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P16 and P53 Expression in Esophageal Squamous Cell Carcinoma: A Brief Report From The Experience of South of Iran, and Review of the Literature. P16和P53在食管鳞状细胞癌中的表达:简述伊朗南部的经验,并复习文献。
IF 1.3 Q3 PATHOLOGY Pub Date : 2021-05-20 eCollection Date: 2021-01-01 DOI: 10.1177/2632010X211013821
Bita Geramizadeh, Alireza Mohammadian, Alireza Shojazadeh, Sahand Mohammadzadeh

Background: Iran is one of the high-risk countries for esophageal squamous cell carcinoma (ESCC). Human papillomavirus (HPV) has been reported as one of the etiologic, pathogenetic, and prognostic factors in this tumor, especially in high-risk geographic areas. Previous reports from our geographic area, that is, the South of Iran failed to show any evidence of HPV in the cases of ESCC by molecular methods.

Objectives: In this study, we evaluated P16 and P53 immunohistochemistry (IHC) expression in the cases of esophageal ESCC from Fars province in the South of Iran to find the presence of any correlation between clinicopathologic findings with P16 and P53 expression by IHC as etiologic and prognostic biomarkers. We also tried to compare the results from other geographic areas of Iran and the world.

Results: P16 and P53 expression were found in 42.9% and 66.12% of ESCCs, respectively. No statistically significant correlation was found between clinicopathologic findings and P16 pr P53 expression.

Conclusion: Although P16 and P53 expression in ESCC in the South of Iran is significant, there is no statistically significant correlation between clinicopathologic findings and outcome in ESCC and expression of these 2 proteins to be considered as biomarkers. Results from other geographic areas of Iran and the world are also very controversial and inconsistent.

背景:伊朗是食管鳞状细胞癌(ESCC)的高危国家之一。人乳头瘤病毒(HPV)已被报道为该肿瘤的病因、发病机制和预后因素之一,特别是在高危地区。以前的报告来自我们的地理区域,即伊朗南部,通过分子方法未能显示ESCC病例中HPV的任何证据。目的:在这项研究中,我们评估了伊朗南部法尔斯省食管ESCC病例中P16和P53免疫组织化学(IHC)的表达,以发现临床病理结果与P16和P53作为病因和预后生物标志物的表达之间是否存在相关性。我们还试图比较伊朗和世界其他地理区域的结果。结果:P16和P53的表达率分别为42.9%和66.12%。临床病理表现与P16 pr P53表达无统计学意义。结论:尽管P16和P53在伊朗南部ESCC中的表达显著,但ESCC的临床病理表现和转归与这两种蛋白的表达没有统计学意义上的相关性,不能作为生物标志物。来自伊朗和世界其他地理区域的结果也非常有争议和不一致。
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引用次数: 0
Uncommon Pigmented Carcinoma In Situ: Case Report and Brief Review. 罕见色素原位癌1例报告及简要回顾。
IF 1.3 Q3 PATHOLOGY Pub Date : 2021-04-20 eCollection Date: 2021-01-01 DOI: 10.1177/2632010X211009819
Andresa Borges Soares, Vera Cavalcanti de Araújo, Fabricio Passador-Santos, Luiz Alexandre Thomaz, Andre Luis Santana de Freitas, Mario Claudio Mautoni, Rafael Fantelli Stelini, Maria Leticia Cintra

