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From the archives of MD Anderson Cancer Center: EBV-positive fibrin-associated large B-cell lymphoma in an ovarian leiomyoma with cystic degeneration: A case report and discussion of differential diagnosis 来自MD安德森癌症中心的档案:ebv阳性纤维蛋白相关大b细胞淋巴瘤合并卵巢平滑肌瘤伴囊性变性:1例报告和鉴别诊断的讨论
IF 1.5 4区 医学 Q3 PATHOLOGY Pub Date : 2024-11-12 DOI: 10.1016/j.anndiagpath.2024.152397
Luana Santos Louro , Roberto N. Miranda , L. Jeffrey Medeiros , Anais Malpica , Mario L. Marques-Piubelli , Preetha Ramalingam
Fibrin-associated large B-cell lymphoma (FA-LBCL) is a rare type of lymphoma usually associated with Epstein-Barr virus (EBV) infection. We report a case incidentally detected in a right ovarian mass of a 53-year-old woman. The patient presented with bloating and weight gain over 8 months. Imaging studies showed a 20.7 cm, complex right adnexal mass. Total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed. Macroscopic examination revealed a 25 x 18.5 x 9.5 cm predominantly cystic right ovarian mass with focal solid areas. Microscopically, most of the mass was a leiomyoma with hyaline necrosis and extensive cystic degeneration. In areas, the cyst showed focally necrotic, fibrinous material associated with small aggregates of round and atypical lymphoid cells with prominent karyorrhexis and mitotic activity These large cells were confined within the cystic spaces. Immunohistochemical analysis showed that the atypical cells were positive for CD20, CD30, CD79a and MUM1/IRF4, and were negative for CD3, CD10 and BCL6, supporting B-cell lineage. In situ hybridization for Epstein-Barr virus-encoded RNA (EBER ISH) was also positive in the atypical cells supporting the diagnosis of EBV-positive fibrin-associated large B-cell lymphoma. The patient subsequently received four cycles of chemotherapy using rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). Computed tomography (CT) scan of the neck, chest, abdomen and pelvis 5 months after the last chemotherapy cycle showed no evidence of disease. After a follow-up of 17 months, the patient is alive with no evidence of disease. This report is being used to discuss the salient features of this rare entity and its differential diagnosis.
纤维蛋白相关性大b细胞淋巴瘤(FA-LBCL)是一种罕见的淋巴瘤类型,通常与eb病毒(EBV)感染有关。我们报告一例偶然发现在一个53岁的妇女右卵巢肿块。患者出现腹胀和体重增加超过8个月。影像学检查显示20.7厘米,复杂的右附件肿块。行全腹子宫切除术和双侧输卵管卵巢切除术。宏观检查示25 x 18.5 x 9.5 cm的右侧卵巢囊性肿块,伴局灶实性区。镜下,大部分肿块为平滑肌瘤伴透明坏死和广泛囊性变性。囊肿局部坏死,纤维性物质与圆形和非典型淋巴细胞的小聚集体相关,具有明显的核分裂和有丝分裂活性,这些大细胞被限制在囊腔内。免疫组化分析显示,非典型细胞CD20、CD30、CD79a和MUM1/IRF4表达阳性,CD3、CD10和BCL6表达阴性,支持b细胞谱系。Epstein-Barr病毒编码RNA (EBER ISH)的原位杂交在非典型细胞中也呈阳性,支持ebv阳性纤维蛋白相关大b细胞淋巴瘤的诊断。患者随后接受了利妥昔单抗、环磷酰胺、阿霉素、长春新碱和强的松(R-CHOP)四个周期的化疗。最后一个化疗周期后5个月的颈部、胸部、腹部和骨盆CT扫描未见疾病迹象。随访17个月后,患者存活,无疾病迹象。本报告被用来讨论这种罕见的实体的显著特征及其鉴别诊断。
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引用次数: 0
PIT-1/SF-1 co-expression in pituitary neuroendocrine tumors (PitNETs) with comprehensive review of the literature: How should we best characterize these neoplasms? 垂体神经内分泌肿瘤(PitNETs)中的 PIT-1/SF-1 共同表达及文献综述:我们应该如何最好地描述这些肿瘤的特征?
