Lymphoma — Clinical Case

DCE Long Case

Patient profile

Mr J is a 34-year-old software engineer who presents to his general practitioner with a three-month history of progressively enlarging painless lumps in his right cervical and supraclavicular regions, drenching night sweats, and 8 kilograms of unintentional weight loss. [1]

Presenting concern: For three months he has noticed progressively enlarging lumps in the right side of his neck and above the right clavicle. They are painless but are now cosmetically obvious. He has been having drenching night sweats three to four times a week — "I have to change the sheets" — for the last eight weeks. He has lost 8 kilograms over three months without trying. He has noticed generalized itch, worse after a glass of wine, and has felt increasingly tired. He has no fever, no cough, no shortness of breath (his exercise tolerance is preserved — he runs 5 km three times a week), no abdominal pain, and no change in bowel habit. [1]

Past medical history: Asthma diagnosed at age 12, currently well controlled with salbutamol inhaler as needed (used two or three times a month) and fluticasone inhaler daily. He had a tonsillectomy at age 8. No other medical history. No prior haematological disease. [1]

Medications and allergies: Salbutamol inhaler 100 micrograms as needed, fluticasone inhaler 100 micrograms twice daily. No allergies. No over-the-counter medications or supplements. [1]

Family and social history: He lives with his partner of 10 years and their two children (aged 3 and 5). He works full-time as a software engineer. He drinks 4 to 6 units of alcohol per week (he has noticed that the itch is worse after a glass of wine). He has never smoked. His father had prostate cancer at age 70 (well); his mother is well; his two siblings are well. No family history of lymphoma or leukaemia. [1]

Examination: He looks well, no cachexia, no pallor, no jaundice, no clubbing. There is a 2.5 cm rubbery, mobile, non-tender right supraclavicular node and a 1.5 cm right cervical chain node; the left cervical chain is also palpable with a 1 cm node. The epitrochlear, axillary, and inguinal nodes are not palpable. The oropharynx is clear. The chest is clear with good air entry and no wheeze (peak flow 620 L/min, normal for him). The abdomen reveals a spleen palpable 3 cm below the costal margin; the liver is not enlarged. There are no cutaneous lesions. Neurological examination is unremarkable. [1]

Investigations: Full blood count is normal (haemoglobin 142, white cell count 7.2, platelets 240). Film is normal. Renal and liver function are normal; albumin 38 g/L; LDH mildly elevated at 320 U/L (normal under 250). Beta-2 microglobulin mildly elevated. HIV and hepatitis B and C serology are negative. Echocardiogram shows an ejection fraction of 62 per cent. Pulmonary function tests show FEV1 3.8 L (95 per cent predicted), FVC 4.7 L, DLCO 85 per cent predicted. [1]

Excisional biopsy of the right supraclavicular node: Nodular sclerosis classical Hodgkin lymphoma. Histology shows Reed-Sternberg cells (large binucleate cells with prominent owl-eye nucleoli) in a background of fibrosis, lymphocytes, eosinophils, and plasma cells. Immunohistochemistry: CD30-positive, CD15-positive, CD20-negative in the Reed-Sternberg cells, with a rich inflammatory background of CD3-positive T cells rosetting around the neoplastic cells. [1]

PET-CT: FDG-avid bulky mediastinal mass (largest diameter 9 cm) with bilateral cervical and supraclavicular lymphadenopathy. No FDG-avid extranodal disease. Bone marrow biopsy: clear of lymphoma. [1]

Candidate task

You have 25 minutes to read this case and prepare a presentation. The examiner will then ask you to present the case (5 minutes), followed by discussion (15 minutes). [1]

Opening statement (SASPOP)

