breast tumor

乳腺肿瘤
  • 文章类型: Case Reports
    Richter转化(RT)代表先前或同时诊断为慢性淋巴细胞白血病(CLL)的个体中侵入性淋巴瘤的发展,其特征是淋巴结肿大。然而,以结外器官受累为首发症状的病例很少见.没有以乳腺病变为首发症状的RT的报道。非特异性和非典型的临床表现是RT的准确诊断和适当治疗的关键挑战。此病例报告描述了一名老年女性患者,该患者以乳腺病变为首发症状。患者入院时左乳房有无痛肿块。检查发现多发性淋巴结病和异常高的白细胞水平。患者经血液学检查确诊为CLL,骨髓形态学评估,和组织活检.钼靶和B超显示左乳实性占位性病变(BI-RADS5类)。最初,患者拒绝乳腺活检,因此接受了伊布替尼治疗,显示出有限的疗效。受累乳房的穿刺活检表明存在弥漫性大B细胞淋巴瘤。根据辅助和病理检查和病史,最终诊断为RT伴乳腺受累.扎努布替尼联合利妥昔单抗,环磷酰胺,阿霉素,长春新碱,和泼尼松治疗提供初始控制;然而,由于患者病情的波动,治疗策略需要调整。患者的当前状态被标记为稳定,显示出部分缓解的总体成就。患者正在接受后续治疗。我们还对RT进行了全面的文献综述,特别强调它的生物学范式,预后影响,现有的治疗方法,以及治疗方式的新兴方向。
    Richter transformation (RT) represents the development of intrusive lymphoma in individuals previously or concurrently diagnosed with chronic lymphocytic leukemia (CLL) and is characterized by lymph node enlargement. However, cases involving extra-nodal organ involvement as the first symptom are rare. There are no reports of RT with breast lesions as the first symptom. Nonspecific and atypical clinical manifestations represent key challenges in the accurate diagnosis and appropriate treatment of RT. This case report describes an elderly female patient who presented with breast lesions as the first RT symptom. The patient was admitted with a painless mass in the left breast. Examination revealed multiple lymphadenopathies and abnormally high white blood cell levels. The patient was diagnosed with CLL after hematological tests, assessments of bone marrow morphology, and tissue biopsy. Mammography and B-ultrasonography showed solid space-occupying lesions (BI-RADS category 5) in the left breast. Initially, the patient declined a breast biopsy and was therefore prescribed ibrupotinib treatment, which showed limited efficacy. A needle biopsy of the affected breast indicated the presence of diffuse large B-cell lymphoma. Based on auxiliary and pathological examinations and medical history, the final diagnosis was RT with breast involvement. Zanubrutinib with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone treatment provided initial control; however, the treatment strategy required adjustment because of the patient\'s fluctuating condition. The current status of the patient is marked as stable, showing an overall achievement of partial alleviation. The patient is in the process of receiving follow-up treatment. We also performed a comprehensive literature review on RT, with particular emphasis on its biological paradigm, prognosis implications, existing therapeutic approaches, and emerging directions in treatment modalities.
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  • 文章类型: Case Reports
    我们介绍了一名52岁的女性,患有巨大的叶状肿瘤(GPT),它通过显示肉质息肉的皮肤形成。组织学分析显示基质异型,有丝分裂活性,和基质过度生长;然而,肿瘤边界清晰,未观察到恶性异源元素。因此,因为存在一些但不是所有的恶性组织学特征,我们诊断患者患有临界GPT。在叶状肿瘤(PT)的情况下,通过皮肤表现出独特的大体表现为肉质息肉样生长,在随后的过程中需要谨慎,因为即使PT在组织学上被分级为良性,可以发生恶性过程。病理学家应注意,采集部位的采样和PT组织学分级的模糊性可能会影响GPT的最终诊断。对于GPT患者,进行手术并充分保留切除的切缘以控制复发也很重要。
    We present the case of a 52-year-old female with a giant phyllodes tumor (GPT), which was fungating through the skin that showed fleshy polypoid outgrowths. Histological analysis revealed stromal atypia, mitotic activity, and stromal overgrowth; however, the tumor border was well-defined, and malignant heterologous elements were not observed. Therefore, as some but not all malignant histological characteristics were present, we diagnosed the patient with borderline GPT. In cases of phyllodes tumor (PT) with the unique gross findings of fungation through the skin as fleshy polypoid outgrowths, caution is required for the subsequent course because even if the PT is graded as benign histologically, a malignant process can occur. Pathologists should note that the sampling of the collection site and the ambiguity of the histological grading of PT may affect the final diagnosis of GPT. It is also important to perform surgery with adequate preservation of the resected margins to control recurrence for patients with GPT.
