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A High-grade PML::JAK1 Fusion Sarcoma. 高级别 PML::JAK1 融合肉瘤
IF 4.5 1区 医学 Q1 PATHOLOGY Pub Date : 2024-11-04 DOI: 10.1097/PAS.0000000000002326
Steven Christopher Smith, Julio A Diaz-Perez, Mark Cameron Mochel, Steven D Billings, Leopoldo Fernandez, Andrew S Poklepovic
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引用次数: 0
High-grade Anaplastic Transformation of Ovarian Serous Borderline Tumor: A Distinctive Morphology With Abundant Dense Eosinophilic Cytoplasm and Dismal Prognosis. 卵巢浆液性边界肿瘤的高级别无性变:嗜酸性细胞质丰富且预后不佳的独特形态
IF 4.5 1区 医学 Q1 PATHOLOGY Pub Date : 2024-11-01 Epub Date: 2024-07-19 DOI: 10.1097/PAS.0000000000002294
Xiaoming Zhang, Kelly A Devereaux, Emily Ryan, Fei Fei, Christian A Kunder, Teri A Longacre

Ovarian serous borderline tumors (SBTs) have a generally favorable prognosis. Although the risk of progression to low-grade serous carcinoma is well documented, progression to high-grade carcinoma is rare. We report the clinicopathologic features of seven SBTs, each associated with the presence of a morphologically unique high-grade component with an extremely dismal prognosis. All of the SBTs exhibited typical hierarchical branching and scattered eosinophilic cells, whereas the high-grade component consisted of a profuse proliferation of epithelioid cells with abundant dense, eosinophilic cytoplasm, variable nuclear pleomorphism, and evident loss of WT1, estrogen receptor, and p16 positivity. In most cases, the SBT demonstrated an abrupt transition to the high-grade component, but one patient initially presented with the usual SBT and developed a recurrent disease that was composed entirely of the high-grade component. Targeted next-generation sequencing revealed identical driver mutations in both the SBT and high-grade components ( BRAF in 3, KRAS in 1), confirming clonality. Three cases, in addition, harbored telomerase reverse transcriptase promoter mutations in both components. One case, despite insufficient material for sequencing, was BRAF V600E-positive by immunohistochemistry. Most patients with available follow-up data died within 9 months of diagnosis. This study confirms prior reports of ovarian SBT transformation to high-grade carcinoma and further characterizes a distinct subset with abundant dense eosinophilic cytoplasm and an extremely dismal prognosis. The presence of BRAF mutations in a major subset of these tumors questions the notion that BRAF is associated with senescent eosinophilic cells and improved outcomes in SBT. The role of the additional telomerase reverse transcriptase promoter mutations merits further investigation.

卵巢浆液性边界肿瘤(SBTs)的预后一般较好。虽然进展为低级别浆液性癌的风险已得到充分证实,但进展为高级别癌的情况却很少见。我们报告了 7 例 SBT 的临床病理特征,每例都伴有形态独特、预后极差的高级别成分。所有的 SBT 都表现为典型的分层分支和散在的嗜酸性细胞,而高级别部分则由大量上皮样细胞增生组成,这些细胞具有大量致密的嗜酸性胞质、多变的核多形性以及 WT1、雌激素受体和 p16 阳性的明显丧失。在大多数病例中,SBT 会突然过渡到高级别成分,但有一名患者最初表现为普通的 SBT,后来病情复发,完全由高级别成分组成。靶向新一代测序发现,SBT 和高级别部分均存在相同的驱动突变(3 例为 BRAF,1 例为 KRAS),证实了克隆性。此外,有三个病例的两个部分都存在端粒酶逆转录酶启动子突变。有一个病例尽管测序材料不足,但免疫组化结果显示 BRAF V600E 阳性。大多数有随访数据的患者在确诊后9个月内死亡。这项研究证实了之前关于卵巢SBT向高级别癌转化的报道,并进一步描述了一个具有大量致密嗜酸性细胞质和预后极差的独特亚组。这些肿瘤的一个主要亚群存在 BRAF 突变,这对 BRAF 与衰老的嗜酸性细胞和改善 SBT 预后有关的观点提出了质疑。其他端粒酶逆转录酶启动子突变的作用值得进一步研究。
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引用次数: 0
Cytoplasmic Lipid Droplets Predict Worse Prognosis in Diffuse Large B-Cell Lymphoma: Next-Generation Sequencing Deciphering Lipogenic Genes. 细胞质脂滴可预测弥漫大 B 细胞淋巴瘤的不良预后:下一代测序解密脂肪生成基因。
IF 4.5 1区 医学 Q1 PATHOLOGY Pub Date : 2024-11-01 Epub Date: 2024-07-09 DOI: 10.1097/PAS.0000000000002280
Shu-Hsien Wang, Po-Min Chiang, Yung-Yeh Su, Yu-Ting Yu, Ya-Ping Chen, Tsai-Yun Chen, L Jeffrey Medeiros, Chang-Yao Chu, Peng-Chieh Chen, Kung-Chao Chang

