RESUMEN
Due to the increasing incidence of malignant gliomas, particularly glioblastoma multiforme (GBM), a simple and reliable GBM diagnosis is needed to screen early the death-threaten patients. This study aimed to identify a protein that can be used to discriminate GBM from low-grade astrocytoma and elucidate further that it has a functional role during malignant glioma progressions. To identify proteins that display low or no expression in low-grade astrocytoma but elevated levels in GBM, glycoprotein fibronectin (FN) was particularly examined according to the mining of the Human Protein Atlas. Web-based open megadata minings revealed that FN was mainly mutated in the cBio Cancer Genomic Portal but dominantly overexpressed in the ONCOMINE (a cancer microarray database and integrated data-mining platform) in distinct tumor types. Furthermore, numerous different cancer patients with high FN indeed exhibited a poor prognosis in the PrognoScan mining, indicating that FN involves in tumor malignancy. To investigate further the significance of FN expression in glioma progression, tumor specimens from five malignant gliomas with recurrences that received at least two surgeries were enrolled and examined. The immunohistochemical staining showed that FN expression indeed determined the distinct progressions of malignant gliomas. Furthermore, the expression of vimentin (VIM), a mesenchymal protein that is strongly expressed in malignant cancers, was similar to the FN pattern. Moreover, the level of epithelial-mesenchymal transition (EMT) inducer transforming growth factor-beta (TGF-ß) was almost recapitulated with the FN expression. Together, this study identifies a protein FN that can be used to diagnose GBM from low-grade astrocytoma; moreover, its expression functionally determines the malignant glioma progressions via TGF-ß-induced EMT pathway.
Asunto(s)
Neoplasias Encefálicas/metabolismo , Fibronectinas/biosíntesis , Regulación Neoplásica de la Expresión Génica , Glioblastoma/metabolismo , Proteínas de Neoplasias/biosíntesis , Transducción de Señal , Factor de Crecimiento Transformador beta/metabolismo , Adulto , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/genética , Bases de Datos de Ácidos Nucleicos , Femenino , Fibronectinas/genética , Glioblastoma/diagnóstico , Glioblastoma/diagnóstico por imagen , Glioblastoma/genética , Humanos , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/genética , Pronóstico , Factor de Crecimiento Transformador beta/genéticaRESUMEN
BACKGROUND/PURPOSE: Lymphoid neoplasms are heterogeneous and types of lymphoma vary in different geographic regions. In this study, we aimed at classifying the lymphoid neoplasms at our institution in Taiwan and to compare the relative frequency of various types of lymphoma in different countries. METHODS: We retrospectively searched the files of patients diagnosed with lymphoma at our institution from 2000 to 2015 based on the 2016 Revision of the World Health Organization classification. RESULTS: We identified 1339 patients with lymphoid neoplasms; among them, eight had two distinct types of lymphoid neoplasms. Of the 1347 neoplasms, 6.09% were Hodgkin lymphomas (HLs) and 93.31%, non-HL (NHLs). Among the 1257 NHLs, 82.66% were of B-cell lineage and 17.34% of T-cell lineage. The most common B-cell lymphoma types were diffuse large B-cell lymphoma, follicular lymphoma, and mucosa-associated lymphoid tissue lymphoma. Among T-cell neoplasms, 37% cases were of nodal origin and 63% cases arose in extranodal sites. The most common nodal and extranodal T-cell neoplasms were angioimmunoblastic T-cell lymphoma and extranodal natural killer/T-cell lymphoma, nasal type, respectively. CONCLUSION: We analyzed the largest series of lymphomas to date from Taiwan and concluded that HL was rare and T-cell neoplasms comprised around 17% of all NHLs in Taiwan. The relative frequency of the major lymphoma types is similar in East Asian countries, with only a minor difference, but the overall pattern in the East is quite different from that in the West, with the latter showing a higher frequency of HL and a lower rate of T-cell neoplasms.
