Hodgkin Lymphoma — FCPS & MRCP Complete Study Note

tags: [medicine, hematology, lymphoma, oncology, mrcp, fcps]

status: full-fcps-mrcp-topic-note

davidson_chapter: Chapter 25: Haematology and transfusion medicine

MRCP High-Yield Hodgkin lymphoma (HL) is a malignant proliferation of Reed-Sternberg cells within a reactive inflammatory background. Bimodal age distribution (15–35 and >55). B symptoms, contiguous nodal spread, and Reed-Sternberg cells on histology are the classic triad. ABVD is first-line chemotherapy. Excellent cure rates (>85% overall).

Learning Objectives

1. Define Hodgkin lymphoma and distinguish it from non-Hodgkin lymphoma
2. Describe the epidemiology and aetiology including EBV association
3. Classify Hodgkin lymphoma (WHO 2016 / 2022 update)
4. Explain the pathophysiology of Reed-Sternberg cells
5. Recognize clinical features including B symptoms and nodal patterns
6. Outline the diagnostic approach (excisional biopsy, staging)
7. Interpret staging (Ann Arbor / Lugano) and prognostic scoring (IPS)
8. Describe management by stage (ABVD, BEACOPP, radiotherapy, BV-AVD)
9. Identify complications: treatment-related second malignancies, cardiac toxicity, infertility
10. Recognize relapsed/refractory disease management
11. Understand interim PET-guided therapy adaptation (escalation and de-escalation)
12. Apply knowledge to special situations: pregnancy, HIV, elderly

Definition

Hodgkin lymphoma is a malignant lymphoma characterized by the presence of Reed-Sternberg cells (or Hodgkin cells) within a background of reactive inflammatory cells. It accounts for approximately 10% of all lymphomas and is one of the most curable cancers.

Normal Values / Important Cut-offs

Parameter	Normal / Cut-off	Relevance
Albumin	≥40 g/L	<40 = IPS risk factor
Hemoglobin	≥105 g/L	<105 = IPS risk factor
WBC	<15 × 10⁹/L	≥15 = IPS risk factor
Lymphocyte count	≥0.6 × 10⁹/L (or ≥8% WBC)	<0.6 or <8% = IPS risk factor
ESR	<50 mm/hr (no B symptoms); <30 (with B symptoms)	Higher = unfavorable early-stage
LDH	Normal lab range	Elevated = tumor burden, adverse prognosis
Platelet count	150–400 × 10⁹/L	Cytopenias suggest marrow involvement
Doxorubicin cumulative lifetime dose	≤450–550 mg/m²	Exceeding = high cardiomyopathy risk
Bleomycin cumulative dose	≤400 units	Exceeding = pulmonary toxicity risk
Mediastinal mass “bulky”	>10 cm or >1/3 thoracic diameter at T5/6	“X” designation, affects management
Deauville score	1–3 = good response; 4–5 = poor response	Guides interim therapy decisions
LVEF (baseline)	≥50%	Required before anthracycline; <50% = relative contraindication
DLCO	≥80% predicted	Baseline before bleomycin; <60% = high risk

Epidemiology

Feature	Detail
Incidence	~2.5–3 per 100,000 per year (UK)
Age	Bimodal: peak 15–35 years AND >55 years
Sex	Slight male predominance (M:F ~1.3:1)
EBV association	~40–50% of cases (higher in mixed cellularity)
Socioeconomic	More common in developed nations; bimodal curve linked to delayed EBV exposure in higher socioeconomic groups
HIV	Increased risk (especially mixed cellularity subtype)

Aetiology / Risk Factors

Established

• EBV infection — detected in ~40–50% of HL (up to 70% in mixed cellularity); EBV-encoded LMP1 mimics CD40 signaling → constitutive NF-κB activation
• HIV infection — 5–20× increased risk
• Family history — 3–5× increased risk in first-degree relatives; HLA-DRB1 and HLA-DPB1 associations
• Young adulthood — infectious mononucleosis history increases HL risk ~3×

Possible

• Immunosuppression (post-transplant)
• Autoimmune conditions
• Smoking (weak association)

Pathophysiology

Reed-Sternberg (RS) Cells

• Origin: Germinal center B cells that have undergone somatic hypermutation but have lost much of B-cell gene expression program
• Morphology: Large binucleated or multilobated cells with prominent eosinophilic nucleoli (“owl-eye” appearance)
• Immunophenotype:
• CD15+ (80%)
• CD30+ (nearly 100%)
• CD45− (leukocyte common antigen negative)
• CD20− or weakly positive (most cases)
• PAX5 weakly positive
• CD79a usually negative

Molecular Mechanisms

1. Constitutive NF-κB activation — key survival pathway for RS cells

• LMP1 (EBV) mimics CD40 → NF-κB
• TNFAIP3 (A20) mutations → loss of NF-κB negative regulation
• NFKBIA mutations

1. JAK-STAT pathway activation — amplification of 9p24.1 (PD-L1/PD-L2 locus)
2. Immune evasion — PD-L1/PD-L2 overexpression, MHC class I downregulation
3. Cytokine milieu — RS cells secrete CCL5, CCL17, CCL22 → recruit T cells, eosinophils, macrophages → reactive background

Why RS Cells Survive Despite Defective B-Cell Receptor

RS cells have “crippling” immunoglobulin gene mutations that should cause apoptosis. They survive because:

• NF-κB provides anti-apoptotic signals
• JAK-STAT activation
• Microenvironment support (T-cell “help” via CD40-CD40L interaction)

Classification

WHO Classification (2016, updated 2022)

1. Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL) — ~5%

• LP cells (lymphocyte-predominant cells, formerly “popcorn cells”)
• CD20+, CD45+, CD15−, CD30− (or weakly +)
• EMA+, BCL6+
• Indolent course; may transform to DLBCL
• Treated differently from classical HL

2. Classical Hodgkin Lymphoma (cHL) — ~95%

Subtype	Frequency	EBV association	Key features
Nodular sclerosis (NSHL)	60–70%	~10–40%	Lacunar cells, fibrous bands, most common in young adults, mediastinal mass
Mixed cellularity (MCHL)	20–25%	~70%	Most EBV+, more common in HIV, males, older adults
Lymphocyte-rich (LRHL)	5%	~40%	Good prognosis, may resemble NLPHL
Lymphocyte-depleted (LDHL)	<5%	~70–80%	Worst prognosis, most common in HIV, abundant RS cells, few lymphocytes

Exam Trap NLPHL is NOT treated the same as classical HL. NLPHL is CD20+ → rituximab has a role. Classical HL is CD20− (usually) → rituximab not standard first-line.