IF 1.5 4区 医学 Q3 PATHOLOGY Pub Date : 2024-11-09 DOI: 10.1016/j.anndiagpath.2024.152398
Christina Abi Faraj , Ian E. McCutcheon , Maria A. Gubbiotti
The nomenclature and classification of neuroendocrine tumors of the anterior pituitary have undergone significant change over the last few years. Despite the updated classification system as devised by the World Health Organization, some tumors do not fit neatly into the currently defined categories. The most common tumor type not defined by the updated guidelines is a pituitary neuroendocrine tumor with co-expression of SF-1 and PIT-1. In this manuscript, we provide our institutional experience with such unusual cases and combine our findings with those in the available literature to provide the largest, most comprehensive dataset regarding clinical and pathologic information for these unique tumors. Based on our findings, we also propose a classification scheme for pituitary neuroendocrine tumors to integrate lineage, hormonal expression, and clinical function as we believe this constellation of information will best help the clinical teams treating these patients.
在过去几年中,垂体前叶神经内分泌肿瘤的命名和分类发生了重大变化。尽管世界卫生组织制定了最新的分类系统,但有些肿瘤并不完全符合目前定义的类别。最新指南未定义的最常见肿瘤类型是同时表达 SF-1 和 PIT-1 的垂体神经内分泌肿瘤。在这篇手稿中,我们介绍了本机构对此类罕见病例的经验,并将我们的研究结果与现有文献结合起来,为这些独特肿瘤的临床和病理信息提供了最大、最全面的数据集。根据我们的研究结果,我们还提出了垂体神经内分泌肿瘤的分类方案,以整合血统、激素表达和临床功能,因为我们相信这些信息将为治疗这些患者的临床团队提供最佳帮助。
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引用次数: 0
Poor response of HER2-positive mucinous carcinomas of breast to neoadjuvant HER2-targeted therapy: A study of four cases HER2阳性乳腺黏液癌对新辅助HER2靶向治疗反应不佳:四例病例研究。
IF 1.5 4区 医学 Q3 PATHOLOGY Pub Date : 2024-11-09 DOI: 10.1016/j.anndiagpath.2024.152396
Min Han , Daniel Schmolze , Javier A. Arias-Stella III , Christina H. Wei , Joanne Mortimer , Fang Fan

Background

Breast mucinous carcinoma (MC) is typically positive for estrogen receptor (ER) and progesterone receptor (PR) expressions and negative for human epidermal growth factor receptor (HER2) overexpression. HER2 positive MC is a rare entity; its response to neoadjuvant HER2-targeted therapy remains unclear.

Methods

Four cases of HER2 positive MC and seven cases of HER2 positive invasive ductal carcinoma with mucinous features (MCF) were identified. Clinicopathologic features were collected. Patients' germline data was gathered if available. Tumor's response to HER2-directed treatment were recorded and compared.

Results

Two HER2 positive MCs were treated with neoadjuvant HER2-directed treatment and showed no response in the subsequent surgical resection specimens including one positive lymph node showing no treatment effect. One patient had upfront surgery. The fourth patient presented with advanced stage and showed progression on HER2-directed treatment. Six HER2 positive MCFs received neoadjuvant HER2-directed therapy; two cases showed complete pathologic response and four had only minimal residual carcinomas in the breast. Two cases with positive lymph nodes had complete response in the lymph nodes. The seventh patient presented at an advanced stage and was stable on HER2-directed treatment.

Conclusions

Our findings suggest that HER2 positive MCs may be resistant to HER2-directed treatment. This is in contrast with the excellent treatment response observed in HER2 positive MCFs. It is important to report mucinous carcinoma percentage in biopsies on HER2 positive tumors as it may be related to treatment response. Further investigation of the underlying mechanisms may help optimize clinical management in this patient population.
