t-cell lymphoma

T 细胞淋巴瘤
  • 文章类型: Journal Article
    在大多数情况下,已知犬胃肠道淋巴瘤是T细胞起源的,但是分子生物学的畸变尚未得到澄清。在人类肠道T细胞淋巴瘤中,经常观察到与Janus激酶/信号转导子和转录激活因子(JAK-STAT)途径相关的基因突变。在这项研究中,本研究在31只患有大细胞胃肠道淋巴瘤(LCGIL)的犬中,重点研究了与JAK-STAT通路相关的基因,对这些基因突变进行了研究.下一代测序分析,以检查STAT3,STAT5B,和整个外显子区域的JAK1基因揭示了两只狗的STAT3基因和一只狗的JAK1基因的突变。总之,在大多数犬类病例中,本研究无法提示JAK-STAT通路基因突变与LCGIL的相关性.
    Canine gastrointestinal lymphoma is known to be of T-cell origin in most cases, but the molecular biological aberrations have not been clarified. In human intestinal T-cell lymphoma, the mutations in the genes associated with Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathway have been frequently observed. In this study, the gene mutations were investigated in 31 dogs with large cell gastrointestinal lymphoma (LCGIL) by focusing on the genes involved in JAK-STAT pathway. Next-generation sequencing analysis to examine the mutations in STAT3, STAT5B, and JAK1 genes throughout the exon regions revealed the mutations in STAT3 gene in two dogs and JAK1 gene in one dog. In conclusion, this study could not indicate the associations of gene mutations in JAK-STAT pathway with LCGIL in most canine cases.
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  • 文章类型: Journal Article
    噬血细胞性淋巴组织细胞增多症(HLH)与恶性肿瘤(M-HLH)相关已被描述了数十年。虽然它的机制是未知的,M-HLH预后不良,总生存率从10%到30%不等。成熟T细胞淋巴瘤,弥漫性大B细胞淋巴瘤,和霍奇金淋巴瘤,有或没有病毒共同触发因素,如爱泼斯坦-巴尔病毒,是最常见的底层实体之一。大多数M-HLH病例发生在恶性肿瘤时,但它们也可能在治疗期间由于化疗引起的免疫损害而发生(HLH在免疫损害的情况下,IC-HLH)和(通常)对感染或免疫激活疗法后的无序反应(Rx-HLH,也被称为细胞因子释放综合征,CRS)。IC-HLH通常发生在真菌诊断后数月,细菌,或者病毒感染,尽管它可能在没有明显触发的情况下发生。Rx-HLH可以与检查点封锁相关联,嵌合抗原受体T细胞疗法,或双特异性T细胞接合疗法。直到最近,从家族性HLH(F-HLH)推断M-HLH诊断和治疗策略,尽管优化的诊断和治疗策略正在出现。
    Hemophagocytic lymphohistiocytosis (HLH) has been described for decades in association with malignancies (M-HLH). While its mechanism is unknown, M-HLH has a poor prognosis, ranging from 10% to 30% overall survival. Mature T-cell lymphomas, diffuse large B-cell lymphoma, and Hodgkin lymphoma, with or without viral co-triggers such as Epstein-Barr virus, are among the most frequent underlying entities. Most M-HLH cases occur at the presentation of malignancy, but they may also occur during therapy as a result of immune compromise from chemotherapy (HLH in the context of immune compromise, IC-HLH) and (typically) disordered response to infection or after immune-activating therapies (Rx-HLH, also known as cytokine release syndrome, CRS). IC-HLH typically occurs months after diagnosis in the context of fungal, bacterial, or viral infection, though it may occur without an apparent trigger. Rx-HLH can be associated with checkpoint blockade, chimeric antigen receptor T-cell therapy, or bispecific T-cell engaging therapy. Until recently, M-HLH diagnosis and treatment strategies were extrapolated from familial HLH (F-HLH), though optimized diagnostic and therapeutic treatment strategies are emerging.
