White blood cell disorders

WBC Basics - The Body's First Responders

• Function: Key mediators of inflammation and the immune response.
• Normal Range: 4,000-11,000/μL.
  • Leukocytosis: >11,000/μL (indicates infection, stress, or inflammation).
  • Leukopenia: <4,000/μL (suggests immunosuppression, marrow failure).
• Differential Count:
  • 📌 Mnemonic (most to least abundant): Never Let Monkeys Eat Bananas (Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils).
• Absolute Neutrophil Count (ANC):
  • $ANC = \text{WBC Count} \times (% \text{Neutrophils} + % \text{Bands})$.
  • Severe Neutropenia: ANC <500/μL; high risk for life-threatening infections.

⭐ A "left shift" indicates an acute inflammatory response (esp. bacterial infection), characterized by the premature release of immature neutrophils (e.g., bands, metamyelocytes) from the bone marrow.

Myeloid Neoplasms - Precursor Pandemonium

• Clonal hematopoietic stem cell disorders causing overproduction of one or more myeloid lineages. Spectrum ranges from ineffective hematopoiesis (MDS) to hyper-proliferation (MPN) to acute leukemia (AML).

• Myelodysplastic Syndromes (MDS): Pancytopenia despite hypercellular marrow. Risk of AML transformation.
• Myeloproliferative Neoplasms (MPN):
  • CML: BCR-ABL fusion gene.
  • Polycythemia Vera, Essential Thrombocythemia, Primary Myelofibrosis: Primarily JAK2, CALR, MPL mutations.

⭐ Auer Rods, eosinophilic needle-like inclusions in cytoplasm, are pathognomonic for Acute Myeloid Leukemia (AML).

Lymphoid Leukemias - Clonal Chaos Crew

• Acute Lymphoblastic Leukemia (ALL):
  • Most common childhood malignancy; blasts are TdT+.
  • B-ALL: CD10+, CD19+, CD20+. Good prognosis with t(12;21).
  • T-ALL: Can present as a mediastinal mass in a teenager.
• Chronic Lymphocytic Leukemia (CLL):
  • Affects adults > 60; often asymptomatic with lymphocytosis.
  • Key finding: Smudge cells on peripheral smear.
  • Co-expression of CD5 and CD20.
  • Can undergo Richter transformation to an aggressive lymphoma.
• Hairy Cell Leukemia:
  • Affects older males; cells have fine, hair-like projections.
  • Stains TRAP+ (Tartrate-Resistant Acid Phosphatase).
  • Causes massive splenomegaly and pancytopenia.

⭐ In CLL, smudge cells are fragile neoplastic lymphocytes crushed during peripheral blood smear preparation. Their presence is characteristic but not pathognomonic.

Plasma Cell Dyscrasias - M-Protein Mayhem

• Multiple Myeloma (MM): Malignant plasma cells producing monoclonal Ig (IgG > IgA).
  • 📌 CRAB criteria: ↑ Calcium (>11 mg/dL), Renal insufficiency, Anemia, lytic Bone lesions.
  • Labs: M-spike on SPEP, Bence-Jones proteinuria, Rouleaux formation (RBC stacks).
• Waldenström Macroglobulinemia: IgM M-spike leading to hyperviscosity syndrome (blurry vision, Raynaud).
• MGUS (Monoclonal Gammopathy of Undetermined Significance): Asymptomatic; precursor with risk of progression.

⭐ Multiple Myeloma is the most common primary malignant bone tumor in adults.

High‑Yield Points - ⚡ Biggest Takeaways

• Leukemoid reaction is distinguished from CML by a high LAP score; CML has a low LAP score and the Philadelphia chromosome (t(9;22)).
• Acute leukemias (ALL, AML) show >20% blasts in the marrow; Auer rods are pathognomonic for AML.
• CLL is characterized by smudge cells and lymphadenopathy in the elderly.
• Hodgkin lymphoma is identified by Reed-Sternberg cells and typically spreads contiguously.
• Multiple myeloma presents with CRAB findings (hypercalcemia, renal failure, anemia, bone lesions) and an M-spike.