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1. Atypical Mature T-Cell Neoplasms: The Relevance of the Role of Flow Cytometry

Author

Statuto, Teodora, D’Auria, Fiorella, Del Vecchio, Luigi, Mansueto, Giovanna Rosaria, Villani, Oreste, Lalinga, Anna Vittoria, Possidente, Luciana, Nozza, Filomena, Vona, Gabriella, Rago, Luciana, Storto, Giovanni, Gasparini, Vanessa Rebecca, Zambello, Renato, D’Arena, Giovanni, and Valvano, Luciana

Subjects
angioimmunoblastic t-cell lymphoma, diagnosis, peripheral t-cell lymphoma not otherwise specified, Angioimmunoblastic T-cell lymphoma, Diagnosis, Flow cytometry, Immunophenotype, Peripheral T-cell lymphoma not otherwise specified, T-cell prolymphocytic leukemia, flow cytometry, Case Series, t-cell prolymphocytic leukemia, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, lcsh:RC254-282, OncoTargets and Therapy, immunophenotype
Abstract

Teodora Statuto,1,* Fiorella D’Auria,2,* Luigi Del Vecchio3,4,†, Giovanna Rosaria Mansueto,5 Oreste Villani,5 Anna Vittoria Lalinga6,†, Luciana Possidente,6 Filomena Nozza,1 Gabriella Vona,1 Luciana Rago,7 Giovanni Storto,8 Vanessa Rebecca Gasparini,9 Renato Zambello,10 Giovanni D’Arena,5,* Luciana Valvano1,* 1Laboratory of Clinical Research and Advanced Diagnostics, Centro Di Riferimento Oncologico Della Basilicata (IRCCS-CROB), Rionero in Vulture, Pz, Italy; 2Unit of Clinical Pathology, Centro Di Riferimento Oncologico Della Basilicata (IRCCS-CROB), Rionero in Vulture, Pz, Italy; 3CEINGE Biotecnologie Avanzate S.c.a.r.l, Federico II University, Naples, Italy; 4Department of Molecular Medicine and Medical Biotechnology (DMMBM), Federico II University, Naples, Italy; 5Hematology Department of Basilicata, Centro Di Riferimento Oncologico Della Basilicata (IRCCS-CROB), Rionero in Vulture, Pz, Italy; 6Pathology Unit, Centro Di Riferimento Oncologico Della Basilicata (IRCCS-CROB), Rionero in Vulture, Pz, Italy; 7Radiotherapy Unit, Centro Di Riferimento Oncologico Della Basilicata (IRCCS-CROB), Rionero in Vulture, Pz, Italy; 8Department of Nuclear Medicine, Centro Di Riferimento Oncologico Della Basilicata (IRCCS-CROB), Rionero in Vulture, Pz, Italy; 9Department of Medicine, University of Padova - Veneto Institute of Molecular Medicine, VIMM, Padova, PD, Italy; 10Hematology and Clinical Immunology, Department of Medicine, Padua School of Medicine, Padova, PD, Italy†Anna Vittoria Lalinga passed away on January 26, 2020 and Luigi Del Vecchio passed away on August 16, 2018*These authors contributed equally to this workCorrespondence: Luciana ValvanoLaboratory of Clinical Research and Advanced Diagnostics, Centro Di Riferimento Oncologico Della Basilicata (IRCCS-CROB), Rionero in Vulture, Pz, ItalyTel +39 0972 726395Fax +39 0972 723509Email luciana.valvano@crob.itAbstract: Lymphoproliferative disorders are a heterogeneous group of malignant clonal proliferations of lymphocytes whose diagnosis remains challenging, despite diagnostic criteria are now well established, due to their heterogeneity in clinical presentation and immunophenotypic profile. Lymphoid T-cell disorders are more rarely seen than B-cell entities and more difficult to diagnose for the absence of a specific immunophenotypic signature. Flow cytometry is a useful tool in diagnosing T-cell lymphoproliferative disorders since it is not only able to better characterize T-cell neoplasms but also to resolve some very complicated cases, in particular those in which a small size population of neoplastic cells is available for the analysis. Here, we report three patients with mature T-cell neoplasms with atypical clinical and biological features in which analysis of peripheral blood and bone marrow specimens by means of multicolor flow cytometry was very useful to identify and characterize three rare T-cell lymphoproliferative disorders, such as angioimmunoblastic T-cell lymphoma, peripheral T-cell lymphoma not otherwise specified and T-cell prolymphocytic leukemia. The aim of this case series report is not only to describe three rare cases of lymphoproliferative neoplasms but also to raise awareness that a fast, highly sensitive, and reproducible procedure, such as flow cytometry immunophenotyping, can have a determinant diagnostic role in these patients.Keywords: flow cytometry, immunophenotype, angioimmunoblastic T-cell lymphoma, peripheral T-cell lymphoma not otherwise specified, T-cell prolymphocytic leukemia, diagnosis

