Plasma Cell Disorder Pathology Study Guide

Plasma Cell Disorders (Dyscrasias)

Plasma Cell Disorders Pathology Video

Plasma cell disorders are also known as plasma cell dyscrasias.

Examples of plasma cell disorders include:

Multiple myeloma (MM)
Monoclonal gammopathy of undetermined significance (MGUS)
Waldenstrom macroglobulinemia (WM)

Multiple Myeloma. (a and b) Histopathological appearance of bone marrow biopsy displaying plasmacytosis (H and E, ×40). Localized cutaneous mucinosis associated with multiple myeloma: a rare presentation. Rather PA, Hussain M, Bagdadi F - Indian journal of dermatology (2014). Not altered. CC.
Plasmacytoma_Microscopy. Histologic examination of the pleural fluid (A), mediastinal mass (B and C), and bone marrow (D, E, and F). (A) Cytospin analysis of pleural fluid shows increased plasma cells with eccentric nuclei and abundant basophilic cytoplasm, consistent with myelomatous pleural effusion (Wright-Giemsa stain, ×200). (B) The histologic examination of mediastinal plasmacytoma reveals diffuse infiltration of mature plasma cells (hematoxylin and eosin stain, ×200). (C) Immunohistochemical staining of mediastinal plasmacytoma shows CD138 positivity (×1,000). (D) Bone marrow aspiration shows moderate proliferation of neoplastic plasma cells, consistent with plasma cell myeloma (Wright-Giemsa stain, ×1,000). (E and F) Immunohistochemical staining of bone marrow shows monoclonal proliferation of lambda-restricted plasma cells (kappa [E] and lambda [F] stains, ×200). A case of salivary-type amylase-producing multiple myeloma presenting as mediastinal plasmacytoma and myelomatous pleural effusion. Ok SJ, Kim IS, Lee EY, Kang JE, Lee SM, Song MK - Annals of laboratory medicine (2014). Not altered. CC.

Multiple Myeloma

Multiple myeloma (MM) is a malignant proliferation of plasma cells.

Multiple myeloma (MM) requires greater than 10% of the bone marrow cells to be malignant plasma cells.

Multiple myeloma (MM) is the most common primary malignancy of bone.

The neoplastic plasma cells produce immunoglobulin.

Multiple myeloma (MM) is associated with high serum levels of IL-6.

The excess immunoglobulin can be detected on serum protein electrophoresis (SPEP), resulting in a monoclonal spike (M spike), most commonly due to monoclonal IgG or IgM.

Osteoclasts that have the RANK receptor are activated by neoplastic plasma cells, and characteristically degrade the bone.

Clinical and laboratory findings of multiple myeloma (MM) include:

Bone pain with hypercalcemia
Lytic, ‘punched-out’ skeletal lesions are seen on x-ray, especially in the vertebrae and skull
Fractures after minor trauma
Elevated serum protein
Increased risk of infections
Rouleaux formation of red blood cells (RBCs) on blood smear due to increased serum protein decreasing charge between RBCs
Primary AL amyloidosis in which kappa free light chains circulate in serum and deposit in tissues
Proteinuria due to kappa or lambda free light chains being excreted in the urine as Bence Jones protein

Monoclonal antibodies of multiple myeloma lack antigenic diversity.

The most common cause of death in patients with multiple myeloma is infection.

Bence Jones protein deposits in kidney tubules, increasing the risk of kidney failure.

Kidney failure secondary to multiple myeloma is myeloma kidney.

Multiple Myeloma. Aspiration cytology smear of a case plasmacytoma in 4 cm diameter chest wall mass in a 69 year male patient. (MGG stain, ×440). Cytology of plasma cell rich effusion in cases of plasma cell neoplasm. Journal of Cytology / Indian Academy of Cytologists. Not altered. CC.
Multiple Myeloma. Bony lesions in multiple myeloma. The skull demonstrates the typical “punched-out” lesions characteristic of multiple myeloma. Multiple cystic swelling: Initial presentation of multiple myeloma. Kumar S, Jain AP, Waghmare S - Indian journal of medical and paediatric oncology : official journal of Indian Society of Medical & Paediatric Oncology (2010). Not altered. CC.
Multiple Myeloma. Atypical plasma cell infiltrate with both Russell (cytoplasmic) and Dutcher (nuclear) bodies (H&E, 50x) Gabriel Caponetti -Not altered. CC BY-SA 3.0
Multiple Myeloma. Micrograph showing myeloma cast nephropathy in a kidney biopsy: Hyaline casts are PAS positive (dark pink/red – right of image). Myelomatous casts are PAS negative (pale pink – left of image), PAS stain. Nephron - Not altered. CC BY-SA 3.0
Multiple Myeloma. Plasmacytoma, H&E stain Nephron - Not altered. CC BY-SA 3.0
Multiple Myeloma. Bone marrow aspirate showing the histologic correlate of multiple myeloma under the microscope, H&E stain No machine-readable author provided. KGH assumed (based on copyright claims). Not altered. CC BY-SA 3.0
Multiple Myeloma. Plasmablast, Wright stain, in a case of multiple myeloma of plasmablastic type. Mikael Häggström, M.D. Not altered. CC0
Multiple Myeloma. Myeloma cells produce monoclonal proteins of varying types, most commonly immunoglobulins (antibodies) and free light chains. Not altered, CC BY-SA 4.0
Multiple Myeloma. (a and b) Histopathological appearance of bone marrow biopsy displaying plasmacytosis (H and E, ×40). Localized cutaneous mucinosis associated with multiple myeloma: a rare presentation. Rather PA, Hussain M, Bagdadi F - Indian journal of dermatology (2014). Not altered. CC.
Multiple myeloma and monoclonal gammopathies @AnnKumfer

Monoclonal Gammopathy of Undetermined Significance (MGUS)

Monoclonal gammopathy of undetermined significance (MGUS) is an increased serum protein with M spike on SPEP.