Burkitt lymphoma is characterized by high cell turnover and numerous cytoplasmic vacuoles that are demonstrated to be lipid droplets (LDs) decorated by adipophilin. By contrast, cytoplasmic vacuoles are variably observed in diffuse large B-cell lymphoma (DLBCL) and less well characterized. In this study, we first validated in DLBCL that cytoplasmic vacuoles are indeed LDs by Oil-red-O stain, Bodipy fluorescent stain, and electron microscopy. Second, in a cohort of DLBCL patients (n=52) we showed that LDs in effusional lymphoma cells were associated with a poorer prognosis ( P =0.029, log-rank test) and higher International Prognostic Index (IPI) score (94% vs. 66%, P =0.026) than those without. Moreover, using adipophilin as a surrogate marker for LDs, we found in another cohort of biopsy specimen (n=85) that expression of adipophilin by lymphoma cells predicted a poorer prognosis ( P =0.007, log-rank test) and higher IPI score (63% vs. 30%, P =0.005). In addition, whole exome sequencing of effusional DLBCL cells showed LD-positive DLBCL shared genetic features with the MCD ( MYD88 and CD79B mutations) subtype and highlighted OSBPL10 and CUBN as the most frequently mutated genes involved in lipogenesis. Whole transcriptome analysis by comparing effusional DLBCL cells with versus without LDs showed upregulation of EHHADH , SLC1A1 , CD96 , INPP4B , and RNF183 relevant for lymphoma lipogenesis and upregulation of epithelial-mesenchymal transition and KRAS signaling pathways. Higher expression of EHHADH and CD96 were validated in LD-positive clinical samples and LD-rich cell lines than LD-poor cells along with the known lipogenic gene, FASN . Our findings highlight the roles of LDs and adipophilin expression in DLBCL, suggest that these markers may predict prognosis and show that lipogenic genes may be potential therapeutic targets.

伯基特淋巴瘤的特点是细胞新陈代谢旺盛,并有大量胞浆空泡,这些空泡被证明是由嗜脂蛋白装饰的脂滴(LD)。相比之下,细胞质空泡在弥漫大 B 细胞淋巴瘤(DLBCL)中的观察结果不尽相同,特征也不明显。在本研究中,我们首先通过Oil-red-O染色法、Bodipy荧光染色法和电子显微镜在DLBCL中验证了细胞质空泡确实是LDs。其次,在一组 DLBCL 患者(n=52)中,我们发现与无 LD 的患者相比,流出淋巴瘤细胞中的 LD 与较差的预后(P=0.029,log-rank 检验)和较高的国际预后指数(IPI)评分(94% vs. 66%,P=0.026)相关。此外,我们还利用嗜脂素作为低密度淋巴瘤的替代标记物,在另一批活检标本(n=85)中发现,淋巴瘤细胞表达嗜脂素预示着较差的预后(P=0.007,log-rank检验)和较高的IPI评分(63% vs. 30%,P=0.005)。此外,流出型DLBCL细胞的全外显子组测序显示,LD阳性DLBCL与MCD(MYD88和CD79B突变)亚型具有共同的遗传特征,并突出显示OSBPL10和CUBN是参与脂肪生成的最常见突变基因。通过比较有无LD的流出型DLBCL细胞,全转录组分析显示,与淋巴瘤脂肪生成相关的EHHADH、SLC1A1、CD96、INPP4B和RNF183上调,上皮-间质转化和KRAS信号通路上调。经验证,在LD阳性的临床样本和富含LD的细胞系中,EHHADH和CD96以及已知的脂肪生成基因FASN的表达高于贫LD细胞。我们的研究结果突显了LDs和嗜脂素表达在DLBCL中的作用,表明这些标志物可预测预后,并显示生脂基因可能是潜在的治疗靶点。
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引用次数: 0
Spinal Cord Astroblastoma With EWSR1-BEND2 Fusion in Female Patients : A Report of Four Cases From China and a Comprehensive Literature Review. 女性脊髓天体母细胞瘤与 EWSR1-BEND2 融合:中国四例病例报告及文献综述
IF 4.5 1区 医学 Q1 PATHOLOGY Pub Date : 2024-11-01 Epub Date: 2024-08-06 DOI: 10.1097/PAS.0000000000002298
Lingyi Fu, I Weng Lao, Liyun Huang, Liqiong Ou, Lei Yuan, Ziteng Li, Shuo Li, Wanming Hu, Shaoyan Xi

