Hematology 2 - Lecture - 13 - Plasma Cell Disorders - Complete

Immature lymphoid neoplasms, Mature lymphoid neoplasms

Lymphoid neoplasm categories

Immature lymphoid neoplasms

Type of lymphoid neoplasm characterized by lymphoblastic proliferation

Mature lymphoid neoplasms

Type of lymphoid neoplasm characterized by proliferation of neoplastic lymphocytes

Immature lymphoid neoplasms

What type of lymphoid neoplasm is ALL?

Mature lymphoid neoplasms

What type of lymphoid neoplasm is CLL?

Plasma Cell Myeloma, Monoclonal Gammopathy of Undetermined Significance, Plasmacytoma, Primary amyloidosis, Heavy-Chain Diseases, Lymphoplasmacytic lymphoma, Waldenstrom macroglobulinemia

Mature B-cell neoplasms with plasma cell or plasmacytoid differentiation

Plasma cell disorders

These neoplasms are characterized by the proliferation of a single clone of immunoglobulin-producing cells or plasma cells.

M-protein

Single class or subunit of immunoglobulin that is almost always secreted in Plasma cell disorders

Paraprotein, M component

M-protein other name

M-protein

This protein, in Plasma cell disorders, is a single class or subunit of immunoglobulin or single class of immunoglobulin light chain, sometimes can even be a single type of heavy chain.

Gamma-globulin region

Plasma cell disorders can be detected as a monoclonal peak at this region on serum or urine protein electrophoresis

Albumin

Most abundant protein in the serum; always seen as the highest peak in the pattern in the leftmost

Gamma region

Region in electrophoresis where Immunoglobulins occupy

T

T/F

In normal conditions, Immunoglobulins are not as plenty and seen as just a broad-based hump, very subtle. (In electrophoresis)

M spike

In plasma cell disorders, the production of very high numbers of immunoglobulins or M proteins results in a characteristic spike at the gamma-globulin region. What do you call this spike?

No

Is an M spike specific for the presence of M-proteins? Yes/No

Monoclonal immunoglobulin

Plasma cell disorders have varying clinicopathologic features but they all have in common the production of this immunoglobulin

M-protein

Monoclonal immunoglobulins are collectively known as:

Monoclonal

Meaning of M in M-protein

2

Most monoclonal proteins consist of how many heavy chains of the same class?

2

Most monoclonal proteins consist of how many light chains of the same type?

T

T/F

In some cases, the monoclonal proteins consist only of a single light chain or fragments of heavy chains.

Renal insufficiency

Clinical manifestation in plasma cell myeloma that is related to the accumulation and deposition of M proteins

Hyperviscosity

High levels of paraprotein in the blood can also cause:

Hint: Something to do with viscosity

Unknown

Etiology of Plasma cell disorders

African-Americans

Plasma cell disorders have a genetic propensity or higher incidence in this group of people

Caucasian-Americans

Plasma cell disorders have lower incidence in African-Americans or Caucasian-Americans?

Plasma cell disorders

It is likely that these disorders result from a multi-step transformation process in which the lymphocytes or plasma cells undergo multiple genetic alterations that prevent normal cell differentiation and cell death with ultimate immortalization of the clone.

Serum or urine protein electrophoresis

Laboratory testing for M-proteins is usually accomplished by:

Gamma globulin region, Beta globulin region

M-proteins appear as a dense spike ('M-spike') at this region and occasionally in this other region too. (2 answers)

Decreased

Normal polyclonal immunoglobulins are usually (Increased/Decreased)

Bence-Jones proteins

Immunoglobulin light chains that are able to pass through the glomerular filter thus they may be detected in urine

Immunofixation

Once an M-protein is identified, it should be characterized by more refined methods as such as ___ to be able to establish what specific type of M protein is present

T

T/F

Knowing the specific identity of the protein in Plasma cell disorders has implications on the aggressiveness and the prognosis of the disease process

