StepWise USMLE
hematopathology · core concepts

Blood & lymphoid system

High‑yield notes for clinical reasoning · USMLE step 1

🩸 Leukocyte count WBC

Leukocytosis

  • Neutrophilia: acute pyogenic infection, tissue necrosis
  • Left shift (bands) + Döhle bodies, toxic granulation
  • Eosinophilia: allergy, parasites, drugs, Hodgkin
  • Monocytosis: TB, collagen vascular disease, IBD
  • Lymphocytosis: viral (EBV, CMV), chronic inflammation
  • Infectious mononucleosis – adolescents, “kissing disease”
  • triad: fever, tonsillar exudate, posterior auricular LAD
  • complications: splenic rupture, hepatic dysfunction
  • Basophilia: myeloproliferative disorders (e.g. polycythemia vera)

Leukopenia

  • Neutropenia: decreased production (aplastic, chemo)
  • Increased destruction (SLE, infection)
  • Eosinopenia: corticosteroids, Cushing
  • Lymphopenia: HIV, DiGeorge, SCID, radiation
  • Lymphocytes most radiosensitive
  • Monospot often negative early in EBV infection

🔬 Lymphadenopathy

  • Acute nonspecific: tender, neutrophils; cat‑scratch (Bartonella) → stellate microabscesses
  • Chronic nonspecific: non‑tender
  • Follicular hyperplasia (B cells): RA, toxoplasmosis, early HIV
  • Paracortical (T cells): viruses, phenytoin, SLE
  • Sinus histiocytosis: macrophages, often draining cancer
  • Neoplastic: metastatic carcinoma (breast, lung, melanoma, GI) most common
  • Malignant lymphoma & leukemic infiltration

🧬 Mature B‑cell neoplasms

  • CLL/SLL – indolent, age ~60, hypogammaglobulinemia
  • CD19⁺, CD20⁺, CD5⁺, CD23⁺, CD10⁻
  • smudge cells (fragile), AIHA in 10%
  • Hairy cell – middle‑aged men, splenomegaly, TRAP⁺
  • dry tap; 2‑CdA (inhibits ADA)
  • DLBCL – most common lymphoma, aggressive but curable
  • Follicular lymphoma – t(14;18) BCL2/IGH, indolent
  • Burkitt – “starry sky” (tingible macrophages), t(8;14) MYC/IGH
  • endemic (jaw, EBV) vs sporadic (abdomen, HIV)
  • Mantle cell – t(11;14) CCND1/IGH, CD5⁺ CD23⁻
  • MALToma – marginal zone, associated with chronic inflammation (H. pylori, Hashimoto)
  • Multiple myeloma – >20% plasma cells, M‑spike (IgG>IgA)
  • lytic bone lesions (IL‑6, osteoclast activation)
  • Bence‑Jones proteinuria, rouleaux, hypercalcemia
  • infection is most common cause of death
  • Waldenström – IgM M‑spike, no lytic lesions, hyperviscosity
  • MGUS – 1‑2%/year risk of progression to myeloma
  • Plasmacytoma: solitary bone or extramedullary (upper respiratory)

⚡ T‑cell / NK neoplasms

  • ATLL – HTLV‑1, Japan/Caribbean, CD4⁺, skin lesions, hypercalcemia, “clover leaf” cells
  • Mycosis fungoides – CD4⁺, better prognosis, no hypercalcemia
  • eczematous → plaque → tumor; Pautrier microabscesses
  • Sézary syndrome: erythroderma + circulating Sézary cells
  • Peripheral T‑cell lymphoma, NOS – heterogeneous “wastebasket”

🔴 Hodgkin lymphoma

  • Reed‑Sternberg cells (binucleate, macronucleoli)
  • Classical (CD15⁺, CD30⁺, CD45⁻) vs lymphocyte‑predominant (CD20⁺, CD45⁺)
  • Nodular sclerosis (65‑70%) – females > males, lacunar cells, collagen bands
  • Mixed cellularity – older males, eosinophilia (IL‑5)
  • Lymphocyte‑depleted – poor prognosis, RS cells predominate
  • Contiguous spread, fever, B symptoms (weight loss, night sweats, fever) → worse prognosis
  • Risk of secondary NHL/AML after therapy
  • EBV associated with 40% of lymphocyte‑rich and PTLD

🦴 Myeloid neoplasms

AML

  • ≥20% blasts in marrow; Auer rods
  • t(15;17) PML‑RARA → APL, ATRA responsive, DIC
  • t(8;21), inv(16) have better prognosis
  • MDS – dysplastic changes (Pelger‑Huet, ring sideroblasts)

CML

  • BCR‑ABL (Philadelphia) t(9;22)
  • massive splenomegaly, trilineage hyperplasia
  • imatinib (blocks P210 tyrosine kinase)
  • blast crisis: 70% myeloid, 30% lymphoid

MPN

  • Polycythemia vera – increased RBC mass, Hct, viscosity, pruritus (histamine), gout
  • decreased EPO, thrombosis, “spent phase” → myelofibrosis
  • Essential thrombocythemia – platelets >450k, bleeding/thrombosis
  • Myelofibrosis – dry tap, teardrop cells, leukoerythroblastosis, extramedullary hematopoiesis (spleen)
CML→accelerated→blast crisis
  • Tumor lysis syndrome: hyperK, hyperP, hyperuricemia, hypocalcemia, AKI

🫘 Spleen & thymus

  • Splenomegaly – portal HTN, reactive hyperplasia, infiltrative (leukemia, amyloid), Gaucher, extramedullary hematopoiesis
  • Hypersplenism → thrombocytopenia
  • Asplenia → Howell‑Jolly bodies, risk of encapsulated organisms (Strep, Haemophilus, Salmonella)
  • Thymoma – low‑grade epithelial tumor, paraneoplastic (MG, pure RBC aplasia)
  • True thymic hyperplasia (post‑chemo) vs lymphoid hyperplasia (germinal centers)