背景:乳腺粘液癌(MC)通常雌激素受体(ER)和孕激素受体(PR)表达阳性,而人类表皮生长因子受体(HER2)过度表达阴性。HER2阳性MC很少见,其对新辅助HER2靶向治疗的反应尚不明确:方法:确定了 4 例 HER2 阳性 MC 和 7 例 HER2 阳性伴粘液性特征的浸润性导管癌(MCF)。收集临床病理特征。收集患者的种系数据(如果有的话)。记录并比较肿瘤对HER2导向治疗的反应:结果:2 例 HER2 阳性 MC 接受了新辅助 HER2 靶向治疗,但在随后的手术切除标本中未显示任何反应,其中 1 例淋巴结阳性未显示治疗效果。一名患者接受了前期手术。第四例患者为晚期,接受 HER2 导向治疗后病情出现进展。6 例 HER2 阳性 MCF 接受了新辅助 HER2 导向治疗;其中 2 例病理反应完全,4 例仅在乳房内有极小的残留癌。两例淋巴结阳性患者的淋巴结完全反应。第 7 例患者为晚期,接受 HER2 导向治疗后病情稳定:我们的研究结果表明,HER2 阳性 MCs 可能对 HER2 导向治疗产生耐药性。结论:我们的研究结果表明,HER2阳性MC可能会对HER2导向治疗产生耐药性,这与在HER2阳性MCF中观察到的良好治疗反应形成了鲜明对比。报告HER2阳性肿瘤活检中的粘液癌比例非常重要,因为这可能与治疗反应有关。对潜在机制的进一步研究可能有助于优化这类患者的临床管理。
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引用次数: 0
TRPS1 expression in cytologic specimens of salivary duct carcinoma and other salivary gland tumors 唾液腺导管癌和其他唾液腺肿瘤细胞学标本中 TRPS1 的表达。
IF 1.5 4区 医学 Q3 PATHOLOGY Pub Date : 2024-11-09 DOI: 10.1016/j.anndiagpath.2024.152406
Minhua Wang , Guoping Cai , Syed M. Gilani
Recent studies suggest that trichorhinophalangeal syndrome type 1 (TRPS1) is sensitive immunomarker for breast carcinoma (BC). Salivary duct carcinoma (SDC) of salivary gland can share similar morphologic and immunophenotypic features with BC. This study aimed to assess the expression of TRPS1 in SDC and other salivary gland tumors (SGTs). Cytology cases and selected surgical specimens of SGTs were retrieved. Forty-three cases were selected and TRPS1 immunohistochemistry (IHC) was performed on cell blocks and some histologic specimens.
Of those 43 cases, all 13 SDC cases showed TRPS1 expression except for one case. The remaining 30 cases include pleomorphic adenoma (n = 7), Warthin tumor (n = 4), basal cell adenoma (n = 3), adenoid cystic carcinoma (n = 2), secretory carcinoma (n = 5), mucoepidermoid carcinoma (n = 4), and acinic cell carcinoma (n = 5). Three of thirty cases were negative for TRPS1 while the remainder showed variable expression of TRPS1 ranging from focal weak to diffuse strong staining. The three negative cases include a case of secretory carcinoma, mucoepidermoid carcinoma and Warthin tumor. Our study confirmed that TRPS1 expression is present in SDC and other SGTs, indicating an overlapping immunoprofile with breast cancer. Additionally, it may not help differentiate SDC or SGTs from each other. Further studies with larger cohorts are needed.
最近的研究表明,毛细血管畸形综合征 1 型(TRPS1)是乳腺癌(BC)的敏感免疫标记物。唾液腺的唾液腺导管癌(SDC)在形态学和免疫表型上与乳腺癌有相似之处。本研究旨在评估 TRPS1 在 SDC 和其他唾液腺肿瘤(SGTs)中的表达。研究人员检索了细胞学病例和部分 SGTs 手术标本。对43个病例的细胞块和部分组织学标本进行了TRPS1免疫组化(IHC)检测。在这43例病例中,除一例外,其余13例SDC病例均有TRPS1表达。其余30例包括多形性腺瘤(7例)、Warthin瘤(4例)、基底细胞腺瘤(3例)、腺样囊性癌(2例)、分泌性癌(5例)、粘液表皮样癌(4例)和棘细胞癌(5例)。30 个病例中有 3 例 TRPS1 阴性,其余病例的 TRPS1 表现不一,从局灶性弱染色到弥漫性强染色不等。三例阴性病例包括一例分泌性癌、粘液表皮样癌和华氏瘤。我们的研究证实,TRPS1 在 SDC 和其他 SGT 中均有表达,这表明其与乳腺癌的免疫图谱存在重叠。此外,它可能无助于区分 SDC 或 SGT。还需要对更大的群体进行进一步研究。
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引用次数: 0
Superficial ALK-rearranged myxoid spindle cell neoplasms: Clinicopathologic and molecular analysis of two cases and a review of the literature 浅表ALK重排肌样纺锤细胞瘤:两例病例的临床病理和分子分析及文献综述。
IF 1.5 4区 医学 Q3 PATHOLOGY Pub Date : 2024-11-08 DOI: 10.1016/j.anndiagpath.2024.152395
Wenwen Luo , Jinyue Zheng , Mengying Hei , Ye Jiang, Bojin Su
Superficial anaplastic lymphoma kinase (ALK)-rearranged myxoid spindle cell neoplasms are a recently identified subtype of cutaneous soft tissue tumors, distinct for their co-expression of CD34 and S100 and characterized by ALK gene rearrangements. Although 72 cases have been reported primarily as isolated case reports, this tumor subtype has yet to be included in the WHO classification of soft tissue tumors, underscoring the need for further study. In this study, we diagnosed two additional cases, both arising in the dermis and subcutaneous tissue. These tumors exhibited characteristic pathological features, including linear or concentric whorl patterns, prominent myxoid and collagenized stroma, mild cellular atypia, and rare mitotic activity. The presence of infiltrative margins and the potential for recurrence after surgery suggest at least locally aggressive clinical behavior. Immunohistochemically, the tumors diffusely expressed S100 and CD34, with strong ALK-D5F3 positivity, confirmed by ALK gene rearrangement. These findings further expand the clinical and pathological spectrum of ALK-rearranged neoplasms and highlight the need for continued research on their biological behavior and classification.