Pigmented lesions of the oral mucosa encompass several benign and malignant conditions that may be a matter of concern under both clinical and histopathological views. We reported a case of a 62-year-old woman, presenting with an asymptomatic, deeply pigmented lesion on the soft palate. On examination, it appeared asymmetrical, with irregular borders and an area of ulceration. A biopsy, taken to rule out melanoma, revealed a pigmented carcinoma in situ. Throughout the tumor thickness, numerous interspersed melanocytes were found that did not extend to neighboring epithelium. These were large, richly dendritic, and presented abundance of melanin granules and small nuclei. Mild melanin incontinence was found. Scanty transfer of pigment to dysplastic epithelial cells was found through Fontana Masson staining. On immunohistochemical analyses, there were pancytokeratin-stained tumor epithelial cells; increased cell proliferation throughout the entire thickness of the tumor was emphasized by Ki-67 immunomarking. P16 was negative. The dendritic cells were selectively stained for S-100, HMB45 and Melan A. Wide spectrum in situ hybridization for human papillomavirus (HPV) was negative. Unfortunately, following diagnosis, the patient refused any treatment option. Pigmented squamous cell carcinoma with melanocyte colonization must be taken into account in the differential diagnosis of pigmented lesions of the oral cavity.

口腔黏膜的色素病变包括几种良性和恶性的情况,可能是一个问题的关注,在临床和组织病理学的观点。我们报告了一个62岁的妇女,提出了一个无症状,深色素病变软腭。检查时,它看起来不对称,边界不规则,有溃疡区。活检,采取排除黑色素瘤,显示一个色素原位癌。在整个肿瘤厚度中,发现大量散布的黑素细胞没有延伸到邻近的上皮。大而丰富的树突,有丰富的黑色素颗粒和小核。发现轻度黑色素失禁。Fontana Masson染色发现少量色素转移到发育不良的上皮细胞。免疫组化分析:肿瘤上皮细胞有泛细胞角蛋白染色;Ki-67免疫标记强调了整个肿瘤厚度细胞增殖的增加。P16为阴性。树突状细胞进行S-100、HMB45和Melan a的选择性染色,人乳头瘤病毒(HPV)广谱原位杂交阴性。不幸的是,确诊后,病人拒绝了任何治疗方案。在口腔色素病变的鉴别诊断中,必须考虑到黑色素细胞定植的着色性鳞状细胞癌。
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引用次数: 0
A Simple Panel of IDH1 and P53 in Differential Diagnosis Between Low-Grade Astrocytoma and Reactive Gliosis. IDH1和P53在低级别星形细胞瘤和反应性胶质瘤鉴别诊断中的应用。
IF 1.3 Q3 PATHOLOGY Pub Date : 2021-02-11 eCollection Date: 2021-01-01 DOI: 10.1177/2632010X20986168
Bita Geramizadeh, Mahsa Kohandel-Shirazi, Ahmad Soltani

Background: Reactive gliosis is a response of glial tissue to different types of injury such as brain abscess, trauma, hemorrhage, or even neoplastic process. In some circumstances, especially when the tissue biopsy is small, there may be difficulty to discriminate this reactive condition with low-grade diffuse astrocytoma (World Health Organization [WHO] grade II) by conventional hematoxylin and eosin (H&E) slides, so some immunohistochemical and molecular markers have been introduced for this differential diagnosis. One of the important aspects of updated WHO classification in 2016 has been dividing some of the glial tumor according to IDH1 (isocitrate dehydrogenase 1) mutation.

Objectives: In this study, we tried to evaluate IDH1 and P53 mutation by immunohistochemistry as a simple and highly specific and sensitive method to differentiate low-grade astrocytoma and reactive gliosis.

Material and methods: For 5 years (2013-2018), 50 cases of clinically documented reactive gliosis and 50 cases of low-grade astrocytoma were evaluated for the presence or absence of IDH1 and P53 mutation by immunohistochemistry.

Results: Isocitrate dehydrogenase 1 was positive in 92% and 4% of the astrocytoma and reactive gliosis cases and P53 was positive in 90% and 4% of the cases with the final diagnosis of astrocytoma and reactive gliosis, respectively.

Discussion and conclusion: Combination of P53 and IDH1 as an immunohistochemical panel showed specificity of 96% and sensitivity of 91% for differential diagnosis of reactive gliosis and low-grade astrocytoma. These 2 markers can be extremely helpful for this differential diagnosis.