Clinical Features

Presenting Features

Feature	Detail
Painless lymphadenopathy	Most common presentation (~80%)
Cervical nodes	Most common site (60–70%), especially posterior cervical chain
Mediastinal mass	Especially NSHL; may cause cough, SOB, SVC obstruction
Contiguous spread	Spreads to adjacent nodal groups (unlike NHL which is non-contiguous)

B Symptoms (Systemic Symptoms)

B Symptoms Definition 1. Fever >38°C, unexplained, recurrent (Pel-Ebstein fever — cyclical fever every 1–2 weeks — classic but rare) 2. Drenching night sweats (requiring change of bedclothes) 3. Weight loss >10% body weight in 6 months

• Present in ~25–30% at diagnosis
• B symptoms = “B” stage in Ann Arbor staging
• Also: pruritus (especially NSHL), alcohol-induced nodal pain (classic but rare), fatigue

Organ Involvement (Stage IV or Extranodal)

Site	Features
Spleen	Splenomegaly (may be only site of subdiaphragmatic disease)
Liver	Hepatomegaly, abnormal LFTs
Lung	Pulmonary infiltrates, pleural effusion
Bone marrow	Pancytopenia (rare at presentation, ~5%)
Bone	Osteolytic or osteoblastic lesions
CNS	Very rare at presentation

Special Clinical Scenarios

• Supraclavicular nodes — always investigate for mediastinal/thoracic pathology
• Mediastinal mass — can be massive; may present with SVC syndrome
• Retroperitoneal nodes — may present with back pain, leg swelling
• Pruritus — may be the only symptom; generalized, worse at night
• Pel-Ebstein fever — cyclical (1–2 weeks fever, 1–2 weeks afebrile); classic but uncommon
• Alcohol-induced nodal pain — rare but highly specific for HL

Approach / Algorithm

Diagnostic Approach to Suspected HL

Painless lymphadenopathy (>4 weeks, no infective cause)
        │
        ▼
Excisional lymph node biopsy (NOT FNA)
        │
        ├── RS cells + CD15+/CD30+/CD45− → Classical HL
        │       │
        │       ▼
        │   Staging: PET-CT + CBC, ESR, LDH, LFTs, albumin, HIV, pregnancy test
        │   Baseline: Echo/MUGA, PFTs (DLCO), fertility counseling
        │       │
        │       ▼
        │   Ann Arbor staging (Lugano modification)
        │       │
        │       ├── Early favorable (I–IIA, no risk factors)
        │       │       → ABVD x2–4 + ISRT
        │       │       → Interim PET: Deauville 1–3 → continue
        │       │       → RAPID trial: early non-bulky, PET-negative after 3 cycles ABVD → omit RT
        │       │
        │       ├── Early unfavorable (I–IIA, with risk factors)
        │       │       → ABVD x4–6 + ISRT
        │       │
        │       └── Advanced (III–IV)
        │               → ABVD x6–8 (or BV-AVD x6 for stage III/IV)
        │               → IPS ≥4 → consider escalated BEACOPP
        │               → Interim PET after 2 cycles
        │                   ├── Deauville 1–3 → continue current regimen
        │                   └── Deauville 4–5 → escalate to BEACOPP or BV-AVD
        │
        └── LP cells + CD20+/CD45+ → NLPHL
                │
                ▼
            Early-stage (IA) → ISRT alone (or watch-and-wait if asymptomatic)
            Advanced → R-CHOP or ABVD; rituximab has key role

Response-Adapted Therapy Algorithm

Interim PET after 2 cycles ABVD
        │
        ├── Deauville 1–3 (CMR)
        │       ├── Standard: continue ABVD to planned cycles
        │       └── Early non-bulky (RAPID): may omit RT if PET-negative after 3 cycles
        │
        └── Deauville 4–5 (poor response)
                │
                ▼
        Escalation options:
        ├── Escalated BEACOPP (GHSG HD18)
        ├── BV-AVD (swap bleomycin for brentuximab)
        └── Consider clinical trial

Investigations

First-Line Investigations

Investigation	Purpose / Expected Finding
Excisional lymph node biopsy	Gold standard — need adequate tissue for architecture assessment
FNA cytology	NOT sufficient alone (cannot assess architecture; RS cells may be missed)
CBC	Anemia (chronic disease, marrow involvement), eosinophilia, lymphopenia (poor prognosis)
ESR / CRP	Elevated; ESR >50 or >30 with B symptoms = adverse prognostic factor
LFTs	Abnormal in liver involvement; albumin (prognostic)
LDH	Elevated = tumor burden, adverse prognosis
Uric acid	Elevated (cell turnover)
Calcium	Hypercalcemia (rare)
HIV test	All patients
EBV serology / EBER-ISH	On biopsy specimen
Pregnancy test	All women of childbearing age before chemotherapy

Biopsy Interpretation

Feature	Classical HL	NLPHL
Malignant cell	Reed-Sternberg cell	LP (“popcorn”) cell
CD15	+ (80%)	−
CD30	+ (100%)	− (or weak)
CD20	− (or weak)	+
CD45	−	+
EMA	−	+
BCL6	−	+
EBER (EBV)	+ in 10–70% by subtype	−
Background	Mixed inflammatory	Nodular, small B cells

Staging Investigations

Investigation	Purpose
CT neck/chest/abdomen/pelvis	Assess nodal groups, organ involvement
PET-CT (FDG-PET)	Standard for staging and response assessment; more sensitive than CT alone
Bone marrow biopsy	Only if PET-negative marrow, or unexplained cytopenias, or stage III/IV
MRI	If bone involvement suspected
Echocardiogram / MUGA	Baseline cardiac function before anthracycline (doxorubicin)
Pulmonary function tests	Baseline before bleomycin (DLCO)
Fertility assessment	Sperm banking / oocyte cryopreservation before chemotherapy

PET-CT in HL PET-CT is the standard imaging modality for staging and interim response assessment. Deauville 5-point scale is used for response evaluation.

Interpretation Frameworks

PET-CT Interpretation (Deauville 5-Point Scale)

Score	Meaning	Action
1	No uptake	CMR — continue current therapy
2	Uptake ≤ mediastinal blood pool	CMR — continue
3	Uptake > mediastinum but ≤ liver	CMR — continue (may consider de-escalation in early-stage)
4	Uptake moderately > liver	Poor response — consider escalation
5	Uptake markedly > liver or new lesions	Treatment failure — escalate therapy
X	New areas of uptake unlikely to be lymphoma	Ignore

IPS Risk Stratification

IPS Score	5-Year PFS	Interpretation
0	~88%	Low risk
1	~84%	Low-intermediate
2	~75%	Intermediate
3	~60%	High-intermediate
4	~50%	High risk
≥5	~40%	Very high risk — consider BEACOPP

Lab Pattern Recognition

Pattern	Suggests
Elevated ESR + anemia + elevated LDH	Advanced disease, high tumor burden
Lymphopenia (<0.6 × 10⁹/L)	Poor prognosis (IPS factor)
Eosinophilia	Classical HL (especially NSHL)
Hypercalcemia	Rare; consider bone involvement or PTHrP
Elevated uric acid	High cell turnover; tumor lysis risk
Abnormal LFTs	Stage IV (liver involvement) until proven otherwise

Staging

Ann Arbor Staging (Modified — Lugano Classification 2014)

Stage	Definition
I	Single nodal group or single extranodal site (IE)
II	≥2 nodal groups on same side of diaphragm
III	Nodal groups on both sides of diaphragm
III1	Spleen/splenic hilar/celiac/portal nodes
III2	Para-aortic/iliac/mesenteric nodes
IV	Diffuse extranodal involvement (liver, bone marrow, lung, etc.)