表皮无性淋巴瘤激酶(ALK)重排肌样纺锤细胞瘤是最近发现的一种皮肤软组织肿瘤亚型,因其共同表达 CD34 和 S100 而与众不同,并以 ALK 基因重排为特征。尽管已有 72 例病例主要作为孤立病例报告,但这一肿瘤亚型尚未被纳入世界卫生组织的软组织肿瘤分类中,这凸显了进一步研究的必要性。在本研究中,我们又诊断出两例病例,均发生于真皮和皮下组织。这些肿瘤表现出特征性的病理特征,包括线状或同心轮纹、突出的肌层和胶原化基质、轻度细胞不典型性和罕见的有丝分裂活动。浸润边缘的存在和术后复发的可能性表明,这些肿瘤至少具有局部侵袭性临床表现。免疫组化方面,肿瘤弥漫表达S100和CD34,ALK-D5F3强阳性,ALK基因重排证实了这一点。这些发现进一步扩展了ALK基因重排肿瘤的临床和病理范围,并强调了继续研究其生物学行为和分类的必要性。
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引用次数: 0
FOXP3 expression in duodenal mucosa: Unique role in pathogenesis and differential diagnosis of celiac disease 十二指肠粘膜中 FOXP3 的表达:在乳糜泻发病机制和鉴别诊断中的独特作用。
IF 1.5 4区 医学 Q3 PATHOLOGY Pub Date : 2024-11-06 DOI: 10.1016/j.anndiagpath.2024.152393
F. Yilmaz , K. Atay
Forkhead box protein P3 (FOXP3) positive regulatory T lymphocytes are indispensable in the inflammatory homeostasis of the gastrointestinal tract and represent a significant subset of regulatory cells in inflammatory, autoimmune, and neoplastic conditions. This study aimed to elucidate the potential of FOXP3 expression in diagnosing and pathogenesis of celiac disease (CD) by comparing duodenal biopsies of CD cases with non-CD ones, some of which had increased intraepithelial lymphocytes (IELs). Two hundred sixty-one duodenal tissues of patients who applied to adult gastroenterology were reevaluated for immunohistochemical analysis. After excluding patients on a gluten-free diet (n = 44), the CD (n = 97) and non-CD (n = 120) groups were divided based on clinical complaints that could be associated with CD (intestinal or extraintestinal), serologic and histologic findings. The specific threshold was determined by receiver operating characteristic (ROC) analysis, and its relationship with CD diagnosis and clinicopathological data was evaluated. ROC analysis offered a “>14” cut-off value for diagnosing CD, for which AUC (Area Under The Curve): 0.968, p < 0.0001, sensitivity: 92.8, specificity: 91.7, positive and negative predictive values were 90 % and 94 %, respectively. High FOXP3 expression was associated with higher IEL, diagnosis of CD, more severe histologic (higher Marsh score) and endoscopic (scalloping) findings, and higher anti-tissue transglutaminase and anti-endomysium IgA titers (p < 0.001). It also correlates with IEL in CD patients and is unaffected by the increase in IEL and the presence of gastric Helicobacter Pylori in the non-CD group. FOXP3 is a sensitive and specific marker for diagnosing CD despite inflammatory conditions resulting from non-CD causes.
