Extramedullary Disease in Myeloma

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

What percentage of patients typically have extramedullary disease (EMD) at the initial diagnosis?

5% to 10%

0% to 1%

1% to 2% (correct)

3% to 4%

What is the likelihood of patients developing extramedullary disease later in their disease course?

20%

15%

8% (correct)

Which statement correctly describes extramedullary disease (EMD)?

EMD is not seen in cancer patients.

EMD can develop later in the disease course. (correct)

All patients will experience EMD.

EMD is only present at the time of initial diagnosis.

Which of the following best describes the timing of extramedullary disease in patients?

At diagnosis or can develop later. Signup and view all the answers

What is a common misconception about extramedullary disease (EMD) at the time of diagnosis?

Only a small percentage exhibit EMD initially. Signup and view all the answers

What type of cells are described as having cherry red refractive round bodies?

Macrophages Signup and view all the answers

Which staining technique is associated with glycogen-rich IgA that leads to the identification of flame cells?

Vermilion staining Signup and view all the answers

What is not a characteristic change associated with myeloma?

Pathognomonic features Signup and view all the answers

Which cells are indicative of Gaucher-like characteristics?

Overstuffed fibrils Signup and view all the answers

Which of the following is considered a non-specific change in the context of myeloma?

Crystalline rods Signup and view all the answers

What is the significance of having multiple focal lesions observed on MRI?

It suggests a higher likelihood of progression to complications. Signup and view all the answers

Which statement accurately reflects the findings related to the new biomarkers?

They are linked to a significant risk of progression to symptomatic end-organ damage. Signup and view all the answers

In how many independent studies are the biomarkers associated with a high risk of progression observed?

In two or more independent studies. Signup and view all the answers

What is the percentage risk of progression to symptomatic end-organ damage associated with the biomarkers?

80% Signup and view all the answers

What might be inferred from observing two or more biomarker associations in studies?

They confirm a strong indicator of potential complications. Signup and view all the answers

What is the range of variation for the number of plasma cells mentioned?

From slightly increased to about 90% Signup and view all the answers

What does the content suggest about plasma cell levels?

They can vary significantly in their increase. Signup and view all the answers

What is the highest percentage mentioned for plasma cells?

About 90% Signup and view all the answers

Which of the following can accurately describe the increase in plasma cells?

Varying from insignificant to very high levels. Signup and view all the answers

In the context of plasma cells, what does 'upwards of 90%' imply?

A potential increase beyond 90%. Signup and view all the answers

What is one reason for using MRI imaging?

To assess extramedullary disease Signup and view all the answers

When is detailed imaging particularly necessary?

When there is suspicion of cord compression Signup and view all the answers

Which scenario would most likely require an MRI?

Suspected cord compression Signup and view all the answers

In what situation might detailed imaging of a specific symptomatic area be warranted?

When assessing extramedullary disease Signup and view all the answers

What can MRI imaging help diagnose besides extramedullary disease?

Detailed injuries to soft tissues Signup and view all the answers

What might trephine biopsy sections indicate in terms of PC presence?

Presence of more PCs with or without clustering Signup and view all the answers

Which structures may be observed alongside the plasma cells in trephine biopsy sections?

Focal clusters or nodular aggregates of PCs Signup and view all the answers

What is indicated by the presence of sheets of PCs in biopsy sections?

A potential abnormal increase of plasma cells Signup and view all the answers

In addition to PCs, what other features might biopsy sections show?

Possible nodular aggregates or sheets formed by PCs Signup and view all the answers

Which of the following statements about trephine biopsy sections is accurate?

They may present with various forms of abnormal plasma cell clustering. Signup and view all the answers

Study Notes

Multiple Myeloma Update - 2024

Multiple myeloma is a clonal plasma cell disorder characterized by an abnormal increase in monoclonal immunoglobulins.
It accounts for approximately 1% of all cancers and 10% of hematological malignancies.
Slightly more common in men than women and twice as common in African-Americans compared to Caucasians.
Median age at diagnosis is about 65 years.