Modifying Factors

Suffix	Meaning
A	No B symptoms
B	B symptoms present (fever, night sweats, weight loss)
E	Extranodal extension from adjacent nodal disease
S	Splenic involvement
X	Bulky disease (mediastinal mass >10 cm or >1/3 thoracic diameter)

Lugano Modifications to Ann Arbor

• PET-CT replaces CT for staging
• “X” (bulky) defined as >10 cm or mediastinal mass ratio >1/3
• Bone marrow biopsy not required if PET-negative marrow
• Complete metabolic response (CMR) on PET = remission

Prognosis

International Prognostic Score (IPS) — for Advanced HL (Stage III/IV)

One point each for:

Factor	Detail
Albumin	<40 g/L
Hemoglobin	<105 g/L
Male sex	—
Age	≥45 years
Stage	IV
WBC	≥15 × 10⁹/L
Lymphocyte count	<0.6 × 10⁹/L or <8% of WBC

IPS Score	5-Year PFS
0	~88%
1	~84%
2	~75%
3	~60%
4	~50%
≥5	~40%

Other Prognostic Factors

• Favorable early-stage (EORTC/GELA criteria): No bulky disease, <3 nodal areas, ESR <50 (or <30 if B symptoms), age <50
• Unfavorable early-stage: Any of the above adverse features
• Interim PET response after 2 cycles of ABVD — strongest predictor of outcome

Management

Overview by Stage

Stage	Treatment
Early favorable (I–IIA, no risk factors)	2–4 cycles ABVD ± involved-site radiotherapy (ISRT)
Early unfavorable (I–IIA, with risk factors)	4–6 cycles ABVD + ISRT
Advanced (III–IV)	6–8 cycles ABVD; escalated BEACOPP if IPS ≥4; or BV-AVD x6 (stage III/IV)

Chemotherapy Regimens

ABVD (First-Line Standard)

Drug	Dose	Route	Day
Adriamycin (doxorubicin)	25 mg/m²	IV	1, 15
Bleomycin	10 U/m²	IV	1, 15
Vinblastine	6 mg/m²	IV	1, 15
Dacarbazine	375 mg/m²	IV	1, 15

• Given on Day 1 and Day 15 of a 28-day cycle
• Standard: 2–6 cycles depending on stage and response

BV-AVD (Frontline for Stage III/IV cHL — ECHELON-1)

Drug	Detail
Brentuximab vedotin	1.2 mg/kg IV (replaces bleomycin)
Doxorubicin	25 mg/m²
Vinblastine	6 mg/m²
Dacarbazine	375 mg/m²

• Given on Day 1 and Day 15 of a 28-day cycle for 6 cycles total
• ECHELON-1 trial: superior modified PFS vs ABVD in stage III/IV cHL
• Avoids bleomycin pulmonary toxicity
• Higher risk of peripheral neuropathy and neutropenia

Escalated BEACOPP (High-Risk Advanced HL)

Drug	Detail
Bleomycin	Day 8
Etoposide	Days 1–3
Adriamycin	Day 1
Cyclophosphamide	Day 1
Vincristine (Oncovin)	Day 8
Procarbazine	Days 1–7
Prednisolone	Days 1–4

• Higher response rates but more toxicity (infertility, secondary leukemia/MDS)
• Used for IPS ≥4 or advanced disease with poor interim PET
• GHSG HD18: response-adapted — escalate to BEACOPP only if interim PET positive

Other Regimens

Regimen	Use
Stanford V	Alternative for bulky early-stage; shorter duration + radiotherapy
Brentuximab vedotin monotherapy	Consolidation after ASCT in high-risk relapse

Radiotherapy

Type	Description
Involved-field RT (IFRT)	Treats involved nodal region + margin
Involved-node RT (INRT)	Treats only PET-positive nodes (more targeted)
Involved-site RT (ISRT)	Current standard — treats the site of original disease with margin

• Dose: typically 20–36 Gy in 1.5–2 Gy fractions
• Used in combination with chemotherapy for early-stage disease
• Consolidation RT for bulky disease after chemo

PET-Guided De-escalation (RAPID Trial)

• Early-stage (I–IIA) non-bulky HL: After 3 cycles ABVD, if PET-negative (Deauville 1–2), radiotherapy can be safely omitted
• Reduces long-term toxicity (secondary cancers, cardiovascular disease) without compromising outcomes
• This is now standard practice in many centers

NLPHL-Specific Management

Stage	Treatment
Early-stage (IA)	Radiotherapy alone (ISRT) — excellent outcomes
Advanced	R-CHOP (rituximab + CHOP) or ABVD; rituximab has key role (CD20+)
Watch and wait	May be appropriate for asymptomatic early-stage NLPHL

NLPHL vs Classical HL NLPHL is managed differently: rituximab-based therapy, possible watch-and-wait for early-stage, and generally more indolent course.

Relapsed / Refractory Disease

Scenario	Management
Relapse >12 months after chemo	Re-challenge with ABVD or salvage chemotherapy
Relapse <12 months / primary refractory	Salvage chemotherapy → autologous stem cell transplant (ASCT)
Post-ASCT relapse	Brentuximab vedotin consolidation; PD-1 inhibitors (nivolumab, pembrolizumab)
PD-1 inhibitors	Nivolumab or pembrolizumab — high response rates (~65–70% ORR) in relapsed/refractory cHL (checkpoint inhibitors exploit 9p24.1 amplification / PD-L1 overexpression)
Allogeneic SCT	Consider for multiply relapsed disease

Response Assessment

Timing	Method	Interpretation
Interim (after 2 cycles ABVD)	PET-CT	Deauville 1–3 = good response; 4–5 = consider escalation
End of treatment	PET-CT	Deauville 1–3 = complete metabolic response (CMR)
Surveillance	Clinical + imaging as indicated	PET-CT not routinely for surveillance (false positives)

Surveillance Guidelines (Post-Treatment)

Timeframe	Follow-up
Years 1–2	Clinical exam every 3–6 months; CT only if symptomatic or clinical concern
Years 3–5	Clinical exam every 6–12 months
>5 years	Annual clinical exam; monitor for late effects
Lifelong	TSH monitoring (if neck RT); breast surveillance (if chest RT at age <30); cardiovascular risk assessment
Do NOT	Use routine PET-CT for surveillance (high false-positive rate)

Drug Interactions / Contraindications / Comorbidity Cautions

ABVD Drug-Specific Cautions

Drug	Key Contraindications / Cautions
Doxorubicin	Pre-existing cardiac disease; LVEF <50%; prior anthracycline exposure (cumulative dose); concurrent trastuzumab
Bleomycin	Pre-existing pulmonary disease; DLCO <60% predicted; elderly (>70 years); renal impairment (dose adjustment); avoid high FiO₂ post-treatment (theoretical risk of pulmonary toxicity)
Vinblastine	Hepatic impairment (dose reduction); pre-existing neuropathy; concurrent CYP3A4 inhibitors
Dacarbazine	Hepatic/renal impairment; avoid alcohol (disulfiram-like reaction)

Regimen Selection Cautions

Clinical Scenario	Preferred Regimen	Avoid
Elderly (>60–70 years)	BV-AVD or AVD (omit bleomycin)	Full ABVD (bleomycin toxicity); BEACOPP
Pre-existing cardiac disease	AVD (omit doxorubicin) or BV-AVD with caution	Standard ABVD
Pre-existing pulmonary disease	AVD (omit bleomycin) or BV-AVD	ABVD (bleomycin)
Renal impairment	Dose-adjust bleomycin; consider AVD	Full-dose bleomycin
Pregnancy (2nd/3rd trimester)	ABVD (bleomycin may be omitted)	Radiotherapy; BEACOPP; BV-AVD
HIV	ABVD + concurrent ART	BEACOPP (excessive immunosuppression)

