Acute myeloid leukemia, lymphoplasmocytic lymphoma

A) Acute myeloid leukemia (AML)

Definition

AML is a myeloid neoplasm where neoplastic cells are blocked at early stages of myeloid development (usually due to mutations in transcription factors required for differentiation) → myeloblasts accumulate in marrow and blood, suppressing normal hematopoiesis.

Myeloblast morphology: 3–5 nucleoli, delicate chromatin, azurophilic granules.

• Auer rods: rod-like cytoplasmic organelles seen in myeloblasts — pathognomonic for AML (especially APL)
• Hiatus leukemicus: gap in maturation — many blasts + many mature neutrophils, no intermediate forms

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Classification (4 categories)

1. AML with recurrent chromosomal translocations

• t(15;17) → PML/RARα fusion → good prognosis (APL; see below)
• t(8;21) → RUNX1/RUNX1T1 → good prognosis
• inv(16)(q22;q22) → CBFβ/MYH11 → good prognosis
• t(11q23;variant) → MLL fusion → poor prognosis

2. AML with multilineage dysplasia (arising from MDS) — poor prognosis

3. AML related to prior chemotherapy/radiation — poor prognosis

4. AML not otherwise classified (FAB-based, by cell lineage)

• M0: without maturation
• M1: minimal maturation
• M2: with maturation
• M3: Acute promyelocytic leukemia (APL)
  • t(15;17) → PML/RARα → blocks differentiation at promyelocyte stage
  • High risk of DIC (granules trigger coagulation)
  • Treatment: ATRA (all-trans retinoic acid) overcomes differentiation block → complete remission; must combine with chemo
• M4: Myelomonocytic (myeloblasts + monoblasts)
• M5: Monocytic
• M6: Erythroid
• M7: Megakaryoblastic (BM fibrosis; untreatable with standard therapy)

Immunophenotype

• Stem cell: CD34
• Myeloblastic: CD13, CD33
• Monoblastic: CD14
• Megakaryoblastic: CD64

Clinical

• Sudden onset; any age/gender
• Symptoms within weeks: anemia, bleeding (nosebleed), fever (neutropenia)
• CNS involvement possible
• Overall survival ~15–30% with chemotherapy or allogenic BM transplant
• APL [M3] has best targeted therapy → higher cure rate with ATRA + chemo

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B) Lymphoid neoplasms — Introduction & classification overview

Classification framework

Hodgkin vs. Non-Hodgkin:

	Hodgkin lymphoma	Non-Hodgkin lymphoma
Origin	B-cell	B- or T-cell
Hallmark cell	Reed-Sternberg cells	No RS cells
Spread	Localized, contiguous	Multiple nodes, non-contiguous
Frequency	Less common	More common

Low-grade vs. High-grade:

	Low-grade	High-grade
Morphology	Mature cells (cytic); no mitoses	Immature cells (blastic); mitoses
Progression	Slow; ~15 yr survival	Rapid; ~5 yr survival
Curability	Incurable	~50% curable
Molecular basis	t(14;18) → BCL2 anti-apoptotic	t(8;14) → MYC proliferation
Prototype	CLL/SLL, FL	Burkitt, DLBCL

Targeted therapy note

• MabThera/rituximab (anti-CD20): chimeric antibody with mouse Fab (anti-CD20) + human Fc → ADCC kills B-cell lymphomas. Changed prognosis significantly.
• BTK inhibitors (ibrutinib): also used in B-cell lymphomas (mantle cell, CLL).

💡 High-yield: AML = myeloblast block + Auer rods + hiatus leukemicus. APL (M3) = t(15;17)/PML-RARα + DIC risk + ATRA therapy. NHL more common than HL. Low-grade = BCL2/t(14;18), incurable; high-grade = MYC, potentially curable.