Haematology and Lymphoma
Report template: F-18 FDG PET/CT (oncology, lymphoma)
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Solve questions (25) →Contents
- 20.1 Lymphoma Staging with FDG PET/CT
- 20.2 Deauville Score (5-Point Scale)
- 20.3 Lugano Classification and Assessment of Treatment Response
- 20.4 Labelled Red Cell Studies (Red Cell Mass, Plasma Volume)
- 20.5 Spleen Scintigraphy (Heat-Damaged Red Cells)
- 20.6 Y-90 Ibritumomab Tiuxetan (Zevalin) – Radioimmunotherapy
- 20.7 Bone Marrow Scintigraphy
- Key Points for the Board
- Current guidelines on this chapter's topics
Learning objectives and modules2 modules · about 2 h
Learning objectives
After this chapter you will be able to:
- Explain the FDG avidity of lymphoma subtypes and the role of PET/CT in staging.
- Apply the Deauville score and classify treatment response with the Lugano criteria.
- Apply the dilution principle to measurement of red cell mass and plasma volume.
- Explain the indications for and interpretation of splenic scintigraphy (heat-damaged red cells) and bone marrow scintigraphy.
- Explain the principle, protocol and toxicity of radioimmunotherapy (Y-90 ibritumomab tiuxetan).
Modules
The chapter is divided into study modules without changing the order of the text: read, watch the animations, then answer the questions linked to those headings.
- Module 120.1–20.3 Lymphoma Staging with FDG PET/CT · Deauville Score (5-Point Scale) · Lugano Classification and Assessment of Treatment Response55 min · 1 animation · 28 questionsAnswer the questions →
- Module 220.4–20.7 Labelled Red Cell Studies (Red Cell Mass, Plasma Volume) · Spleen Scintigraphy (Heat-Damaged Red Cells) · Y-90 Ibritumomab Tiuxetan (Zevalin) – Radioimmunotherapy · Bone Marrow Scintigraphy · +1 more1 h 5 min · 1 animation · 27 questionsAnswer the questions →
Times are estimates: 130 words per minute, 3 min per animation, 1.5 min per question.
MOST FREQUENTLY ASKED IN THIS CHAPTER
20.1 Lymphoma Staging with FDG PET/CT13 questions
General Principles
Lymphoma is one of the strongest indications for FDG PET/CT. Lymphoma cells usually show high glucose metabolism → intense FDG uptake. PET/CT is the standard imaging method both for initial staging and for assessing treatment response.
FDG Avidity and Lymphoma Subtypes
Not all lymphoma subtypes show the same degree of FDG uptake. The degree of FDG avidity varies with the histological subtype:
Lymphomas with High FDG Avidity (Routine PET/CT Indication):
Lymphomas with Variable/Low FDG Avidity:
Figure 20.1: Degree of FDG avidity in lymphoma subtypes; a marked rise in SUV in follicular lymphoma suggests transformation.
→ Hodgkin lymphoma, DLBCL, Burkitt, MCL, FL → all highly avid.
→ SLL/CLL, marginal zone (MALT), Waldenström.
→ Transformation (to DLBCL) → a rise in SUV raises suspicion of transformation → indication for biopsy.
Initial Staging
Ann Arbor Staging System (Modified – Lugano):
Figure 20.2: Distribution of involvement relative to the diaphragm in Ann Arbor (Lugano modification) staging (schematic).
Additional modifiers:
Advantages of PET/CT in Staging:
→ Not if PET/CT is performed → PET/CT detects bone marrow involvement with adequate sensitivity → it has replaced biopsy.
→ May still be needed (especially in low-grade NHL → PET may be falsely negative).
→ Usually upstaging → may change the treatment plan.
Staging PET/CT Protocol
20.2 Deauville Score (5-Point Scale)7 questions
Definition and Principle
The Deauville score is a visual, semi-quantitative PET assessment system used to evaluate treatment response in lymphoma. It compares FDG uptake in the residual mass with reference structures.
Reference Structures
5-Point Scale
Interpretation
Interim PET (during treatment – usually after 2 cycles):
End-of-treatment PET:
Left: coronal FDG PET schematic with a residual mediastinal mass, mediastinal blood pool and liver. Right: Deauville score bands by the SUVmax of the mass. The second step compares baseline and follow-up PET for the Lugano response.
The Deauville score compares residual uptake with blood pool and liver: 1-3 is negative (CMR); with 4-5, comparison with baseline gives PMR, NMR or PMD.
Source: score definitions and Lugano response from book 20.2-20.3; score 5 threshold from Barrington et al., JCO 2014 (2-3× liver). SUV values representative.
How to use: a single click on the drawing pauses and resumes; use the time bar below to set the lesion SUV; in the second step ↑ ↓ or the buttons below change the scenario; ← → change steps.