叉头盒蛋白P3(FOXP3)阳性调节性T淋巴细胞在胃肠道炎症平衡中不可或缺,是炎症、自身免疫和肿瘤性疾病中调节性细胞的重要亚群。本研究旨在通过比较乳糜泻病例和非乳糜泻病例的十二指肠活检组织,阐明 FOXP3 表达在乳糜泻诊断和发病机制中的潜力。我们对 261 名向成人消化内科提出申请的患者的十二指肠组织进行了重新评估,并进行了免疫组化分析。在排除无麸质饮食的患者(44 人)后,根据可能与 CD 相关的临床主诉(肠内或肠外)、血清学和组织学结果,将患者分为 CD 组(97 人)和非 CD 组(120 人)。通过接收器操作特征(ROC)分析确定了特定阈值,并评估了其与 CD 诊断和临床病理数据的关系。ROC 分析为诊断 CD 提供了一个">14 "的临界值,其 AUC(曲线下面积)为 0.968,p 值为 1:0.968, p
{"title":"FOXP3 expression in duodenal mucosa: Unique role in pathogenesis and differential diagnosis of celiac disease","authors":"F. Yilmaz ,&nbsp;K. Atay","doi":"10.1016/j.anndiagpath.2024.152393","DOIUrl":"10.1016/j.anndiagpath.2024.152393","url":null,"abstract":"<div><div>Forkhead box protein P3 (FOXP3) positive regulatory T lymphocytes are indispensable in the inflammatory homeostasis of the gastrointestinal tract and represent a significant subset of regulatory cells in inflammatory, autoimmune, and neoplastic conditions. This study aimed to elucidate the potential of FOXP3 expression in diagnosing and pathogenesis of celiac disease (CD) by comparing duodenal biopsies of CD cases with non-CD ones, some of which had increased intraepithelial lymphocytes (IELs). Two hundred sixty-one duodenal tissues of patients who applied to adult gastroenterology were reevaluated for immunohistochemical analysis. After excluding patients on a gluten-free diet (<em>n</em> = 44), the CD (<em>n</em> = 97) and non-CD (<em>n</em> = 120) groups were divided based on clinical complaints that could be associated with CD (intestinal or extraintestinal), serologic and histologic findings. The specific threshold was determined by receiver operating characteristic (ROC) analysis, and its relationship with CD diagnosis and clinicopathological data was evaluated. ROC analysis offered a “&gt;14” cut-off value for diagnosing CD, for which AUC (Area Under The Curve): 0.968, <em>p</em> &lt; 0.0001, sensitivity: 92.8, specificity: 91.7, positive and negative predictive values were 90 % and 94 %, respectively. High FOXP3 expression was associated with higher IEL, diagnosis of CD, more severe histologic (higher Marsh score) and endoscopic (scalloping) findings, and higher anti-tissue transglutaminase and anti-endomysium IgA titers (<em>p</em> &lt; 0.001). It also correlates with IEL in CD patients and is unaffected by the increase in IEL and the presence of gastric <em>Helicobacter Pylori</em> in the non-CD group. FOXP3 is a sensitive and specific marker for diagnosing CD despite inflammatory conditions resulting from non-CD causes.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"74 ","pages":"Article 152393"},"PeriodicalIF":1.5,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
T-cells are significantly reduced in the luminal gastrointestinal tract of patients with “complete” 22q11.2 deletion syndrome (DiGeorge syndrome): Utilization of chromogenic multiplex immunohistochemistry to define cellular populations 在 "完全 "22q11.2缺失综合征(迪乔治综合征)患者的胃肠道管腔中,T细胞明显减少:利用色原多重免疫组化技术确定细胞群。
IF 1.5 4区 医学 Q3 PATHOLOGY Pub Date : 2024-11-06 DOI: 10.1016/j.anndiagpath.2024.152391
Grace J. Kwon , William R. Jeck , Shannon McCall , Zuowei Su , Avani A. Pendse
Patients with 22q11.2 deletion syndrome or DiGeorge syndrome commonly report gastrointestinal symptoms in addition to more widely understood cardiac and immunodeficiency abnormalities. However, the morphologic features of gastrointestinal tract pathology in these patients are poorly understood. We previously reported that plasma cells are essentially absent from the luminal gastrointestinal tract of patients with “complete” DiGeorge syndrome. Herein, we add to the current understanding of the luminal gastrointestinal tract changes in patients with DiGeorge syndrome. Patients with cytogenetically confirmed DiGeorge syndrome were identified after approval from our institutional review board. Gastrointestinal tract biopsies from patients with DiGeorge syndrome that were severely immunosuppressed (complete DiGeorge syndrome, DGS-I), partially immunocompromised (partial DiGeorge syndrome, DGS), and from control patients were reviewed. Two panels of chromogenic multiplex immunohistochemistry (IHC) were performed to evaluate the immune cell infiltrate in the lamina propria of the duodenum and colon. “Panel #1” was composed of antibodies targeting CD3, CD20, and CD68. “Panel #2” was composed of antibodies targeting CD4, CD8, CD56, and TCRϒδ. Assessment of cell types identified by these antibody targets demonstrated a significant reduction of duodenal and colonic T-cells in patients with complete DiGeorge syndrome. In addition to establishing the morphologic phenotype of the luminal gastrointestinal tract of patients with DiGeorge syndrome, we also highlight our chosen technology of chromogenic multiplex IHC as a relatively accessible research and diagnostic tool with wide potential to be utilized across various disease processes.
