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Expanding the Spectrum of GLI1-rearranged Neoplasms of the Gastrointestinal Tract to Include Monophasic Keratin-positive Epithelial Neoplasms. 将胃肠道 GLI1 重组肿瘤的范围扩大到单相角蛋白阳性上皮肿瘤
IF 4.5 1区 医学 Q1 PATHOLOGY Pub Date : 2024-11-01 Epub Date: 2024-09-18 DOI: 10.1097/PAS.0000000000002303
Dorukhan Bahceci, Grace E Kim, Sanjay Kakar, Dana J Balitzer, Eric D Nguyen, Rageshree Ramachandran, Sarah E Umetsu, Nancy M Joseph

GLI1-altered tumors form a diverse group occurring in various anatomic locations. In the alimentary tract, the most established are gastroblastoma, a biphasic epithelial-mesenchymal neoplasm of the stomach, and plexiform fibromyxoma, a pure spindle cell neoplasm. The spectrum of GLI1-rearranged gastrointestinal tumors has recently expanded with reports of cases in other parts of the GI tract, some exhibiting gastroblastoma-like features and others being pure mesenchymal neoplasms. These tumors often display a nonspecific immunophenotype, with only CD56 and cyclin D1 expression being common. Biphasic GLI1-altered tumors show diffuse keratin positivity in the epithelial component only, and GLI1-altered mesenchymal tumors typically lack or show only focal keratin expression. This study details 2 GLI1-rearranged gastrointestinal tract tumors with diffuse keratin and CD56 expression, composed entirely of epithelial cells with a nested growth pattern and finely stippled monotonous nuclei, leading to an initial suspicion of neuroendocrine tumor in both cases, despite lack of synaptophysin and chromogranin expression. Diffuse strong nuclear cyclin D1 expression was seen in both cases, and conversely, strong cyclin D1 staining was only seen in 5.4% (4/74) of well-differentiated neuroendocrine tumors tested. These 2 GI tract neoplasms highlight a widened spectrum of GLI1-rearranged tumors, now including monophasic epithelial neoplasms with diffuse keratin expression.

GLI1改变的肿瘤种类繁多,发生在不同的解剖部位。在消化道,最常见的是胃母细胞瘤(一种胃部上皮-间质双相肿瘤)和丛状纤维瘤(一种纯纺锤形细胞肿瘤)。最近,GLI1 重组胃肠道肿瘤的范围有所扩大,有报告称胃肠道其他部位也出现了病例,其中一些表现出胃母细胞瘤样特征,另一些则是纯间叶肿瘤。这些肿瘤通常表现为非特异性免疫表型,常见的只有 CD56 和细胞周期蛋白 D1 表达。双相 GLI1 改变的肿瘤仅在上皮成分中显示弥漫性角蛋白阳性,而 GLI1 改变的间质肿瘤通常缺乏或仅显示局灶性角蛋白表达。本研究详细描述了 2 例 GLI1 重组的胃肠道肿瘤,这些肿瘤具有弥漫性角蛋白和 CD56 表达,完全由上皮细胞组成,具有巢状生长模式和细条纹单核细胞,尽管缺乏突触素和嗜铬粒蛋白表达,但最初怀疑这两例肿瘤为神经内分泌肿瘤。两例病例均可见弥漫性强细胞周期蛋白 D1 核表达,相反,强细胞周期蛋白 D1 染色仅见于 5.4%(4/74)的分化良好的神经内分泌肿瘤。这两种消化道肿瘤凸显了 GLI1 重组肿瘤的范围扩大,现在包括具有弥漫角蛋白表达的单相上皮肿瘤。
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引用次数: 0
ALK -rearranged Mesenchymal Neoplasms With Prominent Foamy/Pseudolipogenic Cell Morphology : Expanding the Phenotypic Spectrum of ALK Fusion Neoplasms and Report of Novel Fusion Partners. ALK重排间充质肿瘤具有明显的泡沫/假脂肪细胞形态:扩大 ALK 融合肿瘤的表型范围并报告新型融合伙伴。
IF 4.5 1区 医学 Q1 PATHOLOGY Pub Date : 2024-11-01 Epub Date: 2024-07-09 DOI: 10.1097/PAS.0000000000002283
Abbas Agaimy, Robert Stoehr, Cyril Fisher, John S A Chrisinger, Elizabeth G Demicco, Lars Tögel, Michal Michal, Michael Michal