Published
2020

3. Myelodysplastic disorders carrying both isolated del(5q) and JAK2V617F mutation: concise review, with focus on lenalidomide therapy

Author

D'Arena, Giovanni, Musto,Pellegrino, Simeon,Vittorio, Guariglia,Roberto, Bianchino,Gabriella, Grieco,Vitina, Nozza,Milena, La Rocca,Francesco, Marziano,Gioacchino, Lalinga,Anna Vittoria, Voso,Maria Teresa, Scaravaglio,Patrizia, and Mecucci,Cristina

Subjects
OncoTargets and Therapy
Abstract

Pellegrino Musto,1 Vittorio Simeon,2 Roberto Guariglia,3 Gabriella Bianchino,4 Vitina Grieco,4 Filomena Nozza,4 Francesco La Rocca,2 Gioacchino Marziano,1 Anna Vittoria Lalinga,5 Emiliano Fabiani,6 Maria Teresa Voso,6 Patrizia Scaravaglio,7 Cristina Mecucci,8 Giovanni D'Arena31Scientific Direction, 2Laboratory of Preclinical and Translational Research, 3Unit of Hematology and Stem Cell Transplantation, 4Laboratory of Clinical Research and Advanced Diagnostics, 5Pathology Unit, IRCCS, Centro di Riferimento Oncologico della Basilicata, Rionero in Vulture, Italy; 6Department of Hematology, Universita Cattolica del Sacro Cuore, Rome, Italy; 7Laboratory of Internal Medicine and Hematology, S Luigi Gonzaga Hospital, Orbassano, Italy; 8Hematology and Bone Marrow Transplantation Unit, University of Perugia, Perugia, ItalyAbstract: The concomitant presence of del(5q) and JAK2V617F mutation is an infrequent event which occurs in rare patients with peculiar cytogenetic, molecular, morphological and clinical features, resembling those of both myelodysplastic syndromes and myeloproliferative neoplasms. Lenalidomide may induce rapid, profound, and long-lasting responses in a subset of these patients. However, the mechanism(s) by which the drug acts in these conditions remain not completely elucidated. A new case report and a review of all cases published so far in this setting are provided. Furthermore, the possibility of categorizing – from a clinical, pathological, and biological point of view – for at least some of these patients as a potential distinct entity is discussed.Keywords: myelodysplastic syndromes, myeloproliferative neoplasms, lenalidomide, del(5q), JAK2, World Health Organization

Published
2014

4. Myelodysplastic disorders carrying both isolated del(5q) and JAK2V617F mutation: concise review, with focus on lenalidomide therapy.

