Lymphoma — Viva Defence

Long Case Viva Defence

The scenario

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 that soak the bedclothes three to four times a week, and 8 kilograms of unintentional weight loss over the same period. He has also noticed generalized itch, worse after alcohol. He has a background of asthma (controlled on salbutamol and fluticasone), works full-time, and lives with his partner and two young children. Excisional biopsy of the supraclavicular node confirms nodular sclerosis classical Hodgkin lymphoma (CD30-positive, CD15-positive, CD20-negative in the Reed-Sternberg cells, with a rich inflammatory background). PET-CT shows bulky mediastinal disease (largest mass 9 cm) and bilateral cervical nodes, with no extranodal involvement; bone marrow biopsy is clear. Full blood count, renal and liver function are normal; LDH is mildly elevated; albumin 38 g/L; HIV and hepatitis B and C serology are negative; echocardiogram shows an ejection fraction of 62 per cent. [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 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 with PET-CT (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]

Problem list (numbered, prioritised)

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

Pillar 1 — Confirm diagnosis and staging: "I would review the excisional biopsy histology and immunohistochemistry — CD30-positive, CD15-positive, CD20-negative Reed-Sternberg cells confirm classical Hodgkin lymphoma. Staging PET-CT has been completed and shows bulky stage IIBX disease with no extranodal involvement; bone marrow is clear. By the Lugano classification, the stage is limited (IIBX bulky) to limited advanced; the bulk and B symptoms place him in an unfavourable early-stage or early-advanced category [5]. His IPS is 1 (male sex only — albumin, haemoglobin, age, stage, white cell count, lymphocyte count all normal), which predicts a favourable outcome [1]."

Pillar 2 — Fertility preservation: "Before any chemotherapy, I would urgently refer him for sperm cryopreservation. Alkylating agents (dacarbazine in ABVD, procarbazine in BEACOPP) and anthracyclines carry gonadal toxicity and risk permanent infertility. Sperm banking is rapid (a single sample, ideally two), low-cost, and should be arranged within days so that chemotherapy is not delayed. I would document the discussion and his decision." [1]

Pillar 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 with the patient weighs the pulmonary risk of ABVD against the neuropathy and neutropenia of A+AVD. Both achieve excellent outcomes — 5-year progression-free survival over 80 per cent."

Pillar 4 — PET-adapted therapy: "I would use interim PET after 2 cycles, scored by the Deauville 5-point scale [6]. The RATHL trial showed that patients who are PET-negative (Deauville 1 to 3) after 2 cycles of ABVD can safely de-escalate to AVD (omitting bleomycin) 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, I would continue ABVD or de-escalate to AVD for the remaining cycles; if PET-positive, I would escalate to escalated BEACOPP or switch to a salvage-based approach. The end-of-treatment PET determines whether consolidative ISRT is needed for bulky residual or PET-positive sites — for a bulky mediastinal mass, ISRT is often considered even after a complete metabolic response."

Pillar 5 — Supportive care and comorbidity: "For his asthma, I would optimise before chemotherapy — peak flow, spirometry, review of inhaler technique. I would prescribe antiemetics for the dacarbazine (a 5-HT3 antagonist plus dexamethasone plus aprepitant for the highly emetogenic dacarbazine), pegfilgrastim if neutropenia develops, PJP prophylaxis (co-trimoxazole), and tumour lysis prophylaxis (hydration, allopurinol) given the bulk. Bleomycin pulmonary toxicity must be monitored — baseline pulmonary function tests (spirometry and DLCO), counsel him to report cough or exertional dyspnoea immediately, and hold bleomycin if there is significant decline in DLCO or clinical suspicion of pneumonitis." [1]

Pillar 6 — Survivorship plan: "After treatment, I would institute a structured late-effects surveillance plan: annual TSH (cervical radiotherapy), echocardiographic surveillance at 2 and 5 years (anthracycline cardiomyopathy), pulmonary function if symptomatic (bleomycin), psychological support and screening for anxiety and depression, return-to-work plan, and cancer screening (smoking cessation, skin cancer surveillance). For a young man, the secondary malignancy risks are lung cancer (if he smokes and receives radiotherapy) and secondary leukaemia (from chemotherapy), but the breast cancer screening that applies to young women treated for Hodgkin does not apply here." [1]

Pillar 7 — Communication and shared decision: "I would sit with the patient and his partner, the haematologist and a clinical nurse specialist. I would explain that Hodgkin lymphoma is highly curable (5-year survival over 85 per cent), acknowledge the shock, and set out the two frontline options honestly. I would address fertility (sperm banking before cycle 1), the impact on his work and young family, and the long-term plan. I would document the shared decision, provide written information and a named contact, and arrange follow-up within days." [1]

