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4. Additional Table I from Minimal Residual Disease after Conventional Treatment Significantly Impacts on Progression-Free Survival of Patients with Follicular Lymphoma: The FIL FOLL05 Trial

Author

Galimberti, Sara, primary, Luminari, Stefano, primary, Ciabatti, Elena, primary, Grassi, Susanna, primary, Guerrini, Francesca, primary, Dondi, Alessandra, primary, Marcheselli, Luigi, primary, Ladetto, Marco, primary, Piccaluga, Pier Paolo, primary, Gazzola, Anna, primary, Mannu, Claudia, primary, Monitillo, Luigia, primary, Mantoan, Barbara, primary, Del Giudice, Ilaria, primary, Della Starza, Irene, primary, Cavalli, Marzia, primary, Arcaini, Luca, primary, Tucci, Alessandra, primary, Palumbo, Giuseppe Alberto, primary, Rigacci, Luigi, primary, Pulsoni, Alessandro, primary, Vitolo, Umberto, primary, Boccomini, Carola, primary, Vallisa, Daniele, primary, Bertoldero, Giovanni, primary, Gaidano, Gianluca, primary, Musto, Pellegrino, primary, Petrini, Mario, primary, and Federico, Massimo, primary

Published
2023
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5. Supplemental Figure Legend from Minimal Residual Disease after Conventional Treatment Significantly Impacts on Progression-Free Survival of Patients with Follicular Lymphoma: The FIL FOLL05 Trial

Author

Galimberti, Sara, primary, Luminari, Stefano, primary, Ciabatti, Elena, primary, Grassi, Susanna, primary, Guerrini, Francesca, primary, Dondi, Alessandra, primary, Marcheselli, Luigi, primary, Ladetto, Marco, primary, Piccaluga, Pier Paolo, primary, Gazzola, Anna, primary, Mannu, Claudia, primary, Monitillo, Luigia, primary, Mantoan, Barbara, primary, Del Giudice, Ilaria, primary, Della Starza, Irene, primary, Cavalli, Marzia, primary, Arcaini, Luca, primary, Tucci, Alessandra, primary, Palumbo, Giuseppe Alberto, primary, Rigacci, Luigi, primary, Pulsoni, Alessandro, primary, Vitolo, Umberto, primary, Boccomini, Carola, primary, Vallisa, Daniele, primary, Bertoldero, Giovanni, primary, Gaidano, Gianluca, primary, Musto, Pellegrino, primary, Petrini, Mario, primary, and Federico, Massimo, primary

Published
2023
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6. Primary pulmonary T-cell lymphoproliferative disorders with a limited-stage, low proliferative index, and unusual clinical behavior: two cases of a rare occurrence

Author

Sabattini, Elena, primary, Bertuzzi, Clara, additional, Broccoli, Alessandro, additional, Agostinelli, Claudio, additional, Gazzola, Anna, additional, Mannu, Claudia, additional, Righi, Simona, additional, Ottaviani, Emanuela, additional, Terragna, Carolina, additional, Motta, Giovanna, additional, Melle, Federica, additional, Ricci, Costantino, additional, Ambrosi, Francesca, additional, and Pileri, Stefano A., additional

Published
2022
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8. Quality Assessment for PCR-based Minimal Residual Disease in Lymphoma: 10 Years of Cross-laboratory Standardization Process Within the Fondazione Italiana Linfomi MRD Network

Author

Mantoan, Barbara, primary, Genuardi, Elisa, additional, Ferrante, Martina, additional, Della Starza, Irene, additional, Ciabatti, Elena, additional, Grassi, Susanna, additional, De Novi, Lucia Anna, additional, Cavalli, Marzia, additional, Mannu, Claudia, additional, Gazzola, Anna, additional, Bomben, Riccardo, additional, Degan, Massimo, additional, Alessandria, Beatrice, additional, Pott, Christiane, additional, Delfau-Larue, Marie-Hélène, additional, García-Sanz, Ramon, additional, Agostinelli, Claudio, additional, Gattei, Valter, additional, Galimberti, Sara, additional, Del Giudice, Ilaria, additional, Gaidano, Gianluca, additional, Ladetto, Marco, additional, Ferrero, Simone, additional, and Drandi, Daniela, additional

Published
2021
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13. Systemic Epstein-Barr-virus-positive T cell lymphoproliferative childhood disease in a 22-year-old Caucasian man: A case report and review of the literature

Author

Meloni Giovanna, Sista Maria, Righi Simona, Mannu Claudia, Capria Saveria, Bacci Francesco, Gazzola Anna, Sabattini Elena, Agostinelli Claudio, Tabanelli Valentina, Pileri Stefano A, and Piccaluga Pier

Subjects
Medicine
Abstract

Abstract Introduction Systemic Epstein-Barr-virus-positive T cell lymphoproliferative disease of childhood is an extremely rare disorder, characterized by clonal proliferation of Epstein-Barr-virus-infected T cells with an activated cytotoxic phenotype. The disease is more frequent in Asia and South America, with only few cases reported in Western countries. A prompt diagnosis, though often difficult, is a necessity due to the very aggressive clinical course of the disease. Case presentation We report the clinicopathological features of fulminant T cell lymphoproliferative disease that arose in the setting of acute primary Epstein-Barr virus infection. Our patient, a 23-year-old man, presented to our facility with persisting fever, hepatosplenomegaly and severe pancytopenia. On bone marrow biopsy, an abundant lymphoid infiltrate was observed. Immunophenotypic and molecular studies revealed that the atypical lymphoid cells displayed a CD8+, Epstein-Barr-encoded-RNA-positive T cell phenotype with clonal rearrangement of the T cell receptor genes, the final diagnosis being systemic Epstein-Barr-virus-positive T cell lymphoproliferative disease. On reviewing the literature we found only 14 similar cases, all presenting with very aggressive clinical courses and requiring extensive phenotyping and molecular techniques for final diagnosis. Conclusion Though extremely rare, this disease can occur in Europe, and a comprehensive diagnostic approach is thus recommended in all case of Epstein-Barr-virus-positive lymphoproliferative disorders. Unfortunately, at present no specific treatment is available; however, prompt administration of anti- Epstein-Barr virus treatment and rapid attempts to control the hemophagocytic syndrome are indicated.

