Cavity-based lymphomas: challenges and novel concepts. A report of the 2022 EA4HP/SH lymphoma workshop

Abstract

The 2022 European Association for Haematopathology/Society for Hematopathology lymphoma workshop session on cavity-based lymphomas included sixty-eight cases in seven sections. The disease entities discussed include primary effusion lymphomas (PEL), extracavitary primary effusion lymphomas and confounding entities (ECPEL), HHV8-negative B-lineage lymphomas-effusion based (EBV-negative, EBV-positive, and plasmablastic types), diffuse large B-cell lymphoma associated with chronic inflammation, fibrin-associated diffuse large B-cell lymphoma (FA-DLBCL), breast implant-associated anaplastic large cell lymphoma (BIA-ALCL), and other lymphomas presenting as an effusion. All entities above are discussed; however, three are delved into greater detail given the challenges with classification: ECPEL, HHV8-negative effusion-based lymphomas, and FA-DLBCL. Cases exemplifying the diagnostic difficulty in differentiating ECPEL from HHV8-positive diffuse large B-cell lymphoma and germinotropic lymphoproliferative disorder were discussed. The more recently recognized effusion-based HHV8-negative large B-cell lymphoma is explored, with several cases submitted raising the question if this subset should be carved out as a specific entity, and if so, what should be the refining diagnostic criteria. Case submissions to the FA-DLBCL section yielded one of the largest case series to date, including classic cases, cases furthering the discussion on disease sites and prognosis, as well as novel concepts to be considered in this entity. The 2022 EA4HP/SH workshop cases allowed for further confirmation of the characteristics of some of the more historically accepted cavity-based lymphomas, as well as further inquiry and debate on relatively new or evolving entities.

Keywords: Breast Implant associated anaplastic large cell lymphoma; Effusion-based large B cell lymphoma; Extracavitary primary effusion lymphoma; Fibrin-associated large B cell lymphoma; Fluid overload associated large B cell lymphoma; Germinotropic disorder; HHV8-negative effusion lymphoma; Pleural Effusion Lymphoma.

Fig. 1

Histologic and immunophenotypic features of primary effusion lymphoma. (a–c) Smears from plural effusions demonstrating plasmablastic, immunoblastic, and anaplastic morphology seen in an HIV-positive, EBV-positive patient (a. LYWS-1050 courtesy of A. Shestakov) and an HIV-negative, EBV-negative patient (b–f. LYWS-1194 courtesy of P. Barone). (d) LANA (KSHV/HHV8) positivity, demonstrating the typical speckled pattern. (e–f) CD138 (e) and MUM1 (f) expression in neoplastic cells

Fig. 2

Example of primary effusion lymphoma with expression of T-cell markers (LYWS-1216 courtesy of L. Mescam). (a) Histologic sections from the peritoneal biopsy demonstrating neoplastic cells with immunoblastic cytomorphology within fibrinous material. (b–e) Neoplastic cells are positive for HHV8 (b), CD138 (c), variable CD4 (d), and variable CD3 (e)

Fig. 3

Histologic and immunophenotypic features of extracavitary primary effusion lymphoma (LYWS-1192 courtesy of A. Dashora). (a, b) Histologic sections of the subcutaneous nodule demonstrating diffusely infiltrating neoplastic lymphoid cells with immunoblastic and plasmablastic cytomorphologic features. (c–f) Neoplastic cells are positive for MUM1 (c), EBER (d), HHV8 (e), and variable intensity CD138 (f)

