IM13.1-19 | Common Malignancies and Oncology — Graded Quiz

Correct. Acute promyelocytic leukaemia (APL, AML M3) is defined by the t(15;17) translocation producing PML-RARA fusion. The RARA component disrupts normal myeloid maturation at the promyelocyte stage. Critically, the abnormal promyelocytes release tissue factor and proteases that trigger life-threatening disseminated intravascular coagulation (DIC) — the most dangerous acute complication, responsible for haemorrhagic death in up to 15% of APL patients before or during induction. The DIC manifests as prolonged PT/aPTT, low fibrinogen (<1 g/L), elevated D-dimer, and clinical bleeding. Management: all-trans retinoic acid (ATRA) must be started IMMEDIATELY upon clinical suspicion (even before cytogenetics) because ATRA drives differentiation of the abnormal promyelocytes and rapidly reverses the DIC. Waiting for confirmatory cytogenetics in suspected APL is inappropriate — coagulopathy can be fatal within hours.

APL (AML M3) = t(15;17) PML-RARA + life-threatening DIC. Start ATRA immediately on clinical suspicion (Auer rods + DIC in AML) — do NOT wait for cytogenetics. DIC in APL: fibrinogen <1 g/L = critical danger zone. ATRA + arsenic trioxide is now standard APL treatment with cure rates >90%.

Correct. ALL blasts have high tropism for the CNS. The blood-brain barrier (BBB) represents a pharmacological sanctuary — most systemic chemotherapeutic agents (especially hydrophilic compounds like most cytotoxics) penetrate the CNS poorly, leaving residual leukaemic cells protected from systemic therapy. Without CNS-directed treatment, approximately 50–70% of ALL patients would develop CNS relapse despite achieving systemic complete remission. CNS prophylaxis methods: intrathecal methotrexate (± cytarabine), high-dose systemic methotrexate (which achieves CNS concentrations), and cranial radiotherapy (now largely replaced by intrathecal and systemic approaches to avoid neurocognitive late effects). This principle of pharmacological sanctuary sites also explains the need for testicular irradiation in selected male patients with ALL.

ALL requires CNS prophylaxis because the BBB is a pharmacological sanctuary. Methods: intrathecal methotrexate ± high-dose systemic MTX. Testicular relapse = another sanctuary site in males. AML has less CNS tropism and does not routinely require CNS prophylaxis.

Correct. EGFR mutations — most commonly exon 19 deletion and exon 21 L858R point mutation — are present in approximately 10–15% of Western lung adenocarcinoma patients and up to 30–40% in East and South Asian non-smokers. These mutations result in constitutively activated EGFR signalling driving tumour cell proliferation and survival. First-line treatment with EGFR TKIs (first-generation: erlotinib/gefitinib; third-generation: osimertinib — now preferred due to CNS penetration and targeting T790M resistance mutation) produces higher response rates, longer progression-free survival, and better quality of life than platinum doublet chemotherapy in EGFR-mutated NSCLC. Molecular profiling (EGFR, ALK, ROS1, BRAF, PD-L1, KRAS) is now mandatory for all non-squamous NSCLC before initiating first-line therapy.

EGFR mutations (exon 19 del/exon 21 L858R) in lung adenocarcinoma: common in non-smokers, women, and Asian patients. First-line EGFR TKI (osimertinib preferred) supersedes chemotherapy. ALK rearrangement: alectinib. Always check molecular profile before starting systemic therapy in non-squamous NSCLC.

Correct. The development of a new PET-avid mass at a previously involved site after achieving complete remission constitutes relapsed Hodgkin lymphoma. This is distinct from primary refractory disease (failure to achieve CR with initial therapy). Tissue biopsy should be performed if technically feasible to confirm relapse (rare cases may represent second malignancy or infection). Management: salvage combination chemotherapy (DHAP, ICE, BeGEV) with the goal of achieving remission, followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT) — the standard curative approach for relapsed/refractory HL in transplant-eligible patients. Brentuximab vedotin (anti-CD30 antibody-drug conjugate) has improving outcomes as consolidation post-ASCT and in multiply relapsed/refractory settings. Nivolumab/pembrolizumab (PD-1 inhibitors) also active in relapsed HL.

Relapsed HL after CR: confirm with biopsy; salvage chemo (ICE/DHAP) → autologous SCT for transplant-eligible. Primary refractory: failure to achieve CR or relapse <3 months after treatment. Brentuximab vedotin (anti-CD30) for consolidation post-ASCT or relapsed/refractory. PD-1 inhibitors (nivolumab/pembrolizumab) effective in relapsed HL.