背景:反应性神经胶质瘤是神经胶质组织对不同类型损伤的反应,如脑脓肿、创伤、出血,甚至肿瘤过程。在某些情况下,特别是当组织活检很小时,可能难以通过常规苏木精和伊红(H&E)载玻片将这种反应性疾病与低级别弥漫性星形细胞瘤(世界卫生组织[WHO]分级II级)区分开来,因此引入了一些免疫组织化学和分子标记来进行鉴别诊断。2016年WHO更新分类的一个重要方面是根据IDH1(异柠檬酸脱氢酶1)突变对一些胶质肿瘤进行分类。目的:在本研究中,我们试图通过免疫组织化学方法评估IDH1和P53突变,作为一种简单、高特异性和敏感性的方法来区分低级别星形细胞瘤和反应性胶质瘤。材料与方法:在2013-2018年的5年时间里,对50例临床记录的反应性胶质瘤和50例低级别星形细胞瘤进行免疫组化检测,检测是否存在IDH1和P53突变。结果:异柠檬酸脱氢酶1在星形细胞瘤和反应性胶质瘤中分别为92%和4%阳性,P53在最终诊断为星形细胞瘤和反应性胶质瘤的病例中分别为90%和4%阳性。讨论与结论:P53与IDH1联合作为免疫组化检测对反应性胶质瘤和低度星形细胞瘤鉴别诊断的特异性为96%,敏感性为91%。这两个指标对鉴别诊断非常有帮助。
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引用次数: 2
Prognostic Impact of Sphingosine Kinase 1 in Nonsmall Cell Lung Cancer. 鞘氨醇激酶1对非小细胞肺癌预后的影响。
IF 1.3 Q3 PATHOLOGY Pub Date : 2021-02-10 eCollection Date: 2021-01-01 DOI: 10.1177/2632010X20988531
Nozomu Motono, Yoshimichi Ueda, Miyako Shimasaki, Shun Iwai, Yoshihito Iijima, Katsuo Usuda, Hidetaka Uramoto

Bioactive sphingolipid is clearly relevant to lung physiology. The relationship of the bioactive sphingolipid pathway to pulmonary disease has been studied in cellular, tissue, and animal model, including lung cancer models. The samples of 53 patients diagnosed with nonsmall cell lung carcinoma (NSCLC) between June 2009 and May 2014 at our hospital were analyzed. Immunohistochemical (IHC) analysis was performed. The degree of immunostaining was reviewed and scored. Using this method of assessment, we evaluated the IHC score of sphingosine kinase 1 (SPHK1), vimentin, E-cadherin, and Ki-67. Both invasive adenocarcinoma cell and squamous cell carcinoma cell were well stained by SPHK1, and fibroblasts were also well stained by SPHK1. Although the IHC score of SPHK1 was not significantly differed between invasive adenocarcinoma and squamous cell carcinoma, the IHC scores of fibroblast, vimentin, and Ki-67 were higher in squamous cell carcinoma than invasive adenocarcinoma. Correlation among IHC scores in each of invasive adenocarcinoma and squamous cell carcinoma was performed. SPHK1 had positive correlation with both fibroblast and Ki-67, and fibroblast and Ki-67 had also positive correlation in invasive adenocarcinoma. On the contrary, SPHK1 had no significant correlation with fibroblast, and had negative correlation with Ki-67 in squamous cell carcinoma. Although there was not significant prognostic difference in SPHK1 score (P = .09), IHC score high group tended to be worse on relapse-free survival. SPHK1 might be prognostic factor in lung-invasive adenocarcinoma and novel target for drug against lung-invasive adenocarcinoma.