The category of ALK -rearranged mesenchymal neoplasms has been evolving rapidly, with reports of morphologically diverse lesions of cutaneous, soft tissue, and visceral origin. While some of these represent morphologically defined entities harboring recurrent ALK fusions (inflammatory myofibroblastic tumor and epithelioid fibrous histiocytoma), others are unclassified by morphology with variable overlap with the tyrosine kinase family of neoplasia and their underlying ALK fusions cannot be suspected based on morphology. We herein report 3 cases that expand the anatomic, morphologic, and genotypic spectrum of ALK -rearranged unclassified neoplasms. Patients were all adults aged 46 to 69 (median: 63) who presented with a mass located in the gingiva, subcutis of the back, and submucosal posterior pharyngeal wall. The tumor size ranged from 1 to 2.7 cm (median: 1.6). Conservative surgery was the treatment in all patients. Follow-up was available for one patient who remained disease-free at 14 months. Histologically, all tumors displayed large polygonal cells with foamy to granular and lipogenic-like microvacuolated copious cytoplasm and medium-sized round nuclei with 1 or 2 prominent nucleoli. Mitoses and necrosis were not seen. The initial diagnostic impression was PEComa, inflammatory rhabdomyoblastic tumor and unclassified pseudolipogenic neoplasm. Strong cytoplasmic ALK was detected by immunohistochemistry in all cases. Other positive markers include Cathepsin K (2/2), desmin (1/3), focal MyoD1 (1/1), focal SMA (1/3), and focal EMA (1/2). Targeted RNA sequencing revealed ALK fusions with exon 20 (2 cases) and exon 19 (one case) of ALK fused to RND3 (exon 3), SQSTM1 (exon 6), and desmin (intron 6). Methylation profiling in the desmin-fused case (initially diagnosed as inflammatory rhabdomyoblastic tumor) revealed an inflammatory myofibroblastic tumor match with a low confidence score of 0.5 and a flat copy number variation (CNV) profile. No NF1 mutation was detected in this case, altogether excluding an inflammatory rhabdomyoblastic tumor. Our study highlights and expands the morphologic and anatomic diversity of ALK- fused neoplasms and documents novel fusion partners ( RND3 and desmin).

