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2.
Front Immunol ; 14: 1188818, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37342332

RESUMO

Background: CART therapy has produced a paradigm shift in the treatment of relapsing FL patients. Strategies to optimize disease surveillance after these therapies are increasingly necessary. This study explores the potential value of ctDNA monitoring with an innovative signature of personalized trackable mutations. Method: Eleven FL patients treated with anti-CD19 CAR T-cell therapy were included. One did not respond and was excluded. Genomic profiling was performed before starting lymphodepleting chemotherapy to identify somatic mutations suitable for LiqBio-MRD monitoring. The dynamics of the baseline mutations (4.5 per patient) were further analyzed on 59 cfDNA follow-up samples. PET/CT examinations were performed on days +90, +180, +365, and every six months until disease progression or death. Results: After a median follow-up of 36 months, all patients achieved a CR as the best response. Two patients progressed. The most frequently mutated genes were CREBBP, KMT2D and EP300. Simultaneous analysis of ctDNA and PET/CT was available for 18 time-points. When PET/CT was positive, two out of four ctDNA samples were LiqBio-MRD negative. These two negative samples corresponded to women with a unique mesenteric mass in two evaluations and never relapsed. Meanwhile, 14 PET/CT negative images were mutation-free based on our LiqBio-MRD analysis (100%). None of the patients had a negative LiqBio-MRD test by day +7. Interestingly, all durably responding patients had undetectable ctDNA at or around three months after infusion. Two patients presented discordant results by PET/CT and ctDNA levels. No progression was confirmed in these cases. All the progressing patients were LiqBio-MRD positive before progression. Conclusion: This is a proof-of-principle for using ctDNA to monitor response to CAR T-cell therapy in FL. Our results confirm that a non-invasive liquid biopsy MRD analysis may correlate with response and could be used to monitor response. Harmonized definitions of ctDNA molecular response and pinpointing the optimal timing for assessing ctDNA responses are necessary for this setting. If using ctDNA analysis, we suggest restricting follow-up PET/CT in CR patients to a clinical suspicion of relapse, to avoid false-positive results.


Assuntos
DNA Tumoral Circulante , Linfoma Folicular , Receptores de Antígenos Quiméricos , Humanos , Feminino , DNA Tumoral Circulante/genética , Receptores de Antígenos Quiméricos/genética , Imunoterapia Adotiva , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Recidiva Local de Neoplasia , Terapia Baseada em Transplante de Células e Tecidos
3.
Int J Gynecol Pathol ; 42(2): 147-150, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35551153

RESUMO

COL1A1-PDGFB gene fusion uterine sarcoma is a recently described entity which shows some overlapping features with dermatofibrosarcoma protuberans. To date, only 4 cases have been reported in the literature. Due to its rarity, succinct clinicopathologic characteristics are yet to be established. We report a fifth case initially mistaken as a uterine fibroid which histologically proved to be a CD34 + high-grade spindle cell proliferation which on fluorescence in situ hybridization analysis displayed COL1A1-PDGFB gene rearrangement. With this case description we hope to raise awareness and aid in the characterization of this emerging entity.


Assuntos
Dermatofibrossarcoma , Neoplasias Cutâneas , Neoplasias de Tecidos Moles , Humanos , Dermatofibrossarcoma/genética , Hibridização in Situ Fluorescente , Proteínas de Fusão Oncogênica/genética , Proteínas Proto-Oncogênicas c-sis/genética , Neoplasias Cutâneas/patologia
5.
Am J Dermatopathol ; 42(5): 356-359, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31725482

RESUMO

Langerhans cell histiocytosis (LCH) is a rare proliferative disorder, more frequent in children, characterized by an abnormal accumulation of Langerhans cells admixed with eosinophils, lymphocytes, neutrophils, and macrophages. The clinical presentation is variable and depends on whether a single or multiple organs are affected. Skin lesions are common in LCH (40% of cases) and represent a frequent form of presentation (in up to 80% of cases). Cutaneous manifestations of LCH are highly variable, frequently presenting as crusted papules or scaly seborrheic-like lesions localized in the scalp. We report the first case of a localized acral sclerosing LCH, a new form of LCH. This case highlights the broad and surprising form of presentation of LCH which may be overlooked and can significantly delay its diagnosis. The development of systemic disease may occur months to years after the initial skin presentation. Prompt diagnosis and treatment may prevent progression to systemic disease, as documented in some cases.


Assuntos
Histiocitose de Células de Langerhans/patologia , Dermatopatias/patologia , Adulto , Dedos/patologia , Humanos , Masculino , Esclerose/patologia
6.
J Breast Cancer ; 22(4): 661-666, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31897340

RESUMO

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis belong to a severe dermatopathic spectrum that includes frequently fatal mucocutaneous manifestations consisting of whole epidermal necrosis and sloughing with bullous transformation, blistering, and further skin detachment. Notably, cancer patients are at higher risk of developing SJS than the general population as a consequence of both the nature of neoplastic disease and frequent exposure to anticancer drugs. Ribociclib is a newly approved cycline-dependent kinase inhibitor that has been recently associated with a single case of SJS. We hereby present a case of ribociclib-related SJS. Early detection of threatening skin lesions is crucial to permit the immediate discontinuation of ribociclib given the predictable and unacceptable risk level. In cases of established SJS, early aggressive support should be initiated, ribociclib should be abruptly discontinued, and specific treatment based on actual evidence should be started.

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