A 69‐year‐old man with a medical history of hypertension presented with symptoms of fatigue and weight loss lasting 1 month. The initial laboratory investigation revealed significant anemia (hemoglobin levels: 6.4 g/dL). Then, the anemia‐related work‐up revealed the existence of monoclonal immunoglobulin (M protein: 1.10 g/dL) and positivity for monoclonal IgG kappa gammopathy. No other abnormalities were found upon further evaluation, so bone marrow abnormalities were strongly suspected. He received a bone marrow exam, and the results demonstrated infiltration of lymphocytes, plasmacytoid cells, and plasma cells (Figure 1A). Immunohistochemical (IHC) investigations showed positive results for CD138 and CD20, along with kappa light chain restriction, and negative results for CD3. The initial diagnosis was lymphoplasmacytic lymphoma (LPL). However, the flow cytometric analysis for immunophenotyping showed increased plasma cells (19.4%) characterized by positive expression of CD38, CD138, CD56, and cytoplasmic kappa light chain and negative expression of CD19, CD3, and CD5. Moreover, there was no clonal B‐cell population identified, suggesting the diagnosis of plasma cell myeloma (PCM). Due to the incongruous results obtained earlier, further immunohistochemical evaluations were carried out. The results revealed that these CD138‐expressing cells also exhibited expression of CD56 and cyclin D1 (Figure 1B) but were negative for PAX5 and leukocyte common antigen (LCA), confirming the diagnosis of plasma cell myeloma with lymphoplasmacytic lymphoma‐feature. The patient received triple therapy with bortezomib, lenalidomide, and dexamethasone. After treatment, the patient exhibited improvement of his clinical symptoms and anemia.
FIGURE 1.
(A) Lymphocyte, plasmacytoid cells and plasma cells infiltration into the marrow space occupied approximately 90% of nucleated cells (400×); (B) Positive for cyclin D1 in IHC (200×); (C) Diagnostic flowchart in our case. IHC: immunohistochemistry, LPL: lymphoplasmacytic lymphoma, PCM: plasma cell myeloma.
The case represents a diagnostic challenge in clinical practice because of significant overlaps in morphological and immunohistochemical features between LPL and PCM. Typically, the morphological characteristics of malignant plasma cells, including an eccentric nucleus, perinuclear halo, basophilic cytoplasm, high expression of CD38 and CD138, and low expression of CD20, rarely lead to diagnostic difficulties in PCM. However, there are atypical morphologies of small lymphocyte‐like or lymphoplasmacytoid cells with CD20 expression, which are associated with cytogenetic aberration t(11;14) and may mimic B‐cell lymphoma. 1 On the other hand, LPL is a subtype of B‐cell neoplasm that is positive for CD19, CD20, and CD22 and negative for CD5 or CD10, as well as variable CD38 expression. Importantly, the LPL cells were found to be positive for B‐cell markers, including PAX5, and negative for cyclin D1 and lymphoid enhancer‐binding factor 1 (LEF1) in an IHC study. 2 Therefore, an IHC assessment for cyclin D1 expression and chromosomal translocation t(11;14) detected by fluorescent in situ hybridization (FISH) can help clinicians make an accurate diagnosis. 3 , 4
In regard to clinical relevance, previous studies indicated that PCM exhibiting cyclin D1 expression represents a distinct disease subset characterized by unique biological features, such as harboring t(11;14), higher levels of B‐cell lymphoma 2 (BCL‐2), and frequent CD20 expression. 1 However, the effect of the above factors on prognosis remains undetermined. 1 , 3 , 4 A meta‐analysis suggests that the expression of cyclin D1 may be linked to favorable clinical outcomes in PCM patients treated with bortezomib. 5
In summary, we encountered a diagnostic dilemma between PCM and LPL based on their morphologies. Specific IHC analysis of PCM (cyclin D1 and CD56) and LPL (PAX5 and LCA) markers and flow cytometry provided valuable diagnostic information necessary to make an accurate diagnosis (Figure 1C). 3 , 4 This case emphasizes the significance of comprehensive multiple tests to make an accurate diagnosis in a rare subset of PCM.
CONFLICT OF INTEREST STATEMENT
The authors declare no conflict of interest.
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