Asunto(s)
Linfoma/epidemiología , Humanos , Linfoma/clasificación , Linfoma de Células T/epidemiología , Estudios Retrospectivos , Taiwán/epidemiología , Organización Mundial de la SaludRESUMEN
BACKGROUND/PURPOSE: Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma type. The immunophenotypic and genetic features of DLBCL in Taiwan have not been characterized. METHODS: In this study, we performed immunohistochemical analysis and interphase fluorescence in situ hybridization (FISH) using tissue microarray sections to investigate a cohort of unselected DLBCL cases in a single institution in Taiwan from 1990 to 2010. RESULTS: Of the 153 cases investigated, CD10, bcl-6, and MUM1 were expressed in 16.3%, 71.2%, and 71.9% cases, respectively, with 27.5% (n = 42) of cases being classified as having a germinal center B-cell (GCB) origin by the Hans algorithm. By FISH analysis, 19.6%, 4.6%, 26.1%, and 3.9% cases showed rearrangement at IGH, BCL2, BCL6, and MYC loci, respectively, including three (2.0%) cases of double-hit lymphoma. As compared with the non-GCB tumors, GCB tumors more frequently expressed CD10 (p < 0.001) and bcl-6 (p = 0.001) with less frequent expression of MUM1 (p = 0.007). Moreover, GCB tumors more frequently exhibited rearrangement at the BCL2 (p = 0.024) and MYC (p = 0.038) loci than non-GCB tumors. However, there was no survival difference between these two groups. CONCLUSION: In this first series of DLBCL evaluation from Taiwan, we found that the relative frequency of GCB tumors among DLBCL was low in most East Asian countries. There is a wide range of BCL2 rearrangement rates, higher in the West and lower in East Asia. A larger and/or national study is warranted to better understand the immunophenotypic and molecular features of DLBCL in Taiwan and their respective impact on patient survival.
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Linfocitos B/patología , Genes bcl-2 , Centro Germinal/patología , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Tasa de Supervivencia , Taiwán/epidemiología , Translocación Genética , Adulto JovenAsunto(s)
Virus Linfotrópico T Tipo 1 Humano/aislamiento & purificación , Leucemia-Linfoma de Células T del Adulto , Adulto , Biomarcadores de Tumor/metabolismo , Diagnóstico Diferencial , Virus Linfotrópico T Tipo 1 Humano/inmunología , Humanos , Inmunohistoquímica , Leucemia-Linfoma de Células T del Adulto/diagnóstico , Leucemia-Linfoma de Células T del Adulto/patología , Leucemia-Linfoma de Células T del Adulto/virología , Linfoma Anaplásico de Células Grandes/diagnóstico , Linfoma Anaplásico de Células Grandes/patología , Masculino , Persona de Mediana EdadRESUMEN
Cancer cells can evade immune elimination by activating immunosuppressive signaling pathways in the tumor microenvironment (TME). Targeting immunosuppressive signaling pathways to promote antitumor immunity has become an attractive strategy for cancer therapy. Aurora-A is a well-known oncoprotein that plays a critical role in tumor progression, and its inhibition is considered a promising strategy for treating cancers. However, targeting Aurora-A has not yet got a breakthrough in clinical trials. Recent reports have indicated that inhibition of oncoproteins may reduce antitumor immunity, but the role of tumor-intrinsic Aurora-A in regulating antitumor immunity remains unclear. In this study, we demonstrated that in tumors with high lymphocyte infiltration (hot tumors), higher tumor-intrinsic Aurora-A expression is associated with a better prognosis in CRC patients. Mechanically, tumor-intrinsic Aurora-A promotes the cytotoxic activity of CD8+ T cells in immune hot CRC via negatively regulating interleukin-16 (IL-16), and the upregulation of IL-16 may impair the therapeutic effect of Aurora-A inhibition. Consequently, combination treatment with IL-16 neutralization improves the therapeutic response to Aurora-A inhibitors in immune hot CRC tumors. Our study provides evidence that tumor-intrinsic Aurora-A contributes to anti-tumor immunity depending on the status of lymphocyte infiltration, highlighting the importance of considering this aspect in cancer therapy targeting Aurora-A. Importantly, our results suggest that combining Aurora-A inhibitors with IL-16-neutralizing antibodies may represent a novel and effective approach for cancer therapy, particularly in tumors with high levels of lymphocyte infiltration.
