Hemoblastosis and Leukemias

Tumors derived from hemopoietic stem cells and lymphoid tissue.
Hemopoiesis: Formation of cellular elements of blood, starts in bone marrow.
Multipotential hematopoietic stem cell:
- Gives rise to myeloid and lymphoid progenitors.
- Myeloid progenitors: lead to megakaryocytes (thrombocytes), erythrocytes, mast cells, and myeloid cells.
- Lymphoid progenitors: lead to NK cells and small lymphocytes (T and B lymphocytes).
Approximately $10^{11}$ to $10^{12}$ new blood cells are produced daily.
Mutation in a myeloid or lymphoid cell leads to malignant cell formation in bone marrow, suppressing normal cell lineages.

Normal blood analysis includes a leukocyte formula.
Hemoblastosis: Malignant tumors derived from hemopoietic and lymphoid tissue.
- Systemic: Leukemias
- Regional: Lymphomas

Originate in bone marrow.
Gradually replace normal hemopoiesis by a clone of leukemic cells.
Progression: Center (bone marrow) to periphery (internal organs, brain, lymph nodes).

Originate in lymphatic nodules or extra-nodal locations.
May arise from local lymphocyte aggregation during chronic inflammation.
Metastasize to bone marrow from peripheral lymphoid tissue, typically at terminal stages.

Leukos: White, enea: blood.
Abnormal proliferation of leukemic cells spreading from bone marrow to periphery.
Infiltration of internal organs, causing malfunction.
Decreased apoptosis of leukemic cells.l
Suppression of normal hemopoiesis due to excessive proliferation of abnormal cells.
Target organs: Bone marrow, lymphoid tissue, liver, thymus, spleen, other organs.

Acute vs. Chronic.
- Acute: rapid progression, immature/undifferentiated cells (blasts).
- Chronic: slower progression, more mature cells (cytic).
Lymphocytic vs. Myelocytic (Myeloid).
Leukemias from less differentiated cells have a worsened prognosis.
Well-differentiated tumors progress slower than poorly differentiated tumors.

Physical carcinogenesis: Ionizing radiation.
Chemical carcinogenesis: Benzene, aromatic hydrocarbons.
Biological carcinogenesis: Viruses (telomphotropic virus, Epstein Barr virus), genetic predisposition.

Develops from immature, poorly differentiated cells.
Hiatus leukemicus: Gap between stages of maturation (blasts, no intermediate forms, mature forms).
Affects young children and young adults.
Rapid progression and spread.

Leukopenic: White blood cell count < $4 \, to \, 10^9/L$ .
Sub-leukemic: White blood cell count between $10 \, to \, 50 \, x \, 10^9/L$ , some blasts in peripheral blood.
Leukemic: White blood cell count > $50 \, x \, 10^9/L$ , many blasts in peripheral blood.
Acute leukemia typically shows a significantly increased white blood cell count.

Fever: Due to cytokine release from malignant cell destruction.
Rapidly developing asthenia.
Rapidly progressing severe anemia.
Tendency for bleeding due to suppressed thrombocyte production.
Tender bone due to bone marrow activation.
Pain in joints due to spontaneous bleeding.
Enlargement of lymph nodes (more typical for lymphoid leukemias).
Enlargement of liver and spleen (more typical for myeloid leukemias).
Chloromas: Infiltration by malignant cells in periosteal areas, forming tumor-like masses.
CNS infiltration: Neurological symptoms (typical for acute lymphoblastic leukemia).

Proliferation of immature hemopoietic stem cells that should not be in circulation.
Heterogeneous group based on origin of atypical elements.
Manifestations: Replacement of normal bone marrow, invasion in peripheral blood, infiltration of organs.
Classifications exist (FAB, WHO); diagnosis based on blast cell amount and mutated cell line.
Immunohistochemistry aids diagnosis with clusters of differentiation (CD markers).

Onset sometimes preceded by myelodysplastic syndrome (pre-leukemic syndrome).
Etiological factors:
- Congenital immunodeficiency or prolonged immunosuppressive treatment increases leukemia risk.

Cancer of the myeloid line of white blood cells.
Adults and adolescents are commonly affected.
Malignant white blood cells displace normal hemopoiesis, reducing red blood cells, platelets, and normal white blood cells.
Myeloblasts are large cells with large nuclei and scanty cytoplasm.

Acute Lymphoblastic Leukemia: Many lymphoblasts, some small lymphocytes, increased white blood cells, suppression of RBCs and thrombocytes.
Acute Myeloblastic Leukemia: Many myeloblasts, hiatus leukemia (lack of intermediate forms), fewer lymphocytes, anemia, thrombocytopenia.

Normal bone marrow is polymorphic.
Acute myeloid leukemia: Bone marrow infiltrated with blasts.
More than 20% blasts in bone marrow and peripheral blood are required for diagnosis.
Auer rods (non-specific granules for myeloblasts) may be present.
Promyelocytic leukemia: More differentiated with specific nucleus shape.

Lymphoid hyperplasia of hemopoietic organs (lymph nodes, spleen, bone marrow).
Infiltration of organs and tissues.
Suppression of myelopoiesis; abnormal lymphocyte precursors suppress normal myeloid precursors.
Chronic lymphocytic leukemia: Prolonged, benign course; affects older people; often derives from B lymphocytes; causes immune impairment.
Blood analysis: Few lymphoblasts, many intermediate forms, and small lymphocytes; myeloid precursors diminished, lymphocytes increased.

Abnormal proliferation of myeloid cells; often involves Philadelphia chromosome.
General symptoms: Malaise, fever, impaired immunity, anemia, thrombocytopenia.
Enlargement of liver and spleen due to leukemic infiltration; fatty marrow replaced by myeloid tissue.
No hiatus leukemia; all forms presented; basophilic-eosinophilic association (increased basophils and eosinophils).

Chronic phase: Disease doesn't progress rapidly; symptoms develop gradually.
Accelerated phase: Sudden increase of granulocytes, rapid decrease of RBCs, increase in splenomegaly.
Blast crisis: Leukemia behaves like acute leukemia with myeloblasts in peripheral blood and bone marrow.

Acute leukemias (lymphocytic or myeloid): Large, immature cells with large nuclei.
Difficult to differentiate types based solely on cell appearance.
In myeloid leukemia, cells resemble segments.