Follicular lymphoma

* Context.-CD30+ anaplastic large cell lymphomas were originally described as being of T-cell, null cell, and B-cell origin. CD30, however, is not a specific marker of anaplastic large cell lymphoma and has been found to be expressed in reactive as well as neoplastic populations as a probable activation marker. In addition, CD30+ cells have also been described in both diffuse large B-cell and follicular lymphomas (FLs), resembling the pattern seen in reactive tonsils and lymph nodes.

Objective.-We report an index case of FL with CD30 expression, which on initial touch preparations and flow cytometric immunophenotyping revealed a prominent population of CD30^sup +^ cells with marked cellular pleomorphism (anaplasia) in a background of typical FL. Immunohistochemistry of the paraffin section for CD30 in our index case confirmed unequivocal CD30+ pleomorphic cells

in the malignant nodules in occasional clusters. This case prompted a study of additional cases of FL for pattern of immunoreactivity with CD30 on paraffin sections.

Design.-Twenty-two additional cases of FL (grades 13) were retrieved for CD30 immunoperoxidase staining as in the index case.

Results.-This study demonstrated 32% of the additional cases of FL had definitive CD30^sup +^, large, pleomorphic malignant cells by paraffin immunohistochemistry. In 2 cases (9%), the pattern of immunoreactivity with CD30 showed clustering and variable staining of large cells, as our index case.

Conclusion.-This study underscores the morphologic and immunophenotypic spectrum of FL that includes CD30 staining and cellular pleomorphism.

(Arch Pathol Lab Med 2001;125:1036-1041)

CD30 is a transmembrane glycoprotein and is a member of the tumor necrosis factor receptor superfamily.1 CD30 plays a role in regulating the function or proliferation of normal lymphoid cells.2 The Ki-1 monoclonal antibody was first identified as useful for immunohistochemical staining in identifying Reed-Sternberg cells in Hodgkin lymphoma.2-4 Subsequently, CD30 proved useful in helping define anaplastic large cell lymphoma (ALCL), which was initially known as Ki-1 lymphoma. However, it is now known that morphology, histology, and molecular identification of the t(2;5)(p23;q35) translocation are most critical in identifying ALCL, since numerous other lymphomas and carcinomas may have CD30 expression as a nonspecific indicator of cellular activation. In addition, the t(2;5) of ALCL can now be readily detected in paraffin tissue by the immunohistochemical evaluation of ALK-1.5

CD30^sup +^ B-cell lymphomas have been placed into other categories, most commonly diffuse large B-cell lymphomas.2,6 However, occasional to numerous CD30^sup +^ B cells have been described in sporadic cases of follicular lymphoma (FL),7 resembling the pattern seen in reactive tonsils and lymph nodes.8 CD30 may be present on activated B or T cells, but not resting mature or precursor B or T cells.2,9-11 Benign reactive CD30^sup +^ cells tend to be large, immunoblastic-appearing cells located at the periphery of germinal centers.2,11 In infectious mononucleosis or toxoplasmosis, the CD30^sup +^ cells are also increased in the paracortex.2,12

In reviewing the literature for B-cell lymphomas, we found that some articles noted a difference in the percentage of CD30^sup +^ cases, dependent on whether immunohistochemical stains were performed on frozen or formalin-fixed tissue. There is a difference in CD30 antibodies used for frozen and formalin-fixed tissue. Ki-1 is not reactive in routinely processed histologic material, but may be used in frozen tissue. Ber-H2 is a monoclonal antibody recognizing a formaldehyde-resistant epitope within the same antigen and may be used in frozen or formalin-fixed tissue.2,26,27 The percentage of CD30 immunoreactivity appears to be higher in frozen tissue.21 We did not have difficulty in using Ber-H2 in formalin-fixed tissue using typical antigen retrieval techniques. No prognostic significance has been found in B-cell lymphomas regarding whether they are positive or negative for CD30.21

In summary, we describe a well-defined case of FL with large pleomorphic cells that was CD30^sup +^ by both flow cytometric and immunohistochemical methods. In addition, we reviewed 22 cases of FL and demonstrated that 32% of cases showed definitive CD30 positivity in malignant cells (some with pleomorphic features) by immunohistochemistry. Thus, the finding of CD30 staining and cellular pleomorphism is not uncommon in the morphologic and immunophenotypic spectrum of FL. The lack of ALK-1 staining in our cases supports the hypothesis that this represents an activation phenotype rather than falling within the spectrum of ALCL. The CD30^sup +^ staining was not limited to large cell populations, which are those cells usually described in the literature to express CD30, but involved a spectrum of cell sizes. In addition, CD30 expression was heterogeneous, as previously described, indicating a noninherent quality of the tumor cells. It is uncertain whether the activation of tumor cells imparts different biologic behavior, although studies of CD30+ diffuse large B-cell nonHodgkin lymphoma would suggest no effect on biologic behavior. The effect of CD30 expression on tumor behavior, growth, and response to therapy has not been well investigated in FL. Documentation of CD30 positivity in FL may allow for the use of immunotherapies, such as anti-CD30 alone or in concert with antibodies to CD20, as therapeutic agents.

References

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Laura J. Gardner, MD; Jacek M. Polski, MD; H. Lance Evans, MD; Sherrie L. Perkins, MD, PhD; Cherie H. Dunphy, MD

Accepted for publication March 9, 2001.

From the Division of Hematopathology, Department of Pathology, St Louis University Health Sciences Center, St Louis, Mo (Drs Gardner, Evans, and Dunphy); the Department of Pathology, University of South Alabama, Mobile (Dr Polski); and the Section of Hematopathology, University of Utah Health Sciences Center, Salt Lake City (Dr Perkins).

Reprints: Cherie H. Dunphy, MD, Department of Pathology and Laboratory Medicine, CB#7525, Brinkhous-Bullitt Bldg, University of North Carolina, Chapel Hill, NC 27599-7525 (e-mail: cdunphy@unch.unc.edu).

Copyright College of American Pathologists Aug 2001
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