Procedures / Indications / Contraindications

Excisional Lymph Node Biopsy

Aspect	Detail
Indication	Suspected lymphoma with persistent lymphadenopathy >4 weeks
Contraindication	Bleeding diathesis (relative); inaccessible node
Key principle	Remove entire node with intact capsule — preserves architecture for diagnosis
Viva pearl	FNA is inadequate for lymphoma — cannot assess architecture, RS cells may be sparse

Bone Marrow Biopsy

Aspect	Detail
Indication	Staging in HL — required if PET-negative marrow, unexplained cytopenias, or stage III/IV
Note	Not required if PET-negative marrow (Lugano modification)
Site	Posterior iliac crest

Central Venous Access (Hickman/PICC)

Aspect	Detail
Indication	Chemotherapy administration (vesicant agents — doxorubicin, vinblastine)
Key principle	Essential for ABVD due to vesicant chemotherapy

Stem Cell Transplant (ASCT)

Aspect	Detail
Indication	Relapsed/refractory HL — relapse <12 months or primary refractory
Contraindication	Poor performance status; uncontrolled infection; severe organ dysfunction
Preparative regimen	BEAM (carmustine, etoposide, cytarabine, melphalan) or similar

Complications

Disease-Related

Complication	Mechanism
SVC obstruction	Mediastinal mass compression
Airway compression	Mediastinal / hilar lymphadenopathy
Pleural effusion	Lymphatic obstruction, direct pleural involvement
Pericardial effusion	Direct extension
Pancytopenia	Marrow infiltration
Autoimmune cytopenias	AIHA, ITP (rare)
Paraneoplastic	Nephrotic syndrome (minimal change), cerebellar degeneration, dermatomyositis

Treatment-Related

Complication	Agent	Detail
Cardiomyopathy	Doxorubicin (Adriamycin)	Dose-dependent; lifetime cumulative dose limit ~450–550 mg/m²
Pulmonary fibrosis	Bleomycin	Dose-dependent; avoid high FiO₂ post-treatment; monitor DLCO
Infertility	Alkylating agents (cyclophosphamide, procarbazine), BEACOPP	Sperm banking essential before treatment; ovarian suppression with GnRH agonists
Secondary malignancies	Chemotherapy + radiotherapy	AML/MDS (especially with alkylating agents), breast cancer (chest RT), lung cancer, thyroid cancer
Hypothyroidism	Neck radiotherapy	Monitor TSH lifelong
Peripheral neuropathy	Vincristine, vinblastine	Sensorimotor
Nausea/vomiting	All regimens	Standard antiemetics (5-HT3 antagonist + dexamethasone + NK1 antagonist)
Tumor lysis syndrome	Rapid response to chemo	Hydration, allopurinol/rasburicase
Infection	Immunosuppression	PJP prophylaxis if heavily immunosuppressed; febrile neutropenia = emergency
Neutropenic sepsis	All regimens	Most common treatment-related cause of death during ABVD

Long-Term Survivorship HL survivors have increased risk of: – Secondary cancers: Breast cancer (especially women who received chest RT before age 30), lung cancer, thyroid cancer, AML/MDS – Cardiovascular disease: Anthracycline-related cardiomyopathy, radiation-related coronary artery disease, valvular disease – Pulmonary toxicity: Bleomycin + radiation – Infertility – Psychosocial: Fatigue, anxiety, depression

Red Flags / Emergencies

Emergency	Recognition	Immediate Action
SVC syndrome	Facial/neck swelling, distended neck veins, dyspnoea	Urgent CT, dexamethasone, urgent oncology referral, consider stenting
Airway compression	Stridor, respiratory distress, large mediastinal mass	Urgent CT, dexamethasone, avoid sedation, urgent oncology/anaesthesia
Neutropenic sepsis	Fever ≥38.5°C + neutrophils <1.0 × 10⁹/L	Blood cultures, IV antibiotics within 1 hour (e.g., piperacillin-tazobactam), fluids
Tumor lysis syndrome	Hyperkalaemia, hyperuricaemia, hyperphosphataemia, hypocalcaemia, AKI	Aggressive IV hydration, rasburicase, monitor electrolytes, renal support if needed
Bleomycin lung toxicity	Progressive dyspnoea, dry cough, bilateral infiltrates	Stop bleomycin, high-dose steroids, O₂ cautiously, avoid high FiO₂
Doxorubicin extravasation	Pain, swelling at injection site	Stop infusion, aspirate, cold compress, consider dexrazoxane
Anaphylaxis (bleomycin)	Hypotension, bronchospasm, urticaria	Adrenaline IM, fluids, steroids, antihistamines

Differential Diagnosis

Condition	Distinguishing Features
Non-Hodgkin lymphoma	Non-contiguous spread, no RS cells, different immunophenotype
Infectious lymphadenopathy	Toxoplasmosis, CMV, HIV, TB — tender nodes, positive serology/culture
Sarcoidosis	Bilateral hilar lymphadenopathy, non-caseating granulomas, ACE elevated
Castleman disease	Hyaline vascular or plasma cell type; HHV-8 associated
Metastatic carcinoma	Epithelial markers (cytokeratins), different morphology
Reactive lymphadenopathy	Preserved architecture, no RS cells
Primary mediastinal B-cell lymphoma	CD20+, CD30+ (variable), young women, mediastinal mass — may mimic NSHL
Anaplastic large cell lymphoma (ALCL)	CD30+, ALK+/−, T-cell origin; may mimic HL

Special Situations

HL in Pregnancy

• ABVD can be given in second and third trimesters (avoid first trimester)
• Bleomycin may be omitted if disease allows
• Defer radiotherapy until postpartum
• Close obstetric monitoring
• Avoid methotrexate (if considering alternative regimens)

HL in HIV

• Treat with ABVD (same as immunocompetent)
• Concurrent ART
• Prognosis improving with effective ART
• Higher proportion of mixed cellularity and lymphocyte-depleted subtypes
• More advanced stage at presentation
• Monitor for drug interactions between ART and chemotherapy

Elderly HL

• More aggressive histology
• More advanced stage at presentation
• Worse tolerance of BEACOPP
• Higher bleomycin pulmonary toxicity risk → consider BV-AVD or AVD (omit bleomycin)
• Consider GHSG HD10/HD13 trial-based approaches
• PVAG regimen (prednisolone, vinblastine, doxorubicin, gemcitabine) as alternative for frail patients
• Dose reductions may be needed; assess comorbidities carefully

Nodular Lymphocyte-Predominant HL

• Indolent course
• Late relapses common
• Risk of transformation to DLBCL (~3–5%)
• CD20+ → rituximab-based therapy
• Early-stage: radiotherapy alone may be curative
• Watch-and-wait approach may be appropriate for asymptomatic early-stage

Topic Correlation

Related: Non-Hodgkin Lymphoma · Anemia · Bone Marrow Examination · Transfusion Medicine · Paraneoplastic Syndromes · Superior Vena Cava Obstruction · Tumor Lysis Syndrome · Febrile Neutropenia · Superior Mediastinal Mass · Chemotherapy Toxicities