Probing questions the examiner would ask

Q: What is the Hasenclever IPS and how does it apply to this patient? [1]

A: "The IPS, or International Prognostic Score, for advanced Hodgkin lymphoma was derived by Hasenclever and Diehl in 1998 from over 5000 patients. It assigns one point for each of seven adverse factors: serum albumin below 40 g/L, haemoglobin below 105 g/L, male sex, age 45 or older, Ann Arbor stage IV, white cell count 15 or above, and lymphocyte count below 0.6 or below 8 per cent of white cells [1]. A score of 0 to 1 predicts the best outcome; 4 or more the worst. For this patient, the only adverse factor present is male sex — his albumin is 38 (just below 40, so that may be a second point), his haemoglobin is normal, he is 34 (under 45), he is stage IIBX (not stage IV), white cell count likely normal, and lymphocyte count normal. His IPS is 1 or 2, placing him in a favourable prognostic group. In the modern era with PET-adapted therapy the IPS discriminates less, but it remains a framework for prognostication and trial entry."

Q: He develops cough and exertional dyspnoea after cycle 3 of ABVD. Pulmonary function tests show a 20 per cent decline in DLCO. What do you do? [1]

A: "This is suspected bleomycin pulmonary toxicity — a potentially life-threatening complication. I would hold bleomycin immediately and arrange urgent high-resolution CT of the chest (looking for bilateral ground-glass change or reticulation in the lower zones), review by a respiratory physician, and consider bronchoscopy with bronchoalveolar lavage to exclude infection (Pneumocystis, cytomegalovirus, bacterial). If bleomycin pneumonitis is confirmed or strongly suspected, I would permanently discontinue bleomycin and switch the remaining cycles to AVD (doxorubicin, vinblastine, dacarbazine), supported by the RATHL trial which showed that AVD is non-inferior to ABVD in PET-negative patients after 2 cycles [4]. I would consider corticosteroids (prednisone 1 mg/kg) for severe pneumonitis. The key lesson is that DLCO monitoring and early clinical recognition are essential — a registrar who notices the cough and holds bleomycin may save the patient's life."

Q: How would your management differ if he had stage IV disease with lung and liver involvement? [1]

A: "The stage would shift to advanced disease, and the standard would be 6 cycles of ABVD with PET-adapted escalation to escalated BEACOPP if the interim PET is positive (Deauville 4 to 5). The German Hodgkin Study Group prefers escalated BEACOPP for high-risk advanced disease (IPS 4 or more) because it produces a lower relapse rate, but at the cost of more acute toxicity (myelosuppression, infertility) and a small excess of secondary leukaemia. A+AVD is also an option for stage III to IV disease. His IPS would rise (stage IV adds a point), but the overall approach remains curative — Hodgkin lymphoma is highly curable even in advanced disease. The fertility discussion becomes more important because escalated BEACOPP carries a higher infertility risk than ABVD." [1]

Q: He asks whether his children are at increased risk of Hodgkin lymphoma. How do you answer? [1]

A: "For the vast majority of Hodgkin lymphoma cases the answer is no — Hodgkin is sporadic, driven by acquired somatic mutations in a B lymphocyte, not inherited. There is a modest familial aggregation in some studies (siblings of Hodgkin patients have a slightly higher risk), but the absolute risk to his children remains very low. Environmental factors (EBV infection, socioeconomic factors) and immunogenetic factors play a role, but there is no established inherited predisposition syndrome analogous to familial breast cancer. I would reassure him clearly." [1]

Q: Five years after treatment, he is well. What long-term surveillance do you recommend? [1]

A: "The leading cause of death in long-term Hodgkin survivors is not the lymphoma itself but the late effects of treatment. I would recommend annual TSH (cervical radiotherapy and thyroid risk), echocardiographic surveillance at 5 and 10 years (anthracycline cardiomyopathy, radiation-accelerated coronary disease), pulmonary function if symptomatic (bleomycin), annual skin examination (radiation and chemotherapy), smoking cessation counselling, screening for secondary malignancy (lung if he smoked and received radiotherapy, acute leukaemia in the first 5 to 10 years after chemotherapy), psychological support, and vaccination review. For young women treated for Hodgkin — not relevant here — annual breast MRI from 8 years post-treatment or age 40 is standard. The survivorship plan should be documented and communicated to the general practitioner." [1]

