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Updated: Jun 23, 2026
Flow-sorting and Exome Sequencing of the Reed-Sternberg Cells of Classical Hodgkin Lymphoma
Published on: June 10, 2017
Lymphocyte depleted Hodgkin lymphoma: an evaluation with immunophenotyping and genetic analysis
Graham W Slack1, Judith A Ferry, Robert P Hasserjian
1The James Homer Wright Pathology Laboratories, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Insights
Lymphocyte depleted classical Hodgkin lymphoma (LDHL) is a rare subtype of classical Hodgkin lymphoma (CHL). Our study confirms LDHL as a distinct entity, differentiating it from other lymphomas like grey-zone lymphomas.
Area of Science:
- Hematopathology
- Oncology
- Immunophenotyping
Background:
- Lymphocyte depleted classical Hodgkin lymphoma (LDHL) is a rare and debated subtype of classical Hodgkin lymphoma (CHL).
- Recent classifications and recognition of grey-zone lymphomas challenge the existence of LDHL as a distinct entity.
- This study aimed to re-evaluate LDHL based on the 2008 WHO Classification criteria.
Observation:
- Eight cases meeting LDHL criteria were analyzed, involving lymph nodes and pleura.
- Tumors consistently showed numerous Hodgkin-Reed-Sternberg (HRS) cells with a fibrotic or reticular anaplastic appearance.
- Neoplastic cells expressed CD30, CD15, fascin, weak PAX5, MUM-1, Oct.2, and/or Bob-1, while lacking CD45 and other markers.
Findings:
- Immunophenotypic analysis revealed a distinct profile, with some cases showing variable CD20 expression but negative CD79a.
- Epstein-Barr virus (EBV) was detected in four cases.
- Molecular genetic analysis demonstrated clonal rearrangement of IGH genes in all tested cases, confirming a B-cell origin.
Implications:
- The combined morphological, immunophenotypic, and molecular data support LDHL as a distinct clinicopathologic entity.
- This differentiation is crucial for distinguishing LDHL from other high-grade B-cell lymphomas, including grey-zone lymphomas.
- Accurate classification of LDHL impacts patient diagnosis and treatment strategies.
Abstract:
Lymphocyte depleted classical Hodgkin lymphoma (LDHL) is a vanishing category of classical Hodgkin lymphoma (CHL); many cases previously placed in this category are now recognised as diffuse large B-cell lymphoma (DLBCL), anaplastic large-cell lymphoma (ALCL), or nodular sclerosis CHL with lymphocyte depletion. In addition, the recent recognition of high grade B-cell lymphomas intermediate between DLBCL and CHL (grey-zone lymphomas) raises the question of whether LDHL exists at all as a category of CHL. We studied eight cases that fulfilled diagnostic criteria of LDHL according to the 2008 WHO Classification. The cases involved lymph nodes (7 cases) and pleura (1 case) from four males and four females (age 30-71 years; median 62 years). All tumors contained numerous Hodgkin-Reed-Sternberg (HRS) cells, fibroblasts and histiocytes and scattered lymphocytes. In three cases the tumors had a more diffuse fibrotic appearance, while in five cases they appeared reticular and anaplastic. Neoplastic cells in all cases expressed CD30, CD15, fascin, weak PAX5 and MUM-1 and lacked CD45, Alk-1, EMA, CD3, CD68, Mart-1 and cytokeratin. Oct.2 and/or Bob-1 were expressed in all cases. Two cases variably expressed CD20 but were CD79a negative. Four cases were positive for EBV. All the four cases with adequate DNA had clonally rearranged IGH genes. The combined morphologic, immunophenotypic and molecular genetic features of this group of cases distinguish LDHL from other disease entities, including grey-zone lymphomas.