ALK重排间叶肿瘤的类别发展迅速,有报道称皮肤、软组织和内脏来源的病变形态各异。其中一些代表了形态学上明确的、携带复发性 ALK 融合的实体(炎症性肌纤维母细胞瘤和上皮样纤维组织细胞瘤),而另一些则是形态学上未分类的、与酪氨酸激酶家族肿瘤有不同程度重叠的肿瘤,而且根据形态学无法怀疑其潜在的 ALK 融合。我们在此报告了 3 个病例,这些病例扩大了 ALK 重组未分类肿瘤的解剖、形态和基因型范围。患者均为成年人,年龄在 46 岁至 69 岁之间(中位数:63 岁),表现为位于牙龈、背部皮下和咽后壁粘膜下的肿块。肿瘤大小从 1 厘米到 2.7 厘米不等(中位数:1.6 厘米)。所有患者均接受了保守性手术治疗。一名患者接受了随访,14 个月后仍未复发。从组织学角度看,所有肿瘤均为大的多角形细胞,具有泡沫状至颗粒状和脂原样微空泡的丰富细胞质,中等大小的圆形细胞核具有 1 至 2 个突出的核小体。未见有丝分裂和坏死。初步诊断印象是 PEComa、炎性横纹肌母细胞瘤和未分类的假脂源性肿瘤。免疫组化在所有病例中均检测到强细胞质 ALK。其他阳性标记物包括Cathepsin K(2/2)、desmin(1/3)、灶性MyoD1(1/1)、灶性SMA(1/3)和灶性EMA(1/2)。靶向 RNA 测序发现 ALK 与 RND3(3 号外显子)、SQSTM1(6 号外显子)和 desmin(6 号内含子)的 20 号外显子(2 例)和 19 号外显子(1 例)融合。对融合了 desmin 的病例(最初诊断为炎性横纹肌母细胞瘤)进行甲基化分析后发现,该病例与炎性肌纤维母细胞瘤相匹配,置信度低至 0.5 分,且拷贝数变异(CNV)曲线平坦。该病例未检测到 NF1 基因突变,因此完全排除了炎性横纹肌母细胞瘤的可能性。我们的研究强调并扩展了ALK融合肿瘤在形态学和解剖学上的多样性,并记录了新的融合伙伴(RND3和desmin)。
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引用次数: 0
Papillary Intralymphatic Angioendothelioma Versus Splenic Lymphatic Malformation With Papillary Endothelial Proliferation: Different Terms for the Same Entity. 乳头状淋巴内血管内皮瘤与伴乳头状内皮增生的脾淋巴畸形:同一实体的不同术语。
IF 4.5 1区 医学 Q1 PATHOLOGY Pub Date : 2024-11-01 Epub Date: 2024-03-18 DOI: 10.1097/PAS.0000000000002212
Larisa Debelenko, Fabrizio Remotti
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引用次数: 0
Biomarker Testing in Microinvasive Carcinoma of the Breast. 乳腺微侵袭性癌的生物标志物检测
IF 4.5 1区 医学 Q1 PATHOLOGY Pub Date : 2024-11-01 Epub Date: 2024-05-29 DOI: 10.1097/PAS.0000000000002252
Olivier Michaud, Muhammad Ahmad, Syed A Hoda
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引用次数: 0
PEComa With MITF Overexpression: Clinicopathologic and Molecular Analysis of a Series of 36 Cases. MITF 过度表达的 PEComa:36 例系列病例的临床病理学和分子分析
IF 4.5 1区 医学 Q1 PATHOLOGY Pub Date : 2024-11-01 Epub Date: 2024-06-27 DOI: 10.1097/PAS.0000000000002276
John Hanna, Eleanor Russell-Goldman, Esther Baranov, Daniel Pissaloux, Yvonne Y Li, Franck Tirode, Arnaud de la Fouchardiere, Christopher D M Fletcher

Perivascular epithelioid cell neoplasms (PEComas) are tumors of uncertain cell lineage that occur across a wide age range, at a variety of anatomic sites, and with a female predominance. Most PEComas are associated with dysregulation of the mTOR pathway, most commonly through inactivating mutations of TSC2 or TSC1 . However, a small subset of PEComas are instead associated with TFE3 gene fusions. MITF is closely related to TFE3 and is frequently overexpressed in PEComas, often in a mutually exclusive manner with TFE3. Here we report the clinical, histopathologic, and molecular features of MITF-overexpressing PEComas in a series of 36 cases. The clinical and morphologic features were comparable to conventional PEComa, although the immunohistochemical profile was notable for the relatively limited expression of melanocytic markers, a surprising finding given that MITF is the master regulator of melanocytic differentiation. At the molecular level, 20 cases (56%) showed supernumerary copies of the MITF gene, suggesting a potential explanation for MITF overexpression. A putative genetic driver event within the mTOR pathway was identified in 11 of 15 cases (73%) analyzed by DNA or RNA sequencing. Interestingly, the malignant PEComas showed 2 distinguishing molecular features: they were associated with a complex chromosomal copy number profile, and they tended to show additional genetic changes, most commonly inactivating events involving TP53 , RB1 , and ATRX . These results elucidate key features of PEComas showing MITF overexpression, begin to explain the molecular basis for MITF overexpression in some PEComas and identify potential molecular correlates for malignancy that may be applicable to the broader PEComa family.

