Preface

Tumors derived from T-lymphocytes are uncommon, representing 10% of lymphoid malignancies overall and encompassing several extremely rare different entities. However, they represent an important diagnostic and therapeutic challenge. In fact, on the one hand, their rarity, heterogeneity, as well as the lack of specific diagnostic markers make their diagnosis quite difficult. Indeed, large studies performed in Europe and the United States showed that up to 30% of cases are misdiagnosed. On the other hand, largely due to their rarity, the currently used therapeutic schemes are basically derived from those adopted for B-cell malignancies and appear definitely unsatisfactory. Only recently have specific clinical trials been dedicated to T-cell lymphomas, leading to the approval of a few new drugs for second-line treatments. Hopefully, currently ongoing trials will be able to show some benefit when such new drugs are included in first-line approaches as well.

In this book, a brief overview on the most updated World Health Organization (WHO) classification and the general features of peripheral T-cell lymphomas (PTCLs) is first provided. Thereafter, a few entities have been described in more detail and, eventually, new concepts of personalized targeted treatments are listed and discussed. A particular emphasis has been given to anaplastic large cell lymphomas, the classification of which has been significantly modified in the new WHO blue book, now including anaplastic lymphoma kinase-positive and -negative forms, as well as the cutaneous and breast implant-associated types. Similarly, non-cutaneous and gamma-delta T-cell lymphomas has been described according to their new classification. In all sections and chapters, the role of molecular genetics has been considered, highlighting its role in the development of novel classification as well as of new, more rational targeted approaches. In fact, the better understanding of PTCL pathophysiology, largely based on gene expression profiling and next-generation sequencing studies, had a pivotal role in the definition of novel targets for more effective therapies. As prototypic examples of this process, therapies targeting the epigenetic machinery as well as Aurora kinase inhibitors have been deeply described. It should not be forgotten, nonetheless, that the prognosis of PTCL patients is still generally dismal and extensive basic and clinical research have to be carried out in the future to improve the present scenario.

The book is intended for all health professionals, particularly for those involved in the diagnosis and treatment of oncological diseases, as well as medical students and fellows.

As editor, I am indeed grateful to IntechOpen, and especially Ms. Sara Debeuc, for help and support, as well as to all the authors contributing to this book.

## **Pier Paolo Piccaluga, MD, PhD** Professor, Institute of Hematology and Medical Oncology, Department of Experimental, Diagnostic and Specialty Medicine, Bologna University School of Medicine, Bologna, Italy

**1**

**Chapter 1**

Classification

in Europe where HTVL1 is endemic.

**2. T-follicular helper cell-related lymphomas**

*Pier Paolo Piccaluga*

**1. Introduction**

Introductory Chapter: Updates

2017 Peripheral T-Cell Lymphoma

Peripheral T-cell lymphomas (PTCLs) are relatively rare disorders, representing around 10% of all lymphomas worldwide; however, they are relatively common in specific geographic areas, including Asia, the Caribbean basin, and scattered areas

In the latest edition of the World Health Organisation (WHO) Classification of Tumours of Haematopoietic and Lymphoid Tissues, edited in 2017, nodal, extra nodal and leukaemia forms are listed. Specifically, as many as 31 entities are listed among PTCLs [1]. Compared with the previous edition, in the current classification, a few but quite relevant novelties have been introduced. Generally speaking, as already observed for B-cell derived malignancies, recent discoveries from molecular genetic studies led to a better definition of certain entities and clearly defined a pivotal role for cellular derivation in tumour classification. In the following, the main updates concerning non-cutaneous PTCLs will be briefly discussed.

Among nodal PTCLs, that overall constitute the majority of PTCL cases, a new subgroups has been defined based on the corresponding to a specific cellular counterpart, namely the T-follicular helper (TFH) lymphocytes. The latter is physiologically represented within germinal centres of secondary follicles, providing costimulatory signalling to B-lymphocytes through many different singling pathways [2]. These cells, at immunophenotyping, are characterised by the expression of selected markers, including BCL6, SAP, ICOS, CXCL13 and CD10. Consistently, tutors derived from TFH cells express these molecules. However, likely due to the aberrancy in phenotype, which is typical of PTCLS [3], some of them may lack in a single case. Therefore, an extended panel should be tested to confirm the diagnosis. On the other hand, since non-TFH-derived PTCLs may express one of these markers, it is recommended to detect positive staining for at least two (better would be three) of them to claim a TFH derivation [4]. TFH-related PTCLs currently include three main nodal PTCL types, namely angioimmunoblastic T-cell lymphoma (AITL, the commonest PTCL in northern Europe), follicular T-cell lymphoma (FTCL, formerly accounted among PTCLS not otherwise specified/NOS), and PTCL/NOS not fulfilling the diagnostic criteria for the previous tutors but showing

and New Insights from WHO

## **Chapter 1**