MGUS is common in the elderly population.

Approximately 5% of individuals above 70-years-old have monoclonal gammopathy of undetermined significance (MGUS).

One percent of patients with monoclonal gammopathy of undetermined significance (MGUS) develop multiple myeloma each year.

MGUS. a: Densitometry tracing of gel electrophoresis of normal serum.b: Densitometric tracing of gel electrophoresis of subject with monoclonal band. Prevalence and type of monoclonal gammopathy of undetermined significance in an apparently healthy Nigerian population: a cross sectional study. Onwah AL, Adeyemo TA, Adediran A, Ajibola SO, Akanmu AS - BMC blood disorders (2012). Not altered. CC.
MGUS SPEP. Serum protein electrophoretic patterns on an Agarose gel showing subject’s β band appearing dense and a discrete band in the γ region. This is shown with the arrows. Prevalence and type of monoclonal gammopathy of undetermined significance in an apparently healthy Nigerian population: a cross sectional study. Onwah AL, Adeyemo TA, Adediran A, Ajibola SO, Akanmu AS - BMC blood disorders (2012).
MGUS. Serum immunofixation electrophoresis of subject shows two monoclonal bands: IgA kappa (in β2 position) and IgG lambda (in mid-γ region). Prevalence and type of monoclonal gammopathy of undetermined significance in an apparently healthy Nigerian population: a cross sectional study. Onwah AL, Adeyemo TA, Adediran A, Ajibola SO, Akanmu AS - BMC blood disorders (2012). Not altered. CC.

Waldenstrom Macroglobulinemia

Waldenstrom macroglobulinemia (WM) is B-cell lymphoma with monoclonal IgM production.

Clinical features of Waldenstrom macroglobulinemia (WM) include:

Lymphadenopathy
Increased serum protein with M spike (comprised of lgM)
Visual deficits
Symptoms related to hyperviscous blood due to the IgM (large pentamer) causing serum hyperviscosity
Neurologic deficits such as hemorrhage or stroke
Bleeding due to viscous serum results in defective platelet aggregation

Acute complications are treated with plasmapheresis, which removes lgM from the serum.

Waldenstrom Macroglobulinemia. The tissue or bone marrow involvement pattern and immunophenotypic profiling of the EMWM and BMWM patients. a, b A representative diffuse interstitial pattern of bone marrow biopsy in a patient with BMWM, ×40 and × 80 magnification. c Bone marrow aspirate smear showed many abnormal small lymphoid cells admixed with variable plasmacytoid cells and plasma cells, ×80 magnification. d CD20 stain on the abnormal small lymphoid cells, ×80 magnification. e CD138 stain on the plasmacytoid and plasma cells, ×80 magnification. f, g Immunophenotypic profiling of CD38 and CD138 positive plasmacytoid and plasma cells with strong monotypic cytoplasmic kappa light chain expression. h The abnormal small lymphoid cells were CD20 positive and showed monotypic kappa light chain expression. i, j A representative diffuse infiltrative pattern of a lymph node biopsy in a patient with EMWM, MYD88 mutation positive, ×40 and × 80 magnification. k CD20 stain on abnormal small lymphoid cells, ×80 magnification. l CD138 stain on few admixed plasmacytoid and plasma cells, ×80 magnification. m, o Immunophenotypic profiling of CD19 and CD20 positive small B-cells with kappa light chain restriction and were negative for CD5 and CD10. p Identical monotypic kappa light chain expression in the lymphoid cells was also seen in the plasmacytoid and plasma cells. Waldenström macroglobulinemia with extramedullary involvement at initial diagnosis portends a poorer prognosis. Cao X, Ye Q, Orlowski RZ, Wang X, Loghavi S, Tu M, Thomas SK, Shan J, Li S, Qazilbash M, Yin CC, Weber D, Miranda RN, Xu-Monette ZY, Medeiros LJ, Young KH - Journal of hematology & oncology (2015). Not altered. No license or rights.
The prognosis of Waldenstroms macroglobulinemia is fine. This condition typically effects the elderly, and does not significantly impact life span or activities of daily living.
Waldenstrom Macroglobulinemia. Photomicrograph showing hypercellular marrow with diffuse infiltration by lymphoid cells, plasmacytoid lymphocytes, a few plasma cells, and mast cells (hematoxylin and eosin stain, ×1,000); inset photomicrograph showing strong cytoplasmic positivity for CD20 in the majority of the lymphoid cells (immunohistochemical stain for CD20, ×400). Waldenstrom's macroglobulinemia presenting with lytic bone lesions: a rare presentation. Pujani M, Kushwaha S, Sethi N, Beniwal A, Shukla S - Blood research (2013). Not altered. CC.
Waldenstrom Macroglobulinemia. Photomicrograph showing hypercellular bone marrow smears with the presence of mostly bare nuclei, few lymphoid cells, and plasmacytic cells (Wright's stain, ×1,000). Waldenstrom's macroglobulinemia presenting with lytic bone lesions: a rare presentation. Pujani M, Kushwaha S, Sethi N, Beniwal A, Shukla S - Blood research (2013). Not altered. CC.