Large B-cell Lymphomas with Plasmablastic Differentiation

This chapter discusses the clinicopathologic features of a unique subgroup of aggressive B-cell lymphoma with plasmablastic morphology and immunophenotype, including plasmablastic lymphoma, primary effusion lymphoma, KSHV/HHV8-positive diffuse large B-cell lymphoma (DLBCL), and ALK-positive large B-cell lymphoma. The differential diagnosis among these entities and their key immunophenotypic features, particularly using multiparametric flow cytometric analysis, are compared and highlighted in detail. Differential diagnosis with other unrelated malignant neoplasms such as plasmablastic plasma cell myeloma, immunoblastic variant of DLBCL, non-hematopoietic neoplasms, anaplastic large cell lymphoma, and several other benign and malignant diseases/conditions resembling diagnostic mimics and pitfalls are also discussed.

Keywords

plasmablastic neoplasm plasmablastic lymphoma primary effusion lymphoma KSHV/HHV8-positive diffuse large B-cell lymphoma ALK-positive large B-cell lymphoma plasmablastic plasma cell myeloma immunoblastic diffuse large B-cell lymphoma anaplastic large cell lymphoma effusion-based lymphoma HHV8-negative KSHV/HHV8-associated B-lymphoid proliferations

Information

Type: Chapter
Information: Flow Cytometry in Hematolymphoid Neoplasms
A Comprehensive and Practical Guide to Diagnosis
, pp. 63 - 75
DOI: https://doi.org/10.1017/9781009397797.007 [Opens in a new window]
Publisher: Cambridge University Press
Print publication year: 2026

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Book purchase

Temporarily unavailable

References

Tellier, J, Nutt, SL. Plasma cells: The programming of an antibody-secreting machine. Eur J Immunol 2019; 49(1): 30–37.10.1002/eji.201847517CrossRef Google Scholar PubMed

Perez-Andres, M, Paiva, B, Nieto, WG, Caraux, A, Schmitz, A, Almeida, J, et al. Human peripheral blood B-cell compartments: A crossroad in B-cell traffic. Cytometry Part B. Clinical cytometry 2010; 78 Suppl 1: S47–S60.Google Scholar

Ramirez-Gamero, A, Martinez-Cordero, H, Beltran, BE, Florindez, J, Malpica, L, Castillo, JJ. Plasmablastic lymphoma: 2024 update on diagnosis, risk stratification, and management. Am J Hematol 2024; 99(8): 1586–1594.10.1002/ajh.27376CrossRef Google Scholar PubMed

Bailly, J, Jenkins, N, Chetty, D, Mohamed, Z, Verburgh, ER, Opie, JJ. Plasmablastic lymphoma: An update. Int J Lab Hematol 2022; 44 Suppl 1(Suppl 1): 54–63.10.1111/ijlh.13863CrossRef Google Scholar PubMed

Zhou, J, Nassiri, M. Lymphoproliferative neoplasms with plasmablastic morphology. Arch Pathol Lab Med 2022; 146(4): 407–414.10.5858/arpa.2021-0117-RACrossRef Google Scholar PubMed

Chadburn, A, Said, J, Gratzinger, D, Chan, JK, de Jong, D, Jaffe, ES, et al. HHV8/KSHV-positive lymphoproliferative disorders and the spectrum of plasmablastic and plasma cell neoplasms: 2015 SH/EAHP workshop report–part 3. Am J Clin Pathol 2017; 147(2): 171–187.10.1093/ajcp/aqw218CrossRef Google Scholar PubMed

Garcia-Reyero, J, Martinez Magunacelaya, N, Gonzalez de Villambrosia, S, Loghavi, S, Gomez Mediavilla, A, Tonda, R, et al. Genetic lesions in MYC and STAT3 drive oncogenic transcription factor overexpression in plasmablastic lymphoma. Haematologica 2021; 106(4): 1120–1128.10.3324/haematol.2020.251579CrossRef Google Scholar PubMed

Pather, S, Mashele, T, Willem, P, Patel, M, Perner, Y, Motaung, M, et al. MYC status in HIV-associated plasmablastic lymphoma: Dual-colour CISH, FISH and immunohistochemistry. Histopathology 2021; 79(1): 86–95.10.1111/his.14336CrossRef Google Scholar PubMed

Vega, F, Miranda, RN, Medeiros, LJ. KSHV/HHV8-positive large B-cell lymphomas and associated diseases: A heterogeneous group of lymphoproliferative processes with significant clinicopathological overlap. Mod Pathol 2020; 33(1): 18–28.10.1038/s41379-019-0365-yCrossRef Google Scholar

Pan, Z, Hu, S, Li, M, Zhou, Y, Kim, YS, Reddy, V, et al. ALK-positive large B-cell lymphoma: A clinicopathologic study of 26 cases with review of additional 108 cases in the literature. Am J Surg Pathol 2017; 41(1): 25–38.10.1097/PAS.0000000000000753CrossRef Google Scholar PubMed

Castillo, JJ, Beltran, BE, Malpica, L, Marques-Piubelli, ML, Miranda, RN. Anaplastic lymphoma kinase-positive large B-cell lymphoma (ALK + LBCL): A systematic review of clinicopathological features and management. Leuk Lymphoma 2021; 62(12): 2845–2853.10.1080/10428194.2021.1941929CrossRef Google Scholar

