Malignant myeloma rarely involves the serosal cavities, affecting less than 1% of patients. It usually occurs as a late complication of the disease and is associated with poor prognosis. (1-4) The pleural cavity is involved more commonly than the pericardial and peritoneal cavity. Pleural cavity is involved either due to direct tumor extension from a rib lesion or hematogenous spread or lymphatic obstruction (1). Patients with this disease are often older, with a mean age of 58 years and an age range of 21-77 years. (3, 5) Diagnosis of serous fluid involvement by myeloma is crucial for therapeutic and prognostic considerations and is characterized by a proliferation of plasma cells and secretion of immunoglobulin proteins.

The diagnosis can be missed when the number of plasma cells are few or mature in appearance. A diagnosis can be straightforward if it incorporates patient history and ancillary techniques. A previously established diagnosis or radiological findings of extensive disease such as lytic bone lesions, or new chest wall masses on imaging and demonstration of monoclonal protein in pleural fluid by protein electrophoresis, could also be helpful.(6) Exfoliative cytology still remains the most effective initial diagnostic modality to evaluate malignant effusions. (7)

Cytological features:

Morphologically, the smears are composed of many large cells arranged in isolated cell pattern with a hemorrhagic or necrotic background. Although the cytoplasm is usually abundant and dense with red granules, the degree of plasmacytoid differentiation and nuclear atypia varies from one tumor to another. Interestingly, the characteristic perinuclear hof and clock faced condensed chromatin pattern characteristic of benign plasma cells is usually absent, however other easily recognizable mature plasma cell morphology usually remain such as the eccentric nuclei, round to oval nuclei with clumped chromatin, abundant cytoplasm and low N:C ratio remain. Additional subtypes lacking plasmacytoid features have been described such as plasmablastic morphology (immature blast like plasma cells with enlarged nuclei, high nuclear-to-cytoplasmic ratios, coarse chromatin, and prominent eosinophilic nucleoli), anaplastic subtype (marked nuclear pleomorphism, including binucleated /multinucleated tumor cells), and lymphoplasmacytoid subtype (with small lymphocyte-like plasma cells). (1)

Differential Diagnosis:

For cases which contain plasma cells with plasmablastic or anaplastic morphological appearances, the differential diagnosis includes melanoma, poorly differentiated carcinoma, plasmablastic lymphoma, anaplastic large cell lymphoma (ALCL) and primary effusion lymphoma (PEL). (2) Sometimes reactive mesothelial cells are difficult to differentiate from neoplastic plasma cells. In these cases, IHC for mesothelial cells (calretinin, WT-1) is helpful.

Reactive plasma cells may be present in effusions due to other etiologies like infection, surgery, or carcinoma. In these benign cases, paucity of plasma cells with benign nuclear features and prominent cytoplasmic hof can be seen in an inflammatory background. It is essential to distinguish reactive plasmacytosis from plasma cell neoplasms by determining the expression of Ig heavy and light chains.

Clinical history combined with cytomorphologic features, IHC and flow cytometry are helpful in the differential diagnosis.

Ancillary testing (Immunohistochemistry and Flow cytometry):

Plasma cell myeloma (PCM) typically have monotypic cytoplasmic Ig and lack surface Ig, with IgA, IgG kappa, and lambda light chain as possible globulin types. (8) Additionally, CD79a, CD138 and strong CD38 are usually expressed, similar to normal plasma cells. CD138 is used as the diagnostic marker to isolate and identify plasma cells. PCM are mostly CD19 negative and CD56 is aberrantly expressed in 67-79% of cases. (9) Due to variable and wide spectrum of cytomorphological appearances of the neoplastic plasma cells in serous effusion specimens, IHC or in situ hybridization and flow cytometry for lambda and kappa restriction on a cell block preparation are essential to confirm the clonal nature of the plasma cells.

Flow cytometry is helpful in cases where PCM involvement is suspected but the specimen lacks malignant morphology. If a specimen contains mainly mature appearing plasma cells, flow cytometry could be used to confirm presence of a monoclonal plasma cell population. It could also be used on exudative effusions which are bloody or hypocellular. PCM produces large amounts of light chain immunoglobulins that accumulate in vital organs such as the kidneys and heart and many of these patients develop benign serious effusions with no PCM involvement. (10) If myelomatous involvement in a pleural fluid specimen is suspected flow cytometry can be helpful in ruling out disease in a variety of settings.

In our case, the tumor cells in the cell block sections showed negative staining with pankeratin and SOX-10, arguing against carcinoma and melanoma, positive staining with CD138 (supporting plasma cell lineage) and CD56. However, CD138 expression by a poorly differentiated neoplasm should be interpreted with caution, as it can be expressed by some B-cell lymphomas and is positive in a number of metastatic carcinomas. Immunohistochemical staining for anti-lambda antibody demonstrated monoclonality and stain for anti-kappa antibody was negative. These findings supported lambda restricted plasma cell neoplasm. Our patient had a history of IgG lambda restricted multiple myeloma: the patient’s recent serum protein electrophoresis revealed a spike in the gamma region and the immunofixation revealed IgG lambda monoclonal gammopathy. The bone marrow aspirate demonstrated scattered immature and pleomorphic plasma cells (large size, loss of eccentricity) in a background of mixed hematopoietic precursors. The bone marrow core biopsy also revealed extensive infiltration (greater than 80% of cellularity) by variably immature and pleomorphic plasma cells in a background of moderate-to-marked fibrosis.

Flow cytometric analysis performed on the bone marrow aspirate revealed a CD56-positive monoclonal plasma cell population indicative of a plasma cell dyscrasia.

One third of myelomas show genetic abnormalities detected by conventional cytogenetics and Fluorescence in-situ hybridization (FISH). Both structural and numerical abnormalities are found. In our case, the cytogenetic analysis was performed on the bone marrow aspirate which revealed a normal male chromosome complement, 46,XY (20). FISH with a multiple myeloma panel of probes was performed on CD138-positive sorted cells from the bone marrow aspirate, which demonstrated evidence of 3 copies of the CKS1B locus at 1q21 in cells scored and evidence of t(4;14) resulting in a fusion of IGH and FGFR3 in 54% cells scored. In an additional 43.5 percent cells, this translocation is accompanied by both gain and loss of derivative chromosomes. In multiple myeloma, gain of CKS1B locus and t(4;14) (p16;q32) (FGFR3/IGH) are generally associated with a poor prognosis. (11) Overall, the findings in our case supported a CD56-positive, lambda restricted plasma cell neoplasm, findings similar with patient’s history of plasma cell myeloma.


Myelomatous pleural effusions are associated with advanced disease and poor overall survival irrespective of whether myelomatous pleural effusion develops in the course of their disease or presents as the initial manifestation of multiple myeloma. (3, 4) Correlation with bone marrow biopsy is quite helpful to confirm myeloma and rule out plasmacytoma and other plasma cell neoplasms. Pleural biopsy is sometimes used to confirm cytologic findings, but may be noncontributory and less helpful than fluid cytology.


Diagnosis of myelomatous effusion is critically important due to the poor prognosis and for the treatment. A sufficient workup of these specimens combines cytology, radiology, hematology, immunohistochemistry, flow cytometry, and clinical history for definite diagnosis.