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  • 文章类型: Case Reports
    背景:胃肠道是众所周知的淋巴瘤的结外部位。B细胞淋巴瘤是最常见的类型,而T细胞淋巴瘤并不常见。原发性胃肠道淋巴瘤主要发生在胃和小肠,结肠的受累频率较低,尤其是女性。
    方法:我院收治一名45岁女性进行体检。胃肠镜检查显示横结肠可见有蒂息肉,进行内镜黏膜下剥离术(ESD).病理提示T淋巴细胞高活性增殖伴不典型增生。
    结论:一名中年女性患者经内镜检查发现结肠T细胞淋巴瘤。通过ESD成功切除病变,手术切缘为阴性。提高对结肠T细胞淋巴瘤的认识并选择合适的治疗方法至关重要。
    BACKGROUND: The gastrointestinal tract is a well-known extranodal site of lymphoma. B-cell lymphoma is the most common type, while T-cell lymphoma is uncommon. Primary gastrointestinal lymphoma mainly occurs in the stomach and small intestine, and the colon is less frequently involved, especially in females.
    METHODS: A 45-year-old woman was admitted to our hospital for physical examination. Gastroenteroscopy revealed a visible pedunculated polyp in the transverse colon, for which endoscopic submucosal dissection (ESD) was performed. Pathology suggested highly active proliferation of T lymphocytes with atypical hyperplasia.
    CONCLUSIONS: A middle-aged female patient was found to have colonic T-cell lymphoma by endoscopy. The lesion was successfully removed by ESD, and the surgical margin was negative. It is essential to raise awareness of colonic T-cell lymphoma and choose the appropriate treatment.
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  • 文章类型: Journal Article
    FDA关于CAR-T疗法后T细胞淋巴瘤风险的警报引起了全球关注,然而,目前尚缺乏CAR-T治疗后第二原发恶性肿瘤(SPM)的综合资料.
    我们从FAERS和VigiBase数据库(2017-2023)中提取了具有明确定义的SPM的血液恶性肿瘤(HM)患者的不良事件报告。使用报告比值比(ROR)和调整后的ROR进行不成比例分析,以评估SPM和CAR-T治疗之间的关联。发病时间分析探讨了影响SPM表现的因素。
    CAR-T细胞治疗后的SPM包括HMs和实体瘤。T细胞淋巴瘤和骨髓增生异常综合征在总体和亚组分析中被一致地鉴定为阳性信号。血液学SPM显示,CAR-T治疗后发病较早,年发病率增加,而实体瘤表现为延迟表现。CAR-T接受者的SPM明显比非接受者早。此外,年龄特异性特征揭示了儿科早期的SPM表现,青春期,与CAR-T治疗后的老年人群相比,年轻人群。
    当前的SPM概况强调了对所有CAR-T接受者进行长期安全监测的必要性,因为观察到SPM的逐年增加。在不同年龄段进行长期SPM筛查可能会增强早期发现和干预策略,在CAR-T受者的随访中最终改善患者预后.
    这项工作得到了广东省自然科学基金(2018A030313846和2021A1515012593)的资助,广东省科技规划项目(2019A030317020),国家自然科学基金(81802257,81871859,81772457,82172750,82172811,82260546),广东省基础与应用基础研究基金会(粤广联合基金)(2022A1515111212),广州市科学技术计划(2023A04J1257)。
    UNASSIGNED: The FDA\'s alerts regarding the T-cell lymphoma risk post CAR-T therapy has garnered global attention, yet a comprehensive profile of second primary malignancies (SPMs) following CAR-T treatment is lacking.
    UNASSIGNED: We extracted adverse event reports of hematological malignancies (HMs) patients with clearly definable SPMs from the FAERS and VigiBase databases (2017-2023). Disproportionality analysis using reporting odds ratio (ROR) and adjusted ROR was performed to assess associations between SPMs and CAR-T therapy. Time-to-onset analysis explored factors affecting SPM manifestation.
    UNASSIGNED: SPMs post CAR T-cell therapy include HMs and solid tumors. T-cell lymphoma and myelodysplastic syndromes were consistently identified as positive signals across the overall and subgroup analyses. Hematological SPMs showed earlier onset with increasing annual incidence post CAR-T therapy, whereas solid tumors exhibit delayed manifestation. SPMs in CAR-T recipients had significantly earlier onset than non-recipients. Furthermore, age-specific characteristics reveal earlier SPM manifestations in pediatric, adolescent, and young adult populations compared to older populations post CAR-T therapy.