Astroblastoma is an extremely rare central nervous system tumor characterized by astroblastic pseudorosettes and vascular hyalinization. Despite these histologic hallmarks, its morphology can vary, occasionally resembling other central nervous system tumors such as ependymoma. A novel tumor entity, astroblastoma, meningioma 1 ( MN1 )-altered, has been identified, featuring MN1 gene rearrangements typically involving BEN-domain containing 2 ( BEND2 ) as a fusion partner. Most astroblastomas arise in the cerebral hemisphere. Here, we report 4 cases of spinal cord astroblastoma in female patients, all showing Ewing sarcoma RNA-binding protein 1 fusion with BEND2 , rather than MN1 . These tumors displayed growth patterns akin to traditional intracranial astroblastomas, with three cases demonstrating high-grade histology, including elevated mitotic activity and necrosis. Interestingly, some cases exhibited positive staining for pan-cytokeratin and hormone receptors. DNA methylation profiling clustered three of the four cases with the reference "AB_EWSR," whereas one case exhibited an independent methylation signature near the reference methylation group "AB_EWSR" and "pleomorphic xanthoastrocytoma." Together with the existing literature, we summarized a total of eleven cases, which predominantly affected children and young adults with female predilection. Eight of 10 patients experienced recurrence, underscoring the aggressive nature of this disease. We suggest recognizing a new molecular subgroup of spinal astroblastoma and recommend testing newly diagnosed infratentorial astroblastomas for Ewing sarcoma RNA-binding protein 1-BEND2 fusion.

星形母细胞瘤是一种极为罕见的中枢神经系统肿瘤,其特征是星形母细胞假性增生和血管透明化。尽管有这些组织学特征,但其形态可能会有所不同,偶尔也会与上皮瘤等其他中枢神经系统肿瘤相似。目前已发现一种新的肿瘤实体--星形母细胞瘤、脑膜瘤 1(MN1)改变,其特点是 MN1 基因重排,通常涉及作为融合伙伴的含 BEN-domain2(BEND2)。大多数星形母细胞瘤发生在大脑半球。在此,我们报告了4例女性脊髓星形母细胞瘤病例,所有病例均显示尤文肉瘤RNA结合蛋白1与BEND2而非MN1融合。这些肿瘤的生长模式与传统的颅内星形母细胞瘤相似,其中三个病例的组织学表现为高级别,包括有丝分裂活性升高和坏死。有趣的是,有些病例的泛细胞角蛋白和激素受体染色呈阳性。DNA甲基化分析将四例病例中的三例与参考组 "AB_EWSR "聚集在一起,而一例病例则在参考甲基化组 "AB_EWSR "和 "多形性黄细胞瘤 "附近表现出独立的甲基化特征。结合现有文献,我们共总结了 11 例病例,这些病例主要影响儿童和年轻成人,且女性偏好。10 例患者中有 8 例复发,凸显了这种疾病的侵袭性。我们建议承认脊柱星形母细胞瘤是一种新的分子亚群,并建议对新诊断的幕下星形母细胞瘤进行尤文肉瘤 RNA 结合蛋白 1-BEND2 融合试验。
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引用次数: 0
Pancreatic and Ileal Neuroendocrine Tumors: Metastatic Disease or a Novel MEN Syndrome? 胰腺和回肠神经内分泌肿瘤:转移性疾病还是新型 MEN 综合征?
IF 4.5 1区 医学 Q1 PATHOLOGY Pub Date : 2024-11-01 Epub Date: 2024-07-22 DOI: 10.1097/PAS.0000000000002290
Sylvia L Asa, Amr Mohamed

