How hematologic cancers are tested on Step 1

Start with age and the smear, then use markers and translocations.

ALLChildren; TdT+ lymphoblasts; t(12;21) has a goodprognosisAMLAdults ~65; MPO+ blasts, Auer rods; APL t(15;17) →DICCLLOver 60; smudge cells; CD5+ CD20+ B cellsCML30s–60s; BCR-ABL t(9;22); splenomegaly; imatinibHairy cellMiddle-aged men; TRAP+, BRAF V600E; dry tap;cladribine
Leukemias. Acute leukemias fill the marrow with blasts (>20%), causing anemia, infection, and bleeding.

Lymphomas

Hodgkin lymphoma is defined by Reed-Sternberg cells; non-Hodgkin lymphomas are a varied group, mostly B cell.

HodgkinReed-Sternberg cells: CD15+, CD30+Single node group; contiguous spreadMediastinal mass in young adultsEBV linked in someNodular sclerosis most commonNon-HodgkinMostly B cell (some T cell)Multiple nodes; noncontiguousExtranodal disease commonHIV and immunosuppression increase riskDLBCL most commonvs
Hodgkin vs non-Hodgkin. B symptoms (fever, night sweats, weight loss) occur in both and worsen the prognosis.
LymphomaGenetics or markerClassic features
Burkittt(8;14) MYC"Starry sky" pattern; endemic form in the jaw (EBV), sporadic form in the abdomen
Folliculart(14;18) BCL2Indolent, waxing and waning nodes; can transform to DLBCL
Mantle cellt(11;14) cyclin D1; CD5+Older men; aggressive
Diffuse large B-cellVariedMost common NHL; rapidly enlarging mass
MALT (marginal zone)Chronic inflammationGastric MALT lymphoma may regress after H. pylori treatment
Adult T-cellHTLV-1Skin lesions, lytic bone lesions, hypercalcemia
Mycosis fungoidesCD4+ T cellsSkin plaques; Sézary syndrome when cells circulate

Translocations next to the immunoglobulin heavy chain gene (chromosome 14) drive several B-cell lymphomas.

Plasma cell and myeloproliferative disorders

Monoclonal proteins and overactive marrow lines.

  • Multiple myeloma: CRAB findings, IgG or IgA M spike, light chains in urine (Bence Jones), rouleaux on smear, recurrent infections; may cause AL amyloidosis.
  • MGUS: small M spike without CRAB findings; can progress to myeloma.
  • Waldenström macroglobulinemia: IgM M spike → hyperviscosity (vision changes, headache), no lytic lesions.
  • Polycythemia vera: JAK2 mutation, high red cell mass with low erythropoietin; itching after a warm shower, clots, erythromelalgia.
  • Essential thrombocythemia and primary myelofibrosis: JAK2-associated; myelofibrosis shows teardrop cells and a dry tap.

Complications of treatment

Chemotherapy can kill cells faster than the kidneys can clear their contents.

  • Tumor lysis syndrome: high potassium, phosphate, and uric acid with low calcium after treatment of fast-growing cancers (Burkitt lymphoma, ALL). Prevent with IV fluids plus allopurinol or rasburicase.
  • Targeted therapy links: imatinib (BCR-ABL), all-trans retinoic acid (APL), rituximab (CD20).

Worked example

Separate cancer from a reactive response.

functions Worked example — a very high white count

A 50-year-old has fatigue and early satiety. The spleen is enlarged. WBC is 120,000/µL with neutrophils at every stage of maturation and many basophils. Leukocyte alkaline phosphatase (LAP) score is low. What is the diagnosis and the drug target?

  1. Neutrophils at all stages with basophilia and splenomegaly suggest a myeloproliferative neoplasm.
  2. A leukemoid reaction (for example from infection) would have a high LAP score and no basophilia.
  3. Low LAP fits chronic myelogenous leukemia.
  4. CML is driven by the BCR-ABL fusion from t(9;22), the Philadelphia chromosome.

Answer. Chronic myelogenous leukemia; imatinib inhibits the BCR-ABL tyrosine kinase.