Asunto(s)
Antineoplásicos , Neoplasias Colorrectales , Humanos , Linfocitos T CD8-positivos , Interleucina-16 , Transducción de Señal , Inmunosupresores , Neoplasias Colorrectales/patología , Microambiente TumoralRESUMEN
Cyclin D1 protein-positive diffuse large B cell lymphoma (DLBCL) has an immunophenotype of CD5(-) cyclin D1(+) SOX11(-), and most cases lack a CCND1 rearrangement and have a gene expression profile of DLBCL. Rarely, cyclin D1 protein-positive DLBCL harbors a CCND1 rearrangement, and some genetic copy number features typical of mantle cell lymphoma (MCL) have been detected. Since gene expression studies have not been performed, whether such CCND1-rearranged cases represent cyclin D1 protein-positive DLBCL or CD5/SOX11 double-negative pleomorphic MCL remains unclear. To date, no cases of CD5/SOX11 double-negative MCL have been reported. In this study, we collected eight cases initially diagnosed as cyclin D1 protein-positive DLBCL, including four with a CCND1 rearrangement and four without. Immunohistochemically, all four CCND1-rearranged cases had >50% of tumor cells positive for cyclin D1 protein, whereas only one (25%) non-rearranged case had >50% positive tumor cells. Analysis of genome-wide copy number, mutational, and gene expression profiles revealed that CCND1-rearranged cases were similar to MCL, whereas CCND1-non-rearranged cases resembled DLBCL. Despite the SOX11 negativity by immunohistochemistry, CCND1-rearranged cases had a notable trend (P = 0.064) of higher SOX11 mRNA levels compared to non-rearranged cases. Here, we show for the first time that CCND1 rearrangement could be useful for identifying CD5/SOX11 double-negative pleomorphic MCL in cases diagnosed as cyclin D1 protein-positive DLBCL. Cases with >50% cyclin D1 protein-positive tumor cells immunohistochemically and higher SOX11 mRNA levels are more likely to have a CCND1 rearrangement, and fluorescence in situ hybridization can be used to detect the rearrangement.
Asunto(s)
Biomarcadores de Tumor , Antígenos CD5 , Ciclina D1 , Linfoma de Células del Manto , Factores de Transcripción SOXC , Humanos , Linfoma de Células del Manto/patología , Linfoma de Células del Manto/genética , Linfoma de Células del Manto/diagnóstico , Linfoma de Células del Manto/metabolismo , Factores de Transcripción SOXC/genética , Anciano , Persona de Mediana Edad , Antígenos CD5/metabolismo , Masculino , Femenino , Ciclina D1/genética , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/análisis , Anciano de 80 o más Años , Reordenamiento Génico , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/patología , Linfoma de Células B Grandes Difuso/metabolismo , Inmunohistoquímica , AdultoRESUMEN
Macrophages are abundant immune cells in the microenvironment of diffuse large B-cell lymphoma (DLBCL). Macrophage estimation by immunohistochemistry shows varying prognostic significance across studies in DLBCL, and does not provide a comprehensive analysis of macrophage subtypes. Here, using digital spatial profiling with whole transcriptome analysis of CD68+ cells, we characterize macrophages in distinct spatial niches of reactive lymphoid tissues (RLTs) and DLBCL. We reveal transcriptomic differences between macrophages within RLTs (light zone /dark zone, germinal center/ interfollicular), and between disease states (RLTs/ DLBCL), which we then use to generate six spatially-derived macrophage signatures (MacroSigs). We proceed to interrogate these MacroSigs in macrophage and DLBCL single-cell RNA-sequencing datasets, and in gene-expression data from multiple DLBCL cohorts. We show that specific MacroSigs are associated with cell-of-origin subtypes and overall survival in DLBCL. This study provides a spatially-resolved whole-transcriptome atlas of macrophages in reactive and malignant lymphoid tissues, showing biological and clinical significance.
Asunto(s)
Linfoma de Células B Grandes Difuso , Humanos , Pronóstico , Linfoma de Células B Grandes Difuso/patología , Perfilación de la Expresión Génica , Transcriptoma , Centro Germinal/patología , Microambiente Tumoral/genéticaRESUMEN
AIMS: To investigate t(14;18)/IGH-BCL2 in follicular lymphoma (FL) cases from Taiwan. METHODS AND RESULTS: We retrospectively studied 93 consecutive cases, using immunohistochemistry and fluorescence in-situ hybridization (FISH). Fifty-nine (63%) tumours were low-grade (LG) and 34 (37%) were high-grade (HG; 24% FL3A and 13% FL3B). FISH showed IGH, BCL2 and BCL6 rearrangements in 59%, 47% and 11% of cases, respectively, and MYC rearrangement in 5% of FL3A tumours and 25% of FL3B tumours. The translocation partner of all BCL2 rearrangements was IGH, with IGH-BCL2 fusion in 63% of LG tumours and 18% of HG tumours. LG tumours were enriched with a CD10+/bcl-2+/MUM1- phenotype, and were frequently associated with BCL2 rearrangement but less commonly with BCL6 rearrangement. FL3A tumours were more closely related to FL3B tumours than to LG tumours in immunophenotype and genetic aberrations. There was no statistically significant difference between grade 1 and two tumours, between FL3A and FL3B tumours or between nodal and extranodal tumours in immunophenotypic or FISH findings. The cumulative survival rate was higher in LG FL patients with IGH-BCL2 translocation than in those without rearrangement. CONCLUSIONS: In Taiwan, FL3A tumours were more closely related to FL3B tumours than to LG tumours, and a literature review showed that the frequency of t(14;18)/IGH-BCL2 in FL in Taiwan is among the lowest in the world.