"This is Mr J, a 34-year-old software engineer presenting with a three-month history of painless enlarging cervical and supraclavicular lymphadenopathy, drenching night sweats, and 8 kg of unintentional weight loss, found on excisional biopsy to have nodular sclerosis classical Hodgkin lymphoma with bulky mediastinal involvement and Ann Arbor stage IIBX (bulky) disease. His main problems are the lymphoma itself (bulky stage II disease with B symptoms — managed with PET-adapted ABVD chemotherapy or brentuximab vedotin plus AVD), the acute impact of the diagnosis on his young family and his work, the question of fertility preservation before chemotherapy, his coexisting asthma which raises the risk of bleomycin pulmonary toxicity, and the long-term survivorship plan including secondary malignancy screening and cardiac and pulmonary surveillance. My priorities are to complete staging (done), to address fertility preservation before chemotherapy (urgent sperm cryopreservation), to engage the haematology multidisciplinary team and the patient in a shared decision on ABVD versus A+AVD, and to institute a structured survivorship plan." [1]

Structured problem list

1. Newly diagnosed bulky stage IIBX classical Hodgkin lymphoma — PET-adapted ABVD or A+AVD for 6 cycles; consolidative ISRT for bulky residual or PET-positive disease.
2. B symptoms and bulky mediastinal disease — assess for superior vena cava syndrome and airway compromise (none here).
3. Fertility preservation — urgent sperm cryopreservation before cycle 1.
4. Coexisting asthma — optimise before chemotherapy; bleomycin pulmonary toxicity risk.
5. Psychosocial impact — diagnosis on the patient, his partner, and two young children; employer liaison; financial support.
6. Long-term survivorship plan — secondary malignancy (lung, leukaemia), cardiac (anthracycline), pulmonary (bleomycin), endocrine, psychological surveillance. [1]

Integrated management plan

1. Confirm diagnosis and staging: Review the excisional biopsy histology and immunohistochemistry — CD30-positive, CD15-positive, CD20-negative Reed-Sternberg cells in an inflammatory background confirm classical Hodgkin lymphoma. Staging PET-CT shows bulky stage IIBX disease with no extranodal involvement; bone marrow is clear. By the Lugano classification, this is limited advanced disease; the bulk and B symptoms place him in an unfavourable early-stage or limited advanced category [5]. His IPS is 1 (male sex only — albumin 38 may add a second point), which predicts a favourable outcome [1].

2. Fertility preservation: Before any chemotherapy, urgent referral for sperm cryopreservation. Alkylating agents (dacarbazine, procarbazine in BEACOPP) and anthracyclines carry gonadal toxicity. Sperm banking is rapid, low-cost, and should be arranged within days so that chemotherapy is not delayed. Document the discussion and the patient's decision. [1]

3. Frontline therapy — ABVD versus A+AVD: The standard for bulky stage IIB Hodgkin lymphoma is 6 cycles of ABVD (doxorubicin 25 mg/m2, bleomycin 10 units/m2, vinblastine 6 mg/m2, dacarbazine 375 mg/m2 on days 1 and 15 of each 28-day cycle). The modern alternative is brentuximab vedotin plus AVD (A+AVD) — the ECHELON-1 trial showed a modified progression-free survival advantage over ABVD in stage III to IV classical Hodgkin lymphoma, with less pulmonary toxicity (no bleomycin) but more neuropathy and neutropenia [3]. For a young man with asthma (which increases the risk of bleomycin pulmonary toxicity), A+AVD is an attractive option. The shared decision weighs pulmonary risk against neuropathy.

4. PET-adapted therapy: Interim PET after 2 cycles, scored by the Deauville 5-point scale [6]. The RATHL trial showed that PET-negative patients (Deauville 1 to 3) can de-escalate to AVD without loss of efficacy, while PET-positive patients (Deauville 4 to 5) are escalated to BEACOPP [4]. For this patient, if the interim PET shows a complete metabolic response, continue ABVD or de-escalate to AVD; if PET-positive, escalate to escalated BEACOPP. The end-of-treatment PET determines whether consolidative ISRT is needed for bulky residual or PET-positive sites.