    UNASSIGNED: The current SPM profile highlights the necessity of long-term safety monitoring for all CAR-T recipients given the observed yearly increase of SPMs. Customizing long-term SPM screening across different age groups may enhance early detection and intervention strategies, ultimately improving patient outcomes in the follow-up of CAR-T recipients.
    UNASSIGNED: This work was supported by grants from the Natural Science Foundation of Guangdong Province (2018A030313846 and 2021A1515012593), the Science and Technology Planning Project of Guangdong Province (2019A030317020), the National Natural Science Foundation of China (81802257, 81871859, 81772457, 82172750, 82172811, and 82260546), the Guangdong Basic and Applied Basic Research Foundation (Guangdong-Guangzhou Joint Funds) (2022A1515111212), and the Science and Technology Program of Guangzhou (2023A04J1257).
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  • 文章类型: Journal Article
    背景:Nyctanthesarbor-tristis的花(L.)治愈口腔溃疡。它的酊剂促进胃分泌物,口服时改善肺部排痰。传统上,它被用来治疗sc疮和其他皮肤问题。NAT的叶子(L.)植物在阿育吠陀医学中用于治疗坐骨神经痛,慢性发热,风湿病,内部蠕虫感染,作为泻药,发汗,和利尿剂.用于治疗蛇咬伤和支气管炎的树皮。除了传统用途,从药理学上讲,这种植物具有有效的抗疟药,抗关节炎,抗癌和抗糖尿病活性。然而,NAT的机制抗增殖潜力(L.)花作为抗癌疗法尚未被探索。
    目的:当前的研究基于广泛的科学文献,这些文献强调了NAT的营养和治疗益处(L.).进行了本研究以确定NAT的治疗效果(L.)针对乳腺癌细胞和T细胞淋巴瘤。
    方法:NAT的乙酸乙酯提取物(L.)进行了针对乳腺癌细胞的测试,以评估抗癌潜力。为了评估细胞凋亡,ROS水平和线粒体动力学,采用荧光显微镜和流式细胞术。此外,还进行了细胞周期分析和蛋白质印迹。此外,在携带T细胞淋巴瘤的BALB/c小鼠模型中研究了花提取物的体内抗肿瘤功效。
    结果:我们目前的研究表明NAT(L.)在IC50为320μg/ml时有效地对乳腺癌细胞发挥抗癌活性,而对IC50超过480μg/ml的正常细胞的影响较小。荧光成像显示NAT(L.)处理引起凋亡细胞死亡的浓度依赖性上升,线粒体动力学改变,随后通过流式细胞术证实。Further,流式细胞仪分析描绘了乙酸乙酯花提取物暴露促进细胞停滞在S期的细胞周期。凋亡蛋白如Bax的差异表达,Bcl-2,裂解的PARP-1,裂解的caspase3,细胞色素-c,p53和VEGFA受NAT的影响(L.)治疗。体内抗肿瘤活性研究描述了NAT(L.)治疗可显着增加T细胞淋巴瘤小鼠的寿命,同时减少肿瘤负荷和腹部大小的生长模式,而不会引起明显的其他明显副作用,如组织病理学研究所证明的。
    结论:我们目前的发现揭示了NAT(L.)乙酸乙酯花提取物可能诱导线粒体途径凋亡,促进细胞周期停滞,减少小鼠的肿瘤负荷,增强生存能力,可能是对抗三阴性乳腺癌和淋巴瘤的有希望的药物。
    BACKGROUND: The flowers of Nyctanthes arbor-tristis (L.) heals mouth ulcers. Its tinctures promote gastric secretions, and improve lung expectoration when taken orally. It has traditionally been used to treats scabies and other skin problems. The leaves of NAT(L.) plant are used in Ayurvedic medicine to treat sciatica, chronic fever, rheumatism, internal worm infections, and as a laxative, diaphoretic, and diuretic. The bark used in treatment of snakebite and bronchitis. In addition to traditional uses, pharmacologically this plant has potent antimalarial, antiarthritic, anticancer and antidiabetic activity. However, the mechanistic antiproliferative potentials of NAT(L.) flower as anticancer therapeutics has not yet been explored.