Disease Overview

Unlike other malignancies that metastasize to bone, osteolytic lesions in MM do not exhibit new bone formation. Bone disease is the primary cause of morbidity.
Other major clinical manifestations include anemia, hypercalcemia, renal failure, and an increased risk of infections.
Approximately 1% to 2% of patients have extramedullary disease (EMD) at initial diagnosis, and 8% develop EMD during the disease course.
Common symptoms include hypercalcemia, renal dysfunction, anemia, and bone pain .

Symptoms of Multiple Myeloma

Hypercalcemia
Renal dysfunction
Anemia
Bone pain

Monoclonal Gammopathy of Undetermined Significance (MGUS)

Nearly all MM patients originate from asymptomatic pre-malignant MGUS.
MGUS is found in about 5% of the population over 50, with a higher prevalence in Black individuals compared to Whites.
MGUS progresses to MM or related malignancy at a rate of approximately 1% per year.
Over 50% of individuals diagnosed with MGUS have had the condition for over 10 years before clinical diagnosis.
Some patients develop an intermediate asymptomatic (but more advanced pre-malignant) stage called smoldering MM.

Smoldering Multiple Myeloma (SMM)

SMM is prevalent in approximately 0.5% of the general population aged 40 or older and progresses to MM at a rate of approximately 10% per year for the first five years following diagnosis, 3% per year for the next five years, and 1.5% per year thereafter.
Factors influencing progression rate include disease burden and underlying cytogenetic type. Patients with specific translocations (e.g., t(4;14), del(17p), gain(1q)) have a higher risk of progression to MM.

Diagnosis of Multiple Myeloma

Diagnosis requires the presence of one or more myeloma-defining events (MDE) plus evidence of at least 10% clonal bone marrow plasma cells or a biopsy-proven plasmacytoma.
MDE includes features like CRAB (hypercalcemia, renal failure, anemia and lytic bone lesions) and three specific biomarkers.
Biomarkers for diagnosis may include:
- clonal bone marrow plasma cells ≥60%
- serum free light chain (FLC) ratio ≥100
- more than one focal lesion on MRI
Additional International Myeloma Working Group (IMWG) diagnostic criteria include:
- Clonal bone marrow plasma cells ≥10% or biopsy-proven bony/extramedullary plasmacytoma.
- Presence of any one or more myeloma-defining events. These events include evidence that end-organ damage is attributable to the plasma cell proliferative disorder. Examples of such events include hypercalcemia (serum calcium > 2.5 mmol/L or > 11 mg/dL) and renal insufficiency (creatinine clearance <40 mL/min or serum creatinine >177 µmol/L or > 2 mg/dL).

Complete Blood Count (CBC) and Peripheral Blood Smear

Normochromic normocytic anemia
Variable WBC count and differential
Normal or low platelet count
Rouleaux formation (characteristic feature related to M protein quantity/type)
Circulating plasma cells may be present in low numbers

Bone Marrow Study

Usually hypercellular
Morphology of plasma cells (PCs) varies from mature to immature, plasmablastic, and pleomorphic (including multinucleated and multilobulated forms).
Classical PCs are typically oval-shaped with eccentric nuclei and well-defined or clock-face chromatin, without a nucleolus.
Abundant basophilic cytoplasm with perinuclear hof

Additional Diagnostic Tools

Bone marrow plasmacytosis
Immature PC forms usually have more dispersed nuclear chromatin, high N/C ratio, and prominent nucleoli.
Plasma cells and findings like Mott, Morula, refractive, and flame cell might be observed.
Aspirates or touch imprints, in some cases may show less than 10% plasma cells if suboptimal bone marrow biopsy was collected. A trephine biopsy examination may provide more reliable PC numbers.
Bone marrow PCs might be seen in clusters around arterioles, interstitial clusters, focal nodules, or even diffuse sheets, sometimes even filling bone marrow.