5. Supportive care and comorbidity: Optimise asthma before chemotherapy (peak flow, spirometry, inhaler technique). Antiemetics for dacarbazine (5-HT3 antagonist plus dexamethasone plus aprepitant), pegfilgrastim if neutropenia develops, PJP prophylaxis (co-trimoxazole), tumour lysis prophylaxis (hydration, allopurinol) given the bulk. Bleomycin pulmonary toxicity monitoring — baseline pulmonary function (done — DLCO 85 per cent), counsel to report cough or exertional dyspnoea immediately, hold bleomycin if significant DLCO decline or clinical suspicion of pneumonitis. Hepatitis B, HIV serology, and echocardiogram are complete. [1]

6. Survivorship plan: Annual TSH (cervical radiotherapy), echocardiographic surveillance at 2 and 5 years (anthracycline cardiomyopathy), pulmonary function if symptomatic (bleomycin), psychological support, return-to-work plan, smoking cessation (he is a non-smoker), cancer screening. For a young man, the secondary malignancy risks are lung (if he smoked and received radiotherapy) and leukaemia (chemotherapy); the breast cancer screening that applies to young women does not apply here. [1]

7. Communication and shared decision: Sit with the patient and his partner, the haematologist and a clinical nurse specialist. Explain that Hodgkin lymphoma is highly curable (5-year survival over 85 per cent), acknowledge the shock, set out the two frontline options honestly. Address fertility (sperm banking before cycle 1), the impact on his work and young family, the practicalities of 6 months of treatment. Document the shared decision, provide written information and a named contact, arrange follow-up within days. [1]

Probing questions and discussion

Q: What is the role of interim PET-CT in Hodgkin lymphoma? [1]

A: "Interim PET after 2 cycles of ABVD is now standard, scored by the Deauville 5-point scale. The RATHL trial showed that PET-negative patients (Deauville 1 to 3) can safely de-escalate to AVD (omitting bleomycin) without loss of efficacy, reducing pulmonary toxicity. PET-positive patients (Deauville 4 to 5) are escalated to escalated BEACOPP or to a salvage-based approach. The Deauville score has become the universal language of PET response in lymphoma — scores 1 to 3 are a complete metabolic response in routine practice; scores 4 and 5 are residual or progressive disease. The end-of-treatment PET determines whether consolidative radiotherapy is needed." [1]

Q: How would you counsel this patient about bleomycin pulmonary toxicity? [1]

A: "Bleomycin pulmonary toxicity is a potentially life-threatening complication — it presents with dry cough, exertional dyspnoea, and bilateral ground-glass or reticular change on high-resolution CT, typically during or within 6 months of treatment. Risk factors include age over 40, smoking, reduced renal function, high cumulative dose, and pre-existing lung disease. For this patient, his asthma is a relative consideration. I would do baseline pulmonary function tests (spirometry and DLCO), counsel him to report cough or breathlessness immediately, hold bleomycin if there is a significant DLCO decline (over 15 to 20 per cent) or clinical suspicion of pneumonitis, and consider switching to AVD (supported by the RATHL trial) or to A+AVD as the frontline choice to avoid bleomycin altogether. Corticosteroids are used for severe pneumonitis." [1]

Q: How does your management differ for early-stage favourable Hodgkin lymphoma? [1]

A: "For early-stage favourable Hodgkin lymphoma (stage I to IIA, non-bulky, no B symptoms), the standard established by the GHSG HD10 trial is 2 cycles of ABVD plus 20 Gy involved-site radiotherapy (ISRT) — this minimal regimen achieves 5-year progression-free survival over 90 per cent with the lowest long-term toxicity [2]. Selected young women are increasingly treated with chemotherapy alone (typically 4 to 6 cycles of ABVD) if they achieve a complete metabolic response on interim PET, to avoid the breast cancer risk of thoracic radiotherapy. For early-stage unfavourable disease (B symptoms, bulky, older age), the approach is more chemotherapy (4 cycles of ABVD or escalated BEACOPP) plus ISRT, or PET-adapted chemotherapy alone."

