Pathology of Plasma Cell Lesions

Updated: Oct 25, 2015
  • Author: Lesley Elizabeth Fox, MD; Chief Editor: Francis H Gannon, MD  more...
  • Print


Plasma cell lesions are the neoplastic (clonal) proliferation of plasma cells involving single bones (plasmacytoma) or multiple bones (multiple myeloma).

Plasma cell myeloma (multiple myeloma, myelomatosis, medullary plasmacytoma) is a bone marrow-based, malignant disorder of postgerminal center B-cells that is characterized by a clonal proliferation of plasma cells, with associated serum and/or urine monoclonal proteins. [1, 2, 3, 4] In this disease, the malignant plasma cell clone disrupts the normal marrow microenvironment leading to immune dysfunction, cytopenias, angiogenesis, and osteoclastogenesis. [3, 5]

Osseous solitary plasmacytoma of bone is a localized bone tumor of plasma cells, without evidence of plasma cell myeloma or marrow plasmacytosis. [1] Extraosseous solitary plasmacytoma of bone is a localized, soft-tissue plasma cell neoplasm that occurs in a location other than the bone and does not have evidence of plasma cell myeloma or marrow plasmacytosis.

The etiology of plasma cell neoplasms is unknown in the majority of cases. [1, 6] However, chronic antigenic stimulation, infection, toxic exposure, and radiation have been suggested as potential etiologic events. [1]

A computed tomography (CT) scan demonstrating myeloma is provided below.

Computed tomography scan demonstrates a destructiv Computed tomography scan demonstrates a destructive lesion with an associated soft-tissue mass. This image depicts myeloma.

See also the following:



An estimated 20,180 new cases of plasma cell myeloma were expected to be diagnosed in the United States in 2010, with a median age at diagnosis of 70 years. [6] This disease can occur in younger individuals but is rarely seen before the age of 45 years. [6] In addition, plasma cell myeloma occurs more commonly in Americans of African descent than of European descent. There is also a slight male preponderance (male-to-females ratio, about 1.5:1). [1, 6]

Solitary plasmacytoma of bone comprises 3-5% of all plasma cell neoplasms. It is also seen more commonly in males than females but presents in a younger patient than those with plasma cell myeloma, with a median age at diagnosis of 55 years. [1]


Clinical Features

Plasma cell neoplasms show a spectrum of disease from asymptomatic to symptomatic forms. In either form of plasma cell myeloma, immune dysfunction, cytopenias and lytic bone lesions occur as a result of direct cellular interactions (cytokines, growth factors) and/or mass effect. [3] Readers are referred to the 2008 World Health Organization (WHO) Classification of Tumors of Hematopoietic and Lymphoid Tissues [1] for the specifics of each clinical entity. The key clinical features will be covered in this review.

Plasma cell myeloma presents with generalized marrow involvement, with or without lytic lesions of bone. It tends to involve bones of active hematopoiesis, most commonly the vertebral column, long bones, and skull. [1, 3] When present, extramedullary involvement is generally a feature of clinically aggressive disease.

Asymptomatic plasma cell myeloma

Asymptomatic plasma cell myeloma is a plasma cell neoplasm defined by the presence of serum monoclonal protein of 3.0 gm/dL or greater (by electrophoresis) and/or clonal plasma cells in the bone marrow of 10% or greater, without evidence of end-organ damage (hypercalcemia, renal insufficiency, anemia, lytic lesions of bone). [1]

Symptomatic plasma cell myeloma

Symptomatic plasma cell myeloma is a plasma cell neoplasm defined as the presence of end-organ damage (hypercalcemia, renal insufficiency, anemia, lytic lesions of bone) in a patient with a monoclonal protein (of any amount) and clonal plasma cells in the bone marrow (of any amount) or plasmacytoma. [1]

Patients with symptomatic plasma cell myeloma can present with features of bony involvement (bone pain, pathologic fractures), cytopenias (fatigue, immune dysfunction, infections), hyperviscosity syndrome, venous thromboembolism, and renal insufficiency. [1, 5, 4]

Hypercalcemia results from the increased osteoclastic activity, with resultant lytic bone lesions and pathologic fractures (see the image below). [1, 5] Renal insufficiency is due to hypercalcemia and monoclonal light chain–induced injury to the kidney.

