Plasma cell myeloma-related serous cavity effusion: Cytological and clinical insights from two cases

INTRODUCTION

Plasma cell dyscrasias are hematological neoplasms characterized by clonal proliferation of plasma cells commonly involving the bone marrow. Extra-medullary or disseminated presentation is rare and confers a poorer prognosis. Extra-medullary involvement as well as plasma cell leukemias are associated with a similar immunophenotype and cytogenetic aberrations, and thus, biologically may represent a spectrum of a similar underlying disorder.^[1-3] In addition, plasma cell dyscrasias with plasmablastic morphology involving cavity fluids may be misdiagnosed as primary effusion lymphomas (PELs).^[4] Demonstration of clonality is also essential to distinguish neoplastic involvement from a reactive plasma cell proliferation.^[5] The various causes of plasmacytosis in effusion fluids have been illustrated in Figure 1. A detailed clinical history and flow cytometric analysis of the effusion fluid usually help overcome the diagnostic dilemma. Here, we discuss two cases of plasma cell myelomas presenting with pericardial and pleural effusions, respectively.

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Figure 1: Flowchart demonstrating causes of plasmacytoid cells in effusion fluid cytology.

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CASE REPORT

Case 1

A 55-year-old female patient diagnosed and treated for plasma cell myeloma presented to the emergency with abdominal distension and dyspnea on March 20, 2025. She was initially diagnosed with multiple myeloma and underwent autologous hematopoietic stem cell transplant (HSCT) on February 18, 2023, after chemotherapy with bortezomib, lenalidomide, and dexamethasone (VTD). Post-transplant, she received bortezomib-based therapy and was on bortezomib plus lenalidomide maintenance. There was a history of irregular intake of medications. An echocardiography was performed which was suggestive of a large pericardial effusion with signs of impending cardiac tamponade. Pericardiocentesis was performed, and 650 mL of hemorrhagic fluid was drained and sent for laboratory investigations including cell count, cytology, and biochemical and microbiological tests. After stabilizing the patient, further blood investigations and bone marrow aspiration and biopsy were also performed. Laboratory investigations revealed an M-band of 3.5 g/dL, a free light chain Kappa: Lambda ratio of 3.5:1, and serum immunoglobulin G of 1800 mg/dL. Serum lactate dehydrogenase (LDH) level was 254 U/L (<247 U/L in females). β2-microglobulin and serum albumin levels were 2.7 mg/L and 3.4 g/L, respectively, thus corresponding to the International Staging System (ISS) Stage II multiple myeloma. Bone marrow aspiration revealed a cellular marrow with 38% plasma cells, and trephine biopsy was hypercellular with sheets of abnormal-looking plasma cells. Pericardial fluid analysis revealed a glucose level of 121 mg/dL and total protein of 7 g/dL. The adenosine deaminase (ADA) level was 52.9 U/L. Cytological evaluation showed a total leukocyte count of 2,700 cells/mm³, with differential counts demonstrating 84% atypical plasmacytoid cells, 4% neutrophils, and 12% lymphocytes. GeneXpert testing for Mycobacterium tuberculosis was negative, and bacterial culture showed no growth after 72 h of incubation. Cell block was prepared and immunohistochemical staining (IHC) for cluster of differentiation (CD) 138 revealed plasma cells. Flow cytometric immunophenotyping was performed using a standard antibody panel of CD45, CD19, CD20, CD38, CD138, CD117, CD56, and Kappa and Lambda light chains. CD38 and CD138 gating strategy revealed 55% abnormal plasma cells which showed negative to dim CD45 expression and negative CD56 expression with Kappa light chain restriction. The cytology, cell block, IHC and flow cytometry images have been depicted in Figures 2 and 3. Cytogenetic analysis was not available for the patient. The patient was started on VTD for treatment of myeloma and discharged in a hemodynamically stable condition. The patient was eventually lost to follow-up.

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Figure 2: Cell cytology, cell block, and immunohistochemistry of pericardial fluid, (a) Cytology smears showing marked hemorrhage and plasmacytoid cells (Leishman stain, ×400), (b) The plasmacytoid cells show eccentric nuclei with abundant vacuolated cytoplasm (Leishman stain, ×1000), (c) Cell block shows numerous scattered plasma cells in a hemorrhagic background (hematoxylin and eosin, ×400), (d) Immunostaining for cluster of differentiation 138 highlights the plasma cells (hematoxylin and eosin, ×400).

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Figure 3: Flow cytometric analysis of pericardial fluid reveals 55% immunophenotypically abnormal plasma cells which are positive for CD38 (bright), CD138 (bright), and CD45 (negative to dim) with Kappa light chain restriction, while being negative for CD19, CD20, and CD56. CD: Cluster of differentiation.

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DISCUSSION

Extra-medullary myeloma (EMM) may be a primary presentation of a plasma cell neoplasm or may be secondary at the time of relapse. The essential biological differences between medullary and extra-medullary disease (including plasma cell leukemia) may be rooted in the acquisition of genetic and immunophenotypic characteristics that enable the plasma cells to migrate from the medullary spaces and home in extra-medullary sites.^[6,7] In our case study, both patients presented with an extra-medullary presentation at relapse, thus being consistent with secondary EMM.

Several secondary and terminal genetic events in the natural disease course of myeloma, including high-risk genetic aberrations such as deletion 13q, deletion 17p, and 1q amplification, may have a role in extra-medullary disease and consequent dismal prognosis. Several studies have also revealed that loss of cell adhesion molecules may have a significant role in disease dissemination. As such, authors have reported the absence or downregulation of CD56 in EMM or plasma cell leukemias.^[8] In our study, one patient showed a complete absence of CD56 expression while the other patient reported the presence of 1q amplification, thus showing concordance with published literature.

In general, pericardial effusions are a rarer manifestation of EMM and pericardial tamponade, an even rarer presentation with only a handful of such cases documented in the literature. Pericardial involvement is believed to have an even poorer outcome; however, due to the rarity of such manifestation, no definite prognostic model or consensus on disease management exists at present.^[9]

From a morphological point of view, myeloma presenting as a body cavity effusion may require distinction from PEL, especially in cases having a plasmablastic morphology. Distinction is necessary due to differences in clinical course, biological nature, and management of the disease entities. A clinical history may prove to be useful, considering the strong association of PEL with human herpes virus-8 and Epstein–Barr virus infection. Moreover, PEL cells express differences in immunophenotype from myeloma cells including expression of human leukocyte antigen – DR isotype, CD30, and latency-associated nuclear antigen 1.^[10]

CONCLUSION

Involvement of body cavity fluids, in particular pericardial fluid, by plasma cell neoplasm is an uncommon clinical presentation and requires careful clinical, morphological, and immunophenotypic analysis for diagnosis and exclusion of other morphological mimickers. Disease prognostication and therapy strategies require further studies on EMM and their relevant immunophenotypic and genetic signatures. In general, EMM carries a poorer prognosis than medullary disease, and thus, studies and clinical trials directed at targeted therapeutic strategies may prove to be useful.