Bogusz, AM, Seegmiller, AC, Garcia, R, Shang, P, Ashfaq, R, Chen, W. Plasmablastic lymphomas with MYC/IgH rearrangement: Report of three cases and review of the literature. Am J Clin Pathol 2009; 132(4): 597–605.10.1309/AJCPFUR1BK0UODTSCrossRef Google Scholar PubMed

Schwarz, LW, Love, JE, Naresh, KN, Shameli, A, Fromm, JR. Use of CD32, CD44 and CD71 to differentiate follicular lymphoma and diffuse large B-cell lymphoma subtypes by flow cytometry. J Clin Pathol 2024; 77(7): 500–501.10.1136/jcp-2023-209366CrossRef Google Scholar

Galan, J, Martin, I, Carmona, I, Rodriguez-Barbero, JM, Cuadrado, E, Garcia-Alonso, L, et al. The utility of multiparametric flow cytometry in the detection of primary effusion lymphoma (PEL). Cytometry B Clin Cytom 2019; 96(5): 375–378.10.1002/cyto.b.21637CrossRef Google Scholar PubMed

Zhou, T, Yuan, CM, Lurain, K, Rous, C, Weaver, L, Raffeld, M, et al. A novel approach for characterization of KSHV-associated multicentric Castleman disease from effusions. Br J Haematol 2023; 200(4): 462–475.10.1111/bjh.18518CrossRef Google Scholar PubMed

Pan, ZG, Zhang, QY, Lu, ZB, Quinto, T, Rozenvald, IB, Liu, LT, et al. Extracavitary KSHV-associated large B-cell lymphoma: A distinct entity or a subtype of primary effusion lymphoma? Study of 9 cases and review of an additional 43 cases. Am J Surg Pathol 2012; 36(8): 1129–1140.10.1097/PAS.0b013e31825b38ecCrossRef Google Scholar PubMed

Jiang, XN, Yu, BH, Wang, WG, Zhou, XY, Li, XQ. Anaplastic lymphoma kinase-positive large B-cell lymphoma: Clinico-pathological study of 17 cases with review of literature. PLoS One 2017; 12(6): e0178416.10.1371/journal.pone.0178416CrossRef Google Scholar PubMed

Zimmermann, H, Oschlies, I, Fink, S, Pott, C, Neumayer, HH, Lehmkuhl, H, et al. Plasmablastic posttransplant lymphoma: Cytogenetic aberrations and lack of Epstein-Barr virus association linked with poor outcome in the prospective German Posttransplant Lymphoproliferative Disorder Registry. Transplantation 2012; 93(5): 543–550.10.1097/TP.0b013e318242162dCrossRef Google Scholar PubMed

Liu, CY, Chen, BJ, Chuang, SS. Primary effusion lymphoma: A timely review of the association with HIV, HHV8, and EBV. Diagnostics (Basel) 2022; 12(3): 713.CrossRef Google Scholar PubMed

Alaggio, R, Amador, C, Anagnostopoulos, I, Attygalle, AD, Araujo, IBO, Berti, E, et al. The 5th edition of the World Health Organization classification of haematolymphoid tumours: Lymphoid neoplasms. Leukemia 2022; 36(7): 1720–1748.10.1038/s41375-022-01620-2CrossRef Google Scholar PubMed

Chen, BJ, Wang, RC, Ho, CH, Yuan, CT, Huang, WT, Yang, SF, et al. Primary effusion lymphoma in Taiwan shows two distinctive clinicopathological subtypes with rare human immunodeficiency virus association. Histopathology 2018; 72(6): 930–944.10.1111/his.13449CrossRef Google Scholar PubMed

Gathers, DA, Galloway, E, Kelemen, K, Rosenthal, A, Gibson, SE, Munoz, J. Primary effusion lymphoma: A clinicopathologic perspective. Cancers (Basel) 2022; 14(3): 722.10.3390/cancers14030722CrossRef Google Scholar PubMed

Accessibility standard: Inaccessible, or known limited accessibility

Why this information is here

This section outlines the accessibility features of this content - including support for screen readers, full keyboard navigation and high-contrast display options. This may not be relevant for you.

Accessibility Information

The HTML of this chapter is known to have missing or limited accessibility features. We may be reviewing its accessibility for future improvement, but final compliance is not yet assured and may be subject to legal exceptions. If you have any questions, please contact accessibility@cambridge.org.

Content Navigation

Table of contents navigation
Allows you to navigate directly to chapters, sections, or non‐text items through a linked table of contents, reducing the need for extensive scrolling.

Index navigation
Provides an interactive index, letting you go straight to where a term or subject appears in the text without manual searching.

Reading Order & Textual Equivalents

Single logical reading order
You will encounter all content (including footnotes, captions, etc.) in a clear, sequential flow, making it easier to follow with assistive tools like screen readers.

Short alternative textual descriptions
You get concise descriptions (for images, charts, or media clips), ensuring you do not miss crucial information when visual or audio elements are not accessible.

Visual Accessibility

Use of colour is not sole means of conveying information
You will still understand key ideas or prompts without relying solely on colour, which is especially helpful if you have colour vision deficiencies.

Structural and Technical Features

ARIA roles provided
You gain clarity from ARIA (Accessible Rich Internet Applications) roles and attributes, as they help assistive technologies interpret how each part of the content functions.

Book contents

Chapter 7 - Large B-cell Lymphomas with Plasmablastic Differentiation

Summary