生物活性鞘脂显然与肺生理有关。生物活性鞘脂通路与肺部疾病的关系已经在细胞、组织和动物模型(包括肺癌模型)中进行了研究。对2009年6月至2014年5月在我院诊断为非小细胞肺癌(NSCLC)的53例患者的样本进行分析。免疫组化(IHC)分析。检查免疫染色程度并评分。采用这种评估方法,我们评估了鞘氨酸激酶1 (SPHK1)、vimentin、E-cadherin和Ki-67的IHC评分。侵袭性腺癌细胞和鳞状细胞癌细胞均可通过SPHK1染色,成纤维细胞也可通过SPHK1染色。虽然SPHK1的IHC评分在浸润性腺癌和鳞状细胞癌之间无显著差异,但鳞状细胞癌的成纤维细胞、vimentin、Ki-67的IHC评分高于浸润性腺癌。对浸润性腺癌和鳞状细胞癌的免疫组化评分进行相关性分析。SPHK1与成纤维细胞和Ki-67呈正相关,在侵袭性腺癌中,成纤维细胞和Ki-67也呈正相关。SPHK1在鳞状细胞癌中与成纤维细胞无显著相关性,与Ki-67呈负相关。两组患者SPHK1评分差异无统计学意义(P = 0.09),但IHC评分高的患者无复发生存期较差。SPHK1可能是影响肺浸润性腺癌预后的重要因素,也是抗肺浸润性腺癌药物的新靶点。
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引用次数: 1
Programmed Death Ligand 1 Expression in Laryngeal Squamous Cell Carcinomas and Prognosis. 程序性死亡配体1在喉鳞癌中的表达及预后。
IF 1.3 Q3 PATHOLOGY Pub Date : 2020-11-12 eCollection Date: 2020-01-01 DOI: 10.1177/2632010X20964846
Sebnem Batur, Zeynep Ecem Kain, Emine Deniz Gozen, Nuray Kepil, Ovgu Aydin, Nil Comunoglu

Aim: We aimed to show the immunohistochemical expression of programmed death ligand 1 (PD-L1) in laryngeal squamous cell carcinomas (SCCs).

Materials and methods: The study includes 52 laryngeal SCC cases that underwent surgical resection. Immunohistochemical staining of PD-L1 (Clone 22C3) was applied to the sections obtained from paraffin blocks. Combined Positive Score (CPS) was evaluated as described in manuals. Tumor Proportion Score (TPS) was assessed by the percentage of positive tumor cells which were designated as positive if ⩾1% of the tumor cells showed membranous staining.

Results: There were 35 cases (67.3%) having CPS < 1 and 17 cases (32.7%) having CPS ⩾ 1. There was no relationship between CPS, TPS, and the clinicopathological data.

Conclusion: Further studies with a large number of advanced-stage cases are needed.

目的:研究程序性死亡配体1 (PD-L1)在喉部鳞状细胞癌(SCCs)中的免疫组织化学表达。材料和方法:本研究包括52例手术切除的喉部鳞状细胞癌病例。对石蜡切片进行PD-L1(克隆22C3)免疫组化染色。综合阳性评分(CPS)按照手册中的描述进行评估。肿瘤比例评分(TPS)通过阳性肿瘤细胞的百分比进行评估,如果肿瘤细胞的小于或等于1%显示膜性染色,则阳性肿瘤细胞的百分比被指定为阳性。结果:有35例(67.3%)发生了CPS。结论:需要对大量晚期病例进行进一步的研究。
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引用次数: 5
Histopathological Characteristics of Gastrointestinal Stromal Tumors in a Cohort of Vietnamese Patients. 一组越南患者胃肠道间质瘤的组织病理学特征。
IF 1.3 Q3 PATHOLOGY Pub Date : 2020-11-11 eCollection Date: 2020-01-01 DOI: 10.1177/2632010X20972405
Pham Nguyen Cuong, Nguyen Thanh Xuan, Tran Xuan Tien, Pham Nhu Huy, Pham Nguyen Tuong

Introduction: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal system. Histopathological examination takes an important part in confirming the subtypes of GISTs, to choose appropriate therapeutics for patients. This study aims to explore the histopathological characteristics and evaluate the relationship between malignant risk classification (according to Armed Forces Institute of Pathology criteria) and the histopathological features of GISTs in a cohort of Vietnamese patients.

Methods: We reviewed 89 patients with primary GIST who underwent surgery between 2014 and 2019 at Hue Central Hospital, Vietnam. We investigated histopathological characteristics and immunohistochemical findings of all patients.