Published
2011
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15. Distinctive Histogenesis and Immunological Microenvironment Based on Transcriptional Profiles of Follicular Dendritic Cell Sarcomas

Author

Laginestra, Maria Antonella, primary, Tripodo, Claudio, additional, Agostinelli, Claudio, additional, Motta, Giovanna, additional, Hartmann, Sylvia, additional, Döring, Claudia, additional, Rossi, Maura, additional, Melle, Federica, additional, Sapienza, Maria Rosaria, additional, Tabanelli, Valentina, additional, Pileri, Alessandro, additional, Fuligni, Fabio, additional, Gazzola, Anna, additional, Mannu, Claudia, additional, Sagramoso, Carlo Alberto, additional, Lonardi, Silvia, additional, Lorenzi, Luisa, additional, Bacci, Francesco, additional, Sabattini, Elena, additional, Borges, Anita, additional, Simonitsch-Klupp, Ingrid, additional, Cabecadas, Jose, additional, Campo, Elias, additional, Rosai, Juan, additional, Hansmann, Martin-Leo, additional, Facchetti, Fabio, additional, and Pileri, Stefano Aldo, additional

Published
2017
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16. Minimal residual disease (MRD) in non-Hodgkin lymphomas: Interlaboratory reproducibility on marrow samples with very low levels of disease within the FIL (Fondazione Italiana Linfomi) MRD Network.

Author

Della Starza, Irene, Cavalli, Marzia, De Novi, Lucia Anna, Genuardi, Elisa, Mantoan, Barbara, Drandi, Daniela, Barbero, Daniela, Ciabatti, Elena, Grassi, Susanna, Gazzola, Anna, Mannu, Claudia, Agostinelli, Claudio, Piccaluga, Pier Paolo, Bomben, Riccardo, Degan, Massimo, Gattei, Valter, Guarini, Anna, Foà, Robin, Galimberti, Sara, and Ladetto, Marco

Subjects
MANTLE cell lymphoma, BONE marrow, LYMPHOMAS, POLYMERASE chain reaction, BONE marrow cancer, NUCLEOTIDE sequencing
Abstract

In 2009, the four laboratories of the Fondazione Italiana Linfomi (FIL) minimal residual disease (MRD) Network started a collaborative effort to harmonize and standardize their methodologies at the national level, performing quality control (QC) rounds for follicular lymphoma (FL) and mantle cell lymphoma (MCL) MRD assessment. In 16 QC rounds between 2010 and 2017, the four laboratories received 208 bone marrow (BM) samples (126 FL; 82 MCL); 187 were analyzed, according to the EuroMRD Consortium guidelines, by both nested (NEST) polymerase chain reaction (PCR) and real-time quantitative (RQ) PCR for BCL2/IGH MBR or IGHV rearrangements. Here, we aimed at analyzing the samples that challenged the interlaboratory reproducibility and data interpretation. Overall, 156/187 BM samples (83%) were concordantly classified as NEST+/RQ+ or NEST-/RQ- by all the four laboratories. The remaining 31 samples (17%) resulted alternatively positive and negative in the interlaboratory evaluations, independently of the method and the type of rearrangement, and were defined "borderline" (brd) samples: 12 proved NEST brd/RQ brd, 7 NEST-/RQ brd, 10 NEST brd/RQ positive not quantifiable (PNQ), and 2 NEST brd/RQ-. Results did not change even increasing the number of replicates/sample. In 6/31 brd samples, droplet digital PCR (ddPCR) was tested and showed no interlaboratory discordance. Despite the high interlaboratory reproducibility in the MRD analysis obtained and maintained by the QC round strategy, samples with the lowest MRD levels can still represent a challenge: 17% (31/187) of our samples showed discordant results in interlaboratory assessments, with 6.4% (12/187) remained brd even applying the two methods. Thus, although representing a minority, brd samples are still problematic, especially when a clinically oriented interpretation of MRD results is required. Alternative, novel methods such as ddPCR and next-generation sequencing have the potential to overcome the current limitations. [ABSTRACT FROM AUTHOR]

Published
2019
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17. Comparison of different DNA extraction methods from peripheral blood cells: advice from the Fondazione Italiana Linfomi Minimal Residual Disease Network

Author

Mannu, Claudia, Gazzola, Anna, Ciabatti, Elena, Fuligni, Fabio, Cavalli, Marzia, Della Starza, Irene, Genuardi, Elisa, Mantoan, Barbara, Monitillo, Luigia, Del Giudice, Ilaria, Ladetto, Marco, Gaidano, Gianluca, Sabattini, Elena, Pileri, Stefano A., Galimberti, Sara, Piccaluga, Pier Paolo, and Fondazione Italiana Linfomi Minimal Residual Disease Network, Null

Subjects
0301 basic medicine, DNA extraction, FIL MRD Network, PCR, Hematology, Oncology, Cancer Research, medicine.medical_specialty, business.industry, Genomic research, Bioinformatics, Minimal residual disease, Peripheral blood, 03 medical and health sciences, 030104 developmental biology, Medicine, Primary component, Medical physics, business, Routine analysis
Abstract

Genomic DNA extraction is a primary component of genomic research and diagnostic routine analysis. Recently, the importance of this process has been highlighted by the necessity to standardize the diagnostic procedure. In this regard, the Minimal Residual Disease (MRD) Network of the Fondazione Italiana Linfomi (FIL MRD Network) has performed a comparative study of four different commercially available kits for DNA extraction, applying them on a panel of cellular pellets, with the aim of defining possible technical recommendations in order to harmonize and standardize diagnostic procedures in the clinical setting. Overall, all four kits usually allowed the recovery of a significant quantity of high-quality DNA (in most conditions), although specific indications could be addressed for cellular pellets of different sizes.

