Context.—

Plasmablastic morphology can be seen in several uncommon lymphoproliferative neoplasms. Sometimes it is difficult to distinguish these neoplasms from each other.

Objective.—

To review the current understanding of major lymphoproliferative neoplasms with plasmablastic morphology; summarize the clinical, morphologic, immunophenotypic, cytogenetic, and molecular characteristics of each disease entity; and highlight a practical approach for differential diagnosis.

Data Sources.—

Peer-reviewed medical literature and the authors' personal experience.

Conclusions.—

Plasmablastic lymphoma; plasmablastic myeloma; primary effusion lymphoma; human herpesvirus 8–positive diffuse large B-cell lymphoma, not otherwise specified; and anaplastic lymphoma kinase (ALK)–positive large B-cell lymphoma are major lymphoproliferative neoplasms with plasmablastic morphology. These neoplasms share many common morphologic and immunophenotypic characteristics. Definitive diagnosis requires a thorough understanding of disease phenotype and diagnostic criteria of each category. Recognition of expression pattern of Epstein-Barr virus–encoded small RNA, human herpesvirus 8, and ALK in these neoplasms is critical for diagnosis in cases with typical presentation. Additional ancillary studies and clinical findings may help in difficult cases.

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Author notes

The authors have no relevant financial interest in the products or companies described in this article.