Plasma cell myeloma

It is an aggressive, bone marrow-based neoplasm of plasma cells associated with a monoclonal protein in serum and/or urine

Multiple myeloma

Plasma cell myeloma is also known as

Bone marrow smear examination

Laboratory diagnosis for Plasma cell myeloma

Multiple myeloma

Plasma cell myeloma is also known by this name because of the multicentricity of the lesions (multiple lesions that are spread out)

Clinical, Pathologic, Radiologic findings

The diagnosis for Plasma cell myeloma is based on a combination of:

African-Americans, Caucasians

Plasma cell myeloma is more common in ____ than in ____

Bone pain in the back or chest

Most common presenting symptom of Plasma cell myeloma, it is often associated with pathologic compression fractures of the thoracic or lumbar spine

70%

Radiographic studies show lytic lesions in what % of Plasma cell myeloma patients at the time of diagnosis

Lytic lesions

In Plasma cell myeloma, these are areas where the bone is resorbed either due to plasma cell infiltration or the interactions of plasma cells with bone cells, like osteoclasts (which facilitate the resorption of the bone).

Well-defined, punched out radiolucencies or darker areas

How are Lytic lesions in Plasma cell myeloma described as on X-rays?

Calcium

In X-rays, the whiter a bone is, the more ___ it has

Vertebral column, Ribs, Skull

Most commonly affected bones in Plasma cell myeloma

T

T/F

In Plasma cell myeloma, other areas like in the axial skeleton also have some radiolucencies seen (affected areas are spread out)

Weakness, Fatigue, Bleeding tendencies, Infections, Symptoms related to renal failure

Other physical findings that may be noted in Plasma cell myeloma

Fatigue

Physical finding in Plasma cell myeloma that is often related to anemia

Renal failure

Physical finding in Plasma cell myeloma that is most often due to the deposition of the M proteins (especially the light chains) in the renal vasculature, which causes injury and blockage

Infection

Most common cause of death in Plasma cell myeloma patients, because although the plasma cells produce large amounts of immunoglobulins, but they are non-functional.

M-protein in serum or urine, Bone marrow clonal plasmacytosis or plasmacytoma, Related organ or tissue impairment

World Health Organization diagnostic criteria for Plasma cell myeloma

>30g/L

Plasma cell myeloma

M protein concentration in serum or urine if it's an IgG (Most common)

>25g/L

Plasma cell myeloma

M protein concentration in serum or urine if it's an IgA

>1g/24hr of urine light chain

Plasma cell myeloma

M protein concentration in urine

BM Clonal Plasmacytosis or Plasmacytoma

Plasma cell myeloma

Increased number of plasma cells in the bone marrow

10%

Plasma cell myeloma - BM Clonal Plasmacytosis or Plasmacytoma

Monoclonal plasma cells usually exceed ___% of nucleated cells in the marrow but no minimal level is designated because about 5% of patients with symptomatic myeloma have.

Hypercalcemia, Renal insufficiency, Anemia, Bone lesions

Related organ or tissue impairment in Plasma cell myeloma

End organ damage

The most important criteria for symptomatic Plasma cell myeloma are manifestations of:

Anemia, Hypercalcemia, Lytic bone lesions, Hyperviscosity, Amyloidosis, Recurrent infections

Manifestations of end organ damage in Plasma cell myeloma

Lytic bone lesions

Manifestation of end organ damage in Plasma cell myeloma that is from plasma cell marrow infiltration

Anemia, Leukopenia, Thrombocytopenia

Blood cell results in Plasma cell myeloma

Leukopenia, Thrombocytopenia

Blood cell results in Plasma cell myeloma that are common during advanced stages of the disease

Normocytic, Normochromic type of anemia

Peripheral blood smear finding in most Plasma cell myeloma patients

Rouleaux formation

RBC morphology that is present in more than one half of Plasma cell myeloma patients and may be striking

Monoclonal immunoglobulin, ESR

The degree of rouleaux formation in Plasma cell myeloma correlates with the magnitude of the___ and parallels this lab test

Zeta potential

Feature of RBC that is affected due to large numbers of positively charged plasma proteins (immunoglobulins) in Plasma cell myeloma, leading to rouleaux formation

Faint purple

Rarely, this background color happens during Plasma cell myeloma when M-protein is extremely high in concentration

T

T/F

In Plasma cell myeloma, circulating plasma cells may be seen occasionally, especially when the bone marrow is overrun.

