# Lymphoma Imaging: Staging and Response Assessment

## Introduction

Lymphoma is the most common hematologic malignancy, broadly categorized into **Hodgkin lymphoma (HL)** and **non-Hodgkin lymphoma (NHL)**. Imaging plays a central role in staging, treatment planning, and response assessment. **PET/CT** has become the standard of care for FDG-avid lymphomas, while CT remains important for non-avid subtypes.

## Classification Overview

### Hodgkin Lymphoma

HL has a bimodal age distribution with peaks in the **20s** and after age 55. It is characterized by Reed-Sternberg cells in a reactive cellular background. Subtypes include nodular sclerosis (most common), mixed cellularity, lymphocyte-rich, and lymphocyte-depleted. **Nodular lymphocyte-predominant HL** (NLPHL) is a distinct entity with different biology.

### Non-Hodgkin Lymphoma

NHL is a heterogeneous group of over **80 subtypes**. **Diffuse large B-cell lymphoma (DLBCL)** is the most common aggressive NHL, and **follicular lymphoma** is the most common indolent NHL. Other important subtypes include mantle cell, Burkitt, marginal zone, and T-cell lymphomas. FDG avidity varies by subtype, with most aggressive lymphomas being intensely FDG-avid.

## Imaging Modalities

### PET/CT

PET/CT is the **standard of care** for staging and response assessment of FDG-avid lymphomas (most HL and aggressive NHL). It is superior to CT alone for detecting nodal and extranodal disease. It identifies bone marrow involvement, potentially replacing bone marrow biopsy in HL. SUVmax provides semiquantitative assessment of metabolic activity.

### CT

Contrast-enhanced CT of the neck, chest, abdomen, and pelvis is used for anatomic staging. It remains the primary modality for **non-FDG-avid lymphomas** (such as some marginal zone and small lymphocytic lymphomas). It provides anatomic detail for radiation planning and is used for surveillance in indolent lymphomas where PET is not routinely indicated.

### MRI

MRI has a role in specific scenarios including CNS lymphoma, bone marrow assessment, and pediatric patients (radiation reduction). Whole-body MRI with DWI is an emerging alternative to PET/CT in selected populations.

![Staging PET/CT demonstrating extensive FDG-avid lymphadenopathy above and below the diaphragm in Hodgkin lymphoma](images/lymphoma-staging-petct.jpg)

## Staging: Ann Arbor/Lugano Classification

| Stage | Definition |
|-------|-----------|
| I | Single lymph node region or single extranodal site (IE) |
| II | Two or more lymph node regions on the same side of diaphragm |
| III | Lymph node regions on both sides of diaphragm |
| IV | Diffuse/disseminated extranodal involvement (liver, bone marrow, lung parenchyma) |

**Stage I** indicates a single lymph node region or single extranodal site (IE). **Stage II** indicates two or more lymph node regions on the same side of the diaphragm. **Stage III** indicates lymph node regions on both sides of the diaphragm. **Stage IV** indicates diffuse or disseminated extranodal involvement (liver, bone marrow, lung parenchyma). **Bulky disease** is defined as a single mass of **10 cm or greater** or greater than one-third of the thoracic diameter on CT. Suffixes include A (no B symptoms) and B (fever, night sweats, greater than 10% weight loss). The **Lugano classification** (2014) updated the Ann Arbor system to incorporate PET/CT findings.

## Imaging Findings

### Nodal Disease

**Lymphadenopathy** presents as enlarged nodes, often homogeneous, with variable enhancement. HL typically shows contiguous spread along nodal chains with mediastinal involvement in more than 80% of cases. NHL is more often non-contiguous, with mesenteric and retroperitoneal nodes commonly involved. **Waldeyer ring** involvement suggests NHL (especially DLBCL or mantle cell).

### Extranodal Disease

**Splenic** involvement manifests as diffuse splenomegaly, focal lesions, or a miliary pattern. **Hepatic** involvement presents as focal lesions or diffuse infiltration. **Bone marrow** involvement appears as focal FDG-avid lesions on PET or diffuse marrow signal abnormality on MRI. **Pulmonary** involvement includes parenchymal nodules, consolidation, or direct extension from hilar nodes. **GI tract** involvement is more common with NHL; the stomach and terminal ileum are the most frequent sites.

![Coronal CT showing bulky mediastinal lymphadenopathy with associated right pleural effusion in Hodgkin lymphoma](images/mediastinal-lymphoma-ct.jpg)

## Response Assessment: Deauville Criteria

### PET-Based Response (Lugano)

**Score 1** indicates no uptake above background. **Score 2** indicates uptake at or below mediastinal blood pool. **Score 3** indicates uptake above mediastinal blood pool but at or below liver. **Score 4** indicates uptake moderately above liver. **Score 5** indicates markedly increased uptake above liver or new lesions. **Complete metabolic response (CMR)** is defined as Deauville 1-3 (with or without a residual mass). **Partial metabolic response (PMR)** is reduced uptake but Deauville 4-5 with decreased intensity. **Progressive metabolic disease (PMD)** is Deauville 4-5 with increased intensity or new lesions.

### Interim PET

Interim PET is performed after **2 cycles** of chemotherapy in HL and aggressive NHL. Interim PET negativity (Deauville 1-3) is a strong predictor of favorable outcome. It may guide therapy de-escalation in HL (such as omission of radiotherapy or bleomycin).

## Pitfalls in Lymphoma Imaging

**Thymic rebound** presents as FDG-avid thymic enlargement after chemotherapy in young patients and mimics residual disease. **Sarcoid-like reaction** causes granulomatous inflammation producing FDG-avid lymphadenopathy post-treatment. **Brown fat** creates symmetric FDG uptake in supraclavicular and mediastinal fat, mitigated by warming protocols. **Reactive nodes** from inflammatory or infectious lymphadenopathy may be FDG-avid. Post-treatment flare involves transient increased FDG activity shortly after therapy initiation.

![PET/CT comparison showing pre-treatment FDG-avid disease and post-treatment complete metabolic response](images/lymphoma-response-pet.jpg)

## Key Clinical Pearls

PET/CT is the standard for staging and response assessment of **FDG-avid lymphomas**; CT alone is insufficient for these subtypes. Use the **Deauville 5-point scale** for response assessment; the liver serves as the reference standard for scores 4 and 5. Interim PET after 2 cycles is prognostically significant and may guide treatment modification in HL. Always consider thymic rebound and sarcoid-like reaction as causes of false-positive PET findings after treatment, particularly in young patients.

## References

1. Cheson BD, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. *J Clin Oncol*. 2014;32(27):3059-3068.
2. Barrington SF, et al. Role of imaging in the staging and response assessment of lymphoma: consensus of the ICML Imaging Working Group. *J Clin Oncol*. 2014;32(27):3048-3058.
3. Meignan M, et al. Metabolic tumour volumes measured at staging in lymphoma: methodological evaluation on phantom experiments and patients. *Eur J Nucl Med Mol Imaging*. 2014;41(6):1113-1122.
4. Johnson SA, et al. Imaging for staging and response assessment in lymphoma. *Radiology*. 2015;276(2):323-338.