Results: The average age was 55.9 ± 11.9 years. A tumor size of 2-5 cm accounted for 64.1%. The most common position was at the stomach which accounted for 48.5%. Among the subtypes of GIST, spindle cells were seen in 85.9% of patients; epithelial form 10.9%; multi-morphology (3.2%). 97.4% of the samples were positive for CD117, 61.5% of cases were positive for CD34; and no case was positive for Desmin. The rate of high-risk GIST was dominant (46.9%) as compared to the intermediate-risk (28.1%), low-risk (0.3%-2%), and very low-risk groups (4.7%).

Conclusions: This study demonstrates the histopathological characteristics of GIST and emphasizes the significant rate of high-risk GIST.

胃肠道间质瘤(gist)是胃肠道最常见的间质肿瘤。组织病理学检查是确定胃肠道间质瘤亚型、为患者选择合适治疗方案的重要依据。本研究旨在探讨越南一组患者的组织病理学特征,并评估恶性风险分级(根据武装部队病理研究所的标准)与组织病理学特征之间的关系。方法:我们回顾了2014年至2019年在越南顺化中心医院接受手术的89例原发性GIST患者。我们研究了所有患者的组织病理学特征和免疫组织化学结果。结果:患者平均年龄55.9±11.9岁。肿瘤大小2-5 cm占64.1%。最常见的体位是腹部,占48.5%。在GIST亚型中,85.9%的患者存在梭形细胞;上皮型10.9%;多(3.2%)。97.4%的样本CD117阳性,61.5%的样本CD34阳性;德斯明没有阳性病例。与中危组(28.1%)、低危组(0.3%-2%)和极低危组(4.7%)相比,高危GIST占主导地位(46.9%)。结论:本研究显示了GIST的组织病理学特征,强调了GIST高危率的显著性。
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引用次数: 1
Determination of Vitamin D Levels in Patients With Neurofibromatosis Type 1 in the Pediatric Age Group. 儿科1型神经纤维瘤病患者维生素D水平的测定
IF 1.3 Q3 PATHOLOGY Pub Date : 2020-10-19 eCollection Date: 2020-01-01 DOI: 10.1177/2632010X20928930
Alessandra Santos, Mauro Geller, Spyros Mezitis, Allan E Rubenstein, Lisa Oliveira, Daniel Jm Medeiros Lima, Mendel Suchmacher Neto, Rafael Nigri, Karin Gonçalves Soares Cunha, Sanyu Takirambudde, Marcia Gonçalves Ribeiro

Introduction: Neurofibromatosis type 1 (NF1) is one of the most common autosomal dominant genetic disorders. Some clinical manifestations are present at birth, while some develop during childhood, and others can occur at any age. Given the early age at which patients develop clinical features, diagnosis is often made during childhood. The most prevalent features of NF1 are café au lait spots, dermal and plexiform neurofibromas, and learning disability. A variety of skeletal problems may be seen in NF1, including scoliosis, short stature, and pseudoarthrosis. Reduced skeletal bone mass has been documented to be a common phenomenon in children and adults with NF1. Decreased serum 25-hydroxyvitamin D (vitamin D) levels have been noted in adults and children with NF1 and have been reported to be inversely correlated with the number of dermal neurofibromas in adults. However, the actual correlation of vitamin D level to bone density and dermal neurofibroma number in children with NF1 remains unclear.

Objectives: The primary objective of this study was to evaluate vitamin D levels among children and adolescents with NF1. The secondary objective was to describe the levels of vitamin D among children and adolescents with NF1, to verify in which age group there is a higher frequency of vitamin D alterations, and to explore vitamin D level correlations between age, gender, sun exposure, number of neurofibromas, and number of plexiform neurofibromas.