FCPS/MRCP High-Yield Points

1. Reed-Sternberg cells = binucleated, “owl-eye” nucleoli, CD15+, CD30+, CD45−
2. Bimodal age: 15–35 and >55
3. Contiguous nodal spread (vs NHL = non-contiguous)
4. EBV association: strongest in mixed cellularity subtype
5. NSHL = most common subtype, young women, mediastinal mass, lacunar cells
6. NLPHL = CD20+, indolent, may transform to DLBCL
7. ABVD = standard first-line; bleomycin → pulmonary toxicity; doxorubicin → cardiotoxicity
8. Ann Arbor staging with B symptoms designation
9. PET-CT for staging and interim response (Deauville score)
10. IPS = 7 factors for advanced HL prognosis
11. Relapse management: salvage chemo → ASCT → PD-1 inhibitors
12. Long-term: secondary cancers (breast, lung, AML/MDS), cardiac disease, infertility
13. Pel-Ebstein fever = cyclical fever (classic but rare)
14. Alcohol-induced nodal pain = classic but rare
15. Excisional biopsy = gold standard (not FNA)
16. BV-AVD = frontline for stage III/IV (ECHELON-1); replaces bleomycin with brentuximab
17. RAPID trial: early non-bulky HL, PET-negative after 3 cycles ABVD → omit RT
18. PD-1 inhibitors (nivolumab/pembrolizumab): ~65–70% ORR in relapsed/refractory cHL
19. Surveillance: clinical exam q3–6 months × 2 years, then q6–12 months; NO routine PET-CT
20. Elderly HL: avoid bleomycin; consider BV-AVD or AVD

Common Viva Questions

1. What are Reed-Sternberg cells and what is their immunophenotype?

• Large binucleated cells with prominent nucleoli; CD15+, CD30+, CD45−, PAX5 weak+, CD20−

1. How do you differentiate HL from NHL?

• HL: contiguous spread, RS cells, CD15+/CD30+, inflammatory background
• NHL: non-contiguous, no RS cells, variable immunophenotype

1. What is the significance of B symptoms?

• Indicate systemic disease, upstage to “B” designation, worse prognosis, part of IPS

1. Why is FNA inadequate for lymphoma diagnosis?

• Cannot assess lymph node architecture; RS cells may be sparse; need tissue for immunohistochemistry

1. What is the role of PET-CT in HL?

• Staging, interim response assessment (after 2 cycles), end-of-treatment response, guides therapy escalation/de-escalation

1. When would you use BEACOPP instead of ABVD?

• Advanced-stage HL with IPS ≥4; primary refractory disease; poor interim PET response

1. What are the long-term complications of HL treatment?

• Secondary malignancies (breast, lung, AML/MDS), cardiomyopathy, pulmonary fibrosis, infertility, hypothyroidism

1. How is NLPHL managed differently?

• CD20+ → rituximab; early-stage may be treated with RT alone; more indolent; watch-and-wait possible

1. What is the role of PD-1 inhibitors in HL?

• Relapsed/refractory cHL; exploits 9p24.1 amplification → PD-L1 overexpression; nivolumab/pembrolizumab; ~65–70% ORR

1. What is Pel-Ebstein fever?

• Cyclical fever pattern (1–2 weeks febrile, 1–2 weeks afebrile); classic for HL but uncommon

1. What is the RAPID trial and how does it change management?

• Early-stage non-bulky HL: if PET-negative after 3 cycles ABVD, radiotherapy can be safely omitted

1. When would you choose BV-AVD over ABVD?

• Stage III/IV cHL (ECHELON-1); elderly patients (avoids bleomycin toxicity); pre-existing pulmonary disease

Common Confusions / Exam Traps

Trap	Correction
FNA for lymphoma diagnosis	Excisional biopsy is gold standard
NLPHL treated same as cHL	NLPHL is CD20+ → rituximab-based; different management
All lymphomas have same staging	HL uses Ann Arbor; NHL may use different systems
B symptoms = any fever	Must be >38°C, unexplained, recurrent; drenching night sweats; >10% weight loss in 6 months
Bone marrow biopsy always needed	Not if PET-negative marrow (Lugano modification)
Radiotherapy alone for HL	Only for early-stage NLPHL; cHL needs chemo ± RT
Bleomycin safe in elderly	Higher risk of pulmonary toxicity; consider BV-AVD or AVD
ABVD cycles	28-day cycle, days 1 and 15 (not 21-day)
Secondary cancers only from RT	Also from chemotherapy (alkylating agents → AML/MDS)
PET-CT for surveillance	NOT recommended routinely — high false-positive rate
Platelet count in IPS	Platelet count is NOT part of IPS; lymphocyte count IS
All CD30+ lymphomas is HL	ALCL is also CD30+ but is T-cell lymphoma, not HL

Mnemonics

Reed-Sternberg Immunophenotype

“CHaMP 15-30”

• CD15+
• Hodgkin (CD30+)
• and Minus CD45
• PAX5 weak+
• 15 and 30 = CD15 and CD30

B Symptoms — “Fever, Sweat, Slim”

• Fever >38°C
• Sweats (drenching night sweats)
• Slim (>10% weight loss in 6 months)

ABVD Drugs

“ABVD = Always Beat Very Deadly”

• Adriamycin
• Bleomycin
• Vinblastine
• Dacarbazine

IPS Factors — “ALAWSL + M”

• Albumin <40
• Lymphocytes <0.6 or <8%
• Age ≥45
• WBC ≥15
• Stage IV
• Low Hb <105
• Plus Male sex

Classical HL Subtypes — “No More Lymphocytes”

• Nodular sclerosis (most common)
• Mixed cellularity (most EBV+)
• Lymphocyte-rich
• Lymphocyte-depleted (rarest, worst prognosis)

Deauville Score — “1-2 Fine, 3 Okay, 4-5 Fail”

• 1–2: No/minimal uptake → CMR
• 3: Uptake ≤ liver → CMR
• 4–5: Uptake > liver → poor response

Mind Map

Hodgkin Lymphoma
├── Definition: RS cells + inflammatory background
├── Epidemiology: Bimodal (15-35, >55), M>F, EBV 40-50%
├── Classification
│   ├── NLPHL (5%): CD20+, LP cells, indolent
│   └── Classical HL (95%)
│       ├── Nodular sclerosis (60-70%): lacunar cells, mediastinal, young
│       ├── Mixed cellularity (20-25%): most EBV+
│       ├── Lymphocyte-rich (5%): good prognosis
│       └── Lymphocyte-depleted (<5%): worst, HIV
├── Pathophysiology
│   ├── RS cells from germinal center B cells
│   ├── NF-κB constitutive activation
│   ├── JAK-STAT activation
│   └── Immune evasion (PD-L1)
├── Clinical
│   ├── Painless lymphadenopathy (cervical > mediastinal)
│   ├── B symptoms (fever, sweats, weight loss)
│   ├── Contiguous spread
│   └── Pruritus, Pel-Ebstein fever, alcohol pain
├── Diagnosis
│   ├── Excisional biopsy (gold standard)
│   ├── CD15+, CD30+, CD45−
│   ├── PET-CT staging
│   └── Ann Arbor staging
├── Management
│   ├── Early favorable: 2-4 ABVD ± ISRT (RAPID: omit RT if PET-negative)
│   ├── Early unfavorable: 4-6 ABVD + ISRT
│   ├── Advanced: 6-8 ABVD or BV-AVD (± BEACOPP if IPS≥4)
│   ├── Interim PET-guided adaptation
│   ├── Relapse: salvage → ASCT → PD-1 inhibitors
│   └── NLPHL: RT alone (early) or R-based
├── Complications
│   ├── Cardiotoxicity (doxorubicin)
│   ├── Pulmonary fibrosis (bleomycin)
│   ├── Infertility
│   ├── Secondary malignancies
│   └── Hypothyroidism (RT)
└── Prognosis
    ├── >85% overall cure
    ├── >95% early-stage
    ├── 60-80% advanced (by IPS)
    └── Secondary cancers = #1 cause of death in survivors