22q11.2缺失综合征或迪乔治综合征患者除了普遍存在的心脏和免疫缺陷异常外,通常还伴有胃肠道症状。然而,人们对这些患者胃肠道病变的形态特征却知之甚少。我们以前曾报道,"完全型 "迪乔治综合征患者的胃肠道管腔内基本上没有浆细胞。在此,我们将进一步阐述目前对迪乔治综合征患者胃肠道腔内变化的认识。经本机构审查委员会批准后,我们确定了经细胞遗传学确诊的迪乔治综合征患者。对免疫抑制严重的迪乔治综合征患者(完全性迪乔治综合征,DGS-I)、免疫功能部分低下的患者(部分性迪乔治综合征,DGS)以及对照组患者的胃肠道活检组织进行了审查。为评估十二指肠和结肠固有层的免疫细胞浸润情况,采用了两组色原多重免疫组化(IHC)。"面板 #1 "由针对 CD3、CD20 和 CD68 的抗体组成。"面板 2 "由针对 CD4、CD8、CD56 和 TCRϒδ 的抗体组成。通过评估这些抗体靶标确定的细胞类型,发现完全性迪乔治综合征患者的十二指肠和结肠 T 细胞明显减少。除了确定迪乔治综合征患者管腔胃肠道的形态表型外,我们还强调了我们所选择的色原多重 IHC 技术,它是一种相对容易获得的研究和诊断工具,在各种疾病过程中具有广泛的应用潜力。
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引用次数: 0
PD-L1 (22C3) expression and prognostic implications in esophageal squamous cell carcinoma 食管鳞状细胞癌中 PD-L1 (22C3) 的表达及其预后影响。
IF 1.5 4区 医学 Q3 PATHOLOGY Pub Date : 2024-11-06 DOI: 10.1016/j.anndiagpath.2024.152394
Zhikai Chi, Lan Peng, Dipti M. Karamchandani, Jing Xu
Programmed cell death-ligand 1 (PD-L1) clone 22C3 is the only Food and Drug Administration-approved companion diagnostic test for pembrolizumab for the treatment of esophageal squamous cell carcinoma (ESCC). However, prior studies conducted in Asia and Europe have used various PD-L1 antibody clones other than 22C3. We aimed to study the expression profile of PD-L1, specifically of clone 22C3, in ESCC and its significance with regards to histological features, clinical parameters, and overall survival in a case series from two large US hospital systems. PD-L1 (22C3) immunohistochemistry was performed on 82 specimens obtained from 75 patients. Electronic medical records were reviewed to obtain the clinical and follow-up data. Of these specimens, 39 % (32/82) were negative for PD-L1 (22C3) expression (combined positive score (CPS) of 0). The remaining 50 specimens were positive, with CPSs ranging from 1 to 100. Treated specimens showed decreased PD-L1 (22C3) expression compared to untreated specimens. In the multivariate Cox proportional hazards regression model, PD-L1 (22C3) expression was shown to be a favorable prognostic factor for overall survival (p = 0.03, hazard ratio 0.16) only when the CPSs were ≥ 25, independent of surgery, definitive chemotherapy and/or radiotherapy, immunotherapy, and initial clinical stages. We performed a comprehensive study to investigate the expression profile of PD-L1 clone 22C3 in the US patients with ESCC. Our analysis showed that PD-L1 (22C3) expression decreased in treated specimens, and a CPS of ≥25 was associated with a favorable prognosis.