Asunto(s)
Cromosomas Humanos Par 14/genética , Cromosomas Humanos Par 18/genética , Frecuencia de los Genes , Linfoma Folicular/genética , Translocación Genética , Femenino , Humanos , Inmunofenotipificación , Hibridación Fluorescente in Situ , Linfoma Folicular/etnología , Linfoma Folicular/patología , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Proteínas Proto-Oncogénicas c-bcl-2/genética , Estudios Retrospectivos , Taiwán/epidemiologíaRESUMEN
BACKGROUND/PURPOSE: The gastrointestinal tract is the most common site of primary extranodal non-Hodgkin lymphoma, and the prognostic factors of primary gastric diffuse large B-cell lymphoma (PG-DLBCL) differ in various studies. METHODS: We retrospectively searched for PG-DLBCL in a single institution, performed immunohistochemical analysis, classified tumor phenotype (Hans and Muris algorithms), reviewed medical records, and analyzed the clinical and immunophenotypic variables using Cox proportional hazard regression model. RESULTS: A total of 46 cases were identified including 25 males and 21 females with a median age of 63.5; 18 (39%) were at stage I and 28 (61%) at stage II. Seven (15%) patients underwent surgery as initial treatment including total (n = 3, 7%) and subtotal (n = 4, 9%) gastrectomy. Thirty-three patients (72%) received frontline chemotherapy treatment including ten with additional rituximab (MabThera) injection, and two (6%) of these patients developed perforation after chemotherapy. Four patients passed away shortly after diagnosis and the remaining three were lost to follow-up. The overall 2- and 5- year survival rates were 55% and 50%, respectively. The expression of various differentiation markers was CD10 (25%), bcl-2 (50%), bcl-6 (84%), and MUM1 (64%). Half of the cases studied (22/44) were classified as germinal center B-cell (GCB) phenotype and the remaining half as non-GCB according to Hans algorithm; 66% and 34% cases belonged to groups 1 and 2, respectively, according to Muris algorithm. Univariate analysis showed the expression of bcl-6 by the tumor cells as a favorable factor, while elevated serum lactate dehydrogenase (LDH) level, bcl-2 expression, and Muris group 2 were associated with poorer outcome. Multivariate analysis revealed that the two prognostic factors were bcl-6 expression and elevated LDH level, with hazard ratios of 0.09 (p = 0.002) and 3.72 (p = 0.024), respectively. CONCLUSION: In this retrospective study with heterogeneous treatment modality, we identified bcl-6 expression and elevated LDH level as two prognostic factors for PG-DLBCL.
Asunto(s)
Proteínas de Unión al ADN/análisis , Hidroliasas/sangre , Linfoma de Células B Grandes Difuso/química , Neoplasias Gástricas/química , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Linfoma de Células B Grandes Difuso/enzimología , Linfoma de Células B Grandes Difuso/terapia , Masculino , Persona de Mediana Edad , Fenotipo , Pronóstico , Proteínas Proto-Oncogénicas c-bcl-6 , Estudios Retrospectivos , Neoplasias Gástricas/enzimología , Neoplasias Gástricas/terapia , Tasa de Supervivencia , Adulto JovenRESUMEN
Cancers often overexpress multiple clinically relevant oncogenes, but it is not known if combinations of oncogenes in cellular subpopulations within a cancer influence clinical outcomes. Using quantitative multispectral imaging of the prognostically relevant oncogenes MYC, BCL2, and BCL6 in diffuse large B-cell lymphoma (DLBCL), we show that the percentage of cells with a unique combination MYC+BCL2+BCL6- (M+2+6-) consistently predicts survival across four independent cohorts (n = 449), an effect not observed with other combinations including M+2+6+. We show that the M+2+6- percentage can be mathematically derived from quantitative measurements of the individual oncogenes and correlates with survival in IHC (n = 316) and gene expression (n = 2,521) datasets. Comparative bulk/single-cell transcriptomic analyses of DLBCL samples and MYC/BCL2/BCL6-transformed primary B cells identify molecular features, including cyclin D2 and PI3K/AKT as candidate regulators of M+2+6- unfavorable biology. Similar analyses evaluating oncogenic combinations at single-cell resolution in other cancers may facilitate an understanding of cancer evolution and therapy resistance. SIGNIFICANCE: Using single-cell-resolved multiplexed imaging, we show that selected subpopulations of cells expressing specific combinations of oncogenes influence clinical outcomes in lymphoma. We describe a probabilistic metric for the estimation of cellular oncogenic coexpression from IHC or bulk transcriptomes, with possible implications for prognostication and therapeutic target discovery in cancer. This article is highlighted in the In This Issue feature, p. 1027.