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  • 文章类型: Case Reports
    肿瘤内部乳头状结构的存在是乳腺癌的一个独特且不常见的特征,它被称为乳头状癌。与其他形式的乳腺癌相比,这种变异通常在影像学检查中表现为明确的肿块,并且通常与良好的预后相关.我们介绍了一例72岁女性,其乳腺乳头状癌在出现明显的乳腺肿块后被发现。在进行了左乳房简单切除术和辅助治疗后,组织病理学研究证实了肿瘤内部存在乳头状结构.了解乳腺乳头状癌的临床和病理特征对于准确诊断和制定合适的治疗策略至关重要。需要更多的研究来进一步了解治疗这种罕见的乳腺癌亚型的分子特征和最佳实践。
    The presence of papillary structures inside the tumor is a unique and uncommon characteristic of breast cancer, and it is known as papillary carcinoma. In contrast to other forms of breast cancer, this variant usually manifests as a well-defined mass in imaging investigations and is frequently linked to a good prognosis. We present a case of a 72-year-old female with papillary carcinoma of the breast identified after presenting with a palpable breast lump. Following a left simple mastectomy and adjuvant treatment, the presence of papillary structures inside the tumor was verified by a histopathological study. Understanding the clinical and pathological characteristics of breast papillary carcinoma is crucial for precise diagnosis and suitable therapy strategizing. More research is required to further understand the molecular traits and best practices for treating this uncommon subtype of breast cancer.
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  • 文章类型: Journal Article
    背景:最近的几项研究表明,色域-解旋酶-DNA结合域(CHDs)与癌症有关。我们探索了色域-解旋酶-DNA结合域蛋白与乳腺癌(BrCa)之间的关联,并使用各种数据库介绍了潜在的预后标志物。
    方法:我们通过挖掘UALCAN分析了CHD家族在BrCa中的表达及其预后价值,TIMER,和Kaplan-Meier绘图仪数据库。通过TIMER数据库研究了CHD表达和免疫浸润丰度的关联。此外,通过使用MirTarBase在线数据库鉴定与CHD家族相关的微小RNA。
    结果:本研究表明,与正常组织相比,BrCa组织显示CHD3/4/7的mRNA水平升高,但CHD2/5/9的表达降低。有趣的是,我们还发现CHD基因表达与巨噬细胞浸润呈正相关,中性粒细胞,和BrCa中的树突状细胞,除CHD3/5。Kaplan-MeierPlotter分析显示,CHD1/2/3/4/6/8/9的高表达水平与较短的无复发生存期(RFS)显着相关。而CHD1,CHD2,CHD8和CHD9的mRNA表达较高与BrCa患者的总生存期较长显著相关。hsa-miR-615-3p和hsa-let-7b-5p的miRNA被鉴定为与CHD家族更相关。
    结论:一些CHD成员的表达改变与临床癌症预后显著相关,和CHD1/2/8/9可以作为潜在的预后生物标志物,以提高BrCa患者的生存率。然而,为了详细评估所研究的CHD成员,需要进一步的研究,包括实验验证。
    BACKGROUND: Several recent studies suggest that chromodomain-helicase -DNA-binding domains (CHDs) are linked with cancers. We explored the association between chromodomain-Helicase-DNA-binding domain proteins and breast cancer (BrCa) and introduced potential prognostic markers using various databases.
    METHODS: We analyzed the expression of the CHD family and their prognostic value in BrCa by mining UALCAN, TIMER, and Kaplan-Meier plotter databases. The association of CHD expression and immune infiltrating abundance was studied via the TIMER database. In addition, microRNAs related to the CHD family were identified by using the MirTarBase online database.