Methods: This was an observational, cross-sectional, hospital-based study. We obtained a convenience sample of individuals with confirmed diagnosis of NF1 from patients attending the Medical Genetics Service of the IPPMG-UFRJ and Santa Casa de Misericórdia of Rio de Janeiro over a 24-month period. We evaluated vitamin D levels in blood samples of patients with NF1 by a chemiluminescent immunoassay method, and we correlated the results with gender, age, number of neurofibromas, number of plexiform neurofibromas, and satisfactory sun exposure.

Results: Of the 55 patients, 28 (50.9%) were female and 27 (49.1%) were male. Patient ages ranged from a minimum of 1.2 to a maximum of 19.6 years (mean age 10.95 years) and the median was 11.11 years. Median and mean body mass index (BMI; z score) were -0.09 (minimum value -1.63 and maximum of 4.62) and 0.16, respectively. The mean value of vitamin D was 30.82 ng/mL (±12.31) and the median was 29 ng/mL (minimum value of 10.40 ng/mL and maximum of 79.19 ng/mL).

Conclusions: The levels of vitamin D did not differ according to gender, age group, or the presence or number of cutaneous neurofibromas. Among patients with adequate sun exposure, there was a higher incidence of sufficient serum vitamin D levels. Patients with cutaneous neurofibromas in the 0 to 11 age group had a greater tendency to vitamin D sufficiency in relation to patients aged 11 to 19 years.

1型神经纤维瘤病(NF1)是最常见的常染色体显性遗传疾病之一。有些临床表现在出生时就有,而有些则在儿童时期出现,而另一些则可以在任何年龄出现。考虑到患者出现临床特征的早期年龄,诊断通常在儿童时期进行。NF1最常见的特征是咖啡渍斑点、真皮和丛状神经纤维瘤以及学习障碍。NF1可出现多种骨骼问题,包括脊柱侧凸、身材矮小和假关节。骨量减少已被证明是NF1儿童和成人的常见现象。血清25-羟基维生素D(维生素D)水平降低已在成人和儿童NF1中被注意到,并且据报道与成人真皮神经纤维瘤的数量呈负相关。然而,维生素D水平与NF1儿童骨密度和真皮神经纤维瘤数量的实际相关性尚不清楚。目的:本研究的主要目的是评估患有NF1的儿童和青少年的维生素D水平。次要目的是描述患有NF1的儿童和青少年的维生素D水平,以验证哪个年龄组维生素D改变的频率更高,并探索维生素D水平在年龄、性别、阳光照射、神经纤维瘤数量和丛状神经纤维瘤数量之间的相关性。方法:这是一项以医院为基础的观察性横断面研究。我们从参加IPPMG-UFRJ医学遗传学服务和里约热内卢Santa Casa de Misericórdia的24个月期间的患者中获得确诊为NF1的方便样本。我们用化学发光免疫分析法评估了NF1患者血液样本中的维生素D水平,并将结果与性别、年龄、神经纤维瘤数量、丛状神经纤维瘤数量和满意的日光照射程度相关联。结果:55例患者中,女性28例(50.9%),男性27例(49.1%)。患者年龄最小为1.2岁,最大为19.6岁(平均年龄10.95岁),中位数为11.11岁。中位和平均体重指数(BMI;Z评分)分别为-0.09(最小值-1.63,最大值为4.62)和0.16。维生素D的平均值为30.82 ng/mL(±12.31),中位数为29 ng/mL(最小值10.40 ng/mL,最大值79.19 ng/mL)。结论:维生素D的水平没有因性别、年龄组、皮肤神经纤维瘤的存在或数量而异。在有充足阳光照射的患者中,血清维生素D水平充足的发生率更高。与11至19岁的患者相比,0至11岁的皮肤神经纤维瘤患者更倾向于维生素D充足。
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引用次数: 1
Granulomata in Clear Cell Renal Cell Carcinoma: An Uncommon Presentation of a Common Cancer, Not Two Separate Entities. 透明细胞肾细胞癌中的肉芽肿:一种常见癌症的罕见表现,而不是两个独立的实体。
IF 1.3 Q3 PATHOLOGY Pub Date : 2020-09-29 eCollection Date: 2020-01-01 DOI: 10.1177/2632010X20954215
Daniel Hugh Russell

