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PRKC Fusion Melanocytic Tumors, a Subgroup of Melanocytic Tumors More Closely Aligned to Blue Nevi Than to PRKAR1A-inactivated Pigmented Epithelioid Melanocytomas. PRKC融合型黑素细胞瘤是黑素细胞瘤的一个亚群,它与蓝色痣的关系比与PRKAR1A失活的色素上皮样黑素细胞瘤的关系更为密切。
IF 4.5 1区 医学 Q1 PATHOLOGY Pub Date : 2024-11-01 Epub Date: 2024-06-12 DOI: 10.1097/PAS.0000000000002262
Pragi Patel, Alice Chen, Natasha Sharma, Yongzhan Zhang, Victor L Quan, Shantel Olivares, Pedram Gerami

Tumors morphologically classified as pigmented epithelioid melanocytomas (PEMs) are genomically diverse, with the 2 most common genomic subtypes being PRKC fusions or PRKAR1A inactivating mutations. PRKC fusions activate the Gα q/11 pathway similar to blue nevi. Conversely, inactivating mutations in PRKAR1A activate the Gα s pathway. We hypothesize that PRKC fusions have greater genomic overlap with blue nevi compared with PRKAR1A-inactivated PEMs. We characterized the clinical and morphologic features of 21 PRKC and PRKACB fusion melanocytic tumors and compared this to PRKAR1A mutated PEMs. To test our hypothesis regarding greater genomic overlap between PRKC fusions and blue nevi relative to PRKAR1A mutated PEMs, we performed a principal component analysis (PCA) using mRNA expression data. Lastly, we performed a meta-analysis focusing on the outcome data of PRKC fusions. PRKC fusions occur at a younger median age than PRKAR1A mutated PEMs (16 vs. 27). Histologically, PRKC fusions have solid aggregates of epithelioid melanocytes not typical of PRKAR1A mutated PEMs. The PCA plot showed no overlap between the PRKC fusion group and the PRKAR1A-mutated PEMs. There was a significant overlap between PRKC fusions and blue nevi. A meta-analysis of PRKC fusion cases in the literature suggests melanoma is uncommon, but the loss of BAP-1 nuclear expression may be associated with an adverse prognosis as in tumors from the blue nevus family. PRKC fusion melanocytic tumors have greater genomic overlap with blue nevi compared with PRKAR1A mutated PEMs. We recommend categorizing benign PRKC fusion melanocytic tumors as blue fusion nevi/tumors.

形态上被归类为色素上皮样黑素细胞瘤(PEMs)的肿瘤在基因组上多种多样,最常见的两种基因组亚型是PRKC融合或PRKAR1A失活突变。PRKC 融合会激活 Gαq/11 通路,与蓝痣类似。相反,PRKAR1A 的失活突变会激活 Gαs 通路。我们假设,与 PRKAR1A 失活的 PEMs 相比,PRKC 融合体与蓝痣的基因组重叠程度更高。我们描述了 21 例 PRKC 和 PRKACB 融合型黑素细胞瘤的临床和形态特征,并将其与 PRKAR1A 突变的 PEMs 进行了比较。为了验证我们的假设,即相对于 PRKAR1A 突变的 PEMs,PRKC 融合痣和蓝痣之间的基因组重叠程度更高,我们使用 mRNA 表达数据进行了主成分分析 (PCA)。最后,我们对 PRKC 融合的结果数据进行了荟萃分析。与 PRKAR1A 突变的 PEMs 相比,PRKC 融合发生的中位年龄更小(16 岁对 27 岁)。从组织学角度看,PRKC 融合型上皮样黑素细胞呈实性聚集,这与 PRKAR1A 突变的 PEMs 并不典型。PCA 图显示,PRKC 融合组与 PRKAR1A 突变的 PEM 之间没有重叠。PRKC融合组与蓝痣组之间有明显重叠。文献中对PRKC融合病例的荟萃分析表明,黑色素瘤并不常见,但BAP-1核表达的缺失可能与不良预后有关,正如蓝痣家族的肿瘤一样。与 PRKAR1A 突变的 PEMs 相比,PRKC 融合型黑素细胞瘤与蓝痣的基因组重叠程度更高。我们建议将良性PRKC融合黑素细胞瘤归类为蓝融合痣/瘤。
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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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引用次数: 0
Large-cell Basaloid Adenocarcinoma of the Lung: A Clinicopathologic Study of 12 Cases of a Distinctive Form of Lung Cancer Often Mistaken for Large-cell Neuroendocrine Carcinoma. 肺大细胞基底样腺癌:12例常被误认为大细胞神经内分泌癌的独特形式肺癌的临床病理学研究》(A Clinicopathologic Study of 12 Cases of a Distinctive Form of Lung Cancer Often Makes for Large-cell Neuroendocrine Carcinoma)。
IF 4.5 1区 医学 Q1 PATHOLOGY Pub Date : 2024-10-31 DOI: 10.1097/PAS.0000000000002318
David Suster, Haider A Mejbel, Alexander Craig Mackinnon, Saul Suster

