Oncology — USMLE Step 2 CK Notes

Diagnostic reasoning patterns

• Cancer often masquerades as something else — iron-deficiency anaemia in an older adult is colorectal cancer until proven otherwise (colonoscopy).
• Age clue: ALL peaks in children (2-5y); ALL/AML and CLL in older adults (CLL commonest >65). Hodgkin lymphoma is bimodal (20-30 and >55); non-Hodgkin rises with age.
• Unexplained weight loss, night sweats, fatigue or a new anaemia should trigger a malignancy work-up.

Solid tumours — high-yield

• Lung — small cell (central, smoker): paraneoplastic SIADH, ectopic ACTH (Cushing) and Lambert-Eaton. Non-small cell: adenocarcinoma (peripheral, commonest, rising in non-smokers) and squamous (central, cavitating, PTHrP hypercalcaemia).
• Skin: basal cell carcinoma (pearly papule, telangiectasia, rolled border; H-zone → Mohs); squamous cell (scaly, more likely to metastasise); melanoma (ABCDE, Breslow depth).
• Bone: diaphyseal — Ewing sarcoma (onion-skin, t(11;22)) and osteoid osteoma; metaphyseal — osteosarcoma (sunburst, Codman triangle) and osteochondroma.

Haematological malignancies

• AML — Auer rods; the M3 (APL) variant risks DIC and is treated with all-trans retinoic acid (ATRA).
• CML — Philadelphia chromosome t(9;22)/BCR-ABL, low leukocyte alkaline phosphatase; imatinib.
• CLL — smudge cells; ALL — commonest childhood leukaemia; Hodgkin — Reed-Sternberg cells, contiguous spread.
• Multiple myeloma — CRAB (hyperCalcaemia, Renal failure, Anaemia, Bone lytic lesions), M-spike, Bence-Jones protein, rouleaux, >10% clonal marrow plasma cells.

Oncologic emergencies (time-sensitive)

• Tumour lysis syndrome — after chemo of bulky tumours: high K/phosphate/urate, low calcium, acute kidney injury; hydrate + rasburicase/allopurinol.
• Febrile neutropenia — empiric broad-spectrum antipseudomonal antibiotics immediately.
• Spinal cord compression — back pain with neurology → urgent MRI and steroids.
• Hypercalcaemia of malignancy — IV fluids then bisphosphonate; SVC obstruction from mediastinal tumour.

Tumour markers & paraneoplastic

• AFP (hepatocellular, yolk-sac), CEA (colorectal monitoring), CA 19-9 (pancreatic), CA-125 (ovarian), PSA (prostate), beta-hCG (choriocarcinoma/germ cell), calcitonin (medullary thyroid).
• Paraneoplastic: SIADH/ACTH (small cell lung), PTHrP hypercalcaemia (squamous), polycythaemia (RCC/HCC), Lambert-Eaton, dermatomyositis.

Principles of therapy

• Match the treatment to stage: local disease → surgery/radiotherapy; systemic disease → chemotherapy/targeted/immunotherapy.
• Know the sentinel side effects: doxorubicin (cardiotoxicity), bleomycin (pulmonary fibrosis), cisplatin (nephro/ototoxicity), vincristine (neuropathy), cyclophosphamide (haemorrhagic cystitis).

Molecular drivers (oncogenes & translocations)

• t(9;22) BCR-ABL — Philadelphia chromosome, constitutive tyrosine kinase → CML; targeted by imatinib.
• t(8;14) c-MYC — Burkitt lymphoma ("starry-sky" histology).
• t(14;18) BCL-2 — follicular lymphoma (anti-apoptosis).
• t(11;14) cyclin D1 — mantle cell lymphoma.
• BRAF V600E — melanoma (and hairy cell leukaemia); RET — MEN2/medullary thyroid.

Tumour suppressors & DNA-repair syndromes

• APC loss → familial adenomatous polyposis (near-100% colon cancer).
• BRCA1/2 → breast and ovarian cancer.
• Lynch syndrome (HNPCC) — mismatch-repair defect; Fanconi anaemia — DNA-repair defect.

Oncogenic viruses & carcinogens

• EBV → Burkitt, nasopharyngeal carcinoma, Hodgkin. HPV 16/18 → cervical/vulvar/oropharyngeal SCC. HHV-8 → Kaposi sarcoma. HBV/HCV → hepatocellular carcinoma. H. pylori → gastric adenocarcinoma/MALT.
• UV → skin cancers; tobacco → lung/oesophageal SCC; benzene → acute leukaemia; arsenic → basal cell carcinoma; aflatoxin → HCC.

Tumour markers (use after age/demographics)

• CA-125 (ovarian, not specific), calcitonin (medullary thyroid), gastrin (Zollinger-Ellison), urinary 5-HIAA (carcinoid), thyroglobulin (follow-up of thyroid cancer), PSA (prostate monitoring), M-spike (myeloma), HER2/neu (breast → trastuzumab), AFP (HCC/yolk-sac), CEA (colorectal follow-up), CA 19-9 (pancreatic), beta-hCG (germ cell/choriocarcinoma).

Breast mass — next best step by age

• ≥50y or ≥30y with a discrete mass → mammogram; <30y → ultrasound first.
• Young woman with cyclical pain and multiple lumpy areas soon after menses → reassurance/re-examine.
• DCIS with a positive sentinel node → axillary lymph-node dissection. Klinefelter → ~20× male breast-cancer risk.

Rapid-recall mnemonics

• AML (AMLAUER) — Auer rods, >20% Myeloblasts, Leukostasis, Adults, Uncontrolled bleeding, Emergent DIC (M3/APL), Requires ATRA.
• Hypercalcaemia — "stones, bones, groans, psychic moans": renal calculi, bone pain, constipation/polyuria, confusion/depression.
• Acute intermittent porphyria — 5 P's: Painful abdomen, Port-wine urine, Polyneuropathy, Psychiatric signs, Precipitated by P450 inducers/alcohol/starvation.
• Buzzwords: starry-sky (Burkitt), owl-eye Reed-Sternberg (Hodgkin), sunburst/Codman (osteosarcoma), onion-skin (Ewing), soap-bubble (ameloblastoma/giant-cell tumour).

Cell-cycle-specific chemotherapy

• S-phase (antimetabolites): methotrexate, 5-FU, hydroxyurea. M-phase: vinca alkaloids (spindle) and taxanes (stabilise microtubules). Tumour cells are most radiosensitive during rapid division.

High-yield notes contributed by a StepSherpa clinician reviewer.