    RESULTS: The present study indicated that compared to normal tissues, BrCa tissues showed increased mRNA levels of CHD3/4/7 but decreased CHD2/5/9 expression. Interestingly, We also found a positive correlation between CHD gene expression and the infiltration of macrophage, neutrophil, and dendritic cells in BrCa, except CHD3/5. The Kaplan-Meier Plotter analysis suggested that high expression levels of CHD1/2/3/4/6/8/9 were significantly related to shorter relapse-free survival (RFS), while higher mRNA expression of CHD1, CHD2, CHD8, and CHD9 was significantly associated with longer overall survival of BrCa patients. The miRNAs of hsa-miR-615-3p and hsa-let-7b-5p were identified as being more correlated with the CHD family.
    CONCLUSIONS: The altered expression of some CHD members was significantly related to clinical cancer outcomes, and CHD1/2/8/9 could serve as potential prognostic biomarkers to improve the survival of BrCa patients. However, to evaluate the studied CHD members in detail are needed further investigations including experimental validation.
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  • 文章类型: Journal Article
    已开发出一种新的有效且通用的一锅式三组分合成取代的吡咯并[1,2-a]噻吩并[3,2-e]嘧啶衍生物的方法。它基于2-氨基噻吩和2-羟基-4-氧代-2-烯酸的多步骤级联反应,和二异丙基乙胺催化的氰基乙酸衍生物。因此,在温和的反应条件下合成了新的吡咯并[1,2-a]噻吩并[3,2-e]嘧啶衍生物(21个化合物)。通过NMR和元素分析证实了所开发化合物的结构。已经确定了吸电子或给电子取代基对所开发化合物的抗肿瘤活性的影响。21种化合物的体外筛选分析揭示了6种前导候选物(12aa,12dc,12hc,12ic,12lb,和12mb),证明了对B16-F10,4T1和CT26细胞的最显着的抗肿瘤活性。坏死/凋亡实验表明,凋亡是细胞死亡的主要机制。分子对接分析揭示了测试化合物的几个潜在目标,即磷脂酰肌醇5-磷酸4-激酶(PI5P4K2C),原癌基因丝氨酸/苏氨酸蛋白激酶(Pim-1),烟酰胺磷酸核糖基转移酶(NAMPT)和二氢叶酸还原酶(DHFR)。先导化合物(12aa)能有效诱导细胞凋亡,具有高产率(98%)并且需要低成本的起始化学品用于其合成。用携带黑色素瘤的小鼠进行的体内实验证实,12aa化合物在治疗后15d产生了显着的肿瘤抑制作用。特别是,对于50mg/kg,肿瘤体积为〜0.19cm3,而对于未治疗的小鼠,肿瘤重量为〜2.39cm3,对于50mg/kg,肿瘤重量为〜71.6mg,而对于未治疗的小鼠,肿瘤重量为〜452.4mg。因此,我们的结果表明12aa化合物在治疗黑色素瘤方面具有很高的潜力,可推荐用于进一步的临床前研究。
    A new efficient and versatile one-pot three-component synthesis of substituted pyrrolo[1,2-a]thieno[3,2-e]pyrimidine derivatives has been developed. It is based on a multistep cascade reaction from 2-aminothiophenes and 2-hydroxy-4-oxobut-2-enoic acids, and derivatives of cyanoacetic acid catalyzed by diisopropylethylamine. As a result, novel pyrrolo[1,2-a]thieno[3,2-e]pyrimidine derivatives (21 compounds) were synthesized in a mild reaction conditions with a high yield. The structures of the developed compounds were confirmed by NMR and elemental analysis. The influence of electron-withdrawing or electron-donor substituents on the antitumor activity of the developed compounds has been identified. In vitro screening analysis of 21 compounds revealed six lead candidates (12aa, 12dc, 12hc, 12ic, 12lb, and 12mb) that demonstrated the most significant antitumor activity against B16-F10, 4T1 and CT26 cells. Necrosis/apoptosis assay showed that apoptosis was the predominant mechanism of cell death. Molecular docking analysis revealed several potential targets for tested compounds, i.e. phosphatidylinositol 5-phosphate 4-kinase (PI5P4K2C), proto-oncogene serine/threonine-protein kinase (Pim-1), nicotinamide phosphoribosyltransferase (NAMPT) and dihydrofolate reductase (DHFR). The lead compound (12aa) can effectively induce cell apoptosis, possesses a high yield (98 %) and requires low-cost starting chemicals for its synthesis. In vivo experiments with melanoma-bearing mice confirmed that 12aa compound resulted in the significant tumor inhibition on 15 d after the therapy. In particular, tumor volume was ∼0.19 cm3 for 50 mg/kg versus ∼2.39 cm3 in case of untreated mice and tumor weight was ∼71.6 mg for 50 mg/kg versus ∼452.4 mg when considered untreated mice. Thus, our results demonstrated the high potential of the 12aa compound in the treatment of melanoma and can be recommended for further preclinical studies.