血管周上皮样细胞瘤(PEComas)是一种细胞系不确定的肿瘤,发生在不同年龄段、不同解剖部位,女性占多数。大多数 PEComas 与 mTOR 通路失调有关,最常见的原因是 TSC2 或 TSC1 发生了失活突变。不过,也有一小部分 PEComas 与 TFE3 基因融合有关。MITF 与 TFE3 关系密切,经常在 PEC 瘤中过表达,而且往往与 TFE3 以互斥的方式表达。在此,我们报告了一系列 36 例 MITF 过表达 PEComas 的临床、组织病理学和分子特征。临床和形态学特征与传统的 PEComa 相似,但免疫组化特征的显著特点是黑色素细胞标志物的表达相对有限,鉴于 MITF 是黑色素细胞分化的主要调节因子,这一发现令人惊讶。在分子水平上,20 个病例(56%)显示出 MITF 基因的超数拷贝,这表明 MITF 基因过表达的潜在原因。在通过DNA或RNA测序分析的15个病例中,有11个病例(73%)确定了mTOR通路中的潜在遗传驱动因子。有趣的是,恶性 PEComas 表现出两个显著的分子特征:它们与复杂的染色体拷贝数特征有关,而且往往会出现额外的基因变化,最常见的是涉及 TP53、RB1 和 ATRX 的失活事件。这些结果阐明了显示 MITF 过表达的 PEComa 的主要特征,开始解释一些 PEComa 中 MITF 过表达的分子基础,并确定了可能适用于更广泛的 PEComa 家族的潜在恶性肿瘤分子相关性。
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引用次数: 0
Intraductal Implantation of Biliary Neoplasms: A Potential Cause of "Multifocal" Tumors. 胆道肿瘤的导管内种植:多灶性 "肿瘤的潜在病因。
IF 4.5 1区 医学 Q1 PATHOLOGY Pub Date : 2024-11-01 Epub Date: 2024-07-01 DOI: 10.1097/PAS.0000000000002279
Yoh Zen, Masayuki Akita, Evangelia Florou, Takumi Fukumoto, Tomoo Itoh, Evangelos Prassas, Krishna Menon, Parthi Srinivasan

Multiple biliary tumors rarely develop in patients without underlying chronic hepatobiliary disease. Those lesions are regarded as multifocal neoplasms if there is no interconnecting dysplasia. This study aimed to determine whether 2 separate tumors in the biliary tract represent true multifocal independent tumorigenesis or intraluminal implantation of a single neoplasm. Two separate biliary tumors without intervening dysplasia were identified in 9 cases: biliary intraductal papillary neoplasm (IPNB; n=5) and extrahepatic cholangiocarcinoma (n=4). The 2 tumors were histologically similar in all cases. In 5 metachronous cases, the second tumor developed 2 to 13 years after the complete resection of the first tumor. In 4 synchronous cases, 2 separate neoplasms were identified in a surgical specimen. The metachronous presentation was more common in IPNB cases, whereas the synchronous development was more frequent in cholangiocarcinoma cases. The second tumors in 4 metachronous cases (4/5; 80%) and smaller lesions in all synchronous cases (4/4; 100%) were located in a lower part of the biliary. Immunophenotypes of cytokeratins and mucin core proteins were almost identical between the 2 lesions. Next-generation sequencing also confirmed that the 2 neoplasms shared gene mutations involving KRAS , GNAS , APC , BRAF , CTNNB1 , SMAD4 , TP53 , or ARID1A in all cases. In conclusion, multiple biliary tumors without underlying chronic biliary disease are most likely due to intraductal implantation of a single neoplasm. Thick mucinous bile in IPNB and increasing use of trans-ampullary biliary interventions may contribute to this unique form of tumor extension.