    OBJECTIVE: The current study is based on a broad range of scientific literature that highlights the nutritional and therapeutic benefits of NAT (L.). Present investigation was carried out to determine the therapeutic efficacy of NAT (L.) against breast adenocarcinoma cells and T-cell lymphoma.
    METHODS: The ethyl-acetate extract of NAT(L.) was tested against breast cancer cells to assess the anticancer potential. To evaluate apoptosis, intracellular ROS levels and mitochondrial dynamics, fluorescence microscopy and flow cytometry were employed. Additionally, cell cycle analysis and western blotting were also performed. Furthermore, in vivo antitumor efficacy of flower extracts was investigated in T-cell lymphoma-bearing BALB/c mice model.
    RESULTS: Our present study revealed that NAT (L.) exert anticancer activity against breast cancer cells effectively at IC50 320 μg/ml while having less impact on normal cells with IC50 more than 480 μg/ml. Fluorescence imaging showed that NAT (L.) treatment elicits a concentration-dependent rise in the occurrence of apoptotic cell deaths with altered mitochondrial dynamics and was subsequently confirmed by flow cytometry. Further, flow cytometric analysis delineates ethyl acetate flower extract exposure promotes arrest of cells in S phase of the cell cycle. The differential expression of apoptotic proteins such as Bax, Bcl-2, cleaved PARP-1, cleaved caspase 3, Cytochrome-c, p53 and VEGF A were influenced by NAT (L.) treatment. The in vivo antitumor activity study delineates that NAT(L.) therapy significantly increased the life span of T-cell lymphoma bearing mice while reducing tumor load and belly size growth pattern without causing significant other distinct side effects as evident by histopathological studies.
    CONCLUSIONS: Our current findings unveil that NAT(L.) ethyl acetate flower extract potentially induces mitochondrial pathway of apoptosis, promote cell cycle arrest, reduces tumor load of mice, enhances survivability and could be a promising agent against the triple negative breast cancer and lymphoma.
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  • 文章类型: Journal Article
    Mogamulizumab是一种抗C-C趋化因子受体4抗体,越来越多地用于治疗T细胞恶性肿瘤,例如皮肤T细胞淋巴瘤,成人T细胞白血病淋巴瘤,和外周T细胞淋巴瘤。因为CCR4在恶性T细胞和调节性T细胞(Tregs)上都表达,mogamulizumab可能与免疫相关不良事件(irAEs)增加相关.虽然有大量关于莫加穆利珠单抗相关皮疹(MAR)和移植物抗宿主病(GVHD)的文献,其他报告的irAE尚未整理成单一的审查。
    本叙述性综述涵盖了T细胞淋巴瘤患者与mogamulizumab相关的irAE,专注于MAR和GVHD以外的事件。我们搜索了PubMed和谷歌学者的病例报告,案例系列,图表评论,和临床试验从开始到2024年3月发表。确定的事件包括脱发,白癜风,关节炎,牛皮癣,心肌炎,肌炎/多发性肌炎,肝炎,和其他人。
    Mogamulizumab通过Treg耗竭增强宿主免疫反应的能力增加了其功效,但对多个器官系统的自身免疫具有广泛的影响,类似于免疫检查点抑制剂治疗。irAE的发生可能与改善的总体临床反应有关,尽管需要长期随访研究.
    UNASSIGNED: Mogamulizumab is an anti-C-C chemokine receptor 4 antibody that is increasingly being used to treat T-cell malignancies such as cutaneous T-cell lymphoma, adult T-cell leukemia-lymphoma, and peripheral T-cell lymphoma. Because CCR4 is expressed on both malignant T-cells and regulatory T-cells (Tregs), mogamulizumab can be associated with increased immune-related adverse events (irAEs). While there is abundant literature on mogamulizumab-associated rash (MAR) and graft-versus-host disease (GVHD), other reported irAEs have not been collated into a single review.
    UNASSIGNED: This narrative review covers irAEs associated with mogamulizumab in patients with T-cell lymphomas, focusing on events other than MAR and GVHD. We searched PubMed and Google Scholar for case reports, case series, chart reviews, and clinical trials published from inception to March 2024. Identified events include alopecia, vitiligo, arthritis, psoriasis, myocarditis, myositis/polymyositis, hepatitis, and others.