Published
2014

18. The role of molecular biology in the diagnosis of lymphoid neoplasms

Author

Pizzi, Marco, Gazzola, Anna, Mannu, Claudia, Pileri, Stefano A, and Sabattini, Elena

Subjects
Next-Generation Sequencing, medicine.medical_specialty, Lymphoma, Non-Hodgkin Lymphoma, Review, Biology, Bioinformatics, Sensitivity and Specificity, DNA sequencing, High complexity, Biomarkers, Tumor, medicine, Humans, Lymphoid neoplasms, Molecular Biology, Oligonucleotide Array Sequence Analysis, Chromosome Aberrations, Tumor, Gene Expression Profiling, DNA-arrays, High-Throughput Nucleotide Sequencing, Reproducibility of Results, Genome Expression Profiling, Prognosis, Molecular biology, Clinical Practice, Gene expression profiling, Clonality Test, Identification (biology), Hematopathology, Biomarkers
Abstract

In recent years, DNA-arrays, gene expression profiling and next-generation sequencing have elucidated the high complexity of genomic alterations occurring in lymphoid malignancies. These studies have also contributed to the identification of new diagnostic and prognostic biomarkers, which may represent possible targets for new therapeutic approaches. Such recent advances have significantly expanded the application of molecular tests to routine diagnostic hematopathology. It is thus conceivable that next-generation assays will soon flank traditional clonality tests and chromosomal translocation assays in the diagnostic work-up of difficult cases. This review is focused on the application of molecular biology techniques in the study of lymphoid tumors. Both conventional and next-generation tests will be addressed, with particular attention to their application to clinical practice.

Published
2014

19. Use of IGK gene rearrangement analysis for clonality assessment of lymphoid malignancies: a single center experience

Author

Mannu, Claudia, Gazzola, Anna, Bacci, Francesco, Sabattini, Elena, Sagramoso, Carlo, Roncolato, Fernando, Rossi, Maura, Laginestra, Maria Antonella, Sapienza, Maria Rosaria, Agostinelli, Claudio, Leo, Antonio, MILENA PICCIOLI, Righi, Simona, Artioli, Patrizia, Chilli, Luigi, Da Pozzo, Gianpaolo, Biase, Giuseppe, Sandri, Federica, Pileri, Stefano A., Piccaluga, Pier Paolo, Mannu C., Gazzola A., Bacci F., Sabattini E., Sagramoso C., Roncolato F., Rossi M., Laginestra M.A., Sapienza M.R., Agostinelli C., De Leo A., Piccioli M., Righi S., Artioli P., Chilli L., Da Pozzo G., De Biase G., Sandri F., Pileri S.A., and Piccaluga P.P.

Subjects
IGK, PCR, BIOMED-2, immune system diseases, hemic and lymphatic diseases, Original Article, molecular diagnostic, non Hodgkin lymphoma
Abstract

Diagnosis of B-non Hodgkin lymphomas (NHLs) is based on clinical, morphological and immunohistochemi-cal features. However, in up to 10-15% of cases, analysis of immunoglobulin heavy (IGH) or light (IGK/IGL) chains genes is required to discriminate between malignant and reactive lymphoid proliferations. In this study, we evaluated the feasibility and efficiency of IGK analysis in the routine diagnostic of B-cell lymphoproliferative disorders (B-LD) when applied to formalin-fixed paraffin-embedded (FFPE) tissues. Clonality patterns were studied in 59 B-LD using the BIOMED-2 protocol for IGK assays, after failure of the IGH assay. PCR products were evaluated by both heterodu-plex and GeneScan analysis. IGK analysis was technically successful in all cases. Overall, it supported the histopa-thological suspicion in 52/59 cases (88%), the sensitivity and specificity being 83% and 80%, respectively. Further, positive and negative predictive values were 95% and 50%, respectively. Interestingly, among various lymphoma subtypes, marginal zone lymphoma and follicular lymphoma most frequently required IGK analysis. In conclusion, IGK study according to the BIOMED-2 protocol resulted feasible and extremely useful in supporting challenging diagnosis of B-LD even if applied on FFPE samples. Accordingly, when NHL is suspected, negative results at IGH analysis should not be considered as conclusive and further investigation of IGK is appropriate.

Published
2011

20. Pathobiology of Hodgkin Lymphoma

Author

Piccaluga, Pier Paolo, Agostinelli, Claudio, Gazzola, Anna, Tripodo, Claudio, Bacci, Francesco, Sabattini, Elena, Sista, Maria Teresa, Mannu, Claudia, Sapienza, Maria Rosaria, Rossi, Maura, Laginestra, Maria Antonella, Sagramoso-Sacchetti, Carlo A., Righi, Simona, and Pileri, Stefano A.

Subjects
Article Subject, hemic and lymphatic diseases
Abstract

Despite its well-known histological and clinical features, Hodgkin's lymphoma (HL) has recently been the object of intense research activity, leading to a better understanding of its phenotype, molecular characteristics, histogenesis, and possible mechanisms of lymphomagenesis. There is complete consensus on the B-cell derivation of the tumor in most cases, and on the relevance of Epstein-Barr virus infection and defective cytokinesis in at least a proportion of patients. The REAL/WHO classification recognizes a basic distinction between lymphocyte predominance HL (LP-HL) and classic HL (cHL), reflecting the differences in clinical presentation and behavior, morphology, phenotype, and molecular features. cHL has been classified into four subtypes: lymphocyte rich, nodular sclerosing, with mixed cellularity, and lymphocyte depleted. The borders between cHL and anaplastic large-cell lymphoma have become sharper, whereas those between LP-HL and T-cell-rich B-cell lymphoma remain ill defined. Treatments adjusted to the pathobiological characteristics of the tumor in at-risk patients have been proposed and are on the way to being applied.

Published
2011
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21. Pathobiology of Anaplastic Large Cell Lymphoma

Author

Piccaluga, Pier Paolo, Gazzola, Anna, Mannu, Claudia, Agostinelli, Claudio, Bacci, Francesco, Sabattini, Elena, Sagramoso, Carlo, Piva, Roberto, Roncolato, Fernando, Inghirami, Giorgio, and Pileri, Stefano A.