Sarcoidal-like granulomata (SLG) are known to occur as a response to a variety of tumor types, including lymphomas, prominently seminoma, other miscellaneous carcinomas, and rarely in renal cell carcinoma. There have been a handful of previously reported cases in the literature of SLG occurring in association with RCC. Of those previously reported, none were associated with infection and only 3 patients had a history of sarcoidosis. The prognostic significance of SLG in RCC is unsettled and somewhat complicated by the relative rarity of its occurrence and the paucity of data therein. A case is presented of an otherwise histologically typical clear cell renal cell carcinoma with peri-tumoral and intra-tumoral SLG. Special stains were negative for organisms and past medical history was negative for sarcoidosis and connective tissue disease.

结节样肉芽肿(SLG)是对多种肿瘤类型的反应,包括淋巴瘤、精原细胞瘤和其他杂项癌,很少发生在肾细胞癌中。文献中有少量先前报道的SLG与RCC相关的病例。在先前报道的病例中,没有一例与感染相关,只有3例患者有结节病史。SLG在RCC中的预后意义是不确定的,并且由于其发生的相对罕见和相关数据的缺乏而有些复杂。我们报告一例组织学上典型的透明细胞肾细胞癌伴瘤周及瘤内SLG。特殊染色阴性,既往病史阴性结节病和结缔组织病。
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引用次数: 0
B-Cell-Targeted 3DNA Nanotherapy Against Indoleamine 2,3-Dioxygenase 2 (IDO2) Ameliorates Autoimmune Arthritis in a Preclinical Model. 针对吲哚胺2,3-双加氧酶2 (IDO2)的b细胞靶向3DNA纳米疗法在临床前模型中改善自身免疫性关节炎
IF 1.3 Q3 PATHOLOGY Pub Date : 2020-08-27 eCollection Date: 2020-01-01 DOI: 10.1177/2632010X20951812
Lauren Mf Merlo, Jessica Bowers, Tony Stefanoni, Robert Getts, Laura Mandik-Nayak

The tryptophan catabolizing enzyme indoleamine 2,3-dioxygenase 2 (IDO2) has been identified as an immunomodulatory agent promoting autoimmunity in preclinical models. As such, finding ways to target the expression of IDO2 in B cells promises a new avenue for therapy for debilitating autoimmune disorders such as rheumatoid arthritis. IDO2, like many drivers of disease, is an intracellular protein expressed in a range of cells, and thus therapeutic inhibition of IDO2 requires a mechanism for targeting this intracellular protein in specific cell types. DNA nanostructures are a promising novel way of delivering small molecule drugs, antibodies, or siRNAs to the cytoplasm of a cell. These soluble, branched structures can carry cell-specific targeting moieties along with their therapeutic deliverable. Here, we examined a 3DNA nanocarrier specifically targeted to B cells with an anti-CD19 antibody. We find that this 3DNA is successfully delivered to and internalized in B cells. To test whether these nanostructures can deliver an efficacious therapeutic dose to alter autoimmune responses, a modified anti-IDO2 siRNA was attached to B-cell-directed 3DNA nanocarriers and tested in an established preclinical model of autoimmune arthritis, KRN.g7. The anti-IDO2 3DNA formulation ameliorates arthritis in this system, delaying the onset of joint swelling and reducing total arthritis severity. As such, a 3DNA nanocarrier system shows promise for delivery of targeted, specific, low-dose therapy for autoimmune disease.