Q: He relapses 18 months after completing ABVD. What is the management? [1]

A: "The pathway for relapsed Hodgkin lymphoma is salvage chemotherapy (e.g. ICE — ifosfamide, carboplatin, etoposide — or GDP — gemcitabine, dexamethasone, cisplatin), then autologous stem cell transplant for chemosensitive disease — this is the only curative modality for relapsed Hodgkin and achieves long-term progression-free survival in about 50 to 60 per cent of those transplanted. For patients who relapse after autologous transplant or who are transplant-ineligible, the modern options are brentuximab vedotin (anti-CD30 antibody-drug conjugate) and PD-1 blockade (nivolumab or pembrolizumab — Hodgkin Reed-Sternberg cells frequently amplify 9p24.1, the PD-L1/PD-L2 locus, making the tumour exquisitely sensitive to PD-1 blockade). Pembrolizumab with gemcitabine-based salvage is being explored as a bridge to autologous transplant in chemorefractory disease. Allogeneic stem cell transplant is reserved for selected patients who relapse after autologous transplant." [1]

Q: How would you counsel a young woman about the late effects of Hodgkin lymphoma treatment? [1]

A: "For a young woman, the principal late effects are: breast cancer (from thoracic/mantle radiotherapy — annual breast MRI from 8 years post-treatment or age 40, whichever comes first, is standard), premature ovarian failure and infertility (from alkylating agents and pelvic radiotherapy — discuss fertility preservation before treatment, ideally oocyte or embryo cryopreservation), cardiovascular disease (anthracycline cardiomyopathy, radiation-accelerated coronary and carotid disease — echocardiographic surveillance, lipid management, smoking cessation), pulmonary fibrosis (bleomycin), hypothyroidism (cervical radiotherapy — annual TSH), and secondary leukaemia (chemotherapy). The choice of regimen and radiotherapy field is shaped by these risks — for a young woman, chemotherapy alone (omitting radiotherapy) is preferred if a complete metabolic response is achieved on interim PET. The survivorship plan is long-term and multidisciplinary." [1]

Q: What is the role of PD-1 blockade in Hodgkin lymphoma and why is Hodgkin so sensitive? [1]

A: "Hodgkin Reed-Sternberg cells frequently amplify the 9p24.1 chromosomal region, which encodes PD-L1 and PD-L2 — the ligands for the PD-1 receptor on T cells. This overexpression allows the Reed-Sternberg cells to inhibit the T-cell immune response and evade immune destruction. PD-1 blockade with nivolumab or pembrolizumab releases this brake and restores T-cell killing of the Reed-Sternberg cells. CheckMate 205 and KEYNOTE-087 showed response rates over 65 per cent in relapsed or refractory Hodgkin lymphoma after autologous transplant and brentuximab. Pembrolizumab with gemcitabine-based salvage is now used as a bridge to autologous transplant in chemorefractory disease, and the combination with brentuximab is being explored. This is one of the great success stories of cancer immunotherapy — a genetic lesion (9p24.1 amplification) that predicted sensitivity to a targeted therapy (PD-1 blockade)." [1]

Communication and shared decision-making

"I would sit with Mr J and his partner in a quiet room with the haematologist and a clinical nurse specialist. I would explain that Hodgkin lymphoma is one of the most curable of all cancers — 5-year survival over 85 per cent — and that the immediate plan is clear. I would acknowledge the shock of the diagnosis, the fear of chemotherapy, and the impact on his young family and his work. I would set out the two frontline options honestly — ABVD with PET-adapted de-escalation, or A+AVD — and explain that for a young man with asthma, the lower pulmonary risk of A+AVD may be attractive, balanced against neuropathy and neutropenia. I would address fertility directly — sperm banking before cycle 1 is rapid and important, and I would arrange it within days. I would discuss the practicalities of 6 months of treatment (time off work, financial support, childcare), the late-effects surveillance plan, and the long-term outlook. I would document the shared decision, provide written information, give him a named clinical nurse specialist, and arrange follow-up within days. I would reassure him that the goal is cure, that the team will be with him at every step, and that he can ask anything at any time." [1]

Short Case — Lymphadenopathy Examination

Instruction: "Examine this patient's lymph node regions and abdomen for organomegaly." [1]