Subjects
Article Subject, hemic and lymphatic diseases
Abstract

The authors revise the concept of anaplastic large cell lymphoma (ALCL) in the light of the recently updated WHO classification of Tumors of Hematopoietic and Lymphoid Tissues both on biological and clinical grounds. The main histological findings are illustrated with special reference to the cytological spectrum that is indeed characteristic of the tumor. The phenotype is reported in detail: the expression of the ALK protein as well as the chromosomal abnormalities is discussed with their potential pathogenetic implications. The clinical features of ALCL are presented by underlining the difference in terms of response to therapy and survival between the ALK-positive and ALK-negative forms. Finally, the biological rationale for potential innovative targeted therapies is presented.

Published
2010
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22. Minimal Residual Disease after Conventional Treatment Significantly Impacts on Progression-Free Survival of Patients with Follicular Lymphoma: The FIL FOLL05 Trial

Author

Galimberti, Sara, primary, Luminari, Stefano, additional, Ciabatti, Elena, additional, Grassi, Susanna, additional, Guerrini, Francesca, additional, Dondi, Alessandra, additional, Marcheselli, Luigi, additional, Ladetto, Marco, additional, Piccaluga, Pier Paolo, additional, Gazzola, Anna, additional, Mannu, Claudia, additional, Monitillo, Luigia, additional, Mantoan, Barbara, additional, Del Giudice, Ilaria, additional, Della Starza, Irene, additional, Cavalli, Marzia, additional, Arcaini, Luca, additional, Tucci, Alessandra, additional, Palumbo, Giuseppe Alberto, additional, Rigacci, Luigi, additional, Pulsoni, Alessandro, additional, Vitolo, Umberto, additional, Boccomini, Carola, additional, Vallisa, Daniele, additional, Bertoldero, Giovanni, additional, Gaidano, Gianluca, additional, Musto, Pellegrino, additional, Petrini, Mario, additional, and Federico, Massimo, additional

Published
2014
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23. Abstract 5173: Identification of single-nucleotide variants by high-throughput RNA sequencing in endemic Burkitt Lymphoma

Author

Laginestra, Maria Antonella, primary, Abate, Francesco, additional, Etebari, Maryam, additional, Falco, Giulia D., additional, Fuligni, Fabio, additional, Rossi, Maura, additional, Zairis, Sakellarios, additional, Sapienza, Maria Rosaria, additional, Gazzola, Anna, additional, Mannu, Claudia, additional, Melle, Federica, additional, Agostinelli, Claudio, additional, Navari, Mohsen, additional, Bellan, Cristiana, additional, Gazaneo, Sara, additional, Mundo, Lucia, additional, Ogwang, Martin, additional, Calbi, Valeria, additional, Leoncini, Lorenzo, additional, Pileri, Stefano A., additional, Rabadan, Raul, additional, and Piccaluga, Pier Paolo, additional

Published
2014
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24. Abstract 2362: Identification and characterization of pathogenetic pathways and potential therapeutic targets in tumors derived from histiocytes and follicular dendritic cells

Author

Piccaluga, Pier-Paolo, primary, Rossi, Maura, additional, Motta, Giovanna, additional, Hartmann, Sylvia, additional, Doering, Claudia, additional, Fuligni, Fabio, additional, Agostinelli, Claudio, additional, Sapienza, Maria Rosaria, additional, Laginestra, Maria Antonella, additional, Melle, Federica, additional, Etebari, Maryam, additional, Navari, Mohsen, additional, Gazzola, Anna, additional, Mannu, Claudia, additional, Bertuzzi, Clara, additional, Tripodo, Claudio, additional, Hansmann, Martin L., additional, Facchetti, Fabio, additional, and Pileri, Stefano A, additional

Published
2014
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25. The Evolution of Clonality Testing – Next Generation Sequencing in the Diagnosis and Monitoring of Hematologic Malignancies

Author

Gazzola, Anna, primary, Mannu, Claudia, additional, Rossi, Maura, additional, Laginestra, Maria Antonella, additional, Sapienza, Maria Rosaria, additional, Fuligni, Fabio, additional, Etebari, Maryam, additional, Melle, Federica, additional, Sabattini, Elena, additional, Agostinelli, Claudio, additional, Bacci, Francesco, additional, Sacchetti, Carlo Alberto Sagramoso, additional, Pileri, Stefano Aldo, additional, and Piccaluga, Pier Paolo, additional

Published
2014
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26. The evolution of clonality testing in the diagnosis and monitoring of hematological malignancies

Author

Gazzola, Anna, primary, Mannu, Claudia, additional, Rossi, Maura, additional, Laginestra, Maria Antonella, additional, Sapienza, Maria Rosaria, additional, Fuligni, Fabio, additional, Etebari, Maryam, additional, Melle, Federica, additional, Sabattini, Elena, additional, Agostinelli, Claudio, additional, Bacci, Francesco, additional, Sagramoso Sacchetti, Carlo Alberto, additional, Pileri, Stefano Aldo, additional, and Piccaluga, Pier Paolo, additional

Published
2014
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28. Comparison of two real-time quantitative polymerase chain reaction strategies for minimal residual disease evaluation in lymphoproliferative disorders: correlation between immunoglobulin gene mutation load and real-time quantitative polymerase chain react

Author

Della Starza, Irene, primary, Cavalli, Marzia, additional, Del Giudice, Ilaria, additional, Barbero, Daniela, additional, Mantoan, Barbara, additional, Genuardi, Elisa, additional, Urbano, Marina, additional, Mannu, Claudia, additional, Gazzola, Anna, additional, Ciabatti, Elena, additional, Guarini, Anna, additional, Foà, Robin, additional, Galimberti, Sara, additional, Piccaluga, Pierpaolo, additional, Gaidano, Gianluca, additional, Ladetto, Marco, additional, and Monitillo, Luigia, additional

Published
2013
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29. Molecular Profiling Of Blastic Plasmacytoid Dendritic CELL Neoplasm Reveals A Unique Pattern and Suggests Selective Sensitivity To NF-KB Pathway Inhibition

