Updated World Health Organization Classification Research Articles

The spectrum of peripheral T-cell lymphomas

This review summarizes recent progress that has advanced our understanding of the pathobiology and prognosis of peripheral T-cell lymphomas including the changes introduced to the updated World Health Organization classification of lymphoid neoplasms. The International Peripheral T-Cell Lymphoma Project was a large collaborative project, highlighting the clinico-pathologic and geographic differences of this diverse group of diseases. Peripheral T-cell lymphoma, not otherwise specified, is a biologically heterogeneous subtype, and a number of studies including investigations using molecular profiling have explored whether meaningful prognostic or biologic subgroups can be identified. Angioimmunoblastic T-cell lymphoma demonstrates overlapping immunophenotypical and molecular features with normal follicular T-helper cells, giving some insight into the cell of origin. Systemic anaplastic large cell lymphoma is composed of two disease groups based on the presence or absence of anaplastic lymphoma kinase overexpression. Anaplastic lymphoma kinase-positive anaplastic large cell lymphoma has a significantly better prognosis than anaplastic lymphoma kinase-negative anaplastic large cell lymphoma and molecular studies have illustrated that each entity has a distinct molecular profile. Anaplastic lymphoma kinase-negative anaplastic large cell lymphoma has been recently shown to have a more favourable, but still unsatisfactory, prognosis than peripheral T-cell lymphoma, not otherwise specified, and biological and molecular distinctions confirm that they are separate entities. Advances are being made in understanding the unique pathobiology of the peripheral T-cell lymphoma subtypes that will help to refine diagnoses, identify potential prognostic markers, elucidate the molecular mechanisms critical in disease pathogenesis and define new therapeutic targets in the poor-risk population.

Myelodysplastic syndromes: biology and treatment

Optimal management of patients with myelodysplastic syndromes (MDS) requires an insight into the biology of the disease and the mechanisms of action of the available therapies. This review focuses on low-risk MDS, for which chronic anaemia and eventual progression to acute myeloid leukaemia are the main concerns. We cover the updated World Health Organization classification, the latest prognostic scoring system, and describe novel findings in the pathogenesis of 5q- syndrome. We perform in depth analyses of two of the most widely used treatments, erythropoietin and lenalidomide, discussing mechanisms of action, reasons for treatment failure and influence on survival.

Peripheral T-Cell Lymphomas: An Historical Perspective

Peripheral T-cell lymphomas (PTCL) remain largely unexplored due to disease rarity and biological heterogeneity as well as relatively recent recognition in modern classification systems. Before 1970, classifications of non-Hodgkin’s lymphomas (NHL) were based on morphology. The discovery of distinct T-, B- and natural killer (NK)–cell lineages led to two immunologically based classification systems proposed in 1974: the European Kiel and the North American Lukes-Collins. In 1982, the Working Formulation (WF), based on clinical and morphologic criteria, was developed in the United States. The updated Kiel classification separated B- and Tcell lymphomas but still failed to address some disease types. The addition of molecular genetic features/criteria and increasing immunophenotypic subclassification allowed for more diagnostic standardization and reproducibility. The International Lymphoma Study Group (ILSG) integrated morphologic, phenotypic, molecular and clinical information in the 1994 REAL (Revised European American Lymphoma) classification. The T-cell lymphomas were grouped into “precursor” neoplasms versus “peripheral” or post-thymic T-cell and NK neoplasms, the so-called “PTCLs.” The World Health Organization (WHO) subsequently made the following modifications: PTCLs were subdivided into predominantly leukemic, extranodal and nodal types; cutaneous and systemic anaplastic large cell lymphomas (ALCL) were separated; terminology was updated for some diseases; and subcutaneous panniculitis-type and hepatosplenic γδ T-cell lymphomas were recognized as distinct entities. Almost a decade later, the recently published fourth edition of the WHO classification has refined the classification further, including defining ALK-negative ALCL as a provisional entity, confining subcutaneous panniculitislike T-cell lymphoma to cases with an αβ phenotype and combining the γδ cases with primary cutaneous γδ PTCL. Two other provisional categories have been established under the category of primary cutaneous peripheral T-cell lymphomas: primary cutaneous CD4-positive small/medium-sized pleomorphic T-cell lymphoma and CD8-positive cytotoxic T-cell lymphoma. Several important advances in the pathobiology of PTCL have been made. Unlike mature B-cell lymphomas, there are virtually no recurrent translocations characterizing the PTCLs. The one exception is a proportion of ALCL cases in which a non-random t(2;5)(p23;q35) translocation produces a novel fusion protein composed of the nucleophosmin (NPM) and anaplastic lymphoma (ALK) coding regions. The use of more detailed cytogenetic analysis with comparative genomic hybridization and gene expression profiling now provide evidence for recurrent genetic changes in other PTCL subtypes. Several PTCL subtypes have viral associations that may be involved in disease pathogenesis. In 1982, HTLV1 was found to be the etiologic agent of adult T-cell leukemia and lymphoma. In 1988, T-cell lymphomas were described in patients with chronic Epstein-Barr virus (EBV) infections, and EBV was subsequently found to be associated with extranodal NK/T-cell lymphoma, nasal type and angioimmunoblastic T-cell lymphoma. With the development of molecular techniques in the 1990s, the importance of the γδ T-cell receptor rearrangement and impact on prognosis is apparent. For example, in the updated WHO classification primary cutaneous γδ T-cell lymphoma is recognized by an aggressive course and considered a new provisional entity. Although significant progress has been made in defining specific disease categories within the diverse group of PTCLs and establishing the prognostic significance, advances in therapy have been much slower. In the last several years, attention has turned to testing new chemotherapy combinations, targeted agents and high-dose chemotherapy approaches specifically in PTCL. The hope for the future is that treatment can be tailored better for PTCL and outcomes will more approximate what is observed in aggressive B-cell NHL.

Solitary Fibrous Tumors in the Head and Neck: New Insights and Implications for Diagnosis and Treatment

The solitary fibrous tumor (SFT) is a potentially malignant spindle cell neoplasm of mesenchymal origin that was originally described as a thoracic lesion originating from pleural tissue. Recently, numerous extrapleural sites of origin have been described, frequently affecting the head and neck region. The purpose of this article is to focus on a formerly underestimated neoplasm and to highlight its appearance in the head and neck region. The authors present 2 illustrative cases, including what is probably the first reported case of an SFT arising in the human tonsillar fossa, and give a clinical and pathological literature review. The clinical, histologic, and radiologic features are presented, and the surgical treatment is described. The international medical literature concerning SFTs in general and SFTs of the head and neck in particular is reviewed, and the changing concept of SFTs and hemangiopericytomas is discussed on the basis of the updated World Health Organization classification of soft tissue tumors. It is nowadays recognized that the large majority of lesions formerly classified as hemangiopericytomas are, in fact, variants of SFTs. Although still a rare occurrence, SFTs have become increasingly recognized, and clinicians should be aware of their presentation.