Workshop report on Hodgkin’s disease and related diseases (‘grey zone’ lymphoma)

Abstract

Despite advances in immunohistochemistry and molecular biology, the distinction between classical Hodgkin's lymphoma and related diseases such as nodular lymphocyte-predominant Hodgkin's disease, T-cell rich large B-cell lymphoma or anaplastic large cell lymphoma has remained difficult in rare cases. Lack of clear-cut diagnostic criteria represents a problem for both the pathologist and the clinician. To delineate this 'grey zone' between classical Hodgkin's lymphoma and non-Hodgkin's lymphoma (NHL) and to develop criteria for classification of such cases, 12 expert hematopathologists each submitted one to five borderline cases to a workshop. Cases were reviewed and classified at a multiheaded microscope and criteria were established for the diagnosis of questionable cases. Well established entities such as classical Hodgkin's lymphoma, anaplastic large-cell lymphoma and TCRBCL were defined more strictly and cases with unusual morphology or antigen expression could be identified. A distinctive subset of cases representing mediastinal large B-cell lymphomas with features of Hodgkin's lymphoma was identified.

Angioimmunoblastic T cell lymphoma is derived from mature T‐helper cells with varying expression and loss of detectable CD4

“…These represent cytotoxic T-lymphocytes with some nuclear atypial similar to those found in the inflammatory background infiltrate of T cell rich B-cell lymphoma. 51 These results are comparable to those of Nakamura et al 23 Interestingly, only 50% of the cases proved to be clonal by PCR in these CD8-dominant cases, although 71% were positive among the CD4-dominant ones.…”

Expression of TP73L is a helpful diagnostic marker of primary mediastinal large B-cell lymphomas

“…In accordance with these findings, some authors described the presence of so-called 'grayzone' lymphomas, showing features intermediate between classical nodular-sclerosis Hodgkin's lymphoma and primary mediastinal large B-cell lymphoma. 24,25 Starting from this background, we demonstrated that TP73L really functioned as a watershed between the two related entities, because all primary mediastinal large B-cell lymphoma were TP73L-positive, while all classical Hodgkin's lymphoma were negative. Notably, in addition to primary mediastinal large B-cell lymphoma, TP73L appeared to be expressed in nearly all nodular lymphocyte-predominant Hodgkin's lymphoma, but not in classical Hodgkin's lymphoma.…”

“…These papers also highlighted unexpected similarities between primary mediastinal large B-cell lymphoma and Hodgkin's lymphoma; in accordance with these findings, some authors described the presence of 'gray-zone' lymphomas presenting features intermediate between primary mediastinal large B-cell lymphoma and mediastinal classical Hodgkin's lymphoma. 24,25 TP73L (as defined by the HUGO nomenclature; also known as p63) is a member of the TP53 family, which also includes TP53 itself and TP73. [26][27][28] Unlike TP53, the TP73L gene has two transcriptional starting sites (giving rise either to the transactivating (TA) or to the N-deleted (DN) variants) and its mRNA undergoes complex differential splicing, thus giving rise to at least six different molecular species with different biologic activities.…”

Senile Epstein-Barr Virus-Associated B-Cell Lymphoproliferative Disorders: a Mini Review

“…As the prototypic cytomorphology of HRS cells is shared by transformed large B lymphocytes, especially those harboring EBV, a biologic overlap between HL and NHL does exist. It is tempting to speculate that EBV-positive CHL and EBV-positive B-cell LPD may constitute a continuous spectrum of disease 15 . Further studies, however, are required to understand in detail the clinicopathologic profiles, the immunology, the molecular biology, and the therapeutic strategies for treatment of these diseases.…”