Author

Piccaluga, Pier Paolo, primary, Sapienza, Maria Rosaria, additional, Fabio, Fuligni, additional, Claudio, Agostinelli, additional, Claudio, Tripodo, additional, Simona, Righi, additional, Laginestra, Maria Antonella, additional, Alessandro, Pileri, additional, Maura, Rossi, additional, Ricci, Francesca, additional, Gazzola, Anna, additional, Mannu, Claudia, additional, Ulbar, Francesca, additional, Arpinati, Mario, additional, Paulli, Marco, additional, Gibellini, Davide, additional, Pagano, Livio, additional, Pimpinelli, Nicola, additional, Cerroni, Lorenzo, additional, Croce, Carlo M., additional, Facchetti, Fabio, additional, and Pileri, Stefano A, additional

Published
2013
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30. Molecular Profiling Improves Classification and Prognostication of Nodal Peripheral T-Cell Lymphomas: Results of a Phase III Diagnostic Accuracy Study

Author

Piccaluga, Pier Paolo, primary, Fuligni, Fabio, additional, De Leo, Antonio, additional, Bertuzzi, Clara, additional, Rossi, Maura, additional, Bacci, Francesco, additional, Sabattini, Elena, additional, Agostinelli, Claudio, additional, Gazzola, Anna, additional, Laginestra, Maria Antonella, additional, Mannu, Claudia, additional, Sapienza, Maria Rosaria, additional, Hartmann, Sylvia, additional, Hansmann, Martin L., additional, Piva, Roberto, additional, Iqbal, Javeed, additional, Chan, John C., additional, Weisenburger, Denis, additional, Vose, Julie M., additional, Bellei, Monica, additional, Federico, Massimo, additional, Inghirami, Giorgio, additional, Zinzani, Pier Luigi, additional, and Pileri, Stefano A., additional

Published
2013
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31. Abstract 1951: miRNA expression profile of Blastic plasmacytoid dendritic cell neoplasm.

Author

Sapienza, Maria Rosaria, primary, Fuligni, Fabio, additional, Laginestra, Maria Antonella, additional, Rossi, Maura, additional, Cascione, Luciano, additional, Laganà, Alessandro, additional, Agostinelli, Claudio, additional, Etebari, Maryam, additional, Gazzola, Anna, additional, Mannu, Claudia, additional, Sabattini, Elena, additional, Bacci, Francesco, additional, Croce, Carlo Maria, additional, Pileri, Stefano Aldo, additional, and Piccaluga, Pier Paolo, additional

Published
2013
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32. Abstract 5275: miRNA profiling of peripheral T-cell lymphomas.

Author

Laginestra, Maria Antonella, primary, Fuligni, Fabio, additional, Rossi, Maura, additional, Gibellini, Davide, additional, Sapienza, Maria Rosaria, additional, Gazzola, Anna, additional, Mannu, Claudia, additional, Sabattini, Elena, additional, Bacci, Francesco, additional, Agostinelli, Claudio, additional, Pileri, Stefano Aldo, additional, and Piccaluga, Pier Paolo, additional

Published
2013
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33. Hsa-miR-15a and Hsa-miR-16-1 Expression Is Not Related to Proliferation Centers Abundance and Other Prognostic Factors in Chronic Lymphocytic Leukemia

Author

Rossi, Maura, primary, Fuligni, Fabio, additional, Ciccone, Maria, additional, Agostinelli, Claudio, additional, Righi, Simona, additional, Luciani, Marco, additional, Laginestra, Maria Antonella, additional, Rigolin, Gian Matteo, additional, Sapienza, Maria Rosaria, additional, Gazzola, Anna, additional, Mannu, Claudia, additional, Cuneo, Antonio, additional, Pileri, Stefano, additional, and Piccaluga, Pier Paolo, additional

Published
2013
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34. Clonality and Phenotype in Spleens From Patients with Primary Immune Thrombocytopenia,

Author

Sabattini, Elena, primary, Piccaluga, Pier Paolo, additional, Mannu, Claudia, additional, Candoni, Anna, additional, Gazzola, Anna, additional, Sagramoso, Carlo, additional, Toffoletti, Eleonora, additional, Vianelli, Nicola, additional, Polverelli, Nicola, additional, Pileri, Stefano, additional, Loreto, Carla Di, additional, Pizzolitto, Stefano, additional, and Zaja, Francesco, additional

Published
2011
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35. Molecular Diagnosis of Peripheral T-Cell Lymphoma/NOS From Formalin Fixed Paraffin Embedded Tissues,

Author

Piccaluga, Pier Paolo, primary, De Leo, Antonio, additional, Rossi, Maura, additional, Laginestra, Maria Antonella, additional, Sapienza, maria Rosaria, additional, Gazzola, Anna, additional, Mannu, Claudia, additional, Agostinelli, Claudio, additional, Bacci, Francesco, additional, Sabattini, Elena, additional, Hartmann, Sylvia, additional, Hansmann, Martin Leo, additional, and Pileri, Stefano A, additional

Published
2011
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36. SNPs Array Karyotyping Reveals a Novel Recurrent 20p13 Amplification in Primary Myelofibrosis

Author

Visani, Giuseppe, primary, Sapienza, Maria Rosaria, additional, Isidori, Alessandro, additional, Tripodo, Claudio, additional, Laginestra, Maria Antonella, additional, Righi, Simona, additional, Sagramoso Sacchetti, Carlo A., additional, Gazzola, Anna, additional, Mannu, Claudia, additional, Rossi, Maura, additional, De Nictolis, Michele, additional, Valentini, Massimo, additional, Donati, Meris, additional, Emiliani, Roberto, additional, Alesiani, Francesco, additional, Paolini, Stefania, additional, Finelli, Carlo, additional, Pileri, Stefano A., additional, and Piccaluga, Pier Paolo, additional

Published
2011
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37. Systemic Epstein-Barr-virus-positive T cell lymphoproliferative childhood disease in a 22-year-old Caucasian man: A case report and review of the literature

Author

Tabanelli, Valentina, primary, Agostinelli, Claudio, additional, Sabattini, Elena, additional, Gazzola, Anna, additional, Bacci, Francesco, additional, Capria, Saveria, additional, Mannu, Claudia, additional, Righi, Simona, additional, Sista, Maria Teresa, additional, Meloni, Giovanna, additional, Pileri, Stefano A, additional, and Piccaluga, Pier Paolo, additional

Published
2011
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38. PDGFRA Activity Is Mediated by An Autocrine Loop in Peripheral T-Cell Lymphoma/Not Otherwise Specified (PTCL/NOS).