Fig. 4

Venn diagram demonstrating overlap of HHV8+ diagnostic entities submitted to the workshop. Two challenging cases with a differential diagnosis of extracavitary primary effusion lymphoma and HHV8-positive large B-cell lymphoma, both of which were EBER negative. (a–c) LYWS-1063 (courtesy of K. Karube) demonstrates large, pleomorphic centroblastic/immunoblastic cells on the histologic section of the kidney (a), which are positive for MUM1 (b) and HHV8 (c). (d–f) LYWS-1143 (courtesy of L. Rimsza) demonstrates large, pleomorphic immunoblastic/plasmablastic/anaplastic cells on the histologic section of the bone marrow core biopsy (d), which are positive for CD138 (e) and weak HHV8 (f). A challenging case of extracavitary primary effusion lymphoma that raised consideration of germinotropic lymphoproliferative disorder (LYWS-1464 courtesy of A. Serrano). (g) H&E section of the inguinal lymph node. The large cell infiltrate is predominantly paracortical and sinusoidal. High power view demonstrating the plasmablastic/anaplastic cytomorphology (insert). (h–o) Immunophenotypic features. The neoplastic infiltrate is positive for HHV8 (h), EBER (i), MUM1 (j), EMA (k), CD38 (l), and subset weak CD3 (m)

Fig. 5

HHV8-negative and EBER-negative effusion-based lymphoma/fluid overload large B-cell lymphoma (LYWS-1065 courtesy of N. Aggarwal and A. Davis). (a, b) Histologic sections of the thoracentesis cell block demonstrated large immunoblastic and plasmacytoid/plasmablastic cells. (c, d) The neoplastic population is positive for CD20 (c) and CD138 (d). (e) Flow cytometry demonstrates expression of CD19 and CD20 and lambda light chain without CD5, CD10, or CD103. (f) Next-generation sequencing demonstrates mutations that have been reported in effusion-based lymphoma (including MYD88 and PIM1)

Fig. 6

HHV8-negative and EBV-positive large B-cell lymphoma presenting as an effusion in a CML patient on Dasatinib (LYWS-1161 courtesy of L. Veloza). (a, b) Cytospin and histologic section from cell block of pericardial fluid demonstrating large immunoblastic and plasmacytoid/plasmablastic cells. (c–e) The neoplastic cells are positive for CD79a (c), EBER (d), and EBNA2 (e)

Fig. 7

HHV8-negative and EBV-positive plasmablastic lymphoma, presenting as an effusion, post-transplant (LYWS-1382 courtesy of B. Mai and W. Wang). (a–c) Cell block and cytospins of the ascitic fluid demonstrates large immunoblastic/plasmablastic/anaplastic cells. (d–f) The neoplastic cells are positive for MUM1 (d), negative for HHV8 (e), and positive for EBER (f)

Fig. 8

Histologic and immunophenotypic features of FA-DLBCL involving different anatomical sites. (a–e) Large non-GCB-type B-cells in a left femoral artery thrombi (LYWS-1166 courtesy of R Morse), (a, b) H&E, (c) CD20, (d) MUM1, and (e) EBER; (f–j) Large GCB-type B-cells infiltrating a cardiac myxoma (LWYS-1032, courtesy of AM Perry), (f, g) H&E, (h) CD20, (i) CD10, and (j) EBER; (k–o) Plasmablastic cells infiltrating the fibrous psudocapsule of a pacemaker pocket (LYWS-1307, courtesy of J. Goodlad and G. Horne), (k, l) H&E, (m) CD20, (n) CD138, and (o) EBER; (p–t) Plasmablastic cells within pseudocysts of a post-therapy GIST (LYWS-1122 courtesy of F. Fend) (p) H&E, (q) Giemsa, (r) CD20, (s) CD138, and (t) lambda

Fig. 9

Large cell lymphomas associated with breast implants. (a–h) FA-DLBCL represented by clusters of EBV-infected large B-cells within fibrin infiltrating the capsule (LWYS-1097, courtesy of T. Tousseyn) (a, b) H&E, (c) CD30, (d) CD20, (e) CD19, (f) PAX5, (g) EBER, and (h) LMP1. (i–q) BIA-ALCL composed of aggregates of large anaplastic cells associated with fibrinous material infiltrating the capsule (LYWS-1124 courtesy of A.L. Feldman). (i–l) H&E and the axillary lymph node (m–q) H&E. Tumor cells show strong expression of both CD30 and CA9 in the capsule (k, l) and in the small lymph node tumor aggregates (n, o) but were CD30-positive and CA9-negative (p, q) in the diffuse areas in the lymph node