Asunto(s)
Linfoma de Células B Grandes Difuso , Fosfatidilinositol 3-Quinasas , Humanos , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-bcl-6/genética , Pronóstico , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteínas Proto-Oncogénicas c-myc/genética , Proteínas Proto-Oncogénicas c-myc/metabolismo , Oncogenes , Linfoma de Células B Grandes Difuso/patologíaRESUMEN
AIMS: To characterize the frequency and clinicopathological features of cyclin D1-positive diffuse large B-cell lymphoma (DLBCL) and the usefulness of SOX11 in the differential diagnosis from mantle cell lymphoma (MCL). METHODS AND RESULTS: We retrospectively stained 206 consecutive DLBCLs for cyclin D1, and identified three (1.5%) positive cases, comprising two in the elderly with necrosis, and a third with a starry-sky pattern. All three cases shared the same non-germinal centre B-cell (non-GCB) phenotype [CD5-/CD10-/bcl-6+/MUM1+/SOX11-], Epstein-Barr virus (EBV) negativity, and absence of CCND1 aberrations by fluorescence in-situ hybridization. The third case showed both BCL6 and MYC rearrangements: a double-hit lymphoma. In the same period there were 22 MCLs, all expressing cyclin D1, with 89% cases expressing SOX11, a frequency that is statistically different from cyclin D1-positive DLBCL. Notably, we identified a pleomorphic MCL initially misdiagnosed as DLBCL. A separate cohort of 98 DLBCL cases was negative for SOX11, with only one case expressing cyclin D1 with a GCB phenotype (CD10+/bcl-6+/MUM1-). The two patients with tumour necrosis rapidly died of disease. The other two were in complete remission after immunochemotherapy. CONCLUSION: Cyclin D1-positive DLBCLs are rare, and they are negative for SOX11 or CCND1 aberration. SOX11 is useful in differentiating cyclin D1-positive DLBCL from MCL.
Asunto(s)
Biomarcadores de Tumor/análisis , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células del Manto/diagnóstico , Factores de Transcripción SOXC/biosíntesis , Adulto , Anciano , Ciclina D1/análisis , Ciclina D1/biosíntesis , Diagnóstico Diferencial , Femenino , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Linfoma de Células B Grandes Difuso/metabolismo , Linfoma de Células del Manto/metabolismo , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Transcripción SOXC/análisis , Análisis de Matrices TisularesRESUMEN
Nodal fine needle aspiration (FNA) is usually the first procedure in the work-up of malignancy of unknown primary. Merkel cell carcinoma (MCC) is an aggressive cutaneous cancer more common in Caucasians but rare among Asians. It is a diagnostic challenge in evaluating FNA from a metastatic MCC without the knowledge of a current or prior history of skin cancer. We report the case of a Taiwanese male with cervical and axillary masses. The diagnosis of the FNA from the axillary lymph node was lymphoproliferative lesion suspicious for lymphoma. The histopathological evaluation of nodal biopsy revealed a metastatic neuroendocrine carcinoma and the subsequent excision of the right palm tumor confirmed MCC. Retrospective review of the FNA and imprint cytology smears of the nodal biopsy showed nuclear molding, Indian filing and rare cytoplasmic pale bodies, but no lymphoglandular bodies. Cytologically metastatic MCC may mimic small round cell tumor including lymphoma, we consider these three cytological features as additional diagnostic clues for metastatic MCC. In this report, we present the cytologic and pathological features of this metastatic MCC and discuss the differential diagnosis of the cytologic mimickers.