Author

Rossi, Maura, primary, Alviano, Francesco, additional, Laginestra, Antonella, additional, Tazzari, Pierluigi, additional, Ricci, Francesca, additional, Esposito, Aurora, additional, Agostinelli, Claudio, additional, Sista, Maria Teresa, additional, Gazzola, Anna, additional, Mannu, Claudia, additional, Righi, Simona, additional, Sapienza, Maria Rosaria, additional, Bagnara, Gian Paolo, additional, Hartmann, Sylvia, additional, Hansmann, Martin Leo, additional, Zinzani, Pier Luigi, additional, Pileri, Stefano Aldo, additional, and Piccaluga, Pier Paolo, additional

Published
2009
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39. Identification of Novel Cryptic Chromosomal Abnormalities in Primary Myelofibrosis by Single-Nucleotide Polymorphism Oligonucleotide Microarray.

Author

Visani, Giuseppe, primary, Isidori, Alessandro, additional, Sapienza, Maria Rosaria, additional, Righi, Simona, additional, Laginestra, Antonella, additional, Agostinelli, Claudio, additional, Sabattini, Elena, additional, De Nictolis, Michele, additional, Valentini, Massimo, additional, Donati, Meris, additional, Emiliani, Roberto, additional, Gazzola, Anna, additional, Mannu, Claudia, additional, Rossi, Maura, additional, Alesiani, Francesco, additional, Martinelli, Giovanni, additional, Iacobucci, Ilaria, additional, Paolini, Stefania, additional, Ascani, Stefano, additional, Finelli, Carlo, additional, Vianelli, Nicola, additional, Pileri, Stefano A., additional, and Piccaluga, Pier Paolo, additional

Published
2009
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40. Comparison of different DNA extraction methods from peripheral blood cells: advice from the Fondazione Italiana Linfomi Minimal Residual Disease Network.

Author

Mannu, Claudia, Gazzola, Anna, Ciabatti, Elena, Fuligni, Fabio, Cavalli, Marzia, Della Starza, Irene, Genuardi, Elisa, Mantoan, Barbara, Monitillo, Luigia, del Giudice, Ilaria, Ladetto, Marco, Gaidano, Gianluca, Sabattini, Elena, Pileri, Stefano A., Galimberti, Sara, and Piccaluga, Pier Paolo

Subjects
*NUCLEIC acid isolation methods, *BLOOD cells, *GENOMICS, *COMPARATIVE studies, *CYTODIAGNOSIS
Abstract

Genomic DNA extraction is a primary component of genomic research and diagnostic routine analysis. Recently, the importance of this process has been highlighted by the necessity to standardize the diagnostic procedure. In this regard, the Minimal Residual Disease (MRD) Network of the Fondazione Italiana Linfomi (FIL MRD Network) has performed a comparative study of four different commercially available kits for DNA extraction, applying them on a panel of cellular pellets, with the aim of defining possible technical recommendations in order to harmonize and standardize diagnostic procedures in the clinical setting. Overall, all four kits usually allowed the recovery of a significant quantity of high-quality DNA (in most conditions), although specific indications could be addressed for cellular pellets of different sizes. [ABSTRACT FROM PUBLISHER]

Published
2016
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41. Comparison of two real-time quantitative polymerase chain reaction strategies for minimal residual disease evaluation in lymphoproliferative disorders: correlation between immunoglobulin gene mutation load and real-time quantitative polymerase chain reaction performance

Author

Della Starza, Irene, Cavalli, Marzia, Del Giudice, Ilaria, Barbero, Daniela, Mantoan, Barbara, Genuardi, Elisa, Urbano, Marina, Mannu, Claudia, Gazzola, Anna, Ciabatti, Elena, Guarini, Anna, Foà, Robin, Galimberti, Sara, Piccaluga, Pierpaolo, Gaidano, Gianluca, Ladetto, Marco, and Monitillo, Luigia

Abstract

We compared two strategies for minimal residual disease evaluation of B-cell lymphoproliferative disorders characterized by a variable immunoglobulin heavy chain ( IGH) genes mutation load. Twenty-five samples from chronic lymphocytic leukaemia ( n = 18) or mantle cell lymphoma ( n = 7) patients were analyzed. Based on IGH variable region genes, 22/25 samples carried >2% mutations, 20/25 > 5%. In the IGH joining region genes, 23/25 samples carried >2% mutations, 18/25 > 5%. Real-time quantitative polymerase chain reaction was performed on IGH genes using two strategies: method A utilizes two patient-specific primers, whereas method B employs one patient-specific and one germline primer, with different positions on the variable, diversity and joining regions. Twenty-three samples (92%) resulted evaluable using method A, only six (24%) by method B. Method B poor performance was specifically evident among mutated IGH variable/joining region cases, although no specific mutation load above, which the real-time quantitative polymerase chain reaction failed was found. The molecular strategies for minimal residual disease evaluation should be adapted to the B-cell receptor features of the disease investigated. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Published
2014
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44. Distinctive Histogenesis and Immunological Microenvironment Based on Transcriptional Profiles of Follicular Dendritic Cell Sarcomas