Multiple endocrine neoplasms are a feature of multiple endocrine neoplasia (MEN) syndromes types 1, 2, 4, and 5. However, the ileum is not usually involved in these disorders. We report a series of patients with neuroendocrine tumors (NETs) involving both the pancreas and the ileum. We searched the laboratory information system and personal consultation records of the authors from 2019 to 2023 for patients who had neuroendocrine tumors (NETs) involving both the pancreas and ileum. In a series of 846 patients, we identified 4 patients with pancreatic and ileal NETs, 2 female and 2 male, ages 52 to 75. Two female patients had primary EC cell tumors of the ileum with metastasis to the pancreas that showed expression of CDX2 and serotonin similar to the ileal primary tumors. Two males had primary lesions in the 2 sites with different immunoprofiles; the ileal tumors expressed CDX2 and serotonin and were negative for ARX, whereas the pancreatic tumors expressed ARX, glucagon, and pancreatic polypeptide and were negative for CDX2 and serotonin. In both male patients, the nontumorous pancreas showed preneoplastic changes in the endocrine elements, suggesting germline predisposition to endocrine neoplasia. Testing for known genetic alterations underlying MEN syndromes has not identified a genetic alteration that can be implicated in the development of NETs in both pancreas and ileum. Our series indicates the rare occurrence of NETs in both the pancreas and ileum and emphasizes the importance of using the correct biomarkers to distinguish metastasis from primary neoplasms at the different sites. The rare occurrence of primary ileal and pancreatic NETs may represent a novel MEN syndrome with as yet unknown germline predisposition.

多发性内分泌肿瘤是多发性内分泌肿瘤综合征(MEN)1、2、4 和 5 型的特征之一。然而,这些疾病通常不会累及回肠。我们报告了一系列同时累及胰腺和回肠的神经内分泌肿瘤(NET)患者。我们检索了作者在2019年至2023年期间的实验室信息系统和个人就诊记录,以寻找同时累及胰腺和回肠的神经内分泌肿瘤(NET)患者。在一系列846名患者中,我们发现了4名胰腺和回肠NET患者,2女2男,年龄在52岁至75岁之间。两名女性患者的回肠原发性EC细胞肿瘤转移至胰腺,其CDX2和5-羟色胺的表达与回肠原发性肿瘤相似。两名男性患者的原发病灶位于两个部位,但免疫特征不同;回肠肿瘤表达CDX2和5-羟色胺,ARX阴性;而胰腺肿瘤表达ARX、胰高血糖素和胰多肽,CDX2和5-羟色胺阴性。在这两名男性患者中,非肿瘤性胰腺的内分泌元件出现了肿瘤前病变,这表明他们具有内分泌肿瘤的种系易感性。在对 MEN 综合征的已知基因改变进行检测后,尚未发现一种基因改变可导致胰腺和回肠均发生 NET。我们的系列研究表明,胰腺和回肠均罕见NET,并强调了使用正确的生物标志物区分不同部位的转移瘤和原发性肿瘤的重要性。原发性回肠和胰腺NET的罕见发生可能代表了一种新的MEN综合征,其种系倾向尚不清楚。
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引用次数: 0
p53 Immunohistochemistry Defines a Subset of Human Papillomavirus-Independent Penile Squamous Cell Carcinomas With Adverse Prognosis. p53 免疫组化确定了具有不良预后的人类乳头状瘤病毒依赖性阴茎鳞状细胞癌的一个亚群。
IF 4.5 1区 医学 Q1 PATHOLOGY Pub Date : 2024-11-01 Epub Date: 2024-07-23 DOI: 10.1097/PAS.0000000000002291
Isabel Trias, Ferran Algaba, Inés de Torres, Adela Saco, Lorena Marimon, Núria Peñuelas, Laia Diez-Ahijado, Lia Sisuashvili, Katarzyna Darecka, Alba Morató, Marta Del Pino, Carla Ferrándiz-Pulido, María José Ribal, Tarek Ajami, Juan Manuel Corral, Josep Maria Gaya, Oscar Reig, Oriol Ordi, Inmaculada Ribera-Cortada, Adriana García-Herrera, Natalia Rakislova

