driver mutations of non-small cell lung cancer (NSCLC) in the Western world. Mutations of the KRAS gene are most prevalent in the patient population of current and former cigarette smokers. With the recent pivotal approval of a targeted inhibitor therapy for patients with KRAS p.G12C mutated and pretreated NSCLC, analysis of the heterogeneity of KRAS mutations and concomitant molecular alterations in patients with these tumors at all clinical stages is indicated. Methods: In this retrospective analysis, patient pathology records were reviewed for all cases receiving a pathologic diagnosis of NSCLC within our hospital system. All data were collected with IRB approval. Cases of indeterminate tumor type favoring a non-lung primary, as well as non-adenocarcinoma NSCLC (eg, squamous) were excluded from the cohort. In this hospital system, molecular testing for KRAS mutations is part of a molecular biomarker panel that is reflex ordered at initial diagnosis by the pathologist and may be performed as a single gene test or as a solid organ cancer hotspot panel by next generation sequencing. For each patient, KRAS mutational status and specific KRAS mutations, if present, were collated. Additional information assessed for this study included patient demographics (age, gender, and smoking history), tumor staging if available, PD-L1 expression levels by immunohistochemistry (IHC), and the presence of other genetic alterations (EGFR, ALK, and STK11). Results: Between January 1, 2017 and January 1, 2019, there were 276 patients diagnosed with NSCLC of all stages who had KRAS mutational analysis performed in our hospital system and who met the criteria for inclusion into the study cohort. A KRAS driver mutation was detected in 29% of these patients. The most frequently identified KRAS mutation was p.G12C (38%), followed by p.G12D (21%) and p.G12V (13%). KRAS-mutated lung adenocarcinoma was significantly associated with current or former patient smoking status in this cohort (29/202 (14%) smokers and 1/74 (1%) non-smokers; P = .0006). PD-L1 expression of at least 1% by IHC was present in 43% of KRAS-mutated lung adenocarcinomas and 45% of non-KRAS-mutated adenocarcinomas. In this study, KRAS mutations were not found to co-occur with gene alterations in EGFR, ALK, or STK11. In 48% of cases, at least one genetic alteration (KRAS, ALK, EGFR, or STK11) was identified. Conclusions: In this study cohort, KRAS-mutated lung adenocarcinoma demonstrated significant mutational heterogeneity, which is consistent with previously published studies. KRAS mutational status was also significantly associated with a current or former smoking history. Notably, p.G12C was the most frequently identified KRAS mutation in this cohort, with a frequency of 38%. This finding is particularly relevant given the recent approval of a KRAS p.G12C-specific targeted inhibitor therapy and the continued development of additional KRAS target
背景:KRAS突变是西方非小细胞肺癌(NSCLC)最常见的致癌驱动突变。KRAS基因突变在当前和以前吸烟的患者群体中最为普遍。最近,针对KRAS p.G12C突变和预处理的NSCLC患者的靶向抑制剂疗法获得了关键批准,有必要对这些肿瘤患者在所有临床阶段的KRAS突变的异质性和伴随的分子变化进行分析。方法:在这项回顾性分析中,回顾了我们医院系统内所有接受NSCLC病理诊断的病例的病理记录。所有数据均经IRB批准收集。有利于非肺原发性和非腺癌NSCLC(如鳞状细胞癌)的不确定肿瘤类型的病例被排除在队列之外。在该医院系统中,KRAS突变的分子检测是分子生物标志物小组的一部分,该小组是病理学家在最初诊断时反射命令的,可以作为单基因检测或作为下一代测序的实体器官癌症热点小组进行。对每个患者的KRAS突变状态和特定KRAS突变(如果存在)进行核对。本研究评估的其他信息包括患者人口统计学(年龄、性别和吸烟史)、肿瘤分期(如有)、免疫组织化学(IHC)检测的PD-L1表达水平以及其他基因改变(EGFR、ALK和STK11)的存在。结果:在2017年1月1日至2019年1月一日期间,在我们的医院系统中,共有276名被诊断为所有阶段的NSCLC患者进行了KRAS突变分析,并符合纳入研究队列的标准。在这些患者中有29%检测到KRAS驱动基因突变。最常见的KRAS突变是p.G12C(38%),其次是p.G12D(21%)和p.G12V(13%)。在该队列中,KRAS突变的肺腺癌与当前或以前的患者吸烟状况显著相关(29/202(14%)吸烟者和1/74(1%)非吸烟者;P = .0006)。IHC至少1%的PD-L1表达存在于43%的KRAS突变的肺腺癌和45%的非KRAS突变腺癌中。在这项研究中,没有发现KRAS突变与EGFR、ALK或STK11的基因改变同时发生。在48%的病例中,至少发现了一种基因改变(KRAS、ALK、EGFR或STK11)。结论:在该研究队列中,KRAS突变的肺腺癌表现出显著的突变异质性,这与先前发表的研究一致。KRAS突变状态也与当前或以前的吸烟史显著相关。值得注意的是,p.G12C是该队列中最常见的KRAS突变,频率为38%。鉴于KRAS p.G12特异性靶向抑制剂疗法最近获得批准,以及可能被证明对治疗NSCLC有效的其他KRAS靶向疗法的持续开发,这一发现尤其重要。这些发现还强调了在有吸烟史的NSCLC患者中考虑KRAS突变的分子检测的必要性,因为这一人群最常携带KRAS突变,并可能受益于这些新兴的靶向治疗。
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引用次数: 1
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Clinical Pathology
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