Figure 20.3: Deauville 5-point scale: comparison of residual uptake with the mediastinal blood pool and liver, and its interpretation (schematic).
→ Uptake higher than the mediastinum but lower than or equal to the liver → considered negative on interim PET (response to treatment).
→ 4 = moderately higher than the liver, 5 = markedly higher than the liver and/or new lesion.
→ Mediastinal blood pool and liver.
→ Remember the comparison with mediastinum and liver: 1-2-3 = none/≤ mediastinum/≤ liver, 4-5 = above the liver.
Deauville Score Summary Table
| Score | Uptake Level | Interim PET | End-of-Treatment PET |
|---|---|---|---|
| 1 | No uptake | Negative (CMR) | Negative (CMR) |
| 2 | ≤ Mediastinum | Negative (CMR) | Negative (CMR) |
| 3 | > Mediastinum, ≤ Liver | Negative (CMR) | Probably negative |
| 4 | > Liver (moderate) | Positive | Positive (residual) |
| 5 | >> Liver and/or new lesion | Positive | Positive (progression) |
20.3 Lugano Classification and Assessment of Treatment Response9 questions
Lugano Classification (2014)
The Lugano classification is the current system that standardises staging and response assessment in lymphoma. It modifies the Ann Arbor staging system and puts PET/CT at the centre.
Changes in Staging (Differences from Ann Arbor)
Response Criteria
The Lugano classification defines treatment response separately for FDG-avid and FDG-non-avid lymphomas:
A) Response Assessment in FDG-Avid Lymphomas (PET-Based):
1. Complete Metabolic Response (CMR):
2. Partial Metabolic Response (PMR):
3. No Response / Stable Disease (NR/SD):
4. Progressive Disease (PD):
B) Response Assessment in FDG-Non-Avid Lymphomas (CT-Based):
Figure 20.4: Assessment of treatment response in FDG-avid (PET-based) and FDG-non-avid (CT-based) lymphomas according to the Lugano classification.
→ Deauville 1, 2 or 3 + no new lesions.
→ CT-based (PET not used).
→ Lugano puts PET at the centre, removes the bulky "X" modifier and reduces the need for bone marrow biopsy.
Interim PET Assessment
Causes of False Positives (After Treatment):
Causes of False Negatives:
→ Thymic hyperplasia (thymic rebound) → common after chemotherapy, especially in patients <30 years → triangular, symmetric, homogeneous uptake → must be distinguished from lymphoma recurrence.
20.4 Labelled Red Cell Studies (Red Cell Mass, Plasma Volume)11 questions
General Principle
Red cell mass and plasma volume measurements are used in the diagnosis of polycythaemia vera (PV) and other myeloproliferative disorders. They distinguish whether raised haemoglobin/haematocrit is true erythrocytosis or relative erythrocytosis (reduced plasma volume).
Red Cell Mass (RCM) Measurement
Radiopharmaceutical: Cr-51 (chromium-51) labelled red cells
Method:
1. Blood is drawn from the patient → red cells are separated 2. Labelled with Cr-51 sodium chromate 3. Labelled red cells are reinjected into the patient 4. Wait 15-20 minutes (mixing time) 5. A blood sample is taken → activity is measured 6. Red cell mass is calculated by the dilution principle:
RCM = Injected activity / activity in 1 mL of red cells
Normal Values:
Diagnosis of Polycythaemia Vera:
Plasma Volume Measurement
Radiopharmaceutical: I-125 labelled albumin (RISA – Radioiodinated Serum Albumin)
Method:
1. I-125 albumin is injected IV 2. Wait 10-15 minutes 3. A blood sample is taken → plasma activity is measured 4. Plasma volume is calculated by the dilution principle
Normal Values:
Total Blood Volume:
TBV = Plasma Volume / (1 − Haematocrit)
or
TBV = RCM + Plasma Volume
EANM – Determination of Body Fluid Volumes:
Left: labelled RBCs injected into a circulation of unknown volume mix and are counted in a 1 mL sample. Right: the V = Q / [q] calculation. The second step shows red cell mass and plasma volume bars for normal, absolute and relative erythrocytosis.
V = Q / [q]: after mixing, the concentration in a sample gives the volume; high RCM is absolute and normal RCM with low PV is relative erythrocytosis.
Source: method, mixing time and normal values from book 20.4. Particle count and scenario values representative.
How to use: a single click on the drawing pauses and resumes; in the second step ↑ ↓ or the buttons below change the scenario (normal, absolute, relative polycythaemia); ← → change steps.
Figure 20.5: Measurement of red cell mass and plasma volume by the dilution principle; distinguishing absolute from relative erythrocytosis (schematic).
→ Cr-51.
→ I-125 albumin.
→ 1% elution from red cells per day → source of error in long studies.
→ Relative erythrocytosis (reduced plasma volume → Gaisböck syndrome/stress polycythaemia).