Communication and shared decision-making

"I would frame Mr J's Hodgkin lymphoma as a highly curable diagnosis — 5-year survival over 85 per cent — with a clear immediate plan and a shared decision on the intensity of therapy. I would explain the two pathways in plain language — ABVD with PET-adapted de-escalation, or A+AVD — weighing pulmonary risk (relevant given his asthma) against neuropathy. I would address fertility directly — sperm banking before cycle 1 is rapid and important. I would discuss the impact on his work (he may need 6 months off), his partner and young children, and the practicalities of frequent hospital visits. I would acknowledge his fear and give him space. I would document the shared decision, provide written information, give him a named clinical nurse specialist, and arrange follow-up within days." [1]

Short Case Discussion — 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 Hickman line or port, signs of chemotherapy (alopecia, mucositis), radiation tattoos.
2. Cervical nodes — examine from behind the patient, 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 (soft, rubbery, hard), mobility, and tenderness.
3. Axillary nodes — examine with the patient's arm supported. Central, apical, lateral, pectoral, subscapular. Support the patient's right arm with your left hand and examine the right axilla with your right hand, and vice versa.
4. Epitrochlear nodes — support the elbow at 90 degrees, examine the medial aspect above the medial epicondyle (suggests lymphoma or secondary syphilis).
5. Inguinal nodes — horizontal group (drains lower abdominal wall, external genitalia, anal canal) and vertical group (drains lower limb).
6. Abdomen — inspect, palpate for hepatosplenomegaly (radial border of the right index finger, breath in, move towards the costal margin incrementally; turn slightly to the patient's right to feel the spleen). Percuss Traube's space (dullness suggests splenomegaly).
7. Oropharynx — Waldeyer's ring involvement (tonsillar enlargement), mucosal involvement.
8. Skin — cutaneous deposits, plaques (mycosis fungoides).
9. Testes — testicular masses (testicular lymphoma, a sanctuary site).
10. Complete the examination — chest (mediastinal mass, pleural effusion), brief neurological, fundoscopy, blood pressure. [1]

Presentation template

"I examined Mr J, a 34-year-old man who looks comfortable at rest. He has a 2 cm rubbery, mobile, non-tender right supraclavicular node and a 1.5 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 lymphadenopathy with splenomegaly — in a young man with cervical and supraclavicular nodes and B symptoms, the differential includes Hodgkin lymphoma, non-Hodgkin lymphoma, and tuberculous lymphadenitis. I would specifically arrange an excisional lymph node biopsy for histology, immunohistochemistry, and mycobacterial culture." [1]

Discussion questions

Q: What features of a lymph node suggest malignancy rather than reactive change? [1]

A: "The features that suggest malignancy are: 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) or supraclavicular region rather than cervical chain; 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 a supraclavicular node (Virchow's node)? [1]

A: "A supraclavicular node — classically a left supraclavicular node (Virchow's node, or Troisier's sign when enlarged) — drains the abdomen via the thoracic duct and is strongly associated with malignancy. A left supraclavicular node suggests gastric, pancreatic, hepatic, ovarian, testicular, or prostatic carcinoma; a right supraclavicular node suggests lung, breast, oesophageal, or mediastinal malignancy. Lymphoma can present in either. The discovery of a supraclavicular node mandates thorough investigation for a primary malignancy as well as lymphoma — excisional biopsy is the first step." [1]

Q: How do you distinguish Hodgkin from non-Hodgkin lymphoma at the bedside? [1]

A: "The bedside discrimination is limited — the definitive diagnosis is on histology and immunohistochemistry. But there are clues. Hodgkin lymphoma tends to present with contiguous, often cervical and mediastinal, lymphadenopathy in a young adult with B symptoms and itch; it spreads chain to chain and extranodal involvement is uncommon at diagnosis. NHL is more heterogeneous, tends to affect older adults, often presents with widespread or extranodal disease (gut, skin, bone, CNS, testis), and is less likely to have the classic contiguous pattern. Reed-Sternberg cells on histology (large binucleate cells with owl-eye nucleoli) that are CD30-positive, CD15-positive, and CD20-negative confirm Hodgkin. The key bedside point is that both require excisional biopsy for diagnosis, and the histology determines everything downstream." [1]

Q: What are the B symptoms and why do they matter? [1]

A: "The B symptoms, as defined by the Ann Arbor classification, are: unexplained fever above 38 degrees Celsius, drenching night sweats (the kind that soak the bedclothes and force the patient to change), and unintentional weight loss of more than 10 per cent of body weight over 6 months. Their presence is recorded as the 'B' modifier (stage IIB rather than IIA) and carries prognostic weight — they indicate more aggressive or more advanced disease. Their presence mandates a search for lymphoma; their absence does not exclude it. Itch and alcohol-induced pain in nodes are classically associated with Hodgkin but are not formally part of the B symptom triad." [1]