Flowchart: Diagnostic Approach

Painless lymphadenopathy
        │
        ▼
Excisional lymph node biopsy
        │
        ├── RS cells + CD15/CD30+ → Classical HL
        │       │
        │       ▼
        │   PET-CT staging
        │       │
        │       ├── Early favorable → ABVD x2-4 + ISRT
        │       │       → Interim PET: Deauville 1-3 → continue
        │       │       → RAPID: non-bulky, PET-neg after 3 cycles → omit RT
        │       │
        │       ├── Early unfavorable → ABVD x4-6 + ISRT
        │       │
        │       └── Advanced → ABVD x6-8 or BV-AVD x6
        │               → IPS ≥4 → consider BEACOPP
        │               │
        │               ▼
        │           Interim PET (cycle 2)
        │               │
        │               ├── Deauville 1-3 → Continue current
        │               └── Deauville 4-5 → Escalate (BEACOPP/BV-AVD)
        │
        └── LP cells + CD20+ → NLPHL
                │
                ▼
            Early → ISRT alone (or watch-and-wait)
            Advanced → R-CHOP or ABVD

Flowchart: Relapsed/Refractory Management

Relapse after ABVD
        │
        ├── Relapse >12 months
        │       → Re-challenge with ABVD or salvage chemo
        │
        └── Relapse <12 months / primary refractory
                │
                ▼
        Salvage chemotherapy (e.g., ICE, DHAP, GDP)
                │
                ▼
        Re-evaluate with PET-CT
                │
                ├── PET-negative (chemosensitive)
                │       → Autologous stem cell transplant (ASCT)
                │               │
                │               ▼
                │           Post-ASCT: brentuximab consolidation (AETHERA)
                │
                └── PET-positive (chemorefractory)
                        │
                        ▼
                PD-1 inhibitors (nivolumab/pembrolizumab)
                        │
                        ├── Response → consider allogeneic SCT
                        └── No response → clinical trial / palliative

One-Page Revision Summary

Hodgkin Lymphoma — Rapid Review

Definition: Malignant lymphoma with Reed-Sternberg cells (CD15+, CD30+, CD45−)

Epidemiology: Bimodal 15–35 & >55; M>F; EBV 40–50%

Classification:

• NLPHL (5%): CD20+, LP cells, indolent
• Classical HL (95%):
• Nodular sclerosis (60–70%): lacunar cells, mediastinal mass, young adults
• Mixed cellularity (20–25%): most EBV+
• Lymphocyte-rich (5%): good prognosis
• Lymphocyte-depleted (<5%): worst, HIV-associated

Clinical: Painless lymphadenopathy (cervical), B symptoms (fever >38°C, drenching sweats, >10% weight loss), contiguous spread, pruritus

Diagnosis: Excisional biopsy (NOT FNA), PET-CT staging, Ann Arbor staging

Staging: Ann Arbor (I–IV) + A/B designation; Lugano modifications (PET-CT based)

IPS (7 factors): Albumin <40, Hb <105, Male, Age ≥45, Stage IV, WBC ≥15, Lymphocytes <0.6

Treatment:

• Early favorable: ABVD x2–4 + ISRT (RAPID: omit RT if PET-negative after 3 cycles)
• Early unfavorable: ABVD x4–6 + ISRT
• Advanced: ABVD x6–8 or BV-AVD x6 (BEACOPP if IPS ≥4)
• Relapse: Salvage chemo → ASCT → PD-1 inhibitors
• NLPHL: RT alone (early) or R-based

ABVD: Adriamycin, Bleomycin, Vinblastine, Dacarbazine (Days 1+15, q28 days)

BV-AVD: Brentuximab + AVD (no bleomycin); frontline for stage III/IV

Toxicity: Doxorubicin → cardiomyopathy; Bleomycin → pulmonary fibrosis; Alkylating agents → infertility, AML/MDS; RT → secondary cancers, hypothyroidism

Prognosis: >85% overall cure; >95% early-stage; 60–80% advanced

Key Exam Points:

• Pel-Ebstein fever (cyclical)
• Alcohol-induced nodal pain
• NLPHL ≠ cHL (CD20+, different treatment)
• PET-CT interim response (Deauville score)
• PD-1 inhibitors for relapsed/refractory (~65–70% ORR)
• Long-term: secondary cancers #1 cause of death in survivors
• Surveillance: clinical exam only; NO routine PET-CT
• Elderly: avoid bleomycin; BV-AVD or AVD preferred

24-Hour Recall Prompts

1. What are the immunophenotypic markers of Reed-Sternberg cells?
2. Name the 4 subtypes of classical HL and their key features
3. What is the difference between NLPHL and classical HL in terms of CD20?
4. Define B symptoms precisely
5. What is the first-line chemotherapy regimen for HL?
6. Name 3 long-term complications of ABVD
7. What is the IPS and name 4 of its 7 factors
8. How is relapsed HL managed?
9. What is the role of PET-CT in HL?
10. Why is FNA inadequate for lymphoma diagnosis?
11. What is the RAPID trial and how does it change management?
12. When would you use BV-AVD instead of ABVD?
13. What is the Deauville score and how does it guide therapy?
14. What are the long-term follow-up recommendations for HL survivors?
15. How does HL in HIV differ from HL in immunocompetent patients?

Must Know / Should Know / Nice to Know

Must Know

• Reed-Sternberg cell morphology and immunophenotype
• B symptoms definition
• ABVD regimen and key toxicities
• Ann Arbor staging with A/B designation
• Excisional biopsy = gold standard
• NLPHL vs classical HL differences
• Relapse management (salvage → ASCT → PD-1 inhibitors)
• Long-term complications (secondary cancers, cardiac, pulmonary)
• PET-CT interim response (Deauville score)
• IPS scoring system
• BV-AVD for stage III/IV (ECHELON-1)
• RAPID trial (omit RT if PET-negative)

Should Know

• Deauville 5-point scale
• EBV association by subtype
• NLPHL management
• HL in pregnancy
• HL in HIV
• Pel-Ebstein fever
• Contiguous vs non-contiguous spread
• Surveillance guidelines
• Drug-specific contraindications (bleomycin in elderly, doxorubicin in cardiac disease)
• Red flags: SVC syndrome, neutropenic sepsis, tumor lysis

Nice to Know

• Molecular pathogenesis (NF-κB, JAK-STAT, 9p24.1)
• Stanford V regimen
• BV-AVD frontline data (ECHELON-1 trial details)
• Allogeneic SCT indications
• Detailed WHO 2022 updates
• LP cell biology
• PVAG regimen for elderly
• AETHERA trial (brentuximab post-ASCT consolidation)

My Weak Points

_(Fill in during revision)_

• [ ]
• [ ]
• [ ]

Self-Test Scorecard

Domain	Score /10
Understanding of pathology and classification	/10
Clinical features and staging	/10
Diagnostic approach	/10
Management by stage	/10
Complications and long-term follow-up	/10
Total	/50

Interpretation:

• <25/50 = Weak — re-study the topic
• 25–34/50 = Acceptable but needs reinforcement
• 35–44/50 = Good — minor gaps remain
• 45+/50 = Excellent — exam-ready

7-Day / 15-Day / 30-Day Revision Tracker

Revision	Date	Score	Notes
24-hour recall		/50
7-day revision		/50
15-day revision		/50
30-day revision		/50

Exam Answer Modes

Long-Answer Exam Format (MRCP/FCPS)

Question: Discuss the diagnosis and management of Hodgkin lymphoma.