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  • 文章类型: Journal Article
    等离子体光热疗法(PPTT)涉及使用纳米粒子和近红外辐射来达到肿瘤内热损伤的50°C以上的温度。PPTT主要用于浅表肿瘤,它治疗更深的地下肿瘤的潜力是微弱的,需要评估这种肿瘤的热损伤。在本文中,对于位于3-9mm深度的浸润性导管癌(IDC)的PPTT,对热损伤程度进行了数值分析。使用合适的组织肿瘤模拟体模验证了所开发的数值模型。嵌入有金纳米棒(GNR)的肿瘤(IDC)经受宽带近红外辐射。各种GNR浓度及其空间分布的影响[即均匀分布,静脉内给药(外周分布)和肿瘤内给药(局部分布)]研究了位于不同深度的表面下肿瘤的热损伤。结果表明,较低的GNR浓度导致更均匀的内部发热,最终导致温度均匀上升。此外,纳米颗粒的外周分布提供了肿瘤内更均匀的空间温度上升。总的来说,结论是PPTT有可能诱导表面下肿瘤的热损伤,在高达9毫米的深度,通过适当选择纳米粒子的分布,基于肿瘤位置的剂量/浓度和照射参数。此外,静脉注射纳米颗粒似乎是较浅肿瘤的好选择,而对于更深的肿瘤,均匀分布是必需的,以达到必要的热损伤。在未来,该算法可以进一步扩展,涉及3D患者特异性肿瘤,并通过基于小鼠模型的实验。
    Plasmonic photothermal therapy (PPTT) involves the use of nanoparticles and near-infrared radiation to attain a temperature above 50 °C within the tumor for its thermal damage. PPTT is largely explored for superficial tumors, and its potential to treat deeper subsurface tumors is dealt feebly, requiring the assessment of thermal damage for such tumors. In this paper, the extent of thermal damage is numerically analyzed for PPTT of invasive ductal carcinoma (IDC) situated at 3-9 mm depths. The developed numerical model is validated with suitable tissue-tumor mimicking phantoms. Tumor (IDC) embedded with gold nanorods (GNRs) is subjected to broadband near-infrared radiation. The effect of various GNRs concentrations and their spatial distributions [viz. uniform distribution, intravenous delivery (peripheral distribution) and intratumoral delivery (localized distribution)] are investigated for thermal damage for subsurface tumors situated at various depths. Results show that lower GNRs concentrations lead to more uniform internal heat generation, eventually resulting in uniform temperature rise. Also, the peripheral distribution of nanoparticles provides a more uniform spatial temperature rise within the tumor. Overall, it is concluded that PPTT has potential to induce thermal damage for subsurface tumors, at depths of upto 9 mm, by proper choice of nanoparticle distribution, dose/concentration and irradiation parameters based on the tumor location. Moreover, intravenous administration of nanoparticles seems a good choice for shallower tumors, while for deeper tumors, uniform distribution is required to attain the necessary thermal damage. In the future, the algorithm may be extended further, involving 3D patient-specific tumors and through mice model-based experiments.
