Hodgkin Lymphoma: An Update on its Biology with New Insights into Classification

Abstract

In the last few years, there has been a greater understanding of the spectrum and biology of Hodgkin lymphoma. In standard texts, Hodgkin lymphoma is classified as two distinct entities, namely nodular lymphocyte predominant Hodgkin lymphoma and classical Hodgkin lymphoma. However, recent evidence suggests that classical Hodgkin lymphoma is not a single disease. While the mixed cellularity and lymphocyte depleted subtypes may be part of a biologic continuum, the nodular sclerosis subtype has a distinct epidemiology, clinical presentation and histology. Nodular sclerosis Hodgkin lymphoma may also be related to primary mediastinal B-cell lymphoma and mediastinal grey zone lymphomas. We present an update on the pathobiology of Hodgkin lymphoma and discuss these biologic and clinical differences in this review. KeywordsClassical Hodgkin lymphoma; Nodular lymphocyte predominant Hodgkin lymphoma; Primary mediastinal large B-cell lymphoma; Grey zone lymphomas; Epstein Barr virus; Epidemiology; Biology; ImmunophenotypingThe eponym 'Hodgkin's disease' was conferred by Samuel Wilks in 1856 1, almost 25 years after the first description of 'morbid appearances of the absorbent glands and spleen' by Thomas Hodgkin. Interestingly, of the seven original cases described by Dr. Hodgkin at the Guy's hospital, only three were later shown to be truly Hodgkin's disease in 1926, by the diagnostic criteria in use at that time 2. Also of interest is the fact that Dr. Hodgkin's contributions in other fields of medicine and social sciences were far greater and had much more impact in his lifetime. Hodgkin lymphoma, as it is now termed, has an incidence rate of 2.7 per 100,000 population and is estimated to account for 11.7% of all lymphomas diagnosed in 2006 3 . The last decade has seen tremendous advances in the understanding of its biology and we present an update on the pathobiology of Hodgkin lymphoma [HL] along with newer insights into its classification. HODGKIN LYMPHOMA -HOW MANY DISEASE ENTITIES?Presently, HL is classified into two largely distinct entities, namely nodular lymphocyte predominance HL (NLPHL) and classical HL (CHL), the latter being further subtyped as nodular sclerosis (NSCHL), lymphocyte rich (LRCHL), mixed cellularity (MCCHL), and lymphocyte depletion (LDCHL) subtypes 4 . Salient clinical and histopathologic features of each subtype are shown in tables 1 and 2. While CHL tends to be regarded in the clinical and *Corresponding Author: Elaine S. Jaffe, M.D., Chief, Hematopathology Section, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD -20892, Tel: (301) 496-0184, ejaffe@mail.nih.gov. NIH Public Access Author ManuscriptClin Lymphoma Myeloma. Author manuscript; available in PMC 2010 January 13. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript experimental literature as a single disease, consideration of all epidemiological, biological and clinical data suggests that CHL probably consists of more tha...

Alopecia areata as a paraneoplastic syndrome of Hodgkin’s lymphoma: A case report

“…Alternatively, other studies suggested that the induction of major histocompatibility complex class I and II expression on hair follicles may lead to the activation of CD8 + T-lymphocytes towards hair follicle melanocytes and recruitment of CD4 + T-lymphocytes that further attack the hair follicles, a process that may be perpetuated and amplified by the clonal T-cell proliferation seen in lymphomas (4). There is also a genetic predisposition contributing to such phenomena, given the numerous human leukocyte antigen subtypes shared by AA and HL (1,10). The resolution of AA observed with the remission of HL in our patient and other case reports reaffirms the close association between these two conditions.…”

“…AA, however, as a paraneoplastic syndrome of Hodgkin's lymphoma (HL), remains limited to a few case studies, although its occurrence in HL was anecdotally referenced in the early 1900s (6)(7)(8)(9). The etiology of AA as a paraneoplastic syndrome of HL remains unknown, although it was considered to be a T-lymphocyte-mediated phenomenon involving production of cytokines, initiation of the inflammatory cascade and genetic predisposition (1,4,8,10).…”

Diffuse Large B Cell Lymphoma Relapsing as Classical Hodgkin Lymphoma: Report of Two Cases and Review of Literature

“…While most other subtypes of CHL occur in the peripheral lymph nodes with an apparent male predominance, NSCHL most commonly occurs in the mediastinal region with a roughly 1:1 male to female ratio. Compare to other subtypes, NSCHL is also less likely to be associated with EBV (20%) [24,25]. Accumulating evidence has demonstrated a close link between NSCHL and DLBCL.…”

High tumour-associated macrophages infiltration is correlated with poor survival outcome in classical Hodgkin’s lymphoma

“…cHL represents nearly 95% of HLs. [1][2][3] cHL has a relatively good prognosis and with current chemotherapeutic and radiotherapeutic regimens, patients cure can be achieved in 80% of cases. The remaining 20%, patients may be refractory to primary treatment or show relapse after remission.…”