Mediterranean Journal of Hematology and Infectious Diseases

Hodgkin’s lymphoma is a lymphoid tumour that represents about 1% of all de novo neoplasms occurring every year worldwide. Its diagnosis is based on the identification of characteristic neoplastic cells within an inflammatory milieu. Molecular studies have shown that most, if not all cases, belong to the same clonal population, which is derived from peripheral B-cells. The relevance of Epstein-Barr virus infection at least in a proportion of patients was also demonstrated. The REAL/WHO classification recognizes a basic distinction between nodular lymphocyte predominance HL (NLPHL) and classic HL (CHL), reflecting the differences in clinical presentation, behavior, morphology, phenotype, molecular features as well as in the composition of their cellular background. CHL has been classified into four subtypes: lymphocyte rich, nodular sclerosing, mixed cellularity and lymphocyte depleted. 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 and possible mechanisms of lymphomagenesis. Introduction. In the first half of 19 century, Sir Thomas Hodgkin provided the first macroscopic description of the process, that Samuel Wilkins named Hodgkin Disease (HD) in a paper entitled “On some morbid appearances of the absorbent glands and spleen”. In 1898 and 1902, Carl Sternberg and Dorothy Reed independently described the typical “diagnostic” cells. In 1956, Smetana and Cohen identified a histopathological variant of granulomatous HD, which was characterized by sclerotic changes and better prognosis. This variant was termed “nodular sclerosis HD” in the classification proposed by Lukes, Butler, and Hicks in 1964, and its simplified form, produced by the Rye conference, has been used routinely until 1994 when it was replaced with the revised European– American lymphoma (REAL) classification. In the latter the Hodgkin lymphoma (HL) was listed in and subdivided into two main types: nodular lymphocyte predominant (NLPHL) and classical HL (CHL), in the light of morphological, phenotypic, genotypic, and clinical findings. CHL included the following subtypes: nodular sclerosis (NS-CHL), mixed Mediterr J Hematol Infect Dis 2014; 6; Open Journal System cellularity (MC-CHL), lymphocyte-depleted (LDCHL) and the lymphocyte rich CHL (LR-CHL). This approach has finally been adopted by the World Health Organisation (WHO) scheme in 2001 and confirmed in the WHO classification 2008 (Table 1). Table 1. World Health Organisation classification of Hodgkin Lymphoma. Nodular lymphocyte predominant HL Classical Hodgkin lymphoma • Nodular sclerosis CHL (grades 1 and 2) • Mixed cellularity CHL • Lymphocyte rich CHL* • Lymphocyte depleted CHL *This includes a nodular (common) and a diffuse (rare) form. Nodular Lymphocyte Predominant Hodgkin Lymphoma. NLPHL represents 4–5% of all HL cases. Most patients present with localized disease (stage I or II), usually affecting single cervical, axillary, or inguinal nodes; splenic, bone marrow and mediastinal involvement is rare. The tumour has a very indolent course, with prolonged disease free intervals, despite a high rate of late relapses, which usually respond well to treatment. Progression to a diffuse large B cell lymphoma (DLBCL) has been reported in 3-5% of case, which has a more favourable outcome than de novo large B cell lymphomas. Morphology: NLPHL differs greatly from the classical type in terms of morphology and the only feature shared with CHL is the paucity of the neoplastic population which consists of large elements, formerly called L&H (lymphocytic/histiocytic) or popcorn cells and now designated as LP (lymphocyte predominant) cells (Figure 1, a) in the 4 edition of the WHO Classification. The lymph node architecture is totally or partially effaced by a nodular or a nodular and diffuse infiltrate consisting of small lymphocyte, histiocytes, epitheliod elements admixed with LP cells. The latter show nuclei with a polylobular profile, finely dispersed chromatin and multiple, basophilic small nucleoli resembling those of centroblasts, which are often adjacent to the nuclear membrane. Occasionally, LP may display the features of Hodgkin Reed-Sternberg (HRS) cells and in this settings immunophenotyping plays a pivotal role for the differential diagnosis between NLPHL and LR-CHL. Exceptionally, co-occurrence of clonally related NLPHL and CHL has been reported. In 2003, Fan et al. proposed a sub-classification of LP-HL into 6 categories based on the immunoarchitectural pattern (Table 2): the diffuse (TCRBCL-like) one (pattern E) mimics a Tcell/histiocyte rich large B cell lymphoma (THCRBCL)(). According to the current WHO classification, at least a partial nodular pattern is Table 2. Classification of NLPHL sec. Fan Z et al ( Am J Surg