没有慢性肝胆疾病基础的患者很少会出现多发性胆道肿瘤。如果没有相互关联的发育不良,这些病变被视为多灶性肿瘤。本研究旨在确定胆道中的两个独立肿瘤是真正的多灶性独立肿瘤发生,还是单一肿瘤的腔内种植。在9个病例中发现了2个独立的胆道肿瘤,且无相互间的发育不良:胆管内乳头状瘤(IPNB;n=5)和肝外胆管癌(n=4)。在所有病例中,这两种肿瘤在组织学上相似。在5个同步病例中,第二个肿瘤是在第一个肿瘤完全切除后2至13年出现的。在 4 个同步病例中,在手术标本中发现了 2 个不同的肿瘤。在 IPNB 病例中,同步表现更为常见,而在胆管癌病例中,同步发展更为常见。4 个同步病例(4/5;80%)中的第二个肿瘤和所有同步病例(4/4;100%)中的较小病灶均位于胆管下部。两种病变的细胞角蛋白和粘蛋白核心蛋白的免疫表型几乎相同。下一代测序还证实,所有病例中的两种肿瘤都有涉及 KRAS、GNAS、APC、BRAF、CTNNB1、SMAD4、TP53 或 ARID1A 的基因突变。总之,没有慢性胆道疾病基础的多发性胆道肿瘤很可能是由于单个肿瘤的导管内种植所致。IPNB 中粘稠的胆汁以及越来越多地使用经膀胱胆道介入治疗可能会导致这种独特的肿瘤扩展形式。
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引用次数: 0
Multifocal Papillary Thyroid Carcinomas With Discordant Molecular Drivers: Emphasizing the Morphology and Collision Tumors. 分子驱动因素不一致的多灶性甲状腺乳头状癌:强调形态学和碰撞肿瘤。
IF 4.5 1区 医学 Q1 PATHOLOGY Pub Date : 2024-11-01 Epub Date: 2024-05-31 DOI: 10.1097/PAS.0000000000002256
Jonathan P Rivera, Yi-Chen Yeh, Paul Chih-Hsueh Chen, Jen-Fan Hang

Multifocal papillary thyroid carcinomas (PTCs) are common and the majority of the tumors harbor mutual BRAF p.V600E mutation. This study aimed to investigate a contemporary series of multifocal PTCs with discordant molecular drivers. Consecutive thyroidectomies diagnosed with multifocal PTCs ≥0.5 cm between 2019 and 2023 were reviewed. Immunohistochemistry (IHC) for BRAF VE1 was performed for all tumors. Cases with discordant BRAF IHC results or morphologic discrepancy were identified, and BRAF IHC-negative tumors were subjected to RAS Q61R IHC and/or targeted RNA next-generation sequencing. A total of 770 patients with a main PTC ≥0.5 cm were identified; 255 (33.1%) had multifocal disease, and 142 (18.4%) had at least another PTC ≥0.5 cm. Among them, 13 cases (9.2%, 13/142) had discordant molecular drivers. Twelve cases had one or more BRAF -positive PTCs accompanied by a BRAF -negative PTC (3 with CCDC6::RET fusion, 1 with NCOA4::RET fusion, 1 with ACBD5::RET fusion, 2 with ETV6::NTRK3 fusion, 1 with TG::FGFR1 fusion, 1 with LMTK2::BRAF fusion, 1 with AGK::BRAF fusion and RAS p.Q61R mutation, 1 with RAS p.Q61R mutation, and 1 without detectable molecular drivers). The last case had tumors with discordant fusion drivers ( VIM::NTRK3 and TNS1::BRAF ). Most cases showed tumors that were morphologically distinct (92.3%, 12/13) and occurred in the contralateral lobes (76.9%, 10/13). Notably, we identified 4 cases (30.8%) that presented as collision tumors and 6 cases (46.2%) that showed lymph node metastases, including 2 with simultaneous involvement by tumors with discordant molecular drivers, as novel findings. In summary, a subset (9.2%) of multifocal PTCs had discordant molecular drivers and 84.6% of them were a combination of BRAF -positive and kinase gene fusion-associated PTCs, most with distinct morphologies. Almost half of the cases had nodal metastasis and a third of them showed simultaneous involvement by tumors with discordant molecular drivers. The results highlight the clinical importance of identifying such cases, given the potentially different treatments.

