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Usual and Unusual Patterns of Transformation Among Lymphoid Neoplasms

Diagnostic Considerations for Pathologists

Koka, Rima MD, PhD

doi: 10.1097/PCR.0000000000000331

From the University of Maryland School of Medicine, Baltimore, MD.

Reprints: Rima Koka, MD, PhD, University of Maryland School of Medicine, Baltimore, MD. E-mail:

The author has no funding or conflicts to declare.



The current issue of the American Journal of Surgical Pathology: Reports and Reviews revolves around the various clinical, diagnostic, and therapeutic aspects surrounding transformation of various hematopoietic entities to aggressive lymphoid malignancies. In light of the fact that transformed lymphomas behave more aggressively than their de novo histologic counterparts, pathologists are called upon to make this distinction even in the absence of a clear history of a hematopoietic malignancy. Moreover, in the ever evolving and complex therapeutic landscape that includes stem cell transplantation and targeted immunotherapies, pathologists can often provide input in the choices of therapies and have to make assessments regarding antigenic escape or secondary malignancies in the setting of prior therapy or organ/stem cell transplantation. In this issue, we discuss many of these diagnostic dilemmas encountered in making a diagnosis of an aggressive lymphoma that can arise from an array of preexisting neoplasms.

First, Ware et al discuss transformation of chronic myeloid leukemia to B-lymphoblastic leukemia. This transformation highlights the plasticity of myeloid blasts, and the challenges of distinguishing chronic myeloid leukemia–associated lymphoid blast crisis from de novo Philadelphia chromosome–positive B-lymphoblastic leukemia are discussed.

Second, Merechi et al address the diagnostic dilemma surrounding CD30-positive cutaneous T-cell lymphomas. Cutaneous T-cell lymphomas rely on effective clinical-pathologic correlation because the histologic findings between reactive processes and various varieties of cutaneous T-cell lymphomas show significant overlap. This review focuses on CD30-positive cutaneous T-cell lymphoproliferative disorders in particular, with an emphasis on the diagnostic challenge of distinguishing the de novo CD30-positive cutaneous T-cell lymphoproliferative disorders from transformed mycosis fungoides.

Next, Alqaidy et al present an interesting case of nodular lymphocyte predominant Hodgkin lymphoma that transformed to diffuse large B-cell lymphoma. Not only are the issues surrounding this transformation addressed, but the review also discusses the variants of nodular lymphocyte-predominant Hodgkin lymphoma and addresses the difficulty of distinguishing this entity from classic Hodgkin lymphoma (CHL) and T-cell/histiocyte–rich large B-cell lymphoma. The genetics linking nodular lymphocyte-predominant Hodgkin lymphoma to other entities and the possible role that these play in transformation are also discussed.

We then begin discussion of ways in which low-grade B-cell neoplasms transform to aggressive B-cell lymphomas. The 2 cases that highlight the complexities are provided by Liu et al and Lee et al. Liu et al discuss a case of monoclonal B-lymphocytosis that transformed to Epstein-Barr virus–positive large B-cell lymphoma with features intermediate between diffuse large B-cell lymphoma and CHL. By demonstrating clonal relatedness between the 2 entities, this team shows that even in the setting of monoclonal B-lymphocytosis, typically considered a preneoplastic condition, the occurrence of an aggressive neoplasm must lead to consideration of transformation. Next, Lee et al discuss a case of diffuse large B-cell lymphoma in a patient who has had a history of chronic lymphocytic leukemia and stem cell transplantation. The subsequent development of CHL in this setting led to seeking an answer regarding the clonal link of the CHL to the preceding malignancy. The complexity of assessing whether the CHL represents transformed chronic lymphocytic leukemia (Richter transformation) versus posttransplant lymphoproliferative disorder is addressed.

Crane and Chadburn discuss marginal zone lymphoma, which can range from very indolent clonal proliferations that are difficult to distinguish from reactive processes to those that have a high likelihood of transformation. The ability to risk-stratify patients into those with low risk and high risk of transformation would be extremely helpful. The role of cytogenetic and molecular findings in better understanding risk of transformation in marginal zone lymphomas is discussed.

Finally, in the new era of ever expanding immunotherapeutic targets, the role of the pathologist extends beyond diagnostics. By identifying antigens that can be targeted by immunotherapeutic agents, pathologists can help guide the oncologists' treatment decisions, particularly in cases of transformed or refractory lymphoid malignancies. Pasion et al explore this point in the setting of transformed follicular lymphoma.

Hematopathology has always been at the forefront of utilizing multimodality testing of neoplasms to stratify risk in patients with seemingly similar malignancies. Transformed lymphomas are a great illustration of how clinical, cytogenetic, and molecular methods can help make the critical distinction between transformed and de novo malignancies. This issue assembles a series of reviews that helps the practicing pathologist understand the diagnostic dilemmas as well as the possibilities for influencing therapeutic decisions in lymphoid malignancies.

© 2019 Lippincott Williams & Wilkins, Inc.