    UNASSIGNED: Mogamulizumab\'s ability to augment the host immune response through Treg depletion adds to its efficacy but has wide-ranging implications for autoimmunity across multiple organ systems, similar to immune checkpoint inhibitor therapy. Occurrence of irAEs may be associated with improved overall clinical response, although long-term follow-up studies are needed.
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  • 文章类型: Case Reports
    一名患有月经过多的51岁女性被发现患有宫颈息肉。息肉切除术和子宫内膜刮治显示不典型的淋巴浸润。进行了子宫切除术,显示广泛的子宫肌层浸润,细胞学平淡的CD3阳性αβT细胞,具有非活化的细胞毒性表型和低增殖率。PCR显示克隆TCR-β基因重排。淋巴结未受累。PET-CT阴性。诊断为CD8阳性T细胞淋巴增生性疾病(T-LPD)。6个月时,患者无症状,PET-CT重复检查阴性.淋巴样肿瘤分类的最新进展是对惰性结外T-LPDs的认识,包括胃肠道(T细胞和NK细胞类型)和皮肤(小/中CD4阳性和肢CD8阳性)。然而,子宫的T-LPD很少见。已经报道了两个子宫的惰性T-LPD,都显示CD8阳性,非活化细胞毒性表型,低增殖率,和克隆TCR重排。既未发展为全身性疾病也未复发。惰性T-LPDs的病因及其与明显T细胞淋巴瘤的关系仍然知之甚少。子宫的T-LPD可能来自建立长期的效应记忆T细胞,在先前怀孕期间暴露于胎儿绒毛外滋养层细胞同种异体抗原后,组织免疫记忆。我们的患者和先前报告的2人都没有当前怀孕或最近已知的感染或毒性暴露。并且触发演变为T-LPD的事件是未知的。在新的和不寻常的结外部位可以遇到惰性T-LPDs;了解其临床病理特征将有助于避免不必要的细胞毒性化疗并增进对这组疾病的了解。
    A 51-year-old female with menorrhagia was found to have a cervical polyp. Polypectomy and endometrial curettage showed an atypical lymphoid infiltrate. Hysterectomy was performed, showing extensive myometrial infiltration by small, cytologically bland CD3-positive αβ T cells with a non-activated cytotoxic phenotype and a low proliferative rate. PCR showed clonal TCR-β gene rearrangement. Lymph nodes were uninvolved. PET-CT was negative. A diagnosis of CD8-positive T-cell lymphoproliferative disorder (T-LPD) was made. At 6 months, the patient was asymptomatic with a negative repeat PET-CT. A critical recent advance in the classification of lymphoid neoplasms is the recognition of indolent extranodal T-LPDs, including those of the gastrointestinal tract (T-cell and NK-cell types) and skin (small/medium CD4-positive and acral CD8-positive). However, T-LPDs of the uterus are rare. Two indolent T-LPDs of the uterus have been reported, both showing a CD8-positive, nonactivated cytotoxic phenotype, low proliferative rate, and clonal TCR rearrangement. Neither developed systemic disease nor recurrence. The etiology of indolent T-LPDs and their relationship to overt T-cell lymphomas remain poorly understood. T-LPDs of the uterus may arise from effector memory T-cells that establish long-term, tissueresident immunologic memory following exposure to fetal extravillous trophoblastic cell alloantigens during a previous pregnancy. Neither our patient nor the 2 previously reported had a current pregnancy or a known recent infection or toxic exposure, and the event(s) triggering evolution into T-LPD are unknown. Indolent T-LPDs can be encountered at new and unusual extranodal sites; knowledge of their clinicopathological features will help avoid unnecessary cytotoxic chemotherapy and improve understanding of this group of disorders.