Answer Structure:

1. Definition and epidemiology
2. Pathophysiology (RS cells, molecular mechanisms)
3. Classification (WHO: NLPHL vs classical, 4 subtypes)
4. Clinical features (lymphadenopathy, B symptoms, contiguous spread)
5. Diagnosis (excisional biopsy, immunophenotype, PET-CT)
6. Staging (Ann Arbor/Lugano, IPS)
7. Management by stage (ABVD, BV-AVD, BEACOPP, radiotherapy)
8. Response assessment (interim PET, Deauville, RAPID)
9. Relapsed/refractory (salvage → ASCT → PD-1 inhibitors)
10. Complications (acute and long-term)
11. Special situations (pregnancy, HIV, elderly)
12. Prognosis

Short Note Format

• 1-page rapid review (see above)
• Focus on: definition, classification, clinical features, diagnosis, staging, management, complications

Viva Answer Format

• Be concise and structured
• Use tables for comparisons
• Highlight exam traps
• Mention recent evidence (ECHELON-1, RAPID, AETHERA)

Ward-Case Discussion

• Present a case scenario
• Discuss differential diagnosis
• Plan investigations
• Outline management
• Address complications and follow-up

MCQs (15)

Q1

A 24-year-old man presents with painless cervical lymphadenopathy and drenching night sweats. Excisional biopsy shows large binucleated cells with prominent nucleoli that are CD15+ and CD30+. What is the most likely diagnosis?

A. Diffuse large B-cell lymphoma

B. Hodgkin lymphoma

C. Follicular lymphoma

D. Tuberculous lymphadenitis

E. Cat-scratch disease

Q2

Which subtype of classical Hodgkin lymphoma has the strongest association with EBV?

A. Nodular sclerosis

B. Mixed cellularity

C. Lymphocyte-rich

D. Lymphocyte-depleted

E. Nodular lymphocyte-predominant

Q3

A 30-year-old woman with newly diagnosed stage IIA Hodgkin lymphoma (no B symptoms, no bulky disease) should receive which first-line treatment?

A. Radiotherapy alone

B. ABVD x2–4 cycles + involved-site radiotherapy

C. ABVD x6 cycles + radiotherapy

D. R-CHOP x6 cycles

E. Watch and wait

Q4

Which drug in the ABVD regimen is most likely to cause pulmonary fibrosis?

A. Doxorubicin

B. Bleomycin

C. Vinblastine

D. Dacarbazine

E. Cyclophosphamide

Q5

A patient with relapsed Hodgkin lymphoma 8 months after completing ABVD should receive:

A. Re-challenge with ABVD

B. Palliative care only

C. Salvage chemotherapy followed by autologous stem cell transplant

D. Radiotherapy alone

E. Rituximab monotherapy

Q6

Which of the following is NOT part of the International Prognostic Score for advanced Hodgkin lymphoma?

A. Albumin <40 g/L

B. Hemoglobin <105 g/L

C. Platelet count <100 × 10⁹/L

D. WBC ≥15 × 10⁹/L

E. Age ≥45 years

Q7

Nodular lymphocyte-predominant Hodgkin lymphoma differs from classical HL in that it:

A. Has Reed-Sternberg cells

B. Is CD15+ and CD30+

C. Is CD20+ and CD45+

D. Has a worse prognosis

E. Requires BEACOPP chemotherapy

Q8

Pel-Ebstein fever is best described as:

A. Continuous low-grade fever

B. Fever with rigors every 48 hours

C. Cyclical fever alternating with afebrile periods

D. Fever only at night

E. Fever responsive only to NSAIDs

Q9

A 28-year-old woman is about to start ABVD for stage IIIB Hodgkin lymphoma. Which pre-treatment assessment is most important?

A. Colonoscopy

B. Echocardiogram

C. Lumbar puncture

D. Bone scan

E. Upper GI endoscopy

Q10

Which long-term complication is the leading cause of death in Hodgkin lymphoma survivors?

A. Relapsed lymphoma

B. Secondary malignancies

C. Cardiovascular disease

D. Pulmonary fibrosis

E. Infection

Q11

A 70-year-old man with stage IIIA Hodgkin lymphoma and pre-existing COPD is being planned for chemotherapy. Which regimen is most appropriate?

A. Standard ABVD

B. Escalated BEACOPP

C. BV-AVD (brentuximab + AVD, no bleomycin)

D. Radiotherapy alone

E. R-CHOP

Q12

After 2 cycles of ABVD, PET-CT shows Deauville score 3. What is the most appropriate next step?

A. Escalate to BEACOPP

B. Continue ABVD as planned

C. Proceed to ASCT

D. Stop chemotherapy

E. Switch to BV-AVD

Q13

Which of the following is the mechanism of action of brentuximab vedotin?

A. Anti-CD20 antibody-drug conjugate

B. Anti-CD30 antibody-drug conjugate delivering monomethyl auristatin E

C. PD-1 checkpoint inhibitor

D. BTK inhibitor

E. Anti-CD52 monoclonal antibody

Q14

A patient with relapsed HL after ASCT is started on nivolumab. What is the mechanism of action?

A. Anti-CD30 antibody

B. PD-1 checkpoint inhibitor

C. CTLA-4 inhibitor

D. JAK-STAT inhibitor

E. NF-κB inhibitor

Q15

A 25-year-old woman completed ABVD + mediastinal radiotherapy for stage IIA NSHL 5 years ago. She now presents with a breast lump. What is the most likely diagnosis?

A. Fibroadenoma

B. Breast cyst

C. Radiation-induced breast cancer

D. Lymphoma recurrence

E. Fat necrosis

SBA Questions (15)

SBA 1

A 22-year-old man presents with a 3-month history of painless left cervical lymphadenopathy. He reports no fever, night sweats, or weight loss. Examination reveals a 3 cm firm, non-tender lymph node. What is the most appropriate next step?

A. Prescribe antibiotics and review in 2 weeks

B. Fine needle aspiration cytology

C. Excisional lymph node biopsy

D. CT scan of the neck

E. Observe for 4 weeks

SBA 2

A 35-year-old woman with nodular sclerosis Hodgkin lymphoma has a 12 cm mediastinal mass on CT. She is staged as IIAX. What does the “X” designation indicate?

A. Extranodal disease

B. Bulky disease (>10 cm mass)

C. Bone marrow involvement

D. Splenic involvement

E. Elevated LDH

SBA 3

A patient on cycle 3 ABVD develops progressive dyspnoea and dry cough. Chest X-ray shows bilateral interstitial infiltrates. What is the most likely cause?

A. Doxorubicin cardiomyopathy

B. Bleomycin pulmonary toxicity

C. Pneumocystis pneumonia

D. Lymphoma progression

E. Pulmonary embolism

SBA 4

A 60-year-old man with HIV presents with stage IVB Hodgkin lymphoma. Which subtype is most likely?

A. Nodular sclerosis

B. Mixed cellularity

C. Lymphocyte-rich

D. Nodular lymphocyte-predominant

E. Lymphocyte-depleted

SBA 5

After 2 cycles of ABVD, PET-CT shows Deauville score 5 (new areas of uptake). What is the most appropriate next step?