Systematic examination routine

1. End of bed — observe for cachexia, pallor, jaundice, clubbing, visible masses, any central line, signs of chemotherapy.
2. Cervical nodes — examine from behind, in sequence: submental, submandibular, pre-auricular, post-auricular, occipital, tonsillar, upper cervical, middle cervical, lower cervical, posterior triangle, supraclavicular (Virchow). Use the pads of the index and middle fingers with a rolling motion in both axes. Document size, shape, consistency, mobility, tenderness.
3. Axillary nodes — examine with the arm supported. Central, apical, lateral, pectoral, subscapular.
4. Epitrochlear nodes — support the elbow at 90 degrees, examine the medial aspect above the medial epicondyle.
5. Inguinal nodes — horizontal and vertical groups.
6. Abdomen — palpate for hepatosplenomegaly; percuss Traube's space.
7. Oropharynx — Waldeyer's ring involvement, mucosal involvement.
8. Skin — cutaneous deposits, plaques (mycosis fungoides).
9. Testes — testicular masses (testicular lymphoma).
10. Complete — chest (mediastinal mass, effusion), neurological, fundoscopy, blood pressure. [1]

Key physical signs (for this patient)

• 2.5 cm rubbery, mobile, non-tender right supraclavicular node
• 1.5 cm right cervical chain node
• 1 cm left cervical chain node
• Spleen palpable 3 cm below the costal margin
• No hepatomegaly, no epitrochlear, axillary, or inguinal nodes
• No pallor, jaundice, or clubbing
• Chest clear; no cutaneous lesions [1]

Presentation template

"I examined Mr J, a 34-year-old man who looks well at the end of the bed. He has a 2.5 cm rubbery, mobile, non-tender right supraclavicular node, a 1.5 cm right cervical chain node, and a 1 cm left cervical chain node. The epitrochlear, axillary, and inguinal nodes are not palpable. The abdomen reveals a spleen palpable 3 cm below the costal margin; the liver is not enlarged. The chest is clear. There is no pallor, jaundice, or clubbing. These findings are consistent with cervical and supraclavicular lymphadenopathy with splenomegaly. In a young man with progressively enlarging painless nodes and B symptoms, the differential diagnosis includes Hodgkin lymphoma, non-Hodgkin lymphoma, and tuberculous lymphadenitis. I would arrange an excisional lymph node biopsy for histology, immunohistochemistry, flow cytometry, and mycobacterial culture, and I would request a full blood count, film, LDH, HIV and hepatitis serology, and a PET-CT for staging." [1]

Discussion

Q: What features suggest that a lymph node is malignant rather than reactive? [1]

A: "Painless rather than tender; progressively enlarging rather than resolving over weeks; rubbery or hard rather than soft; fixed or matted rather than mobile; located in the supraclavicular fossa (Virchow); accompanied by B symptoms (fever above 38, drenching night sweats, weight loss more than 10 per cent in 6 months); associated with hepatosplenomegaly; and persistent beyond 4 to 6 weeks without resolution. Any node that does not resolve in 4 to 6 weeks, or that grows, or that is accompanied by B symptoms, mandates excisional biopsy." [1]

Q: What is the significance of alcohol-induced pain in lymph nodes? [1]

A: "Alcohol-induced pain in lymph nodes is a classic but rare feature of Hodgkin lymphoma — the patient describes pain in involved nodes within minutes of drinking alcohol. The mechanism is uncertain but may relate to vascular changes within the node. It is not a formal part of the diagnostic criteria but is highly suggestive when present. Other classic features of Hodgkin include generalized itch (also non-specific but suggestive) and the Pel-Ebstein fever (cyclical fever, though this is rare). The key point is that these features, when present, point toward Hodgkin lymphoma and mandate excisional biopsy." [1]

Q: When would you perform a bone marrow biopsy in a patient with lymphoma? [1]

A: "In the PET era, bone marrow biopsy is no longer routinely required for Hodgkin lymphoma or DLBCL if PET is clearly negative for marrow involvement — PET detects marrow disease with high sensitivity and is now the standard. Marrow biopsy is still required for the indolent NHLs (follicular, marginal zone, mantle cell, small lymphocytic lymphoma/CLL, lymphoplasmacytic), for Waldenstrom macroglobulinaemia, for patients with unexplained cytopenias (which may indicate marrow involvement), and when PET is equivocal or unavailable. The Lugano classification explicitly states that PET can replace marrow biopsy in Hodgkin and DLBCL when PET clearly shows or excludes marrow involvement." [1]