Penile squamous cell carcinoma (PSCC) is classified into 2 prognostically distinct types: human papillomavirus (HPV)-associated and HPV-independent. However, the impact of p53 status on prognosis remains controversial. We correlated HPV and p53 status with the prognosis of a large series of patients with PSCC. p53 was analyzed according to a recently described immunohistochemical (IHC) pattern-based framework that includes 2 normal and 4 abnormal patterns and closely correlates with TP53 mutational status. A total of 122 patients with surgically treated PSCC in 3 hospitals were included. Based on HPV in situ hybridization and p16 and p53 IHC, the tumors were classified into 3 subtypes: HPV-associated, HPV-independent/p53 normal, and HPV-independent/p53 abnormal. All patients were followed up for at least 22 months (median: 56.9 months). Thirty-six tumors (29%) were HPV-associated, 35 (29%) were HPV-independent/p53 normal, and 51 (42%) were HPV-independent/p53 abnormal. Disease-related deaths were observed in 3/36 (8%), 0/35 (0%) and 14/51 (27%) of the patients, respectively ( P < 0.001). A total of 7/14 deaths in the latter group were patients with tumors showing p53 abnormal patterns not recognized in the classic p53 IHC interpretation (basal, null, and cytoplasmic). According to our multivariate analysis, HPV-independent/p53 abnormal tumors and advanced stage were associated with impaired disease-specific survival (hazard ratio = 23.4, 95% CI = 2.7-3095.3; P = 0.001 and 16.3, 95% CI = 1.8-2151.5; P = 0.008, respectively). In conclusion, compared with patients with HPV-associated and HPV-independent/p53-normal PSCC, patients with HPV-independent/p53 abnormal PSCC have worse clinical outcomes. p53 IHC results define 2 prognostic categories in HPV-independent PSCC: HPV-independent/p53-normal tumors as low-risk tumors, whereas HPV-independent/p53-abnormal tumors as aggressive neoplasms.

阴茎鳞状细胞癌(PSCC)分为两种预后不同的类型:人类乳头瘤病毒(HPV)相关型和HPV独立型。然而,p53 状态对预后的影响仍存在争议。我们将 HPV 和 p53 状态与大量 PSCC 患者的预后相关联。p53 根据最近描述的基于免疫组化(IHC)模式的框架进行分析,该框架包括 2 种正常模式和 4 种异常模式,并与 TP53 突变状态密切相关。研究共纳入了3家医院的122名接受过手术治疗的PSCC患者。根据HPV原位杂交、p16和p53 IHC将肿瘤分为3个亚型:HPV相关型、HPV独立型/p53正常型和HPV独立型/p53异常型。所有患者均接受了至少 22 个月(中位数:56.9 个月)的随访。36例肿瘤(29%)与HPV相关,35例(29%)与HPV无关/p53正常,51例(42%)与HPV无关/p53异常。与疾病相关的死亡病例分别为 3/36(8%)、0/35(0%)和 14/51(27%)(P< 0.001)。后一组中共有 7/14 例死亡患者的肿瘤显示出经典 p53 IHC 解释(基底、无效和胞质)无法识别的 p53 异常模式。根据我们的多变量分析,HPV 依赖性/p53 异常肿瘤和晚期分期与疾病特异性生存受损有关(危险比分别为 23.4,95% CI = 2.7-3095.3; P= 0.001 和 16.3,95% CI = 1.8-2151.5; P= 0.008)。总之,与HPV相关型和HPV独立型/p53正常型PSCC患者相比,HPV独立型/p53异常型PSCC患者的临床预后较差。p53 IHC结果定义了HPV独立型PSCC的两种预后类别:HPV独立型/p53正常型肿瘤为低危肿瘤,而HPV独立型/p53异常型肿瘤为侵袭性肿瘤。
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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
Sinonasal Squamous Cell Carcinoma with DEK::AFF2 Rearrangement : An Aggressive Cancer with Bland Morphology. 伴有 DEK::AFF2 重排的鼻窦鳞状细胞癌:形态平淡的侵袭性癌症
IF 4.5 1区 医学 Q1 PATHOLOGY Pub Date : 2024-11-01 Epub Date: 2024-08-12 DOI: 10.1097/PAS.0000000000002281
Aude Trinquet, Marick Laé, Charles Lépine, Marie-Delphine Lanic, Vanessa Lacheretz-Szablewski, Caroline Shaar Chneker, Jean-Michel Goujon, Valentin Favier, Valérie Costes-Martineau

Aims: DEK::AFF2 squamous cell carcinoma is a recently described cancer entity, with 29 cases reported to date. Occasionally, these carcinomas appear deceptively indistinguishable; however, specific morphological and phenotypic features suggest the presence of this rearrangement. However, the prognostic value of this diagnosis remains unclear. We aimed to report a new case series with histological, molecular, and clinical features.

Methods: We collected data from 15 patients and investigated their phenotypes, including the expression profiles of CK7, P63/P40, PDL1, AFF2, and P16, morphological features, and associated prognostic data. We analyzed these data along with the previously published data.