Correct. Response milestones for CML on TKI therapy (ELN 2020 recommendations): at 3 months, BCR-ABL1 ≤10% IS (early molecular response) is optimal; at 12 months, BCR-ABL1 ≤1% IS (complete cytogenetic response = 0% Philadelphia+ metaphases = BCR-ABL1 ≤1% IS) is the target; at any time, BCR-ABL1 ≤0.1% IS is major molecular response (MMR). A BCR-ABL1 of 12% IS at 12 months indicates treatment failure — the patient has NOT achieved complete cytogenetic response and is at higher risk of disease progression to accelerated/blast phase. Management: switch to second-generation TKI (dasatinib, nilotinib, bosutinib) and test for BCR-ABL1 kinase domain mutations (especially T315I, which confers resistance to all TKIs except ponatinib). This is NOT an indication for immediate transplant unless blast crisis develops.

CML TKI response milestones (ELN 2020): 3 months BCR-ABL1 ≤10% IS; 12 months ≤1% IS (CCyR); MMR = ≤0.1% IS. At 12 months >1% IS = treatment failure → switch TKI; test for ABL kinase mutations (T315I → ponatinib). Haematological response alone does NOT guarantee molecular response.

Correct. This question tests the integration of NMC competencies IM13.6 (curative vs palliative distinction), IM13.16 (patient-centred decision-making), and IM13.18 (ethics in end-of-life care). ECOG performance status 3 (confined to bed/chair >50% of waking hours, limited self-care) predicts poor chemotherapy tolerance and high toxicity-to-benefit ratio in pancreatic adenocarcinoma. The correct approach is shared decision-making — not paternalistic refusal, not unconditional deference to patient/family demand, and not bypassing the patient. The oncologist should: (1) acknowledge the patient's desire to 'fight', (2) explain clearly what ECOG 3 predicts about chemotherapy toxicity, (3) present honest survival data, (4) explore the patient's values, goals, and fear of dying, and (5) introduce palliative care as active, expert symptom management — not 'giving up'. Early palliative care integration (Temel et al., 2010) improves both quality of life and, in some settings, survival.

ECOG performance status: 0=fully active; 1=light work restricted; 2=ambulatory, no work; 3=limited self-care; 4=bedridden. ECOG ≥3 = poor chemotherapy tolerance. Shared decision-making: patient capacity + honest prognosis + patient values + early palliative care integration. Autonomy does not obligate the clinician to provide harmful or futile treatment.

Correct. AJCC/UICC TNM for breast cancer: T2 = tumour >2 cm to ≤5 cm in greatest dimension; N1 = metastasis in 1–3 ipsilateral axillary lymph nodes (or internal mammary with axillary node involvement); M0 = no distant metastasis. This patient is clinical stage IIA/IIB, and a minimum staging work-up for stage II disease includes CT chest-abdomen-pelvis (to exclude lung, liver, bone, adrenal metastases) and bone scan (most sensitive for osteoblastic metastases); alternatively, a whole-body PET-CT covers both. For early stage I (T1N0), systemic staging may be deferred, but once node-positive or T2, distant staging is standard practice before committing to a definitive surgical or neoadjuvant approach.

Breast cancer TNM: T1 ≤2 cm; T2 >2–5 cm; T3 >5 cm; T4 = skin/chest wall. N1 = 1–3 axillary LN; N2 = 4–9; N3 = ≥10 or supraclavicular. M0 vs M1. Staging work-up for stage II+: CT thorax-abdomen-pelvis + bone scan (or PET-CT). ER/PR/HER2 status drives systemic therapy selection.

Correct. The constellation of CRAB criteria — Calcium elevation, Renal impairment (creatinine >177 μmol/L), Anaemia (Hb <10 g/dL), Bone lesions (lytic) — with an M-protein on SPEP and Bence Jones proteinuria (free light chains in urine) is the classic presentation of multiple myeloma. Myeloma is a plasma cell neoplasm; the M-protein represents monoclonal immunoglobulin secreted by neoplastic plasma cells (usually IgG 60%, IgA 20%, light chain only 20%). Bone marrow biopsy (trephine) showing ≥10% clonal plasma cells confirms the diagnosis and characterises the M-protein isotype by immunophenotyping. 'Punched-out' skull lesions are a classic radiological finding. MGUS has M-protein <30 g/L, bone marrow plasma cells <10%, and NO CRAB features — this patient has multiple CRAB criteria, ruling out MGUS.