Red Cell Survival Study
Figure 20.6: Cr-51 red cell survival curves and site of sequestration by spleen/liver ratio (schematic).
Platelet Survival (EANM):
→ Splenic sequestration → splenectomy beneficial.
→ 25-35 days (measured as shorter than the true 120 days because of elution).
20.5 Spleen Scintigraphy (Heat-Damaged Red Cells)6 questions
Principle
The spleen is an organ that clears damaged or abnormal red cells from the circulation. This property can be used for spleen imaging.
Method
Radiopharmaceutical: Tc-99m labelled, heat-damaged red cells
1. Blood is drawn from the patient → red cells are labelled with Tc-99m (in-vitro method) 2. Labelled red cells are heated at 49-50°C for 20 minutes → the red cell membrane is damaged (becomes spherocytic)
3. Damaged red cells are reinjected into the patient 4. The spleen recognises these damaged red cells and clears them from the circulation → intense splenic uptake
Critical Temperature:
Indications
Spleen Imaging with Tc-99m Sulphur Colloid (Comparison)
Figure 20.7: Effect of heating temperature on spleen/liver uptake of heat-damaged red cells and comparison with Tc-99m sulphur colloid (schematic).
→ Heat-damaged Tc-99m red cells (spleen-specific).
→ 49-50°C, 20 minutes.
→ Excessive damage → the liver also clears them → splenic specificity falls.
→ Assessment of functional asplenia → no uptake means autoinfarction.
20.6 Y-90 Ibritumomab Tiuxetan (Zevalin) – Radioimmunotherapy8 questions
General Principle
Radioimmunotherapy (RIT) works on the principle of delivering radiation to target cells by attaching a radionuclide to monoclonal antibodies. Y-90 ibritumomab tiuxetan (Zevalin) is a radioimmunotherapy agent used to treat CD20-positive B-cell non-Hodgkin lymphoma.
Structure and Components
Treatment Protocol
Figure 20.8: Structure of Y-90 ibritumomab tiuxetan (Zevalin) and treatment protocol by platelet count.
Indications
Contraindications
Side Effects
→ Thrombocytopenia (myelosuppression).
→ Pure beta emitter → no gamma emission (very limited imaging possible with bremsstrahlung).
→ Clears circulating normal B cells → increases delivery of Zevalin to the tumour + reduces normal organ dose.
→ 32 mCi (regardless of weight).
Former Agent: I-131 Tositumomab (Bexxar):
20.7 Bone Marrow Scintigraphy2 questions
General Principle
Bone marrow scintigraphy is used to assess the distribution and function of bone marrow. Bone marrow consists of two components: haematopoietic (red) and fatty (yellow) marrow.
Radiopharmaceuticals
A) Tc-99m Sulphur Colloid:
B) Tc-99m Nanocolloid:
C) In-111 Chloride:
D) FDG PET/CT:
Indications
Normal Bone Marrow Distribution
Adult:
Child:
Pathological Patterns
1. Bone Marrow Expansion (Peripheral Expansion):
2. Bone Marrow Contraction/Reduction:
3. Focal Defects:
4. Extramedullary Haematopoiesis:
Figure 20.9: Normal adult and child distribution and pathological patterns on bone marrow scintigraphy (schematic).
→ Bone marrow activity in the distal limbs → chronic anaemia or myeloproliferative disorder (compensatory expansion).
→ Reduced uptake in the axial skeleton + peripheral expansion + extramedullary haematopoiesis (liver, spleen).
→ Diffuse bone marrow FDG uptake → false positive → PET should be performed at least 2-4 weeks after G-CSF.
Key Points for the Board
FDG PET/CT and Lymphoma Staging:
Deauville Score:
Lugano Classification:
False Positives (Post-Treatment PET):
False Negatives:
Red Cell Mass and Plasma Volume:
Red Cell Survival:
Spleen Scintigraphy:
Y-90 Ibritumomab Tiuxetan (Zevalin):
Bone Marrow Scintigraphy:
Ann Arbor Staging (Lugano Modification):
Additional Notes from EANM Guidelines:
Current guidelines on this chapter's topics
The latest guidelines and consensus documents on the procedures covered in this chapter (official EANM index and primary sources, November 2026). Comparison of the text with these versions is in progress; consult the guideline itself for details.
- 2025[18F]FDG PET/CT: EANM procedure guidelines for tumour imaging: version 3.0 (opens in a new tab)
- 2024EANM guidelines on the use of [18F]FDG PET/CT in diagnosis, staging, prognostication, therapy assessment, and restaging of plasma cell disorders (opens in a new tab)
- 2022Joint EANM/SNMMI/ANZSNM practice guidelines/procedure standards on recommended use of [18F]FDG PET/CT imaging during immunomodulatory treatments in patients with solid tumors version 1.0 (opens in a new tab)
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