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1.
Exp Mol Pathol ; 116: 104517, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32791064

RESUMO

Primary liposarcoma of thymic stroma is an exceptionally rare tumor. Histological findings are often definitive for diagnosis, however due to the variability of nuclear atypia and the overlapping with other adipocytic tumors, ancillary techniques are helpful as confirmatory tools. Currently, Fluorescent in situ hybridization for MDM2 is the gold standard for diagnosis of well-differentiated and dedifferentiated liposarcomas, however a panel of immunohistochemical stainings, including MDM2, CDK4 and p16 is available as alternative method, helping to distinguish liposarcoma from its benign counterpart lipoma, especially in borderline cases. We describe the case of a young female diagnosed with a well-differentiated lipomatous tumor primary of thymic stroma with near cut-off result for MDM2-FISHand positive immunohistochemical staining for the panel described above. We discuss the challenges in the diagnosis of this rare entity andpresent an updated literature review.


Assuntos
Lipossarcoma/diagnóstico , Proteínas Proto-Oncogênicas c-mdm2/genética , Neoplasias do Timo/diagnóstico , Quinase 4 Dependente de Ciclina/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Feminino , Humanos , Hibridização in Situ Fluorescente , Lipossarcoma/genética , Lipossarcoma/patologia , Masculino , Pessoa de Meia-Idade , Células Estromais/patologia , Neoplasias do Timo/genética , Neoplasias do Timo/patologia
2.
Front Immunol ; 15: 1258369, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38933266

RESUMO

Autoantigen-specific immunotherapy using peptides offers a more targeted approach to treat autoimmune diseases, but clinical implementation has been challenging. We previously showed that multivalent delivery of peptides as soluble antigen arrays (SAgAs) efficiently protects against spontaneous autoimmune diabetes in the non-obese diabetic (NOD) mouse model. Here, we compared the efficacy, safety, and mechanisms of action of SAgAs versus free peptides. SAgAs, but not their corresponding free peptides at equivalent doses, efficiently prevented the development of diabetes. SAgAs increased the frequency of regulatory T cells among peptide-specific T cells or induce their anergy/exhaustion or deletion, depending on the type of SAgA used (hydrolysable (hSAgA) and non-hydrolysable 'click' SAgA (cSAgA)) and duration of treatment, whereas their corresponding free peptides induced a more effector phenotype following delayed clonal expansion. Over time, the peptides induced an IgE-independent anaphylactic reaction, the incidence of which was significantly delayed when peptides were in SAgA form rather than in free form. Moreover, the N-terminal modification of peptides with aminooxy or alkyne linkers, which was needed for grafting onto hyaluronic acid to make hSAgA or cSAgA variants, respectively, influenced their stimulatory potency and safety, with alkyne-functionalized peptides being more potent and less anaphylactogenic than aminooxy-functionalized peptides. Immunologic anaphylaxis occurred in NOD mice in a dose-dependent manner but not in C57BL/6 or BALB/c mice; however, its incidence did not correlate with the level of anti-peptide antibodies. We provide evidence that SAgAs significantly improve the efficacy of peptides to induce tolerance and prevent autoimmune diabetes while at the same time reducing their anaphylactogenic potential.


Assuntos
Diabetes Mellitus Tipo 1 , Tolerância Imunológica , Camundongos Endogâmicos NOD , Peptídeos , Animais , Camundongos , Diabetes Mellitus Tipo 1/imunologia , Peptídeos/imunologia , Peptídeos/administração & dosagem , Feminino , Autoantígenos/imunologia , Linfócitos T Reguladores/imunologia , Imunoterapia/métodos , Anafilaxia/prevenção & controle , Anafilaxia/imunologia , Dessensibilização Imunológica/métodos , Dessensibilização Imunológica/efeitos adversos
3.
Diagn Cytopathol ; 49(6): 691-699, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33600080

RESUMO

BACKGROUND: The Paris system (TPS) for Reporting Urinary Cytology provides a standardized reporting system whose main focus is the diagnosis of high-grade urothelial carcinoma (HGUC). We conducted a study to see the impact of The Paris System on our cytologic diagnoses with associated histology. MATERIALS AND METHODS: We reviewed our pathology database regarding urinary specimens in the year before implementation of The Paris System and the year after. We gathered the data regarding cytologic diagnosis and concurrent/subsequent histology. RESULTS: Over a 1-year period from 2016-2017, 486 urine cytology specimens were identified before implementation of The Paris System and diagnosed as follows: 83% benign/negative, 10% atypical, 2% suspicious, 5% HGUC, 0.2% low grade urothelial neoplasm (LGUN), and 0.2% unsatisfactory. Over a next 1-year period from 2017 to 2018, 602 specimens used TPS and diagnosed as follows: 85% negative for HGUC, 6% atypical, 3% suspicious, 4% HGUC, 0.17% LGUN, and 2% unsatisfactory. Although, not listed as a standardized category in The Paris System, our institution used "Negative for high-grade, cannot rule out low-grade urothelial neoplasm (NHL)" as a subcategory of Negative for HGUC. 4% of the cases fell into this category. Focusing on the Atypical category before TPS, histology was available in 15/49 (31%) cases. Of these, 40% had HGUC. Regarding the Atypical category after TPS, histology was available in 21/36 (58%) cases. Of these, 52% were HGUC. For the NHL category, concurrent histology was available in 13/26 (50%) cases. Of these, 67% were low grade urothelial neoplasms. CONCLUSION: Our study showed that TPS lowered the rate of Atypical from 10% to 6%. After the implementation of TPS, Atypical corresponded to a higher rate of high-grade urothelial carcinoma. Also, the NHL subcategory had a high positive predictive value for diagnosing low grade urothelial neoplasms.


Assuntos
Carcinoma de Células de Transição/diagnóstico , Citodiagnóstico/métodos , Citodiagnóstico/normas , Neoplasias da Bexiga Urinária/diagnóstico , Urina/citologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
4.
Case Rep Pathol ; 2020: 8875547, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33489398

RESUMO

Plasmablastic lymphoma (PBL) is an aggressive high-grade B cell lymphoma, considered a variant of diffuse large B cell lymphoma with approximately 75% mortality within 6-7 months. We describe an unusual case of PBL arising as a maxillary mass in an HIV-negative, nontransplanted 78-year-old female. Histologic examination revealed a diffuse infiltrate of anaplastic appearing cells exhibiting plasmablastic morphology with an adjacent contiguous infiltrate of mature appearing plasma cells. The PBL and mature plasma cell components both demonstrated an immunophenotype of CD20(-), CD38(+), and CD138(+). The two populations differed by the PBL featuring a high proliferation rate by Ki-67 (~95%) with coexpression of both c-MYC and EBV, while the mature plasma cell component featured a low proliferation rate by Ki-67 (~5%) without coexpression of c-MYC or EBV. Kappa/lambda staining demonstrated lambda light chain restriction involving the PBL, while the mature plasma cell infiltrate revealed kappa light chain restriction. Our findings describe the rare association of PBL with a synchronous distinct population of mature plasma cells exhibiting opposite light chain restriction.

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