Multiple myeloma CRAB criteria: Calcium >2.75, Renal impairment (Cr >177), Anaemia (Hb <10), Bone lytic lesions. M-protein on SPEP + Bence Jones protein + ≥10% plasma cells on marrow biopsy = diagnostic triad. Treat with bortezomib-based regimens ± autologous SCT. MGUS = M-protein <30 g/L + <10% plasma cells + no CRAB features.

Correct. This question integrates IM13.5 (end-of-life issues), IM13.18 (ethics and medico-legal), and IM13.19 (alleviating suffering). The key distinction is between palliative sedation (titrating sedatives to relieve refractory, intractable symptoms — dyspnoea, pain, agitation — in a dying patient, with the intent of relieving suffering, not hastening death) and euthanasia (administering drugs with the primary intent to end life). Palliative sedation is ethically and legally permissible under the doctrine of double effect, provided the intent is symptom relief and the dose is proportionate. Active euthanasia (deliberately inducing death) is illegal in India. The Supreme Court of India, in Aruna Shanbaug (2011) and Common Cause (2018), legalised passive euthanasia (withdrawal of futile life-sustaining treatment) in irreversible conditions with prior informed consent/advance directive — not active euthanasia. The physician should: acknowledge the son's distress, clarify the legal and ethical context, and actively address the patient's dyspnoea with evidence-based palliative measures.

Palliative sedation vs euthanasia: palliative sedation = relieve refractory suffering (intent: comfort, not death) — legal; euthanasia = intent to end life — illegal in India. Passive euthanasia (withdrawal of LST) legalised in India via Supreme Court (Common Cause 2018) with advance directive. Opioids for dyspnoea in advanced cancer are appropriate (rule of double effect).

Correct. Ann Arbor staging for lymphoma: Stage I = single lymph node region or single extranodal site; Stage II = ≥2 node regions on the SAME side of diaphragm; Stage III = node regions on BOTH sides of diaphragm; Stage IV = disseminated extranodal involvement (bone marrow, liver, lung, multiple extranodal sites). Bone marrow involvement constitutes extranodal disease = Stage IV. The A/B suffix denotes absence (A) or presence (B) of B symptoms. Stage IV in DLBCL correlates with a higher International Prognostic Index (IPI) score — elevated LDH, more than one extranodal site, stage IV, ECOG ≥2, age >60 each contribute 1 point; IPI 3–5 = high-risk. Despite stage IV, R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) can achieve cure in DLBCL because it is chemosensitive, even at stage IV.

Ann Arbor staging: I=single region; II=same side diaphragm; III=both sides; IV=extranodal (bone marrow, liver). A/B suffix = B-symptoms absent/present. E suffix = single extranodal site contiguous. IPI (DLBCL): age >60, ECOG ≥2, LDH elevated, >1 extranodal site, stage III/IV = 1 point each; IPI 0–1=low risk, 4–5=high risk.

Correct. The biochemical pattern of hypo-osmolar hyponatraemia (serum Na 118, osmolality 245) with inappropriately concentrated urine (urine osmolality 520 = well above the 100 mOsm/kg that would be expected if ADH were correctly suppressed) and elevated urine sodium (>40 mEq/L) in a euvolaemic patient with normal thyroid, adrenal, and renal function is the hallmark of SIADH (syndrome of inappropriate antidiuretic hormone secretion). In the context of a known malignancy, paraneoplastic ectopic ADH secretion is the most likely cause — most commonly from small cell lung cancer, though it also occurs with other cancers. Colon cancer is less commonly associated but does occur. First-line management of SIADH: fluid restriction (500–800 mL/day), which treats the dilutional hyponatraemia without adding sodium. Severe symptomatic hyponatraemia (Na <120 with neurological symptoms): cautious correction with 3% NaCl (maximum 1–2 mEq/L per hour; total correction ≤8–10 mEq/L in 24 hours to prevent osmotic demyelination). Tolvaptan (V2 receptor antagonist) is used for persistent or severe SIADH.

SIADH paraneoplastic = ectopic ADH from SCLC most commonly; also other tumours. Biochemistry: low serum Na, low serum osmolality, high urine osmolality (>100), high urine Na (>40), euvolaemia. First-line: fluid restriction. Avoid rapid correction (≤8–10 mEq/L per 24h) — osmotic demyelination syndrome if overcorrected.