Computed tomography scan demonstrates a destructiv Computed tomography scan demonstrates a destructive lesion with an associated soft-tissue mass. This image depicts myeloma.

Anemia results from bone marrow replacement by plasma cell myeloma and/or the loss of erythropoietin as a result of renal injury. [1, 5] Hyperviscosity is a rare occurrence and is caused by increased circulating serum immunoglobulin. [7] Venous thromboembolism occurs in plasma cell myeloma, particularly in patients receiving multiagent chemotherapy or anti-angiogenesis drugs. [5]

Clinical variants

Symptomatic plasma cell myeloma has the following related clinical variants and features [1] :

  • Asymptomatic plasma cell myeloma: Absence of end-organ damage
  • Nonsecretory plasma cell myeloma: Absence of monoclonal protein on immunofixation (IFE)
  • Plasma cell leukemia: Increase in circulating clonal plasma cells greater than 20% of the leukocyte count or greater than 2.0 × 10 9 cells/L

Gross and Microscopic Features

On gross examination, a typical plasma cell neoplasm will present as a soft to gelatinous, tan to yellow to hemorrhagic, bony defect or soft-tissue tumor. [1]

Microscopically, the morphologic features are similar for plasma cell myeloma and solitary plasmacytoma of bone. Normally, plasma cells reside in the marrow and represent less than 1% of nucleated cells. In plasma cell neoplasms, a clonal population of plasma cells proliferates, forming a tumor either in bone or soft tissue.

A variety of pathologic specimens can be received in the evaluation of a patient suspected to have a plasma cell neoplasm, including peripheral blood, urine, bone biopsies (core, incisional, or excisional), and bone marrow aspirate smears, clot sections, or core biopsies. Regardless of the specimen type received, clonal plasma cells show a similar morphology with variable degrees of maturation, form immature plasmablastic forms (with dispersed chromatin with conspicuous nucleoli and high nuclear-to-cytoplasmic ratio) to more mature forms (with eccentric nucleus with blocked chromatin, perinuclear cuff, and basophilic cytoplasm) to pleomorphic forms (with multinucleation and/or hyperlobation). [1, 4]

Immature and pleomorphic morphologic features are more consistent with a plasma cell neoplasm than a reactive proliferative process. [1] High cytoplasmic immunoglobin content of the clonal plasma cells is associated with morphologic findings of Mott cells, Russell bodies, Dutcher bodies, flame cells, and Gaucher-like cells. [1, 4]

Bone marrow biopsies will show sheets and clusters of plasma cells, with either focal or diffuse marrow involvement. [1, 4] A CD138 immunohistochemical stain can be used to aid in quantifying plasma cells (in core biopsy or clot sections) in diagnostically challenging cases (see Immunohistochemistry).

Plasma cell myeloma is a likely consideration if greater than 30% plasma cells or the presence of a tumoral mass of plasma cells is seen. [1] The number of plasma cells can be quite variable on marrow aspirate smears, from scattered and more limited in number to markedly increased in number with focal clustering. See the images below.

Histology shows sheets and clusters of atypical pl Histology shows sheets and clusters of atypical plasma cells and plasmablasts. The cells have eccentric nuclei and a clock-face-like chromatin. The cytoplasm is usually eosinophilic owing to the protein production in myeloma.
A by-product of these tumors is the production of A by-product of these tumors is the production of amyloid. On routine hematoxylin and eosin (H&E) sections, amyloid appears as eosinophilic, amorphous deposits. Special stains are helpful in identifying these deposits.
Examination by polarized light reveals an apple gr Examination by polarized light reveals an apple green coloring to the amyloid. This is often a helpful adjunct in interpreting suspected cases of amyloid deposition.