A distinctive form of lung adenocarcinoma that closely mimics large-cell neuroendocrine carcinoma is described. The tumors arose in 6 women and 6 men aged 46-86 years (mean=58.4). They presented as peripheral subpleural masses measuring 2-12 cm (mean=6.5 cm). Histologically they were characterized by islands or anastomosing and serpiginous strands of large, atypical cells showing striking peripheral palisading of nuclei, with high mitotic activity and prominent comedo-like areas of necrosis. Because of the striking resemblance to neuroendocrine tumors, some of the cases were initially diagnosed as large-cell neuroendocrine carcinoma despite the absence of neuroendocrine markers. Immunohistochemistry showed positivity of the tumor cells for TTF1 and napsin-A, and negative staining for p40. The tumors were also uniformly negative for multiple neuroendocrine markers, including chromogranin, synaptophysin, CD56, and INSM1. Electron microscopy performed in 2 cases was negative for membrane-bound dense core neurosecretory granules. Pathogenic alterations were detected in 5 of 8 tumors tested by next-generation sequencing. Point mutations in KRAS and TP53 were identified in 5 patients. Low-level amplification of GNAS , KIT , and FGFR1 was present in 2 patients. No RB1 mutations were identified. Clinical follow-up in 10 cases showed that 2 patients died of their tumors, 2 experienced distant metastases, and 6 were alive and well from 1 to 13 years after diagnosis (median=7.1 y). Large-cell basaloid adenocarcinoma is an unusual variant of lung cancer that is easily confused with large-cell neuroendocrine carcinoma. Awareness of this unusual variant of lung adenocarcinoma is important for treatment and prognosis and for avoiding misdiagnosis.

本文描述了一种近似大细胞神经内分泌癌的独特肺腺癌。肿瘤发生在 6 名女性和 6 名男性身上,年龄在 46-86 岁之间(平均=58.4 岁)。它们表现为周围胸膜下肿块,大小为 2-12 厘米(平均=6.5 厘米)。从组织学角度看,它们的特征是由大的非典型细胞组成的岛状、吻合状和绢丝状细胞串,显示出明显的核周围钙化、高有丝分裂活性和突出的粉瘤样坏死区。由于与神经内分泌肿瘤极为相似,其中一些病例最初被诊断为大细胞神经内分泌癌,尽管没有神经内分泌标记物。免疫组化结果显示,肿瘤细胞的TTF1和napsin-A呈阳性,p40呈阴性。肿瘤的多种神经内分泌标记物也一致呈阴性,包括嗜铬粒蛋白、突触素、CD56和INSM1。在 2 个病例中进行的电子显微镜检查显示,膜结合致密核心神经分泌颗粒呈阴性。在通过新一代测序检测的 8 例肿瘤中,有 5 例检测到致病性改变。在 5 例患者中发现了 KRAS 和 TP53 的点突变。2名患者存在GNAS、KIT和FGFR1的低水平扩增。未发现 RB1 基因突变。对10例患者的临床随访显示,2例患者死于肿瘤,2例患者出现远处转移,6例患者在确诊后1至13年(中位数=7.1年)生存良好。大细胞基底样腺癌是一种不常见的肺癌变异,很容易与大细胞神经内分泌癌混淆。认识这种不常见的肺腺癌变体对于治疗和预后以及避免误诊非常重要。
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American Journal of Surgical Pathology
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