Author

Luisa Lorenzi, Silvia Lonardi, Elena Sabattini, Stefano Pileri, Claudio Agostinelli, Maria Antonella Laginestra, Anna Gazzola, Carlo Sagramoso, Valentina Tabanelli, Federica Melle, Fabio Fuligni, Francesco Bacci, José Cabeçadas, Fabio Facchetti, Alessandro Pileri, Claudio Tripodo, Claudia Döring, Sylvia Hartmann, Maura Rossi, Anita Borges, Juan Rosai, Giovanna Motta, Ingrid Simonitsch-Klupp, Maria Rosaria Sapienza, Martin-Leo Hansmann, Elias Campo, Claudia Mannu, Laginestra, Maria Antonella, Tripodo, Claudio, Agostinelli, Claudio, Motta, Giovanna, Hartmann, Sylvia, Döring, Claudia, Rossi, Maura, Melle, Federica, Sapienza, Maria Rosaria, Tabanelli, Valentina, Pileri, Alessandro, Fuligni, Fabio, Gazzola, Anna, Mannu, Claudia, Sagramoso, Carlo Alberto, Lonardi, Silvia, Lorenzi, Luisa, Bacci, Francesco, Sabattini, Elena, Borges, Anita, Simonitsch-Klupp, Ingrid, Cabecadas, Jose, Campo, Elia, Rosai, Juan, Hansmann, Martin-Leo, Facchetti, Fabio, and Pileri, Stefano Aldo

Subjects
0301 basic medicine, Algorithms, B7-H1 Antigen, Castleman Disease, Chromatin, Cluster Analysis, Dendritic Cell Sarcoma, Follicular, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Programmed Cell Death 1 Ligand 2 Protein, Programmed Cell Death 1 Receptor, Signal Transduction, T-Lymphocytes, Helper-Inducer, T-Lymphocytes, Regulatory, Up-Regulation, Gene Regulatory Networks, Molecular Biology, Oncology, Cancer Research, Biology, Transcriptome, 03 medical and health sciences, medicine, Regulation of gene expression, Cluster Analysi, Gene Regulatory Network, Follicular dendritic cells, Mesenchymal stem cell, medicine.disease, Algorithm, Gene expression profiling, 030104 developmental biology, Cancer research, Immunohistochemistry, Sarcoma, Human, Extracellular matrix organization
Abstract

Follicular dendritic cell (FDC) sarcomas are rare mesenchymal tumors with variable clinical, morphologic, and phenotypic characteristics. Transcriptome analysis was performed on multiple FDC sarcomas and compared with other mesenchymal tumors, microdissected Castleman FDCs, and normal fibroblasts. Using unsupervised analysis, FDC sarcomas clustered with microdissected FDCs, distinct from other mesenchymal tumors and fibroblasts. The specific endowment of FDC-related gene expression programs in FDC sarcomas emerged by applying a gene signature of differentially expressed genes (n = 1,289) between microdissected FDCs and fibroblasts. Supervised analysis comparing FDC sarcomas with microdissected FDCs and other mesenchymal tumors identified 370 and 2,927 differentially expressed transcripts, respectively, and on the basis of pathway enrichment analysis ascribed to signal transduction, chromatin organization, and extracellular matrix organization programs. As the transcriptome of FDC sarcomas retained similarity with FDCs, the immune landscape of FDC sarcoma was investigated by applying the CIBERSORT algorithm to FDC sarcomas and non-FDC mesenchymal tumors and demonstrated that FDC sarcomas were enriched in T follicular helper (TFH) and T regulatory (TREG) cell populations, as confirmed in situ by immunohistochemistry. The enrichment in specific T-cell subsets prompted investigating the mRNA expression of the inhibitory immune receptor PD-1 and its ligands PD-L1 and PD-L2, which were found to be significantly upregulated in FDC sarcomas as compared with other mesenchymal tumors, a finding also confirmed in situ. Here, it is demonstrated for the first time the transcriptional relationship of FDC sarcomas with nonmalignant FDCs and their distinction from other mesenchymal tumors. Implications: The current study provides evidence of a peculiar immune microenvironment associated with FDC sarcomas that may have clinical utility. Mol Cancer Res; 15(5); 541–52. ©2017 AACR.

Published
2017
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45. Aberrant expression of CD10 and BCL6 in mantle cell lymphoma

Author

Francesco Piazza, Francesca Galuppini, Elena Sabattini, Claudio Agostinelli, Matteo Fassan, Massimo Rugge, Marco Pizzi, Simona Righi, Gianpietro Semenzato, Andrea Visentin, Claudia Mannu, Anna Gazzola, Pizzi, Marco, Agostinelli, Claudio, Righi, Simona, Gazzola, Anna, Mannu, Claudia, Galuppini, Francesca, Fassan, Matteo, Visentin, Andrea, Piazza, Francesco, Semenzato, Gianpietro C, Rugge, Massimo, and Sabattini, Elena

Subjects
Adult, Male, Pathology, medicine.medical_specialty, Histology, Proliferation index, Somatic cell, BCL6, mantle cell lymphoma, Lymphoma, Mantle-Cell, Biology, Pathology and Forensic Medicine, Young Adult, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, Cyclin D1, FISH, immune system diseases, hemic and lymphatic diseases, Biomarkers, Tumor, medicine, Humans, CD10, immunohistochemistry, 2734, Aged, Aged, 80 and over, Sanger sequencing, medicine.diagnostic_test, General Medicine, Middle Aged, medicine.disease, 030220 oncology & carcinogenesis, Proto-Oncogene Proteins c-bcl-6, symbols, Immunohistochemistry, Female, Neprilysin, Mantle cell lymphoma, Immunoglobulin Heavy Chains, 030215 immunology, Fluorescence in situ hybridization
Abstract

Aims Mantle cell lymphoma (MCL) is characterized by distinctive histologic and molecular features. Aberrant expression of BCL6 and CD10 has occasionally been reported, but the biological features of such cases are largely unknown. This study aimed to define the epidemiologic, histologic and cytogenetic characteristics of BCL6 and CD10-positive MCLs, also investigating possible biological features. Methods and Results 165 cases of cyclin D1 and t(11;14)(q13;q34) positive MCLs were studied for CD10 and BCL6 immunohistochemical expression which was documented in 26/165 (15.8%) cases (BCL6 17/165; CD10 11/165; BCL6 and CD10 co-expression 2/165). CD10-positivity was significantly more frequent in females (63.3%; p

Published
2017

46. Conventional PCR-based versus next-generation sequencing-based approach for T-cell receptor γ gene clonality assessment in mature T-cell lymphomas: A phase 3 diagnostic accuracy study.