Asunto(s)
Carcinoma de Células de Merkel , Linfoma , Neoplasias Cutáneas , Biopsia con Aguja Fina , Carcinoma de Células de Merkel/diagnóstico , Carcinoma de Células de Merkel/patología , Citodiagnóstico , Humanos , Linfoma/patología , Masculino , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/patologíaRESUMEN
RATIONALE: Primary nasopharyngeal papillary adenocarcinoma is a rare nasopharyngeal neoplasm with a good prognosis and a low propensity for regional recurrence. To date, only few cases of primary nasopharyngeal papillary adenocarcinoma have been reported in the literature. PATIENT CONCERNS: A 24-year-old female patient presented with intermittent hemoptysis and blood tinge nasal discharge. DIAGNOSIS: An exophytic and pedunculated mass over the roof of the nasopharynx was found on nasopharyngoscope. Biopsy was done and the pathology confirmed well-differentiated primary nasopharyngeal papillary adenocarcinoma, strongly positive for CK7, and transcription termination factor 1; but negative for thyroglobulin. The final diagnosis was primary nasopharyngeal papillary adenocarcinoma, well-differentiated, pT1N0M0, stage I. INTERVENTIONS: The patient underwent excision of nasopharyngeal tumor under sinuscopic assistance. OUTCOMES: : No local recurrence or distant metastasis was noted during the 6âmonths of follow-up. LESSONS: We aim at highlighting the importance of a thorough differential diagnosis of nasopharyngeal tumor. Further investigation is still needed for providing evidence to standardize the treatment protocol.
Asunto(s)
Adenocarcinoma Papilar/diagnóstico , Carcinoma Nasofaríngeo/diagnóstico , Neoplasias Nasofaríngeas/diagnóstico , Adenocarcinoma Papilar/cirugía , Diagnóstico Diferencial , Femenino , Hemoptisis/etiología , Humanos , Carcinoma Nasofaríngeo/cirugía , Neoplasias Nasofaríngeas/cirugía , Nasofaringe , Adulto JovenRESUMEN
BACKGROUND: Thyroid transcription factor-1 (TTF-1) is a useful marker for identifying thyroid and lung cancers in diagnostic pathology, particularly for the investigation of unknown primary cancers. However, some other tumors such as colorectal cancer might aberrantly express TTF-1, particularly with the less specific clone SPT24. Occasional diffuse large B-cell lymphoma (DLBCL) cases have been reported to be TTF-1-positive, yet there is no information on TTF-1 expression in peripheral T-cell lymphoma (PTCL). METHODS: We investigated a series of PTCL and DLBCL by immunohistochemistry for TTF-1 expression using 2 commercially available clones. RESULTS: We found that 33% (5/15) adult T-cell leukemia/lymphomas (ATLLs) and 25% (2/8) angioimmunoblastic T-cell lymphomas (AITLs) were positive by clone SPT24 and only 2ATLL cases were positive by clone 8G7G3/1. Overall TTF-1 expression rates of PTCL by SPT24 and 8G7G3/1 were 16% (7/43) and 5% (2/43), respectively. All DLBCLs were negative. CONCLUSION: Although TTF-1 is a relatively specific marker for thyroid and lung cancers, it might be expressed in some lymphomas, particularly PTCL when using clone SPT24. Pathologist should be aware of this possible diagnostic pitfall when using TTF-1 in investigating tumors of unknown origin.
