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Blood, 1 May 2002, Vol. 99, No. 9, pp. 3376-3382
NEOPLASIA
In situ localization of follicular lymphoma: description and
analysis by laser capture microdissection
Peijie Cong,
Mark Raffeld,
Julie Teruya-Feldstein,
Lynn Sorbara,
Stefania Pittaluga, and
Elaine S. Jaffe
From the Hematopathology Section, Laboratory of
Pathology, Center for Cancer Research, National Cancer Institute,
Bethesda, MD.
From 1992 to 2000, we identified 23 lymph node biopsies with focal
germinal centers (GCs) containing centrocytes staining strongly for
bcl-2 protein, whereas most of the remaining lymph node showed
bcl-2-negative follicular hyperplasia. We propose the designation in
situ localization of follicular lymphoma (FL) for this phenomenon. In 2 additional cases, bcl-2+ follicles with features of in situ
FL were identified in association with other low-grade B-cell
lymphomas. To investigate the clonality of the bcl-2+
follicles, we performed laser capture microdissection of
bcl-2+ and bcl-2 follicles from the same lymph node in 5 cases, and analyzed them in parallel by polymerase chain reaction (PCR)
amplification of immunoglobulin heavy chain (IgH) genes. In 4 of 5 cases the bcl-2+ follicles contained monoclonal IgH gene
rearrangements, whereas the bcl-2 GCs exhibited a
polyclonal ladder. A BCL2/JH gene rearrangement was
detected in 6 of 14 (43%) evaluable cases. There were 5 patients with
synchronous evidence of FL at another site. There were 13 patients who,
without a prior diagnosis of FL, had clinical follow-up; one developed
FL in an adjacent lymph node within one year, and 2 manifested FL at 13 and 72 months, respectively. There are 10 patients who have not yet
shown other evidence of FL. These results suggest that at least close
to half of these cases (8/18; 44%) represent homing to and early
colonization of reactive GCs by FL. Other cases might represent FL at
the earliest stage of development, or a preneoplastic event, requiring
a second hit for neoplastic transformation. These findings provide
insight into the pathophysiology of early FL, and illustrate the
utility of immunohistochemistry for early diagnosis.
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