# Hodgkin Lymphoma

Confirm Hodgkin lymphoma on adequately sampled tissue, stage with FDG-PET/CT, and use disease extent, bulk, prognosis, and PET-adapted response to select curative-intent treatment while minimizing late toxicity.

**Clinical question:** How should physicians confirm, stage, and direct initial management of suspected or newly diagnosed Hodgkin lymphoma?

Updated: 2026-08-21T02:15:12.977747+00:00

## What matters in practice
- Establish the diagnosis with an excisional lymph node biopsy whenever feasible because intact architecture and sufficient tissue are central to lymphoma classification.[22]
- Classical Hodgkin lymphoma usually shows Hodgkin/Reed-Sternberg cells with CD30 and CD15 expression plus weak PAX5; strong background B-cell marker expression should prompt reassessment for a CD30-positive non-Hodgkin lymphoma.[9][12][22]
- Use FDG-PET/CT for initial staging and response assessment; routine blind bone marrow biopsy has limited clinical yield when newly diagnosed Hodgkin lymphoma is staged by PET/CT.[15][20][23]
- For early-stage favorable disease, two cycles of ABVD followed by 20 Gy involved-field radiotherapy achieved effective disease control in a randomized trial, illustrating the curative efficacy of reduced-intensity combined-modality treatment in selected patients.[2]
- In limited-stage nonbulky disease, chemotherapy alone avoids radiation exposure but must be weighed against the durable disease-control benefit and late-effect tradeoffs of combined-modality treatment.[3]

## Confirm Hodgkin lymphoma before staging or treatment

Avoid assigning therapy from cytology or a limited immunophenotype alone.

Obtain an excisional biopsy of the most accessible abnormal lymph node when feasible. Excision preserves nodal architecture, permits full histologic assessment, and allows flow cytometry and molecular studies to be directed by the pathologic differential; it remains the diagnostic reference procedure for malignant lymphomas.[22] Core-needle biopsy may be necessary for deep or unsafe nodal targets, but nondiagnostic or discordant core results should lead to excision rather than empiric lymphoma treatment.[10][22]

For classical Hodgkin lymphoma (cHL), correlate morphology with immunohistochemistry rather than relying on CD30 alone. Hodgkin/Reed-Sternberg cells commonly coexpress CD30 and CD15, show weak PAX5 expression, and lack CD45; CD20 may be absent or variable.[8][9][22] CD15-negative cHL occurs, so absent CD15 should trigger expanded evaluation rather than automatic exclusion of cHL.[9]

Escalate the pathology review when the specimen contains Reed-Sternberg-like cells within a population of atypical B cells, because diffuse large B-cell lymphoma and small lymphocytic lymphoma can contain cells with a CD30-strong, PAX5-weak phenotype resembling cHL.[12] A background population that is CD20- and PAX5-positive favors a B-cell non-Hodgkin lymphoma with Reed-Sternberg-like cells rather than cHL.[12]
- Request correlation of morphology with CD30, CD15, PAX5, CD45, CD20, CD3, and B-cell transcription-factor patterns when cHL is in the differential.[8][9][22]
- Treat persistent CD30-negative cHL on limited tissue as an exceptional diagnostic problem: when feasible, obtain complete excision and use expanded immunohistochemistry before final classification.[10]

*Pathology patterns that change the next diagnostic action.[8][9][10][12][22]*

| Finding | Interpretation | Next action |
| --- | --- | --- |
| CD30+/CD15+ large atypical cells; weak PAX5; CD45 negative | Pattern supports cHL when morphology and background are concordant.[8][9][22] | Complete subtype classification and proceed to PET/CT staging. |
| CD15 absent but cHL morphology and weak PAX5 retained | CD15-negative cHL is possible; CD15 absence is not independently exclusionary.[9] | Expand the panel and exclude CD30-positive NHL. |
| Reed-Sternberg-like cells with CD20/PAX5-positive atypical background B cells | Consider B-cell NHL with Reed-Sternberg-like cells.[12] | Obtain expert hematopathology review; do not apply cHL treatment solely from CD30 positivity. |
| CD30-negative limited core biopsy with cHL-like morphology | Exceptionally rare diagnostic scenario; limited tissue can be misleading.[10] | Pursue excisional biopsy when feasible and expanded immunohistochemistry. |

## Stage with FDG-PET/CT and reserve marrow biopsy for unresolved questions

The staging study should also establish the baseline for response-adapted management.