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  • 文章类型: Journal Article
    尽管先前的研究表明,注射造影剂可以改善图像质量,在乳腺癌诊断中,这对T2加权脂肪抑制(T2FS)和弥散加权成像(DWI)序列的具体影响尚不完全清楚.特别是,关于对比剂如何影响信噪比(SNR)的研究不足,对比噪声比(CNR),和这些序列中的表观扩散系数(ADC)值,以及这些变化如何影响良性和恶性乳腺肿瘤的诊断。
    在3T扫描仪上从178名连续患者获得乳腺磁共振图像(MRI)。计算造影剂注射前后T2FS序列上病变的SNR和CNR,并进行比较。使用Kruskal-WallisH检验和配对比较检验比较对比前和后ADC在识别不同肿瘤类型方面的差异。使用受试者工作特征(ROC)曲线评估对比前后ADC值在区分良性和恶性乳腺肿块中的准确性。
    造影剂注射后T2FS序列的SNR和CNR增加,尤其是浸润性癌症和良性肿瘤,增幅显著。对于DWI,造影剂注射后ADC值略有增加或减少,但对比前后的ADC值在识别不同类型的肿瘤方面具有相似的效果。在评估良性和恶性乳腺肿瘤的ROC曲线分析中,对比前后曲线下面积(AUC)结果相似。
    造影剂注射可以提高T2FS序列的SNR和CNR,从而为乳腺病变的诊断提供更高质量的图像。此外,对比剂注射对ADC值识别不同类型病变的能力影响不大,对比剂前后的ADC值能够以几乎相同的准确度区分良恶性肿瘤.
    UNASSIGNED: Although previous studies have shown that the injection of contrast agents can improve image quality, the specific impact of this on T2-weighted fat-suppressed (T2 FS) and diffusion-weighted imaging (DWI) sequences in the diagnosis of breast cancer remains incompletely understood. In particular, there is insufficient research on how contrast agents affect the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and apparent diffusion coefficient (ADC) values within these sequences, and how these changes influence the diagnosis of benign and malignant breast tumors.
    UNASSIGNED: Breast magnetic resonance images (MRI) were obtained from 178 consecutive patients on a 3T scanner. The SNR and CNR of lesions on T2 FS sequence were calculated before and after contrast agent injection and compared. Differences between pre- and post-contrast ADC in identifying different tumor types were compared using the Kruskal-Wallis H-test and the paired comparison test. The accuracy of ADC values between pre- and post-contrast in distinguishing benign and malignant breast masses was assessed using receiver operating characteristic (ROC) curves.
    UNASSIGNED: The SNR and CNR of T2 FS sequence increased after contrast injection, and especially for invasive cancer and benign tumor, the increase was significant. For DWI, there was a slight increase or decrease of ADC values after contrast injection, but the ADC values before and after contrast had a similar effect in identifying different types of tumors. In the ROC curve analysis for assessing benign and malignant breast tumors, the area under the curve (AUC) before and after contrast showed similar results.
    UNASSIGNED: Contrast agent injection can improve the SNR and CNR of T2 FS sequence, thus providing higher quality images for the diagnosis of breast lesions. Furthermore, injection of contrast agent had little effect on the ability of ADC values to identify different types of lesions and both ADC values before and after the contrast agent were able to distinguish between benign and malignant tumors with almost the same accuracy.
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  • 文章类型: Journal Article
    虽然,超级杀手复合蛋白8(SKI8),以前被称为WDR61已被识别并绘制在乳腺肿瘤中,目前对其功能知之甚少。本研究旨在阐明WDR61在乳腺肿瘤发展中的作用及其作为治疗靶点的潜力。这里,我们表明,他莫昔芬诱导的Wdr61基因敲除降低了乳腺肿瘤的风险,导致更小的肿瘤大小和重量,并提高总体生存率。此外,我们发现,WDR61的敲减损害了乳腺肿瘤细胞的增殖,并降低了集落形成能力.进一步的研究表明,WDR61丢失对乳腺肿瘤发展的保护作用是由于基因组不稳定。机理研究表明,WDR61与R环相互作用,WDR61的缺失导致R-loop在乳腺肿瘤细胞中积累,引起DNA损伤并随后抑制细胞增殖。总之,这项研究强调了乳腺肿瘤对WDR61的关键依赖性,WDR61抑制R-loop并抵消肿瘤细胞的内源性DNA损伤.