Immunophenotypic features of plasma cell myeloma and solitary plasmacytoma of bone are similar. Immunophenotyping by flow cytometry may show an aberrant clone of plasma cells with the following phenotype: CD45-, CD79a+, CD19+, CD38+, CD138+ with monoclonal expression of cytoplasmic light chains. More than 50% of cases will express CD43, CD117, and/or CD56. Aberrant expression of CD20, CD10, and CD52 is seen to a lesser degree. [1, 4]

An important consideration is the frequent underestimation of plasma cells by flow cytometry. As such, immunohistochemical stains may be necessary in problematic cases (see the following images). Differential diagnosis by immunophenotype includes, but is not limited to, the following [1, 4] :

  • Reactive plasma cell proliferations
  • Lymphoplasmacytic lymphoma
  • Plasmablastic lymphoma, lymphomas with plasmablastic or plasmacytoid features
  • Nonlymphoid malignancies with CD56 expression (acute myeloid leukemia, carcinoma)
    Immunohistochemistry is useful in demonstrating th Immunohistochemistry is useful in demonstrating the clonality of the lesion. Occasionally, the stains can be hard to interpret, but in general, either the kappa (pictured here) or the lambda light chain will show positivity. If both stains are positive, a tumor diagnosis should be questioned.
    Immunohistochemistry for lambda light chains is in Immunohistochemistry for lambda light chains is intensely positive, and in the presence of a negative kappa light chain stain, helps in the identification of the diagnosis.

Correlation of the immunophenotype with clinical, radiologic, and morphologic features will aid in distinguishing these entities from plasma cell myeloma or solitary plasmacytoma of bone, as well as in distinguishing plasma cell myeloma from solitary plasmacytoma of bone.



At the time of isotype switching, complex genetic events occur which transform normal plasma cells into a malignant population of plasma cells, with clonally rearranged heavy and light chain genes and immunoglobulin heavy chain variable (IgH-V) gene somatic hypermutation. [1, 5] Numeric and structural abnormalities are seen, and plasma cell myeloma can be divided into 2 groups based on cytogenetic and molecular findings, as follows: (1) a nonhyperdiploid karyotype with a high incidence of recurrent immunoglobulin heavy chain (IgH) translocations and/or abnormalities of chromosome 13 and (2) a hyperdiploid karyotype with multiple associated trisomies (chromosomes 3, 5, 7, 9, 11, 15, 19, 21) but with a low incidence of IgH translocations or chromosome 13 abnormalities. [1, 3, 5]

Routine cytogenetic studies detect a limited portion of the underlying chromosomal abnormalities commonly seen in plasma cell myeloma, and fluorescence in situ hybridization (FISH) (or other molecular methods) should be combined with conventional cytogenetics to detect cryptic translocations that are known to occur in plasma cell myeloma. [1, 5]

A working model of multistep development has been proposed for plasma cell neoplasms, suggesting a portion of monoclonal gammopathy of undetermined significance (MGUS) progresses to asymptomatic (smoldering) plasma cell myeloma, and a portion of these cases will then progress onto symptomatic plasma cell myeloma, with or without evidence of disease progression (plasma cell leukemia and/or extramedullary disease). [3]

A study estimated the impact of prior knowledge of monoclonal gammopathy of uncertain significance (MGUS) diagnosis and comorbidities on multiple myeloma (MM) survival. The study found that patients with MM with prior knowledge of MGUS had better MM survival, suggesting that earlier treatment of MM leads to better survival. [8, 9]


Prognosis and Predictive Factors

In the majority of cases, plasma cell myeloma is not curable and has a median survival of 3-4 years. Nonetheless, in the last few decades, significant improvement has been seen in overall 5-year survival of plasma cell myeloma. [1, 6] Complete response (CR) is defined as absence of detectable serum or urine monoclonal protein, a normal percentage of plasma cells in the marrow and peripheral blood, no increase in size or number of lytic bone lesions, and/or reduction in the size of soft-tissue plasmacytoma. [10]

The disordered bone marrow milieu of plasma cell myeloma results in angiogenesis and increased microvascular density, which correlates clinically with disease progression and poor prognosis. [3] A worse prognosis is also associated with following features [1, 4] :

  • Extensive marrow involvement (>50%)
  • Immature plasmablastic morphology
  • Increased monoclonal protein
  • Multiple bony lesions, anemia, decreased albumin
  • Increased lactate dehydrogenase (LDH) levels
  • Increased beta-2-macroglobulin
  • Renal insufficiency
  • t(4;14), t(14;16) and/or deletions of 17p or 13q [5]

Plasma cell myeloma with a hyperdiploid karyotype (ie, without recurrent translocations) tends to have a better prognosis.