Perform baseline whole-body FDG-PET/CT after tissue confirmation. The Lugano classification applies FDG-PET/CT to lymphoma staging and response assessment, making the scan the central imaging study for defining nodal and extranodal disease distribution and for comparison with interim or end-of-treatment studies.[20]

Do not routinely add a blind iliac-crest bone marrow biopsy when a newly diagnosed patient with Hodgkin lymphoma has been staged by FDG-PET/CT. A meta-analysis specifically evaluated whether PET/CT can replace blind marrow biopsy in newly diagnosed Hodgkin lymphoma, and an accompanying clinical analysis found that routine marrow biopsy added limited useful information without therapeutic consequences after PET/CT staging.[15][23]

Reconsider marrow sampling when PET/CT findings, cytopenias, or an alternative hematologic diagnosis create a question that would change classification or management. PET/CT and single-site biopsy assess marrow differently, and diffuse marrow FDG uptake has uncertain specificity for infiltration; discordance should be resolved in the clinical-pathologic context rather than assumed to represent Hodgkin lymphoma involvement.[13]
- Document baseline PET/CT disease sites before treatment so subsequent PET-based response can be interpreted against pretreatment distribution.[20]
- Use a focal or diffuse marrow PET finding as an imaging result, not as a substitute for pathology when a competing marrow disorder is clinically plausible.[13]

*Initial staging decisions in newly diagnosed Hodgkin lymphoma.[13][15][20][23]*

| Clinical scenario | Staging action | Reasoning |
| --- | --- | --- |
| Tissue-confirmed cHL | Obtain FDG-PET/CT.[20] | Lugano staging and response assessment use FDG-PET/CT.[20] |
| PET/CT completed; no separate marrow-management question | Omit routine blind bone marrow biopsy.[15][23] | Routine biopsy has limited additional clinical value after PET/CT staging.[23] |
| Unexplained cytopenias, equivocal diffuse marrow uptake, or concern for another marrow process | Individualize marrow biopsy.[13] | Diffuse FDG uptake does not reliably establish marrow infiltration, and PET/CT versus single-site biopsy discordance requires contextual interpretation.[13] |

## Match initial therapy intensity to stage, bulk, prognosis, and late-effect tradeoffs

Use a multidisciplinary treatment plan after PET/CT-based staging and risk assignment.

For early-stage favorable Hodgkin lymphoma, combined-modality therapy can achieve high cure rates with reduced treatment intensity. In a randomized trial, two cycles of ABVD followed by 20 Gy involved-field radiotherapy was an effective regimen for patients with early-stage favorable disease.[2] This evidence supports a discussion centered on whether a patient meets the favorable-risk population studied and whether the expected benefit of radiation outweighs site-specific late toxicity.

For stage IA or IIA nonbulky Hodgkin lymphoma, chemotherapy plus radiation controlled disease in approximately 90% of patients in trial evidence, but radiation-based treatment carries late-effect considerations.[3] Chemotherapy-only strategies are therefore a deliberate tradeoff rather than a default: they avoid radiotherapy exposure while accepting a different balance of relapse control, salvage treatment, and long-term toxicity.[3]

Use interim FDG-PET response as part of response-adapted management where the selected protocol incorporates it. PET-guided approaches have been studied to reduce chemotherapy intensity and direct radiotherapy in advanced-stage Hodgkin lymphoma, and contemporary reviews identify interim FDG-PET as a key component of response-adapted therapy.[16][18] The regimen, scan timing, and PET interpretation framework should follow the specific protocol rather than ad hoc treatment changes.
- Early-stage favorable disease: discuss reduced-intensity ABVD plus 20 Gy involved-field radiotherapy as a trial-supported combined-modality option.[2]
- Limited-stage nonbulky disease: explicitly document the radiation-versus-chemotherapy-alone tradeoff, including disease control and anticipated late effects.[3]
- Advanced-stage disease: use a protocolized interim PET strategy if treatment de-escalation or radiotherapy decisions will depend on response.[16][18]

*Initial management branches supported by treatment-trial populations.[2][3][16][18]*

| Disease setting | Decision framework | Supported treatment implication |
| --- | --- | --- |
| Early-stage favorable Hodgkin lymphoma | Minimize intensity while retaining curative control.[2] | Two cycles of ABVD followed by 20 Gy involved-field radiotherapy was effective in the randomized trial population.[2] |
| Stage IA-IIA nonbulky Hodgkin lymphoma | Balance disease control against late effects of radiation.[3] | Chemotherapy plus radiation produced disease control in about 90%; chemotherapy alone avoids radiation exposure but changes the control-to-toxicity balance.[3] |
| Advanced-stage Hodgkin lymphoma | Use baseline and interim FDG-PET within a defined response-adapted protocol.[16][18] | PET-guided treatment strategies have been studied to reduce treatment intensity and guide radiotherapy decisions.[16][18] |

## Rebiopsy suspected relapse when feasible and plan salvage around transplant eligibility

Confirm that recurrent PET-avid disease represents lymphoma before committing to salvage therapy.

