Blood, Vol. 94 No. 7 (October 1), 1999:
pp. 2247-2251
Simultaneous Phenotypically Distinct but Clonally Identical
Mucosa-Associated Lymphoid Tissue and Follicular Lymphoma in a Patient
With Sjögren's Syndrome
Antonella Aiello,
Ming-Qing Du,
Tim C. Diss,
Huai-Zheng Peng,
Francesco Pezzella,
Daniela Papini,
Roberto Giardini,
Silvana Pilotti,
Lang-Xing Pan, and
Peter G. Isaacson
From the Department of Histopathology, University College London
Medical School, London, UK; and the Divisione Di Anatomia Patologica,
Istituto Nazionale Tumori, Milano, Italy.
A 44-year-old woman with a 12-year history of Sjögren's
syndrome (SS) developed a low-grade mucosa-associated lymphoid tissue (MALT) lymphoma in the parotid gland. Two years later, she presented with generalized lymphadenopathy and hepatosplenomegaly and a follicular lymphoma was diagnosed. To investigate the relationship of
the two histologically distinct lymphomas, we re-examined their histology and immunophenotype and studied the lymphomatous tissue from
the parotid, cervical lymph node, and spleen using molecular genetic
methods. Histologic and immunophenotypic studies confirmed the previous
diagnoses and also identified a previously unnoticed focus of
follicular lymphoma in the second parotid gland biopsy. Polymerase
chain reaction (PCR) amplification of the rearranged Ig heavy-chain
gene showed the same sized dominant product in the MALT lymphoma and
the follicular lymphoma. Similarly, PCR analysis of the t(14:18)
translocation yielded an identical sized band from both MALT and
follicular lymphoma. Cloning and sequencing of the Ig PCR products
showed an identical CDR3 sequence from each lesion,
indicating a common clonal lineage. The follicular lymphoma of the
parotid gland lymph node and the follicular lymphoma of the spleen
showed an identical mutation signature to that of the salivary gland
MALT lymphoma. We propose that follicular lymphoma in the parotid gland
lymph node may have resulted from colonization of lymphoid follicles by
MALT lymphoma cells, following which the tumor cells were induced to
express a follicular lymphoma phenotype, due to Bcl-2 overexpression
caused by t(14;18), leading to a change in clinical behavior resulting
in rapid widespread dissemination of disease. These observations
suggest that the distinct phenotypes of low-grade B-cell lymphomas may
be the consequence of interplay between genetic and local
microenvironmental factors.