Bone marrow aspirates and biopsies

Recommended procedures from the diagnosis and to evaluate the appearance of the plasma cells in Plasma cell myeloma

Peripheral blood smears

Not the typical specimen used for Plasma cell myeloma

Visualize rouleaux formation, Morphology of the anemia

Peripheral blood smears are useful for examining these findings in Plasma cell myeloma

Myeloid and erythroid cells in varying stages of maturation

Normal BM finding

Plasma cells

These cells are strikingly increased in number in Multiple myeloma

Large with abundant basophilic cytoplasm, round eccentrically placed nuclei, lighter staining perinuclear area or area of hof

Moderate to abundant basophilic cytoplasm

Mature plasma cells in plasma cell myeloma

Cytoplasm

Larger than normal, Multinucleation or lobated, Concentric

Mature plasma cells in plasma cell myeloma

Nucleus

Dispersed, Fine reticular chromatin

Mature plasma cells in plasma cell myeloma

Nuclear chromatin

Prominent

Mature plasma cells in plasma cell myeloma

Nucleoli

High

Mature plasma cells in plasma cell myeloma

N:C Ratio

Flame cells

Plasma cells with red-tinged cytoplasm.

Hyaline inclusions, Crystalline inclusions, Vacuoles, Granules

Cytoplasmic inclusions in plasma cells in plasma cell myeloma

Plasmablastic appearance

Appearance of the neoplastic cells that has been associated with a poorer prognosis

Arterioles

Normally, plasma cells are seen clustered in ___

Marrow

In plasma cell myeloma, plasma cells may diffusely infiltrate the ___ and replace other marrow elements.

Bone marrow studies

These studies are able to give an idea on tumor burden (via percentage involvement) in Plasma cell myeloma, thus it can be a tool for prognostication and it is also used by doctors to monitor the patients' response to therapy

Bone marrow aspirates

Specimen that shows the exact morphology of the plasma cells in Plasma cell myeloma (what they look like, more mature, plasmablastic).

Plasmablasts

Plasma cell variation

Have higher N:C ratio, finer, and more reticular chromatin, and have a lot more prominent nucleoli than mature plasma cells

Flame cell

Plasma cell variation

Retaining the abundant cytoplasm and eccentric nuclear placement of a regular plasma cell, with a reddish tinge to the cytoplasm

Mott cell

Plasma cell variation

Numerous globules filling the cytoplasm, and these represent aggregates of immunoglobulins that are produced by that plasma cell

Russell bodies

Plasma cell component

Pinkish or eosinophilic cytoplasmic globules which represent produced immunoglobulins

Dutcher body

Plasma cell inclusion

Intranuclear inclusions that can easily be mistaken for nucleoli

Mott or Morula cells

Cytoplasmic changes in Plasma cells in PCM

Pale, clustered grape-like inclusions

Russell bodies

Cytoplasmic changes in Plasma cells in PCM

Round cherry-red inclusions

Flame cells

Cytoplasmic changes in Plasma cells in PCM

Vermilion red staining

Gaucher-like cells

Cytoplasmic changes in Plasma cells in PCM

Overstuffed fibrils

Flame cell

What Plasma cell variant is this?

Skip

Type "Skip"

Just showing a pic of BM touch preparation showing mature and immature plasma cells, one of which is binucleate

Light chain restriction

The neoplastic plasma cells in plasma cell myeloma exhibit a monoclonal pattern of reactivity with either κ or λ light chains. This is known as:

2:1

Normal kappa(κ) to gamma(λ) light chain ratio

5:1

κ light chain monotypism K:G ratio