多灶性甲状腺乳头状癌(PTC)很常见,大多数肿瘤都携带BRAF p.V600E基因突变。本研究旨在调查一系列分子驱动因素不一致的多灶性PTC。研究回顾了2019年至2023年期间诊断为多灶PTC≥0.5厘米的连续甲状腺切除术。对所有肿瘤进行了 BRAF VE1 免疫组化(IHC)检查。确定了 BRAF IHC 结果不一致或形态学差异的病例,并对 BRAF IHC 阴性肿瘤进行了 RAS Q61R IHC 和/或靶向 RNA 下一代测序。共发现 770 例主要 PTC ≥0.5 厘米的患者;255 例(33.1%)患有多灶性疾病,142 例(18.4%)至少有另一个 PTC ≥0.5 厘米。其中,13 例(9.2%,13/142)的分子驱动因素不一致。12 例患者有一个或多个 BRAF 阳性 PTC,同时伴有一个 BRAF 阴性 PTC(3 例伴有 CCDC6::RET 融合、1 例伴有 NCOA4::RET 融合、1 例伴有 ACBD5::RET 融合、2 例伴有 ETV6::NTRK3 融合、1 例伴有 TG::FGFR1 融合、1 例伴有 LMTK2::BRAF 融合、1 例伴有 AGK::BRAF 融合和 RAS p. Q61R 突变、1 例伴有 BRAF 阳性 PTC 和 BRAF 阴性 PTC)。Q61R突变,1例有RAS p.Q61R突变,1例未检测到分子驱动因素)。最后一个病例的肿瘤具有不一致的融合驱动因子(VIM::NTRK3 和 TNS1::BRAF)。大多数病例的肿瘤形态独特(92.3%,12/13 例),且发生在对侧肺叶(76.9%,10/13 例)。值得注意的是,我们发现有 4 例(30.8%)表现为碰撞性肿瘤,6 例(46.2%)表现为淋巴结转移,包括 2 例同时受累于分子驱动因素不一致的肿瘤,这些都是新发现。总之,一部分(9.2%)多灶性 PTC 具有不一致的分子驱动因素,其中 84.6% 是 BRAF 阳性和激酶基因融合相关 PTC 的组合,大多数具有不同的形态。近一半的病例有结节转移,其中三分之一的病例同时受累于分子驱动因素不一致的肿瘤。鉴于治疗方法可能不同,这些结果凸显了识别此类病例的临床重要性。
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引用次数: 0
Clinicopathological and Molecular Characteristics of Rare EBV-associated Diffuse Large B-cell Lymphoma With IRF4 Rearrangement. IRF4重排的罕见EBV相关弥漫大B细胞淋巴瘤的临床病理和分子特征
IF 4.5 1区 医学 Q1 PATHOLOGY Pub Date : 2024-11-01 Epub Date: 2024-08-22 DOI: 10.1097/PAS.0000000000002301
Yuxiu Zhang, Anqi Li, Yimin Li, Binshen Ouyang, Xuan Wang, Lei Zhang, Haimin Xu, Yijin Gu, Xinyuan Lu, Lei Dong, Hongmei Yi, Chaofu Wang

Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) is a rare form of aggressive B-cell lymphoma with limited molecular information reported regarding interferon regulatory factor 4 ( IRF4 ) status. Here, we presented 3 EBV-positive DLBCL cases with IRF4 rearrangement (EBV+DLBCL- IRF4 -R) verified by fluorescence in situ hybridization (FISH). Three patients, including 1 male and 2 females (median age: 64 y; range: 45 to 68 y), had normal immune function. During a median follow-up of 12 months (range: 0 to 24 mo), 2 patients succumbed to the disease, and 1 patient achieved complete response. Three tumors were present in the mediastinum, stomach, and thalamus, respectively. All three tumors exhibited DLBCL morphology and were identified as the non-germinal center B-cell subtype, with EBV-encoded small RNA positivity ranging from 70% to 80%. RNA sequencing was able to identify RHOH and IGH as fusion partners of IRF4 in two cases. No MYC and BCL2 rearrangements were detected in 3 cases by FISH and RNA sequencing. Next-generation sequencing revealed a low mutation burden, and only IRF4 was recurrently mutated in two EBV+DLBCL- IRF4 -R cases. Using the LymphGen 2.0 classifier, 1 case was classified as the MCD (including MYD88L265P and CD79B mutations) subtype. We report rare EBV+DLBCL- IRF4 -R that may enhance our understanding of the diverse spectrum of large B-cell lymphoma.