At suspected relapse or refractory disease, obtain tissue confirmation when an accessible lesion is available and when histology could alter management. This is particularly important after a limited original specimen or when imaging findings are discordant with the clinical course, because CD30-positive non-Hodgkin lymphomas and cHL can overlap morphologically and immunophenotypically.[9][12]

Salvage management should distinguish patients being considered for transplant-based therapy from those receiving nontransplant approaches. Contemporary work specifically evaluates transplant and nontransplant salvage strategies in relapsed/refractory Hodgkin lymphoma, while pediatric low-risk relapse studies have examined transplant-free approaches; selection therefore depends on relapse-risk setting and treatment strategy rather than a single universal salvage regimen.[6][7]

Brentuximab vedotin is a CD30-directed agent relevant to cHL, but this article does not specify a regimen or dose because treatment selection and dosing require protocol- and patient-specific prescribing information. Before using a CD30-directed strategy, confirm tumor classification and CD30 expression in the relevant specimen, especially when pathology is atypical.[8][9][10]
- Rebiopsy relapse when feasible if pathology confirmation would distinguish cHL from an alternative lymphoma or other PET-avid process.[9][12]
- Refer transplant-eligible relapsed/refractory patients early to a lymphoma/transplant program so response assessment and salvage sequencing do not delay definitive planning.[6]

*Relapsed or refractory disease decisions.[6][7][9][12]*

| Decision point | Action | Why it matters |
| --- | --- | --- |
| PET-avid lesion at suspected relapse | Biopsy an accessible lesion when the result could alter management.[9][12] | Morphologic and immunophenotypic mimics can change the lymphoma classification and treatment pathway.[9][12] |
| Relapsed/refractory cHL with potential transplant candidacy | Coordinate salvage planning with a transplant program.[6] | Transplant and nontransplant salvage pathways are distinct therapeutic strategies.[6] |
| Low-risk pediatric relapse | Use pediatric relapse-risk protocols rather than extrapolating adult transplant pathways.[7] | A trial evaluated transplant-free salvage in a low-risk pediatric population.[7] |

## References
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3. ABVD Alone versus Radiation-Based Therapy in Limited ... — www.nejm.org — https://www.nejm.org/doi/full/10.1056/NEJMoa1111961
4. Brentuximab Vedotin with Chemotherapy in Pediatric High ... — www.nejm.org — https://www.nejm.org/doi/full/10.1056/NEJMoa2206660
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6. Transplant and Nontransplant Salvage Therapy in ... — jamanetwork.com — https://jamanetwork.com/journals/jamaoncology/fullarticle/2828594
7. Transplant-Free Salvage Therapy for Low-Risk Relapsed ... — jamanetwork.com — https://jamanetwork.com/journals/jamaoncology/fullarticle/2828596
8. Hodgkin Lymphoma Treatment With Brentuximab... : eJHaem — journals.lww.com — https://journals.lww.com/02186220-202504010-00048
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10. Diagnostic challenges and considerations in CD30-negative classical Hodgkin lymphoma from biopsy specimens - ScienceDirect — www.sciencedirect.com — https://www.sciencedirect.com/science/article/abs/pii/S1092913425001212
11. FDG PET/CT may replace bone marrow biopsy for the evaluation of bone marrow involvement in selected mature T- and natural killer-cell lymphomas: A meta-analysis - ScienceDirect — www.sciencedirect.com — https://www.sciencedirect.com/science/article/abs/pii/S0720048X2400069X
12. ORAL PAPER ABSTRACTS : Indian Journal of Pathology and Microbiology — journals.lww.com — https://journals.lww.com/ijpm/fulltext/2022/65002/oral_paper_abstracts.11.aspx
13. Whole body FDG-PET/CT for the assessment of bone marrow infiltration in patients with newly diagnosed lymphoma - ScienceDirect — www.sciencedirect.com — https://www.sciencedirect.com/science/article/abs/pii/S2387020619305364
14. Journal of Pediatric Hematology/Oncology — journals.lww.com — https://journals.lww.com/jpho-online/fulltext/2024/08000/combining_brentuximab_vedotin_with_dexamethasone,.23.aspx
15. Systematic review and meta-analysis on the diagnostic performance of FDG-PET/CT in detecting bone marrow involvement in newly diagnosed Hodgkin lymphoma: is bone marrow biopsy still necessary? - ScienceDirect — www.sciencedirect.com — https://www.sciencedirect.com/science/article/pii/S0923753419347684
16. Hodgkin Lymphoma — academic.oup.com — https://academic.oup.com/jnci/article-pdf/109/4/djw249/9731612/djw249.pdf
17. Recommendations for Clinical Trial Development in Follicular ... — academic.oup.com — https://academic.oup.com/jnci/article/109/3/djw255/2758474
18. Hodgkin Lymphom S3-Leitlinie Diagnostik, Therapie und ... — extranet.who.int — https://extranet.who.int/ncdccs/Data/DEU_D1_Hodgkins%20lymphoma.pdf
19. CT, MRI, and FDG PET/CT in the Assessment of Lymph ... — pubs.rsna.org — https://pubs.rsna.org/doi/10.1148/radiol.232650
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22. Complete Issue (PDF) — www.ccjm.org — https://www.ccjm.org/content/ccjom/90/8/local/complete-issue.pdf
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24. Non-Hodgkin Lymphoma Involving the Gallbladder | ACS — www.facs.org — https://www.facs.org/for-medical-professionals/news-publications/journals/case-reviews/issues/v4n8/10-romero-velez-nhl-lymphoma

## Editorial note

Prepared from cited clinical literature using Astra's research workflow. Verify recommendations against current guidance and patient-specific factors.