Late-delayed cerebral involvement in systemic non-Hodgkin lymphoma: a second primary tumor or a tardy recurrence?
BACKGROUND
Central nervous system involvement is a well recognized complication of systemic non-Hodgkin lymphoma. Most central nervous system recurrences occur within the first 2 years after the initial diagnosis and are considered to represent clonally related recurrence of systemic disease. The authors attempted to investigate the clonal relation between the late-delayed central nervous system involvement and the original systemic tumor.


METHODS
The authors studied archival, formalin fixed, paraffin embedded tissue samples from 8 patients with isolated cerebral involvement diagnosed > 3 years after their initial presentation with aggressive, systemic, B-cell non-Hodgkin lymphoma. The rearranged immunoglobulin heavy-chain variable region genes (VH) from both sites were amplified by polymerase chain reaction and were sequenced when necessary.


RESULTS
In three of five patients who had interpretable results, a distinct, monoclonal, VH family-specific band profile was obtained from the cerebral and systemic lymphoma. In the other two patients, a similar VH band pattern was observed and also was compared using direct sequencing, which demonstrated sequence differences between tumors from the two sites.


CONCLUSIONS
Clonal variance between the cerebral and systemic lymphoma in these patients suggested the possibility that some instances of late-delayed recurrence in the central nervous system represent a second, new B-cell lymphoma rather than a true recurrence of the original systemic tumor, a finding that may have significant clinical and biologic implications.
Lossos
Alexander
A
Leslie and Michael Gaffin Center for Neuro-Oncology, Hadassah-Hebrew University Hospital, Jerusalem, Israel. alos@hadassah.org.il
Ashhab
Yaqoub
Y
Sverdlin
Elena
E
Amir
Gail
G
Ben-Yehuda
Dina
D
Siegal
Tali
T
D000328:Adult; D000368:Aged; D001483:Base Sequence; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology* / Q000556:secondary*; D003937:Diagnosis, Differential; D005260:Female; D005500:Follow-Up Studies; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain / Q000235:genetics; D005803:Genes, Immunoglobulin / Q000235:genetics; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D016609:Neoplasms, Second Primary / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D012689:Sequence Homology, Nucleic Acid