PMC9745170_01
Cytological findings. (A) Proliferation of mononuclear cells admixed with multinucleated giant cells (Papanicolaou staining, original magnification x20); (B) Multinucleated giant cells with dozens of nuclei (Papanicolaou staining, original magnification x40). Histological findings. (C) The lymph node was almost replaced by the tumor, and its original architecture was lost (hematoxylin and eosin staining; original magnification x10); (D) Predominant mononuclear neoplastic cells with prominent nucleoli and basophilic cytoplasm (hematoxylin and eosin staining; original magnification x60); (E) Multinucleated giant cells with dozens of nuclei (hematoxylin and eosin staining; original magnification x60).
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Computed tomography revealed enlarged cervical lymph nodes and involvement of the mandible and Th1 vertebral body ( Supplemental Figure 1 ). A fine-needle aspiration biopsy of a cervical lymph node was performed, and the cytological findings suggested plasma cell neoplasm ( Figure 1 ). The multinucleated giant cells had dozens of nuclei, mimicking osteoclasts ( Figure 1 ).
Immunohistochemistry and Epstein-Barr virus-encoded RNA (EBER) in-situ hybridization findings (original magnification x40). Yellow arrows indicate multinucleated cells. Both multinucleated giant cells and mononuclear cells were positive for (A) CD138 (a plasma cell marker; membranous positive), (B) light chain restriction of kappa>lambda (suggesting monoclonality), (C) cyclin D1 (a marker for plasma cell myeloma), and (D) EBER (suggesting Epstein-Barr virus-associated neoplasm). (E) Both cell types were negative for CD68 (a histiocyte marker). (F) Mononuclear cells were positive, but multinuclear giant cells were negative for OCT4 (Yamanaka factor). (G, H) c-Myc (Yamanaka factor) expression was stronger in mononuclear than in multinucleated cells, and multinucleated cells with a larger number of nuclei (G) showed weaker positivity than those with a smaller number of nuclei (H). (I) KLF4 (Yamanaka factor) was positive in some of the mononuclear cells, but negative in the multinucleated giant cells. (J) CD44 (a marker for cancer stem cells) was positive in both cell types. (K) Mib1/Ki67 showed strong positivity in the mononuclear cells, while the multinucleated cells were almost negative.
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Blood analysis showed increased serum immunoglobulin G (IgG) levels ( Supplemental Table 2 ), and serum immunofixation electrophoresis detected IgG-kappa type M-protein ( Supplemental Figure 2 ) which demonstrates the results of serum immunofixation electrophoresis). Figure 2A ) and revealed light chain restriction of kappa>lambda ( Figure 2B ), suggesting monoclonal plasma cell proliferation. Furthermore, both cell types were positive for cyclin D1 ( Figure 2C ) and EBER-ISH ( Figure 2D ). However, both cell types were negative for CD68, a marker for histiocytes ( Figure 2E ). Some of the mononuclear cells exhibited strong cytoplasmic immunopositivity to OCT4, which was not the case with any of the multinucleated cells ( Figure 2F ). As for c-Myc, the mononuclear cells showed stronger nuclear immunopositivity than the multinucleated cells ( Figures 2G, H ). Among the multinucleated cells, those with a larger number of nuclei ( Figure 2G ) showed weaker positivity than those with a smaller number of nuclei ( Figure 2H ). As for KLF4, some of the mononuclear cells showed nuclear positivity, while multinucleated cells were consistently negative ( Figure 2I ). Figure 2J ) and negative for SOX2. Furthermore, the mononuclear cells had a high Mib1/Ki67 index, while multinucleated cells were scarcely positive ( Figure 2K ).
Comparison of our case with previous studies.
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We have summarized these results in  Figure 3  and compared them to the results of previous studies.