Author

Musto, Pellegrino, Simeon, Vittorio, Guariglia, Roberto, Bianchino, Gabriella, Grieco, Vitina, Nozza, Filomena, Rocca, Francesco La, Marziano, Gioacchino, Lalinga, Anna Vittoria, Fabiani, Emiliano, Voso, Maria Teresa, Scaravaglio, Patrizia, Mecucci, Cristina, and D'Arena, Giovanni

Subjects
MYELODYSPLASTIC syndromes, CYTOGENETICS, MYELOPROLIFERATIVE neoplasms, TUMORS, BONE marrow diseases, THERAPEUTICS
Abstract

The concomitant presence of del(5q) and JAK2V617F mutation is an infrequent event which occurs in rare patients with peculiar cytogenetic, molecular, morphological and clinical features, resembling those of both myelodysplastic syndromes and myeloproliferative neoplasms. Lenalidomide may induce rapid, profound, and long-lasting responses in a subset of these patients. However, the mechanism(s) by which the drug acts in these conditions remain not completely elucidated. A new case report and a review of all cases published so far in this setting are provided. Furthermore, the possibility of categorizing - from a clinical, pathological, and biological point of view - for at least some of these patients as a potential distinct entity is discussed. [ABSTRACT FROM AUTHOR]

Published
2014
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7. Mast cell sarcoma of the scalp: The first sign of undisclosed systemic mastocytosis?

Author

Falleti, Jessica, Borgia, Ludovica, Lalinga, Anna Vittoria, De Cecio, Rossella, Natella, Valentina, Patitucci, Giuseppe, and Vita, Giulia

Subjects
*SARCOMA, *MAST cell disease, *SCALP, *DISEASES, *CD34 antigen, *RARE diseases, *CELL growth
Abstract

Abstract: Mastocytosis is a neoplastic disease of mast cells and their CD34+ precursors, including a heterogeneous group of disorders. It is characterized by abnormal growth and accumulation of mast cells in one or more organ systems. Mast cell sarcoma is an extremely rare and aggressive disease characterized by local proliferation of atypical mast cells, destructive growth and poor prognosis, without systemic involvement. Very few clinical cases describing this entity have been reported in the literature. In this paper, we report a case of a mast cell sarcoma, localized in the scalp of a 63-year-old woman; it appears to be the first manifestation of undisclosed systemic mastocytosis. [Copyright &y& Elsevier]

Published
2012
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8. Myelodysplastic disorders carrying both isolated del(5q) and JAK2V617F mutation: concise review, with focus on lenalidomide therapy

Author

Pellegrino Musto, Gabriella Bianchino, Anna Vittoria Lalinga, Roberto Guariglia, Francesco La Rocca, Vittorio Simeon, Gioacchino Marziano, Vitina Grieco, Filomena Nozza, Giovanni D'Arena, Emiliano Fabiani, Patrizia Scaravaglio, Maria Teresa Voso, Cristina Mecucci, Musto, Pellegrino, Simeon, Vittorio, Guariglia, Roberto, Bianchino, Gabriella, Grieco, Vitina, Nozza, Filomena, La Rocca, Francesco, Marziano, Gioacchino, Lalinga, Anna Vittoria, Fabiani, Emiliano, Voso, Maria Teresa, Scaravaglio, Patrizia, Mecucci, Cristina, and D'Arena, Giovanni

Subjects
Lenalidomide therapy, Pathology, medicine.medical_specialty, JAK2, World Health Organization, del(5q), lenalidomide, myelodysplastic syndromes, myeloproliferative neoplasms, Review, Bioinformatics, lcsh:RC254-282, medicine, Pharmacology (medical), Pathological, Lenalidomide, Mechanism (biology), business.industry, Myelodysplastic syndromes, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, myelodysplastic syndrome, Settore MED/15 - MALATTIE DEL SANGUE, Oncology, Concomitant, Mutation (genetic algorithm), business, JAK2 V617F, medicine.drug
Abstract