Results: Most of these cases exhibited indicative morphological features, such as exophytic and endophytic papillary growth, nuclear monomorphism, and abundant neutrophil-rich inflammatory infiltrates. Immunohistochemical analysis revealed the expression of AFF2 and squamous cell markers in all the patients. Overexpression of P16 was not detected, whereas CK7 and PDL1 were expressed variably. In our study cohort, a 50% progression or recurrence rate, 25% lymph node metastasis, 17% distant metastasis, and 18% disease-related death were identified, with a short follow-up time.

Conclusion: DEK::AFF2 squamous cell carcinoma incidence is probably underestimated. The low-grade appearance of these tumors sometimes limits their detection. The rates of recurrence and metastasis seem to be high despite an often bland morphology. We propose AFF2 immunohistochemistry as an effective tool, and a diagnostic algorithm has been established to support accurate diagnosis of these tumors.

目的:DEK::AFF2 鳞状细胞癌是最近描述的一种癌症实体,迄今已报道 29 例。有时,这些癌症看起来难以区分;但是,特定的形态和表型特征表明存在这种重排。然而,这种诊断的预后价值仍不明确。我们旨在报告一个具有组织学、分子学和临床特征的新病例系列:我们收集了 15 例患者的数据,研究了他们的表型,包括 CK7、P63/P40、PDL1、AFF2 和 P16 的表达谱、形态学特征以及相关的预后数据。我们将这些数据与之前发表的数据一起进行了分析:这些病例大多表现出指示性形态特征,如外生性和内生性乳头状生长、核单形性和大量富含中性粒细胞的炎性浸润。免疫组化分析显示,所有患者均表达 AFF2 和鳞状细胞标志物。未检测到 P16 的过表达,而 CK7 和 PDL1 的表达则各不相同。在我们的研究队列中,发现了50%的进展或复发率、25%的淋巴结转移、17%的远处转移和18%的疾病相关死亡,且随访时间较短:结论:DEK::AFF2鳞状细胞癌的发病率可能被低估了。结论:DEK::AFF2 鳞状细胞癌的发病率可能被低估了。尽管肿瘤形态平淡,但其复发率和转移率似乎很高。我们建议将 AFF2 免疫组化作为一种有效的工具,并建立了一种诊断算法,以支持对这些肿瘤的准确诊断。
{"title":"Sinonasal Squamous Cell Carcinoma with DEK::AFF2 Rearrangement : An Aggressive Cancer with Bland Morphology.","authors":"Aude Trinquet, Marick Laé, Charles Lépine, Marie-Delphine Lanic, Vanessa Lacheretz-Szablewski, Caroline Shaar Chneker, Jean-Michel Goujon, Valentin Favier, Valérie Costes-Martineau","doi":"10.1097/PAS.0000000000002281","DOIUrl":"10.1097/PAS.0000000000002281","url":null,"abstract":"<p><strong>Aims: </strong>DEK::AFF2 squamous cell carcinoma is a recently described cancer entity, with 29 cases reported to date. Occasionally, these carcinomas appear deceptively indistinguishable; however, specific morphological and phenotypic features suggest the presence of this rearrangement. However, the prognostic value of this diagnosis remains unclear. We aimed to report a new case series with histological, molecular, and clinical features.</p><p><strong>Methods: </strong>We collected data from 15 patients and investigated their phenotypes, including the expression profiles of CK7, P63/P40, PDL1, AFF2, and P16, morphological features, and associated prognostic data. We analyzed these data along with the previously published data.</p><p><strong>Results: </strong>Most of these cases exhibited indicative morphological features, such as exophytic and endophytic papillary growth, nuclear monomorphism, and abundant neutrophil-rich inflammatory infiltrates. Immunohistochemical analysis revealed the expression of AFF2 and squamous cell markers in all the patients. Overexpression of P16 was not detected, whereas CK7 and PDL1 were expressed variably. In our study cohort, a 50% progression or recurrence rate, 25% lymph node metastasis, 17% distant metastasis, and 18% disease-related death were identified, with a short follow-up time.</p><p><strong>Conclusion: </strong>DEK::AFF2 squamous cell carcinoma incidence is probably underestimated. The low-grade appearance of these tumors sometimes limits their detection. The rates of recurrence and metastasis seem to be high despite an often bland morphology. We propose AFF2 immunohistochemistry as an effective tool, and a diagnostic algorithm has been established to support accurate diagnosis of these tumors.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141915915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
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
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
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American Journal of Surgical Pathology
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