    Although, superkiller complex protein 8 (SKI8), previously known as WDR61 has been identified and mapped in breast tumor, little is currently known about its function. This study aims to elucidate the role of WDR61 in breast tumor development and its potential as a therapeutic target. Here, we show that tamoxifen-induced knockout of Wdr61 reduces the risk of breast tumors, resulting in smaller tumor size and weight, and improved overall survival. Furthermore, we show that knockdown of WDR61 compromises the proliferation of breast tumor cells with reduced colony-forming capacity. Further investigations demonstrate that the protective effect of WDR61 loss on breast tumor development is due to genomic instability. Mechanistic studies reveal that WDR61 interacts with the R-loop, and loss of WDR61 leads to R-loops accumulation in breast tumor cells, causing DNA damage and subsequent inhibition of cell proliferation. In summary, this study highlights the critical dependence of breast tumors on WDR61, which suppresses R-loop and counteracts endogenous DNA damage in tumor cells.
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  • 文章类型: Case Reports
    叶状肿瘤(PT),占乳腺肿瘤的不到1%,由上皮和基质成分组成。如果遇到恶性异源成分,PT被认为是恶性的。恶性叶状肿瘤(MPT)仅占PT的8%至20%。我们报告一例MPT伴骨肉瘤和软骨肉瘤分化的病例,并复习文献讨论其鉴别诊断和治疗。
    一名59岁的中国妇女来到我们医院,因为她的左乳房有一个明显的肿块,持续了1个月。于2023年1月11日对左乳腺肿块进行术前粗针活检(CNB)。病理诊断为恶性肿瘤,具体类型不清楚。对左乳进行乳房切除术和前哨淋巴结活检。通过碳纳米颗粒和亚甲蓝双重染色鉴定,在3个前哨淋巴结中未发现转移。观察到叶状肿瘤的异源骨肉瘤和软骨肉瘤分化。免疫组织化学:梭形肿瘤细胞ER(-),PR(-),HER-2(-),CK-pan(-),CK7(-),CK8(-),SOX10(-),S100(-),和MDM2(-),CK5/6(-),P63(-),P40(-)均为阴性。CD34:(+),SATB2(+),P53(90%强),CD68(+),Ki-67(LI:约60%)。乳腺内未发现导管原位癌。荧光原位杂交(FISH)表明USP6在福尔马林固定的上呈阴性表达,石蜡包埋(FFPE)组织切片。
    MPT很少见,MPT中的异源分化非常罕见。它可以通过病理诊断为化生性癌,原发性骨肉瘤,或骨化性肌炎被排除。该病例可以帮助临床医生改善该病的预后和治疗。
    UNASSIGNED: Phyllodes tumors (PTs), which account for less than 1% of mammary gland tumors, composed of both epithelial and stromal components. If a malignant heterologous component is encountered, PT is considered malignant. Malignant phyllodes tumors (MPTs) only account for 8% to 20% of PTs. We report a case of MPT with osteosarcoma and chondrosarcoma differentiation and review the literature to discuss the differential diagnosis and therapy.
    UNASSIGNED: A 59-year-old Chinese woman come to our hospital because of a palpable mass she had had for 1 months in the left breast. Preoperative core needle biopsy (CNB) was performed on the left breast mass on January 11, 2023. Pathological diagnosis was malignant tumor, the specific type was not clear. Mastectomy and sentinel lymph node biopsy of the left breast was performed. No metastasis was found in 3 sentinel lymph nodes identified by carbon nanoparticles and methylene blue double staining. Heterologous osteosarcoma and chondrosarcomatous differentiation of phyllodes tumor were observed. Immunohistochemistry: spindle tumor cells ER(-), PR(-), HER-2(-), CK-pan(-), CK7(-), CK8(-), SOX10(-), S100(-), and MDM2(-), CK5/6(-), P63(-), P40(-) were all negative. CD34:(+), SATB2(+), P53(90% strong), CD68 (+), Ki-67(LI: about 60%). No ductal carcinoma in situ was found in the breast. Fluorescence in situ hybridization (FISH) indicated USP6 was negatively expressed on formalin-fixed, paraffin-embedded (FFPE) tissue sections.
    UNASSIGNED: MPTs are rare, and heterologous differentiation in MPTs is exceedingly rare. It could be diagnosed by pathology when metaplastic carcinoma, primary osteosarcoma, or myositis ossificans were excluded. This case could help clinicians to improve the prognosis and treatment of this disease.
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