Different morphologies might range from PC morphology to lymphoid, immunoblastic, spindle/oval to signet ring cells. Normal hemopoiesis is usually preserved except for diffuse involvement; scattered osteoclasts and fibrosis may be observed in some cases.

Imaging such as low-dose WB-CT or PET-CT for assessment of bone disease, MRI for assessing SMM, suspected cord compression or detailed imaging of areas.

Non-IgM monoclonal gammopathy of undetermined significance (MGUS): characterized by less than 3 gms/dl monoclonal protein, less than 10% plasma cells in bone marrow, without end-organ damage

Smoldering Multiple Myeloma

Serum monoclonal protein (IgG or IgA) ≥3 g/dL, or urinary monoclonal protein ≥500 mg/24 h OR clonal bone marrow plasma cells of 10-60%
No myeloma defining events or amyloidosis.

Plasma Cell Leukemia

Meets full criteria for multiple myeloma, but with more than 5% plasma cells in peripheral blood.

IgM MGUS

Serum IgM-monoclonal protein < 3g/dL.
Bone marrow lymphoplasmacytic infiltration <10%
No evidence of associated anemia, constitutional symptoms, hyperviscosity, lymphadenopathy or hepatosplenomegaly

Light Chain MGUS

Abnormal FLC ratio (< 0.26 or > 1.65)
Increased level for the involved light chain
No immunoglobulin heavy chain expression on immunosfixation
Absence of end-organ damage related to the PC proliferative disorder
Clonal bone marrow plasma cells ≤10%
Urinary monoclonal protein ≤ 500 mg per 24 hours

Solitary Plasmacytoma

Biopsy-proven solitary lesion (bone/soft tissue) with evidence of clonal plasma cells.
Normal bone marrow
No evidence of end-organ damage (CRAB)
Normal skeletal survey and MRI/CT spine/pelvis

Solitary Plasmacytoma with Minimal Marrow Involvement

Biopsy proven solitary lesion (bone/soft tissue) with evident clonal plasma cells.
Clonal bone marrow plasma cells ≤10%.
Normal skeletal survey/MRI/CT spine/pelvis (except primary lesion).
Absence of end-organ damage (CRAB)

Molecular Cytogenetic Classification of Multiple Myeloma

Table 1 details primary molecular cytogenetic classification.

Prognosis and Risk Stratification

Overall survival for transplant-eligible myeloma patients is more than 10 years.
Elderly (≥75 yrs) patients show a lower, approximately 5-year median OS, which likely underestimate present-day survival.
Monoclonal antibodies and other recent advancements may affect survival estimates.
Accurate prognosis involves considering host characteristics, tumor burden (stage), cytogenetic abnormalities, and therapeutic response.
Tumor assessment traditionally employs Durie-Salmon Staging and International Staging System (ISS)

Disease Biology

Multiple myeloma biology is best judged by molecular subtype and also the presence or absence of secondary cytogenetic abnormalities (such as del(17p) gain(1q), or del(1p)).
Elevated serum lactate dehydrogenase is another marker of potential risk.
Plasma cell leukemia (presence of plasma cells in the blood) is an additional marker.

Risk Groups of Multiple Myeloma

Standard risk: Trisomies t(11;14) ,t(6:14)
High risk: t (4:14), t(14:16), t(14:20), del(17p) , gain(1q)
Double-hit/triple-hit myeloma (based on combinations of high risk factors)

References

https://onlinelibrary.wiley.com/doi/full/10.1002/ajh.27422
WHO Haematolymphoid Tumours (5th ed.)

Studying That Suits You

Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

Description

This quiz assesses your knowledge of extramedullary disease (EMD) in patients with myeloma. It covers topics such as incidence rates, misconceptions, and specific cell characteristics linked to EMD. Test your understanding of the implications of both initial diagnosis and disease progression regarding EMD.