Pellegrino Musto,1 Vittorio Simeon,2 Roberto Guariglia,3 Gabriella Bianchino,4 Vitina Grieco,4 Filomena Nozza,4 Francesco La Rocca,2 Gioacchino Marziano,1 Anna Vittoria Lalinga,5 Emiliano Fabiani,6 Maria Teresa Voso,6 Patrizia Scaravaglio,7 Cristina Mecucci,8 Giovanni D'Arena31Scientific Direction, 2Laboratory of Preclinical and Translational Research, 3Unit of Hematology and Stem Cell Transplantation, 4Laboratory of Clinical Research and Advanced Diagnostics, 5Pathology Unit, IRCCS, Centro di Riferimento Oncologico della Basilicata, Rionero in Vulture, Italy; 6Department of Hematology, Universita Cattolica del Sacro Cuore, Rome, Italy; 7Laboratory of Internal Medicine and Hematology, S Luigi Gonzaga Hospital, Orbassano, Italy; 8Hematology and Bone Marrow Transplantation Unit, University of Perugia, Perugia, ItalyAbstract: The concomitant presence of del(5q) and JAK2V617F mutation is an infrequent event which occurs in rare patients with peculiar cytogenetic, molecular, morphological and clinical features, resembling those of both myelodysplastic syndromes and myeloproliferative neoplasms. Lenalidomide may induce rapid, profound, and long-lasting responses in a subset of these patients. However, the mechanism(s) by which the drug acts in these conditions remain not completely elucidated. A new case report and a review of all cases published so far in this setting are provided. Furthermore, the possibility of categorizing – from a clinical, pathological, and biological point of view – for at least some of these patients as a potential distinct entity is discussed.Keywords: myelodysplastic syndromes, myeloproliferative neoplasms, lenalidomide, del(5q), JAK2, World Health Organization

Published
2014

9. Cardiovascular risk of smoking and benefits of smoking cessation.

Author

Gallucci G, Tartarone A, Lerose R, Lalinga AV, and Capobianco AM

Abstract

Smoking increases mortality from all causes and has a crucial role in atherosclerotic cardiovascular disease (ASCVD). Active smoking and secondhand smoke exposure determine more than 30% of coronary heart disease (CHD) mortality. The exact mechanisms of cardiovascular damages are not well known, but the detrimental effect of smoking on endothelial function has long been recognized. Smoking elicits oxidative processes, negatively affects platelet function, fibrinolysis, inflammation and vasomotor function; all these proatherogenic effects double the 10-year risk of fatal events in smokers compared to non smokers. An intriguing issue about smoking is the vulnerability of female gender. The mortality from cardiovascular diseases (CVDs) is higher in female than male smokers and female smokers show a 25% higher risk of developing CHD than men with the same exposure to tobacco smoke. This female vulnerability seems to be related to genes involved in thrombin signaling. The effects of smoking cessation have also been extensively studied. Cessation at an early age (40 years) has an impressive 90% reduction in the excess risk of death. In this review we report recent data about the causal link between smoking and CVDs and about the benefits of smoking cessation., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd.2020.02.47). The series “Improving Outcomes in Lung Cancer Through Early Diagnosis and Smoking Cessation” was commissioned by the editorial office without any funding or sponsorship. AT served as the unpaid Guest Editor of the series and serves as an unpaid editorial board member of Journal of Thoracic Disease from Aug 2019 to Jul 2021. The authors have no other conflicts of interest to declare., (2020 Journal of Thoracic Disease. All rights reserved.)

Published
2020
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10. Macrophage migration inhibitory factor protein and mRNA expression in cutaneous melanocytic tumours.

Author

Miracco C, De Nisi MC, Arcuri F, Cosci E, Pacenti L, Toscano M, Lalinga AV, Biagioli M, Rubegni P, Vatti R, Maellaro E, Del Bello B, Massi D, Luzi P, and Tosi P

Subjects
Cell Nucleus metabolism, Cytoplasm metabolism, Humans, Immunohistochemistry, Macrophage Migration-Inhibitory Factors genetics, Melanoma pathology, Neoplasm Metastasis, Nevus, Pigmented pathology, Reverse Transcriptase Polymerase Chain Reaction, Skin Neoplasms pathology, Macrophage Migration-Inhibitory Factors metabolism, Melanoma metabolism, Nevus, Pigmented metabolism, RNA, Messenger metabolism, Skin Neoplasms metabolism
Abstract