Asunto(s)
Biomarcadores de Tumor/análisis , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células T Periférico/diagnóstico , Factor Nuclear Tiroideo 1/análisis , Biomarcadores de Tumor/metabolismo , Diagnóstico Diferencial , Humanos , Inmunohistoquímica , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Linfoma de Células B Grandes Difuso/patología , Linfoma de Células T Periférico/patología , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/patología , Factor Nuclear Tiroideo 1/metabolismoRESUMEN
BACKGROUND: Primary intestinal follicular lymphoma (PI-FL) is a rare and indolent lymphoma and is challenging for diagnosis with endoscopic biopsy specimens. Whole slide imaging (WSI) has been increasingly used for assisting pathologic diagnosis, but not for lymphoma yet, probably because there are usually too many immunostained sections in a single case. In this study we attempted to identify morphological clues of PI-FL in the endoscopic biopsy specimens by measuring various parameters using WSI. METHODS: We retrospectively investigated 21 PI-FL cases, and scanned the HE sections from 17 of these cases with endoscopic biopsy specimens. Sections from 17 intestinal biopsies showing reactive lymphoid hyperplasia were scanned for comparison. The density and diameter of lymphoid follicles and the shortest distance of these follicles to the surface epithelia were measured on WSI. Comparisons of the aforementioned parameters were made between the neoplastic and reactive follicles. RESULTS: The density of follicles was significantly higher in PI-FL than that of reactive hyperplasia (median 0.5 vs. 0.2/mm2; p < 0.01). Furthermore, the neoplastic follicles were significantly larger (median diameter 756.9 vs. 479.7 µm; p < 0.01). The shortest distance of follicles to the surface epithelia tended to be closer in PI-FL (104.7 vs. 177.8 µm, p = 0.056), but not statistically significant. CONCLUSIONS: In this study we found that in PI-FL the density and diameter of lymphoid follicles as measured from WSI were significantly different from that of intestinal reactive lymphoid hyperplasia. When facing the diagnostic challenge between these two entities in routine practice, pathologists might be alerted by these morphological clues and request for immunohistochemistry for differential diagnosis.
Asunto(s)
Interpretación de Imagen Asistida por Computador/métodos , Enfermedades Intestinales/diagnóstico , Neoplasias Intestinales/diagnóstico , Linfoma Folicular/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Diagnóstico Diferencial , Femenino , Humanos , Hiperplasia/diagnóstico , Hiperplasia/patología , Enfermedades Intestinales/patología , Neoplasias Intestinales/patología , Linfoma Folicular/patología , Masculino , Persona de Mediana Edad , Seudolinfoma/diagnóstico , Seudolinfoma/patología , Estudios RetrospectivosRESUMEN
Pleomorphic mantle cell lymphoma (PMCL) can closely mimic diffuse large B-cell lymphoma (DLBCL) morphologically, and expression of CD5 and cyclin D1 is helpful for differential diagnosis. To date, no cases of CD5/cyclin D1 double-negative PMCL have been reported. Four cases of B-cell lymphoma with an immunophenotype of CD5(-) cyclin D1(-) SOX11(+) and morphologic features compatible with DLBCL were included. Two were previously identified, and the other 2 were screened from 500 cases of B-cell lymphoma. We analyzed their clinicopathologic, immunophenotypic, genetic, and gene expression features. Cases of cyclin D1-positive PMCL, cyclin D1-negative PMCL, germinal center B-cell (GCB) DLBCL, and activated B cell (ABC) DLBCL were also studied for comparison. Similar to other PMCL cases, these 4 patients were mainly elderly male individuals with an aggressive clinical course. None of these tumors had detectable translocations involving CCND1, CCND2, CCND3, CCNE1, CCNE2, MYC, BCL2, or BCL6. The genome-wide copy number profile of these 4 cases was similar to that of cyclin D1-negative PMCL. None of these tumors had high expression of cyclin D1, cyclin D2, or cyclin D3. Similar to cyclin D1-negative PMCL, these cases had higher expression of cyclin E1 and cyclin E2 compared with cyclin D1-positive PMCL. The gene expression pattern of these tumors was also similar to that of cyclin D1-negative PMCL. Here we report for the first time 4 cases of CD5/cyclin D1 double-negative PMCL. SOX11 positivity is useful to identify these rare tumors, and further genetic and gene expression analysis can be used to confirm the diagnosis.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Antígenos CD5/metabolismo , Ciclina D1/metabolismo , Regulación Neoplásica de la Expresión Génica , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células del Manto/diagnóstico , Factores de Transcripción SOXC/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Antígenos CD5/genética , Ciclina D1/genética , Diagnóstico Diferencial , Perfilación de la Expresión Génica , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/patología , Linfoma de Células del Manto/genética , Linfoma de Células del Manto/patología , Masculino , Persona de Mediana Edad , Fenotipo , Factores de Transcripción SOXC/genéticaRESUMEN
Methotrexate-associated lymphoproliferative disorder (MTX-LPD) is a lymphoid proliferation or lymphoma in a patient immunosuppressed with MTX, which is usually administered for treating autoimmune diseases. The majority of MTX-LPD cases develop in patients with rheumatoid arthritis and occasionally with psoriasis who had been treated with MTX. Here, we report on a 50-year-old Taiwanese male with severe psoriasis, who received high doses of MTX. The patient developed EBV-positive MTX-LPD at nodal and extranodal sites. The diffuse and polymorphic lymphoid infiltrate consisted predominantly of immunoblasts and plasmablasts expressing B-cell markers, CD138, Epstein-Barr virus (EBV)-LMP1, and EBNA2, and these were monotypic for kappa light chain. The tumor cells were also positive for EBV by in situ hybridization. These findings indicated a type III latency infection of EBV. The patient died of progressive disease after 19 months. A review of the previously reported cases shows that MTX-LPD, in association with psoriasis, occurs in middle-aged males. The tumors are diffuse large B-cell lymphomas with immunoblastic morphology, and frequently show plasmacytic differentiation.
