The Separate Diagnosis of Hodgkin Lymphoma (HL) and Non-Hodgkin Lymphoma (NHL) In a Single Patient May Not Signify a Common Clonal Origin

HL and NHL have traditionally been considered as two distinct entities. However, there have been reported rare cases of patients that over time develop both diseases. It is an unresolved issue whether the origin of the two diseases is from the same clone. The literature is replete with anecdotal reports but it has never been prospectively or retrospectively evaluated in consecutive patients from a large series. In this study we attempted to retrospectively investigate this phenomenon by reviewing the clinical and molecular aspects of a group of patients who developed both lymphomas. Although not absolutely definitive, a differing gene rearrangement (GR) pattern is currently thought to be highly suggestive of a different clonal origin.

Study patients were all patients treated at the Hadassah University Medical Center, Jerusalem, Israel, who developed both kinds of lymphoma throughout their lives and were treated for at least one of the lymphomas during the period 1989–2010. The clinical and pathologic records of these patients were reviewed.

Archival, formalin fixed, paraffin embedded tissue samples from all the patients that had available samples from both diseases were obtained. The rearranged immunoglobulin heavy-chain variable region genes from both diagnoses were amplified by polymerase chain reaction (PCR) and were compared to each other.

There were 26 patients who presented with two diagnoses. Twelve had HL as the primary disorder and the majority of these (75%) presented with aggressive lymphoma as the second lymphoma. The mean survival from the second lymphoma was 4.06 years. Five patients are still alive. In contrast, in the 11 patients where NHL was the primary disorder, this was usually (82%) of low grade histology. The mean survival in this case was 2.16 years. Four patients are still alive. Three patients were diagnosed concurrently with both diseases.

For 11 patients there were available diagnostic samples for molecular analyses from both diagnoses of HL and NHL. In 6 of these 11 patients gene rearrangement studies were informative providing data for both diagnoses. The same GR was not found in any of the 6 patients.

DLBCL=Diffuse Large B Cell Lymphoma, CLL/SLL=Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, marginal=marginal zone lymphoma, low grade=low grade B cell lymphoma unspecified

Although the numbers are small, these data suggest that it is likely that in the case of two different lymphoproliferative disorders they are of separate clonal origin.

The development of HL and NHL at different time points should be assumed to be a different biologic disease, until proven otherwise.

No relevant conflicts of interest to declare.