爱泼斯坦-巴尔病毒(EBV)阳性弥漫大B细胞淋巴瘤(DLBCL)是一种罕见的侵袭性B细胞淋巴瘤,有关干扰素调节因子4(IRF4)状态的分子信息报道有限。在此,我们介绍了3例经荧光原位杂交(FISH)验证为IRF4重排(EBV+DLBCL-IRF4-R)的EBV阳性DLBCL病例。三例患者的免疫功能正常,其中包括一名男性和两名女性(中位年龄:64 岁;范围:45 至 68 岁)。中位随访时间为12个月(0至24个月),2名患者死亡,1名患者获得完全应答。三个肿瘤分别位于纵隔、胃和丘脑。这三个肿瘤均表现为DLBCL形态,被鉴定为非生殖中心B细胞亚型,EBV编码的小RNA阳性率为70%至80%。在两个病例中,RNA测序能够确定RHOH和IGH是IRF4的融合伙伴。在3个病例中,通过FISH和RNA测序未检测到MYC和BCL2重排。下一代测序显示突变负荷较低,在两个EBV+DLBCL-IRF4-R病例中,只有IRF4发生了复发性突变。利用 LymphGen 2.0 分类器,1 例病例被归类为 MCD(包括 MYD88L265P 和 CD79B 突变)亚型。我们报告了罕见的EBV+DLBCL-IRF4-R病例,这可能会加深我们对大B细胞淋巴瘤多样性的了解。
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引用次数: 0
Reporting of Incidental Thrombotic Arteriopathy in Lung Resection Specimens: Examination of Clinical Impact. 报告肺切除标本中的意外血栓性动脉病变:临床影响研究。
IF 4.5 1区 医学 Q1 PATHOLOGY Pub Date : 2024-11-01 Epub Date: 2024-07-17 DOI: 10.1097/PAS.0000000000002292
Andréanne Gagné, Robert F Padera, Rachel K Putman, Lynette M Sholl

Pulmonary thrombotic arteriopathy (PTA) can be an incidental finding in lung resections performed for various indications. Historic studies largely examined PTA in autopsies. Thus, the prevalence in surgical samples, particularly in the modern era of lung cancer screening, is poorly defined. Detection of PTA in surgical samples may provide an opportunity for therapeutic intervention, but the impact of this finding on clinical management is unknown. We retrospectively examined consecutive lung surgical resections containing a report of incidental PTA between 2019 and 2022 in our institution. A retrospective chart review was performed to determine the history of systemic thromboembolism and clinical and radiographic follow-up. All slides were reviewed to morphologically characterize the vascular changes. Among 2930 pulmonary resections, 66 (2.3%) reportedly contained PTA. Twenty-four (36.4%) patients had a clinically recognized thromboembolic event either before or after surgical resection. Patients with clinically recognized thromboembolic disease were significantly more likely to have both acute and organized thrombi affecting large arteries. The presence of infarct, chronic hypertensive vasculopathy, or number of vessels with thrombi were not significantly associated with a clinically detected event. Reporting of incidental PTA led to clinical intervention in six patients and confirmed systemic thromboembolic disease in 2. Moreover, 2 patients with no further workup based on the incidental pathology findings subsequently developed pulmonary embolism. PTA is incidentally detected in 2.3% of surgical lung resections, and in two-thirds of cases, there is no clinical suspicion of thromboembolic disease. Pathologic reporting of PTA rarely led to clinical intervention, suggesting a need for improved communication of incidental pathology findings.