程序性细胞死亡配体 1(PD-L1)克隆 22C3 是美国食品和药物管理局批准的唯一用于治疗食管鳞状细胞癌(ESCC)的 pembrolizumab 伴行诊断检测。然而,之前在亚洲和欧洲进行的研究使用了 22C3 之外的各种 PD-L1 抗体克隆。我们的目的是研究PD-L1(特别是克隆22C3)在ESCC中的表达谱,以及它在组织学特征、临床参数和总生存期方面的意义。研究人员对 75 名患者的 82 份标本进行了 PD-L1 (22C3) 免疫组化。研究人员查阅了电子病历,以获得临床和随访数据。在这些标本中,39%(32/82)的 PD-L1 (22C3) 表达为阴性(综合阳性评分(CPS)为 0)。其余 50 个标本为阳性,CPS 从 1 到 100 不等。与未经治疗的标本相比,经过治疗的标本显示出较低的 PD-L1 (22C3) 表达。在多变量 Cox 比例危险回归模型中,只有当 CPS ≥ 25 时,PD-L1(22C3)表达才是总生存期的有利预后因素(p = 0.03,危险比 0.16),且不受手术、明确化疗和/或放疗、免疫治疗和初始临床分期的影响。我们对美国 ESCC 患者中 PD-L1 克隆 22C3 的表达谱进行了全面研究。我们的分析表明,PD-L1(22C3)在治疗后的标本中表达减少,CPS≥25与预后良好相关。
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引用次数: 0
Large language models in pathology: A comparative study of ChatGPT and Bard with pathology trainees on multiple-choice questions 病理学中的大语言模型:ChatGPT 和 Bard 与病理学学员在选择题上的比较研究。
IF 1.5 4区 医学 Q3 PATHOLOGY Pub Date : 2024-11-02 DOI: 10.1016/j.anndiagpath.2024.152392
Wei Du , Xueting Jin , Jaryse Carol Harris , Alessandro Brunetti , Erika Johnson , Olivia Leung , Xingchen Li , Selemon Walle , Qing Yu , Xiao Zhou , Fang Bian , Kajanna McKenzie , Manita Kanathanavanich , Yusuf Ozcelik , Farah El-Sharkawy , Shunsuke Koga
Large language models (LLMs), such as ChatGPT and Bard, have shown potential in various medical applications. This study aimed to evaluate the performance of LLMs, specifically ChatGPT and Bard, in pathology by comparing their performance with those of pathology trainees, and to assess the consistency of their responses. We selected 150 multiple-choice questions from 15 subspecialties, excluding those with images. Both ChatGPT and Bard were tested on these questions across three separate sessions between June 2023 and January 2024, and their responses were compared with those of 16 pathology trainees (8 junior and 8 senior) from two hospitals. Questions were categorized into easy, intermediate, and difficult based on trainee performance. Consistency and variability in LLM responses were analyzed across three evaluation sessions. ChatGPT significantly outperformed Bard and trainees, achieving an average total score of 82.2% compared to Bard's 49.5%, junior trainees' 45.1%, and senior trainees' 56.0%. ChatGPT's performance was notably stronger in difficult questions (63.4%–68.3%) compared to Bard (31.7%–34.1%) and trainees (4.9%–48.8%). For easy questions, ChatGPT (83.1%–91.5%) and trainees (73.7%–100.0%) showed similar high scores. Consistency analysis revealed that ChatGPT showed a high consistency rate of 80%–85% across three tests, whereas Bard exhibited greater variability with consistency rates of 54%–61%. While LLMs show significant promise in pathology education and practice, continued development and human oversight are crucial for reliable clinical application.