Author

Donelli R, Gazzola A, Mannu C, Etebari M, Navari M, and Piccaluga PP

Abstract

Background: Clonality assessment is currently the major molecular analysis utilized to support the diagnosis of suspicious lymphoid malignancies. Clonal rearrangements of the V-J segments of T-cell receptor G chain locus (TCRγ or TRG) have been observed in almost all types of T neoplasms, such as T-cell-related non-Hodgkin lymphomas and leukemias. At present, the gold standard for clonality evaluation is multiplex polymerase chain reaction (PCR), plus subsequent capillary electrophoresis/heteroduplex analyses, and/or Sanger sequencing. This approach overcomes the problem with the conventional Southern blot hybridization and is more efficient, simple, fast, and reproducible. In the recent years, the new next-generation sequencing (NGS) technologies provided alternative techniques for the analysis of antigen receptors genes, which presented several advantages, such as increased efficiency, specificity (SP), sensitivity (ST), resolution, and objectivity of the results, leading to a better classification, stratification, and monitoring of lymphoid malignancies. Nonetheless, these technologies are still far from being the new gold standard since further studies are warranted to prove their utility. The present study aimed to assess the diagnostic accuracy of these two methods by comparing a commercial NGS-based assay for the evaluation of TRG locus with the gold standard PCR-based one, to fulfill the requirements of a phase 3 diagnostic accuracy study., Methods: We assessed the TRG gene rearrangements in 72 cases using the conventional and highly-validated PCR-based assay proposed by EuroClonality consortium, an alternative commercial PCR-based assay, namely, IdentiClone® TCR Gamma Gene Rearrangement Assay 2.0, and a commercial NGS-based assay, that is, Invivoscribe LymphoTrack® Dx MiSeq® (both by Invivoscribe Technologies Inc., San Diego, CA, USA), to determine the diagnostic accuracy of the latter, and compare them with reference diagnoses made based on observation of clinical manifestations, cytohistological, and immunohistochemical analyses. Statistical values were calculated using the Oxford CATmaker software package., Results: Using standardized criteria of interpretation, the obtained results showed a diagnostic accuracy of 90.3% (correspondence in 65 out of 72 cases) of the test under investigation, with a ST of 86%, a SP of 95%, a positive predicting value of 94%, and a negative predicting value of 88%, demonstrating that it had high efficiency and reliability in detecting clonal TRG gene rearrangements in T-cell non-Hodgkin lymphomas., Conclusions: This diagnostic accuracy study yielded comparable results using a validated PCR-based approach and a new NGS-based one. Subsequent studies and cost-effectiveness evaluation are needed to put the NGS-based clonality assessment into routine diagnostic practice., Competing Interests: The funding agency had no role in the design of the study, the collection, analyses or interpretation of data, the writing of the manuscript, or the decision to publish the results. The authors have no conflicts of interest to disclose., (© 2024 The Journal of Biological Methods, All rights reserved.)

Published
2024
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47. The role of molecular biology in the diagnosis of lymphoid neoplasms.

Author

Pizzi M, Gazzola A, Mannu C, Pileri SA, Sabattini E, and Pileri SA

Subjects
Biomarkers, Tumor genetics, Chromosome Aberrations, Humans, Prognosis, Reproducibility of Results, Sensitivity and Specificity, Gene Expression Profiling methods, High-Throughput Nucleotide Sequencing methods, Lymphoma diagnosis, Lymphoma genetics, Oligonucleotide Array Sequence Analysis methods
Abstract

In recent years, DNA-arrays, gene expression profiling and next-generation sequencing have elucidated the high complexity of genomic alterations occurring in lymphoid malignancies. These studies have also contributed to the identification of new diagnostic and prognostic biomarkers, which may represent possible targets for new therapeutic approaches. Such recent advances have significantly expanded the application of molecular tests to routine diagnostic hematopathology. It is thus conceivable that next-generation assays will soon flank traditional clonality tests and chromosomal translocation assays in the diagnostic work-up of difficult cases. This review is focused on the application of molecular biology techniques in the study of lymphoid tumors. Both conventional and next-generation tests will be addressed, with particular attention to their application to clinical practice.

Published
2014
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48. Use of IGK gene rearrangement analysis for clonality assessment of lymphoid malignancies: a single center experience.

Author

Mannu C, Gazzola A, Bacci F, Sabattini E, Sagramoso C, Roncolato F, Rossi M, Laginestra MA, Sapienza MR, Agostinelli C, De Leo A, Piccioli M, Righi S, Artioli P, Chilli L, Da Pozzo G, De Biase G, Sandri F, Pileri SA, and Piccaluga PP

Abstract

Diagnosis of B-non Hodgkin lymphomas (NHLs) is based on clinical, morphological and immunohistochemi-cal features. However, in up to 10-15% of cases, analysis of immunoglobulin heavy (IGH) or light (IGK/IGL) chains genes is required to discriminate between malignant and reactive lymphoid proliferations. In this study, we evaluated the feasibility and efficiency of IGK analysis in the routine diagnostic of B-cell lymphoproliferative disorders (B-LD) when applied to formalin-fixed paraffin-embedded (FFPE) tissues. Clonality patterns were studied in 59 B-LD using the BIOMED-2 protocol for IGK assays, after failure of the IGH assay. PCR products were evaluated by both heterodu-plex and GeneScan analysis. IGK analysis was technically successful in all cases. Overall, it supported the histopa-thological suspicion in 52/59 cases (88%), the sensitivity and specificity being 83% and 80%, respectively. Further, positive and negative predictive values were 95% and 50%, respectively. Interestingly, among various lymphoma subtypes, marginal zone lymphoma and follicular lymphoma most frequently required IGK analysis. In conclusion, IGK study according to the BIOMED-2 protocol resulted feasible and extremely useful in supporting challenging diagnosis of B-LD even if applied on FFPE samples. Accordingly, when NHL is suspected, negative results at IGH analysis should not be considered as conclusive and further investigation of IGK is appropriate.

Published
2011

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