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  • 文章类型: Case Reports
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  • 文章类型: Journal Article
    乳房植入物插入乳房重建或隆胸是一个发展中的程序,在全球范围内具有很高的需求-截至2022年,它是美国第二大最常见的整形手术。乳房植入物相关的间变性大细胞淋巴瘤(BIA-ALCL)是T细胞,非霍奇金淋巴瘤,通常是CD30+,ALK-,在大多数患者中,在植入物周围囊的内部方面表现出液体收集,发病超过植入后1年。乳房植入物插入和BIA-ALCL发展之间的平均时间为7-10年。主要风险因素是使用纹理植入物,因为它们容易引发局部炎症和免疫刺激,最终导致淋巴增生。遗传性乳腺癌的遗传易感性也会增加疾病发展的风险。在许多国家,BIA-ALCL似乎被低估了,最初的症状-血清肿可能会被忽视和误诊。尽管它很罕见,应提高患者和医务人员对这种疾病的认识。本文总结了流行病学,病因,鉴别诊断,和治疗-手术和血液学方法。
    Breast implant insertion for breast reconstruction or breast augmentation is a developing procedure, with high demand worldwide-being the second most common plastic surgery in the US as of 2022. Breast-implant-associated anaplastic large cell lymphoma (BIA-ALCL) is T-cell, non-Hodgkin lymphoma, typically CD30+, ALK-, presenting with fluid collection in the inner aspect of the peri-implant capsule in most patients, with the onset exceeding 1-year after implantation. The mean time between breast implant insertion and BIA-ALCL development is 7-10 years. The main risk factor is the use of textured implants because of their susceptibility to triggering local inflammation and immune stimulation finally leading to lymphoproliferation. Genetic predispositions to hereditary breast cancer increase the risk of disease development as well. BIA-ALCL seems to be underestimated in many countries and the initial symptom-seroma might be overlooked and misdiagnosed. Despite its rarity, the awareness of the disease should be improved among patients and medical professionals. This paper summarizes epidemiology, etiopathogenesis, differential diagnosis, and treatment-both surgical and hematological approaches.
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  • 文章类型: Journal Article
    我们报告了一例难以控制的真菌病(MF),牙科医生的作用对于疾病的控制和预后至关重要。一名被诊断为MF的62岁女性患者先前有面部红色斑块和小凸起的肿块的记录,伴随着宫颈和外阴区域的癌变。患者最初接受甲氨蝶呤和局部放疗治疗,但未消退。环磷酰胺化疗,阿霉素,长春新碱,然后开始泼尼松(CHOP方案)。咨询了一家参考医院的牙科团队,以评估腭前部区域的肿胀,已经发展了两个月,吃饭时报告不适。牙科团队在口腔病变与牙齿感染的鉴别诊断中的作用至关重要,第二次瘤形成,甚至是新的疾病表现,除了控制化疗引起的粘膜变化。排除牙齿感染后,牙科团队进行了病变活检以确认诊断。组织病理学和免疫组织化学分析显示T细胞的非典型淋巴样浸润(CD3+/CD4+/CD3-/CD8-),CD25的共表达和CD30细胞的存在,对应于MF的发现。确定CD30+允许使用本妥昔单抗vedotin(BV)联合吉西他滨的新化疗方案。该协议有效地控制了MF,以前的协议未能做到这一点。牙科团队的诊断对于治疗性改变和改善患者的临床状况至关重要,而无需进行侵入性医疗程序。
    We report a case of difficult-to-control mycosis fungoides (MF), where the role of the dental surgeon was crucial for the control and prognosis of the disease. A 62-year-old female patient diagnosed with MF had a previous record of red patches and small raised bumps on the face, along with a cancerous growth in the cervical and vulvar region. The patient was initially treated with methotrexate and local radiotherapy without resolution. Chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone was then started (CHOP protocol). The dental team of a reference hospital was consulted to evaluate swelling in the anterior region of the palate, which had been developing for two months, reporting discomfort when eating. The role of the dentistry team was fundamental in the differential diagnosis of oral lesions with dental infections, second neoplasia, or even a new site of disease manifestation, in addition to controlling mucosal changes resulting from chemotherapy. After ruling out dental infection, the dentistry team performed a lesion biopsy to confirm the diagnosis. The histopathological and immunohistochemical analysis showed atypical lymphoid infiltration of T cells (CD3+/CD4+/CD7-/CD8-), coexpression of CD25, and presence of CD30 cells, corresponding to the finding for MF. Identifying CD30 + allowed for a new chemotherapy protocol with brentuximab vedotin (BV) combined with gemcitabine. This protocol effectively controlled MF, which previous protocols had failed to do. The diagnosis by the dental team was essential for therapeutic change and improvement of the patient\'s clinical condition without the need for invasive medical procedures.
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