大语言模型(LLM),如 ChatGPT 和 Bard,已在各种医疗应用中显示出潜力。本研究旨在评估大型语言模型(特别是 ChatGPT 和 Bard)在病理学中的表现,将其与病理学学员的表现进行比较,并评估其回答的一致性。我们从 15 个亚专科中选择了 150 道选择题,其中不包括有图像的题目。ChatGPT 和 Bard 在 2023 年 6 月至 2024 年 1 月期间分三次对这些问题进行了测试,并将他们的回答与来自两家医院的 16 名病理学学员(8 名初级学员和 8 名高级学员)的回答进行了比较。根据学员的表现,问题被分为简单、中等和困难三个等级。我们分析了三个评估环节中 LLM 回答的一致性和可变性。ChatGPT 的表现明显优于 Bard 和受训者,平均总分达到 82.2%,而 Bard 为 49.5%,初级受训者为 45.1%,高级受训者为 56.0%。与巴德(31.7%-34.1%)和受训者(4.9%-48.8%)相比,ChatGPT 在难题(63.4%-68.3%)上的表现更为突出。在容易的问题上,ChatGPT(83.1%-91.5%)和受训人员(73.7%-100.0%)也表现出相似的高分。一致性分析表明,ChatGPT 在三次测试中表现出 80%-85% 的高一致性,而 Bard 则表现出 54%-61% 的差异性。虽然 LLM 在病理学教育和实践中大有可为,但持续开发和人工监督对于可靠的临床应用至关重要。
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引用次数: 0
Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP): Prevalence, cyto-histo correlation, and molecular and ultrasonographic profile 具有乳头状核特征的非侵袭性甲状腺滤泡性肿瘤(NIFTP):发病率、细胞组学相关性、分子和超声图谱。
IF 1.5 4区 医学 Q3 PATHOLOGY Pub Date : 2024-10-31 DOI: 10.1016/j.anndiagpath.2024.152390
Zhengfan Xu, Alyssa Vitale, Christian Keller, Wamidh Alkhoory, Ziying Zhang, Lisi Yuan
Non-invasive follicular thyroid neoplasm with papillary like nuclear features (NIFTP) was introduced in 2017 WHO Classification of Endocrine Tumors. In this study, we aim to characterize the molecular and ultrasonographic profiles of NIFTP and evaluate the performance of fine needle aspiration (FNA) cytology. Consecutive thyroid resections at our institution between 2018 and 2022 were collected; 1282 thyroid resections were identified. NIFTP was diagnosed in 109 cases (prevalence: 8.5 %); 65 (60 %) were the targeted nodules with an average size of 2.5 cm. Among these 65 targeted, 27 had Afirma testing results, 44 had Thyroid Imaging Reporting and Data System (TIRADS) scores, and 53 had FNA results. Of the 27 cases with Afirma reports, 23 were labeled “suspicious”, including 5 with RAS-related mutations (risk of malignancy (ROM) 75 %) and 17 without a reportable genetic alternation (ROM 50 %). 60 % cases with TIRADS scores were classified as TIRADS 4, while 16 % were classified as TIRADS 5. The majority of the 53 FNA cases had a diagnosis of AUS/FLUS (53.7 %) or FN (31.5 %). One additional targeted nodule with a diagnosis of NIFTP had BRAFV600E mutation and was reclassified as papillary thyroid carcinoma. In summary, the majority of the targeted NIFTPs had “suspicious” Afirma testing results (85 %), TIRADS 4 scores (60 %) and either AUS/FLUS (53.7 %) or FN (31.5 %) FNA results. The sensitivity and specificity of cytology for diagnosing NIFTP were 90 % and 57 %, respectively, with a positive predictive value (PPV) of 16 % and negative predictive value of 98 %.
2017年世界卫生组织内分泌肿瘤分类中引入了具有乳头状核特征的非侵袭性滤泡性甲状腺肿瘤(NIFTP)。在本研究中,我们旨在描述 NIFTP 的分子和超声特征,并评估细针穿刺(FNA)细胞学的性能。研究收集了我院2018年至2022年间连续进行的甲状腺切除术,共确定了1282例甲状腺切除术。109例确诊为NIFTP(发病率:8.5%);65例(60%)为靶向结节,平均大小为2.5厘米。在这 65 例目标病例中,27 例有 Afirma 检测结果,44 例有甲状腺成像报告和数据系统 (TIRADS) 评分,53 例有 FNA 结果。在 27 例有 Afirma 报告的病例中,23 例被标记为 "可疑",其中 5 例有 RAS 相关突变(恶性肿瘤风险 (ROM) 75%),17 例没有可报告的遗传变异(ROM 50%)。60% 的 TIRADS 评分病例被归类为 TIRADS 4 级,16% 被归类为 TIRADS 5 级。53 个 FNA 病例中,大多数诊断为 AUS/FLUS(53.7%)或 FN(31.5%)。另有一个诊断为 NIFTP 的靶向结节发生了 BRAFV600E 突变,被重新分类为甲状腺乳头状癌。总之,大多数目标 NIFTP 的 Afirma 检测结果为 "可疑"(85%),TIRADS 4 评分为 "可疑"(60%),FNA 结果为 AUS/FLUS(53.7%)或 FN(31.5%)。细胞学诊断 NIFTP 的敏感性和特异性分别为 90% 和 57%,阳性预测值 (PPV) 为 16%,阴性预测值为 98%。
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Annals of Diagnostic Pathology
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