肺血栓性动脉病变(PTA)可能是因各种原因进行肺切除术时偶然发现的。以往的研究主要是对尸检中的 PTA 进行研究。因此,手术样本中的发病率,尤其是在现代肺癌筛查时代的发病率尚不明确。在手术样本中发现 PTA 可为治疗干预提供机会,但这一发现对临床管理的影响尚不清楚。我们回顾性地检查了本院在 2019 年至 2022 年期间连续进行的肺部手术切除,其中包含一份附带 PTA 的报告。我们进行了回顾性病历审查,以确定全身血栓栓塞病史以及临床和影像学随访情况。对所有切片进行了复查,以确定血管病变的形态特征。在2930例肺部切除术中,有66例(2.3%)报告含有PTA。24例(36.4%)患者在手术切除之前或之后发生了临床公认的血栓栓塞事件。临床公认的血栓栓塞性疾病患者中,有急性和有组织血栓影响大动脉的几率明显更高。是否存在梗死、慢性高血压血管病变或有血栓的血管数量与临床发现的血栓事件无明显关联。6名患者因报告偶然的PTA而接受了临床干预,2名患者确诊为全身性血栓栓塞性疾病。此外,2名患者因偶然的病理发现而未接受进一步检查,随后发展为肺栓塞。2.3%的肺切除手术会偶然发现PTA,其中三分之二的病例临床上并未怀疑有血栓栓塞性疾病。PTA 的病理报告很少会导致临床干预,这表明需要改进偶然病理发现的交流。
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引用次数: 0
High Prevalence of MYD88 and CD79B Mutations in Primary Sinonasal Diffuse Large B-Cell Lymphoma: Identification of an MCD-like Subtype. 原发性鼻窦弥漫性大 B 细胞淋巴瘤中 MYD88 和 CD79B 基因突变的高发率:MCD样亚型的鉴定
IF 4.5 1区 医学 Q1 PATHOLOGY Pub Date : 2024-10-31 DOI: 10.1097/PAS.0000000000002329
Fangli Peng, Takuro Igawa, Tomohiro Urata, Hiroki Kobayashi, Tetsuya Isoda, Sawako Ono, Takehiro Tanaka, Daisuke Ennisshi, Yoshinobu Maeda, Hidetaka Yamamoto

Primary sinonasal diffuse large B-cell lymphoma (PSDLBCL) is a rare aggressive lymphoma. Recently, genetic classification using Next Generation Sequencing (NGS) demonstrated that PSDLBCL largely consists of the MCD genotype, which has a poor prognosis mainly driven by MYD88 L265P and CD79B gene abnormalities. This study investigated the prevalence and clinicopathological significance of MYD88 L265P and CD79B Y196 mutations using droplet digital PCR in 55 patients with PSDLBCL, as well as the translocation of BCL2/BCL6/c-Myc with FISH. We found mutations in MYD88 L265P (29/55, 52.7%) and CD79B Y196 (20/55, 36.4%). The MCD-like subtype, defined by the mutation of MYD88 and/or CD79B, was found in 32 out of 55 cases (58.2%). This subtype largely consists of non-GCB type (31/32, 96.9%; P<0.01) and double-expressor cases (20/32, 62.5%; P=0.01) compared with the MYD88/CD79B co-wild type, with BCL6 translocation in a small subset (2/32, 6.3%) and no translocations of BCL2 (0/32) or c-Myc (0/32). The MCD-like subtype tended to relapse in specific sites such as the central nervous system, testis, and/or skin compared with the co-wild type (P=0.03), showing poorer outcomes in overall survival (P=0.02) and progression-free survival (P=0.01). In conclusion, our study highlights a high prevalence of MYD88 and CD79B mutations in PSDLBCL, identifying an aggressive MCD-like subtype with a distinct relapse pattern. This molecular subclassification can be helpful for both prognostic prediction and therapeutic strategy in patients with PSDLBCL.

原发性鼻窦弥漫性大B细胞淋巴瘤(PSDLBCL)是一种罕见的侵袭性淋巴瘤。最近,利用下一代测序技术(NGS)进行的基因分类表明,PSDLBCL 主要由 MCD 基因型组成,其预后较差,主要由 MYD88 L265P 和 CD79B 基因异常驱动。本研究利用液滴数字 PCR 技术研究了 55 例 PSDLBCL 患者中 MYD88 L265P 和 CD79B Y196 基因突变的发生率和临床病理意义,并利用 FISH 技术研究了 BCL2/BCL6/c-Myc 的易位情况。我们发现了 MYD88 L265P 突变(29/55,52.7%)和 CD79B Y196 突变(20/55,36.4%)。55 例病例中有 32 例(58.2%)属于 MCD 样亚型,其定义是 MYD88 和/或 CD79B 发生突变。该亚型主要包括非GCB型(31/32,96.9%;P
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American Journal of Surgical Pathology
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