Macrophage migration inhibitory factor (MIF) is a widely expressed cytokine involved in various biological processes. Although MIF's functions in cancer have not been completely elucidated, its expression has usually been correlated with tumour progression and aggressiveness, and it is currently discussed as a new promising target for novel therapies. Recent studies seem to confirm its active role in melanoma pathobiology; however, its expression has not yet been extensively studied in melanocytic tumours. We evaluated MIF protein expression in 126 skin lesions, including benign and atypical nevi, melanoma and melanoma metastases. In 55 cases, we also assessed MIF mRNA expression by real-time RT-PCR. Benign nevi were subdivided into nevocytic and Spitz/blue types; and melanomas into the radial, and vertical growth phase. A strong cytoplasmic MIF positivity was found in most samples, although it was more heterogeneous in malignant tumours; MIF nuclear expression characterized Spitz/blue nevi, atypical nevi, melanomas and metastases. All samples expressed MIF mRNA but it was significantly lower in benign nevi vs atypical nevi, melanomas and metastases (p=0.001; p<0.0001; p=0.002, respectively). Our study shows a widespread distribution of MIF among melanocytic tumours. Whereas we observed a trend towards higher expression levels of mRNA in atypical and malignant tumours, MIF protein was highly expressed in all lesions, although limited to the cytoplasm in most benign nevi. These observations suggest differences in MIF protein storage, subcellular location and properties in most benign nevi vs atypical and malignant tumours that should be confirmed by further investigation and correlation with clinical outcome.

Published
2006

11. In situ detection of telomeres by fluorescence in situ hybridization and telomerase activity in glioblastoma multiforme: correlation with p53 status, EGFR, c-myc, MIB1, and Topoisomerase IIalpha protein expression.

Author

Miracco C, De Santi MM, Luzi P, Lalinga AV, Laurini L, De Nisi MC, Angeloni G, Brogi M, Cardone C, Carducci A, Arcuri F, Tosi P, Rubino G, and Pirtoli L

Subjects
Acid Phosphatase metabolism, Adolescent, Adult, Antigens, Neoplasm, Brain Neoplasms enzymology, Cell Division, Child, DNA Topoisomerases, Type II metabolism, DNA-Binding Proteins, ErbB Receptors metabolism, Glioblastoma metabolism, Glioblastoma pathology, Humans, Image Processing, Computer-Assisted, Isoenzymes metabolism, Ki-67 Antigen biosynthesis, Ki-67 Antigen metabolism, Middle Aged, Polymorphism, Single-Stranded Conformational, Proto-Oncogene Proteins c-myc metabolism, Tartrate-Resistant Acid Phosphatase, Tumor Suppressor Protein p53 metabolism, Glioblastoma enzymology, In Situ Hybridization, Fluorescence methods, Telomerase metabolism, Telomere ultrastructure
Abstract

Aberrations of genes/proteins regulating cell cycle and growth, increased proliferation and telomerase activity (TA) are documentable in glioblastoma multiforme. TA is more frequently detectable in secondary glioblastoma, which is also characterized by p53 mutation/overexpression. Discordant telomere (Te) length values have been reported in glioblastomas with and without TA. In 31 glioblastomas, in which pre-existing astrocytoma was not documented, we compared cases with and without TA for the expression of p53, EGFR, c-Myc, MIB-1 and Topoisomerase IIalpha; p53 mutations were also investigated by SSCP-PCR. Correlations were made with Te parameters [TePs: number (TeNo), length and area] as evaluated by image analysis in interphase nuclei of fluorescence in situ hybridization (FISH)-processed sections. We found no differences in the expression of the proteins evaluated and in TePs, except Te/nuclear area %, which was significantly lower in TA+ cases (p=0.02). TePs were, instead, inversely correlated with TA (p=0.0001). TA was positively correlated with MIB1 staining index in the TA+ cases (p=0.033), which also showed a positive correlation between TeNo and EGFR expression (p=0.042), and a trend towards a negative correlation between TeNo and p53 expression (p=0.05). Tumors overexpressing EGFR had a significantly shorter lifetime (p=0.0001). TeNo seems to be inversely correlated to tumor proliferation and lifetime in glioblastoma multiforme.

Published
2003

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