色氨酸分解酶吲哚胺2,3-双加氧酶2 (IDO2)已在临床前模型中被确定为促进自身免疫的免疫调节剂。因此,寻找靶向B细胞中IDO2表达的方法有望为治疗衰弱性自身免疫性疾病(如类风湿关节炎)提供新的途径。与许多疾病驱动因子一样,IDO2是一种在一系列细胞中表达的细胞内蛋白,因此治疗性抑制IDO2需要一种在特定细胞类型中靶向这种细胞内蛋白的机制。DNA纳米结构是一种很有前途的将小分子药物、抗体或sirna递送到细胞质的新方法。这些可溶的分支结构可以携带细胞特异性靶向部分以及它们的治疗递送物。在这里,我们研究了一个3DNA纳米载体,专门针对B细胞的抗cd19抗体。我们发现这个3DNA被成功地传递到B细胞并被内化。为了测试这些纳米结构是否可以提供有效的治疗剂量来改变自身免疫反应,将修饰的抗ido2 siRNA附着在b细胞导向的3DNA纳米载体上,并在已建立的自身免疫性关节炎临床前模型KRN.g7中进行测试。抗ido2 3DNA制剂可改善该系统的关节炎,延缓关节肿胀的发作,降低关节炎的总严重程度。因此,3DNA纳米载体系统有望为自身免疫性疾病提供靶向、特异性、低剂量的治疗。
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引用次数: 8
Calcifying Fibrous Tumor of the Mesentery: A Case Report and a Review of the Literature. 肠系膜钙化纤维瘤1例报告及文献复习。
IF 1.3 Q3 PATHOLOGY Pub Date : 2020-06-23 eCollection Date: 2020-01-01 DOI: 10.1177/2632010X20930689
Derqaoui Sabrine, Elouazzani Hafsa, Ratbi Amine, Bernoussi Zakia, Zouaidia Fouad

Background: Calcifying fibrous tumor (CFT) is a rare entity, with a distinctive histological presentation, initially reported as childhood fibrous tumor with psammoma bodies. It is a benign hypocellular fibrous neoplasm calcifications and lymphoplasmacytic infiltrate. The CFTs may involve many sites, including gastrointestinal tract, pleura, abdominal cavity, and neck. The diagnosis might be challenging due to histological overlaps with other mesenchymal tumors. The prognosis is good. We describe herein the case of a 53-year-old woman with an incidentally diagnosed CFT of the mesentery.

Case presentation: A 53-year-old woman presented to the surgery department with a 2-year history of an anterior abdominal hernia. A computed tomographic scan of the abdomen failed to demonstrate any evidence of a mesenteric nodule. The patient underwent surgical treatment. Careful exploration during the excision of herniated sac revealed a solitary nodule of the mesentery. Local excision was performed. On gross, it was a well-demarcated nodule. Microscopically, the tumor consisted of an abundant paucicellular hyalinized collagen with calcifications; associated to a sparse mononuclear inflammatory infiltrate.

Conclusions: Calcifying fibrous tumor is a benign lesion. The diagnosis is based on histology, because clinical and radiological features are nonspecific. Awareness of this entity is crucial to distinguish it from other mesenchymal tumors especially in the gastrointestinal tract.

背景:钙化纤维性肿瘤(CFT)是一种罕见的肿瘤,具有独特的组织学表现,最初报道为儿童纤维性肿瘤伴沙粒体。它是一种钙化、淋巴浆细胞浸润的良性低细胞纤维性肿瘤。CFTs可累及多个部位,包括胃肠道、胸膜、腹腔和颈部。由于与其他间充质肿瘤的组织学重叠,诊断可能具有挑战性。预后良好。我们在此描述的情况下,一个53岁的妇女偶然诊断CFT的肠系膜。病例介绍:一名53岁的女性,因2年的前腹疝病史来到外科。腹部计算机断层扫描未能显示任何肠系膜结节的证据。病人接受了手术治疗。在切除疝囊时仔细检查发现肠系膜上有一个孤立的结节。局部切除。肉眼可见,这是一个界限清晰的结节。显微镜下,肿瘤由丰富的透明胶原蛋白组成,并伴有钙化;与稀疏的单核炎性浸润有关。结论:钙化纤维瘤是一种良性病变。诊断是基于组织学,因为临床和放射学特征是非特异性的。认识到这一实体是至关重要的,以区分它与其他间充质肿瘤,特别是在胃肠道。
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Clinical Pathology
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