A. Continue ABVD for 4 more cycles

B. Switch to escalated BEACOPP or BV-AVD

C. Proceed to autologous stem cell transplant

D. Add radiotherapy

E. Stop treatment and observe

SBA 6

A 25-year-old woman completed ABVD + mediastinal radiotherapy for stage IIA NSHL 5 years ago. She now presents with a breast lump. What is the most likely diagnosis?

A. Fibroadenoma

B. Breast cyst

C. Radiation-induced breast cancer

D. Lymphoma recurrence

E. Fat necrosis

SBA 7

Which of the following is the mechanism of action of brentuximab vedotin?

A. Anti-CD20 antibody-drug conjugate

B. Anti-CD30 antibody-drug conjugate delivering monomethyl auristatin E

C. PD-1 checkpoint inhibitor

D. BTK inhibitor

E. Anti-CD52 monoclonal antibody

SBA 8

A patient with relapsed HL after ASCT is started on nivolumab. What is the mechanism of action?

A. Anti-CD30 antibody

B. PD-1 checkpoint inhibitor

C. CTLA-4 inhibitor

D. JAK-STAT inhibitor

E. NF-κB inhibitor

SBA 9

A 19-year-old man with stage IA NLPHL (left cervical node) should receive which treatment?

A. ABVD x4 cycles

B. Involved-field radiotherapy alone

C. R-CHOP x6 cycles

D. Watch and wait

E. Rituximab monotherapy

SBA 10

Which of the following is the most common cause of treatment-related death in patients receiving ABVD?

A. Cardiomyopathy

B. Pulmonary fibrosis

C. Febrile neutropenia / sepsis

D. Secondary AML

E. Tumor lysis syndrome

SBA 11

A 28-year-old woman with stage IA NSHL (non-bulky) is PET-negative after 3 cycles of ABVD. According to the RAPID trial, what is the most appropriate next step?

A. Continue ABVD for 3 more cycles

B. Proceed with involved-site radiotherapy

C. Omit radiotherapy and observe

D. Switch to BV-AVD

E. Proceed to ASCT

SBA 12

A 75-year-old woman with stage IIA HL and DLCO 55% predicted is being planned for treatment. Which regimen is most appropriate?

A. Standard ABVD

B. AVD (omit bleomycin)

C. Escalated BEACOPP

D. Stanford V

E. Radiotherapy alone

SBA 13

A 32-year-old woman is diagnosed with HL at 16 weeks gestation. What is the most appropriate management?

A. Terminate pregnancy and start ABVD

B. Wait until delivery, then start ABVD

C. Start ABVD in 2nd/3rd trimester (bleomycin may be omitted)

D. Start escalated BEACOPP immediately

E. Radiotherapy with abdominal shielding

SBA 14

Which of the following is NOT a component of the IPS for advanced HL?

A. Lymphocyte count <0.6 × 10⁹/L

B. Albumin <40 g/L

C. LDH > upper limit of normal

D. Age ≥45 years

E. WBC ≥15 × 10⁹/L

SBA 15

A patient with HL develops SVC syndrome at presentation. What is the most appropriate immediate management?

A. Urgent radiotherapy

B. Dexamethasone + urgent chemotherapy

C. Surgical debulking

D. Anticoagulation alone

E. Observation

Flashcards (20)

• Q: What are the immunophenotypic markers of Reed-Sternberg cells?

A: CD15+ (80%), CD30+ (100%), CD45−, PAX5 weak+, CD20− (usually)

• Q: What is the most common subtype of classical HL?

A: Nodular sclerosis (60–70%)

• Q: Which HL subtype has the strongest EBV association?

A: Mixed cellularity (~70% EBV+)

• Q: What is the first-line chemotherapy for classical HL?

A: ABVD (Adriamycin, Bleomycin, Vinblastine, Dacarbazine)

• Q: What is the gold standard for lymphoma diagnosis?

A: Excisional lymph node biopsy (NOT FNA)

• Q: Define B symptoms in HL.

A: Fever >38°C (unexplained), drenching night sweats, weight loss >10% in 6 months

• Q: What does “X” mean in Ann Arbor staging?

A: Bulky disease (>10 cm mass or mediastinal mass >1/3 thoracic diameter)

• Q: What is the most common long-term cause of death in HL survivors?

A: Secondary malignancies

• Q: Which drug in ABVD causes pulmonary fibrosis?

A: Bleomycin

• Q: How is relapsed HL (<12 months) managed?

A: Salvage chemotherapy → autologous stem cell transplant

• Q: What is the role of PD-1 inhibitors in HL?

A: Treatment of relapsed/refractory cHL; exploits 9p24.1 amplification → PD-L1 overexpression; ~65–70% ORR

• Q: How does NLPHL differ from classical HL immunophenotypically?

A: NLPHL is CD20+, CD45+, EMA+, CD15−, CD30− (opposite of cHL)

• Q: What is Pel-Ebstein fever?

A: Cyclical fever pattern (1–2 weeks febrile, 1–2 weeks afebrile); classic for HL

• Q: What is the Deauville score used for?

A: PET-CT response assessment in lymphoma (1–5 scale)

• Q: What is the IPS for advanced HL?

A: International Prognostic Score — 7 factors: albumin <40, Hb <105, male, age ≥45, stage IV, WBC ≥15, lymphocytes <0.6

• Q: What is BV-AVD and when is it used?

A: Brentuximab vedotin + AVD (no bleomycin); frontline for stage III/IV cHL (ECHELON-1); also used when bleomycin is contraindicated

• Q: What does the RAPID trial tell us?

A: Early-stage non-bulky HL: if PET-negative after 3 cycles ABVD, radiotherapy can be safely omitted

• Q: What are the surveillance recommendations for HL survivors?

A: Clinical exam q3–6 months × 2 years, then q6–12 months; NO routine PET-CT; lifelong TSH monitoring (if neck RT); breast surveillance (if chest RT at age <30)

• Q: How should HL in pregnancy be managed?

A: ABVD in 2nd/3rd trimester; avoid 1st trimester; defer radiotherapy; bleomycin may be omitted

• Q: What are the red flags in HL that require emergency action?

A: SVC syndrome, airway compression, neutropenic sepsis, tumor lysis syndrome, bleomycin lung toxicity

Suggested Video References

1. Osmosis — Hodgkin Lymphoma (pathology, clinical features, treatment)
2. Armando Hasudungan — Hodgkin vs Non-Hodgkin Lymphoma
3. Ninja Nerd — Hodgkin Lymphoma pathophysiology
4. Zero to Finals — Haematology: Lymphoma overview
5. Oncology for Medical Students — PET-CT and Deauville scoring
6. MedCram — ABVD chemotherapy and toxicity management
7. Dr. Najeeb — Reed-Sternberg cells and HL classification

Suggested Visuals / Image Notes

1. Reed-Sternberg cell morphology (owl-eye nucleoli) — histology image
2. Lacunar cells in nodular sclerosis — histology image
3. Ann Arbor staging diagram — nodal regions and diaphragm
4. PET-CT images: pre-treatment vs post-treatment response
5. ABVD chemotherapy cycle diagram
6. Deauville 5-point scale visual reference
7. Mediastinal mass on CXR/CT — NSHL presentation
8. Long-term survivorship complication timeline
9. SVC syndrome clinical photograph
10. Bleomycin pulmonary toxicity — CXR/CT appearance

Tags

#medicine #hematology #lymphoma #hodgkin #oncology #mrcp #fcps #davidson #chapter25