Asunto(s)
Fármacos Dermatológicos/efectos adversos , Infecciones por Virus de Epstein-Barr/inducido químicamente , Inmunosupresores/efectos adversos , Linfoma de Células B Grandes Difuso/inducido químicamente , Linfoma de Células B Grandes Difuso/virología , Metotrexato/efectos adversos , Psoriasis/tratamiento farmacológico , Progresión de la Enfermedad , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/tratamiento farmacológico , Infecciones por Virus de Epstein-Barr/genética , Infecciones por Virus de Epstein-Barr/patología , Resultado Fatal , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND AND OBJECTIVE: Ciprofloxacin, moxifloxacin and levofloxacin are recognized immunomodulators. Their effects in acute lung injuries have not been tested. This study compared the immunoprotective effects of these agents in mice with lung injuries induced by LPS by measuring the cytokine profiles in the injured lung and the associated mortality. METHODS: The development of lung injury and mortality was compared in mice pretreated with either ciprofloxacin, levofloxacin, moxifloxacin or saline (control group) after the intratracheal administration of LPS. BALF and serum were collected at 1, 3 and 6 h to measure the concentrations of tumour necrosis factor-alpha (TNF-alpha), IL-1beta, IL-6, IL-10 and macrophage inflammatory protein-2 (MIP-2) using enzyme-linked immunoassay. RESULTS: Levels of TNF-alpha, IL-1beta and MIP-2 in the BAL of the ciprofloxacin group were significantly lower compared with those of controls (all P < 0.0083) at 3 and 6 h after LPS challenge. There were no significant differences in the levels of these cytokines in the moxifloxacin and levofloxacin groups compared with controls. Overall, the 96-h survival for the mice pretreated with ciprofloxacin, but not for those pretreated with moxifloxacin or levofloxacin, was significantly greater than that of the control animals (P = 0.019). CONCLUSIONS: In the setting of LPS-induced lung injuries, ciprofloxacin appears to provide better anti-inflammatory properties and survival benefits than the other fluoroquinolones tested.
Asunto(s)
Antiinfecciosos/uso terapéutico , Compuestos Aza/uso terapéutico , Ciprofloxacina/uso terapéutico , Levofloxacino , Ofloxacino/uso terapéutico , Quinolinas/uso terapéutico , Síndrome de Dificultad Respiratoria/tratamiento farmacológico , Animales , Citocinas/metabolismo , Modelos Animales de Enfermedad , Fluoroquinolonas , Lipopolisacáridos , Ratones , Ratones Endogámicos BALB C , Moxifloxacino , Síndrome de Dificultad Respiratoria/etiología , Síndrome de Dificultad Respiratoria/patologíaRESUMEN
There are three clinicopathological entities of marginal zone lymphoma (MZL), including extranodal or mucosa-associated lymphoid tissue (MALT) lymphoma and MZL of nodal (NMZL) or splenic (SMZL) type. Of these, leukemic presentation, usually as small or villous lymphocytes, is more common in SMZL, while leukemic change in NMZL is rare, and the morphology has not been characterized. We present a stage 4 MZL involving lymph node, spleen, and bone marrow with two relapses after chemotherapy. The leukemic cells at the second relapse revealed irregular nuclear contours with multilobated nuclei (so-called flower cells or floral cells) mimicking the neoplastic cells in adult T-cell leukemia/lymphoma (ATLL). The absence of leukemic change and splenic hilar lymphadenopathy at initial presentation, expression of IgD by tumor cells, and cytogenetic changes of +7 suggested that this tumor might be a NMZL. Although the cytomorphologic features of floral leukemic cells might suggest ATLL, thorough clinical and laboratory workup helped to reach a correct diagnosis. Our findings broaden the cytological spectra of leukemic cells in MZL and illustrate the importance of immunophenotyping.