Atlas
 

Non-tumorous Lesions of Bone Marrow



3  Bone Marrow Pathology

3.3  Non-tumorous Lesions of Bone Marrow

3.3.1  Reactive Hematopoietic Changes

3.3.1.1  Erythroid hyperplasia

Etiology, pathogenesis:

  • results from increased erythropoietin production due to chronic hypoxemia (high altitude stays, chronic lung diseases, cyanotic heart defects) or (rarely) due to erythropoietin-producing tumors (for example renal cell carcinoma)
  • or from an increased peripheral erythrocyte loss (for example hemolytic anemias)

Histology:

The marrow is normo- or hypercellular with increased normoblastic erythropoiesis, which is organised in clusters. Erytropoietic precursors mature, often there is a left shift. Other hematopoietic lineages are normal.

3.3.1.2  Myeloid Hyperplasia

Etiology, pathogenesis:

  • Results from acute or chronic inflammation of various origin (infections, autoimmune diseases, extensive necrosis, burns etc.) and in various malignancies
  • from an extensive loss of peripheral leukocytes

Histology:

The marrow is normo- or hypercellular with increased myelopoiesis, where neutrophils predominate. Myelopoietic precursors mature, often there is a left shift, however the number of myeloblasts is normal. Myeloid hyperplasia may sometimes be so extensive that it resembles hemoblastosis (leukemic reaction). Other lineages are either normal or also display reactive changes (for example an increased number of megakaryocytes caused by an inflammation).

3.3.1.2.1  Eosinophilia

Etiology, pathogenesis:

Is most often caused by allergic disorders or parasitic infections, but other causes are also possible, for example. autoimmune diseases, dermathology deseases, Hodgkin's disease. When the cause is not identified, we talk of the hypereosinophilic syndrome which is near to myeloproliferative disorders.

Histology:

The marrow is normo- or hypercellular with an elevated eosinophil count. Other lineages remain normal.

3.3.1.3  Increased Number of Megakaryocytes

Etiology, pathogenesis:

  • repeated or prolonged hemorrhage
  • acute or chronic inflammation of various origin (infection, autoimmune disorders etc.)
  • malignancies
  • increased peripheral loss of thrombocytes (ITP, hypersplenism)

Histology:

The marrow is normocellular with an elevated megakaryocyte count. The megakaryocytes are separate and do not form larger clusters, there is a majority of immature hypolobulated forms. Other lineages are either normal or with reactive changes (myeloid hyperplasia caused by inflammation)

3.3.2  Bone Marrow Hypoplasia and Aplasia

Introduction:

Bone marrow failure either affects all hematopoietic lienages (aplastic anemia) or selectively only one of them (pure red cell aplasia, agranulocytosis, amegakaryocytic thrombocytopenia).

3.3.2.1  Aplastic Anemia

Etiology, pathogenesis:

Overall bone marrow failure may be congenital (such as Fanconi's syndrome) or aquired after exposition to myelotoxic agents (chemotherapeutics and other drugs, toxins, some (especially viral) infections etc.

Histology:

The marrow is hypocellular (0 – 30%) with reduced trilinear hematopoiesis. The depression of myelopiesis and megakaryocytes is usually more distinct than erytropoietic depression, therefore erytropoiesis relatively predominates. Lymphocytes, plasma cells, mast cells and macrophages with abundant iron deposits are reactively increased in number.

3.3.2.2  Pure red cell aplasia

Classification:

Pure red cell aplasia may be acute or chronic. Chronic aplasia is either congenital (for example Blackfan-Diamond syndrome) or acquired (thymoma, systemic lupus erythematosus, autoimmune thyreoiditis).

Histology:

Bone marrow is normocellular or only slightly hypocellular with normal megakaryocytes and normal myelopoiesis. Erythropoietic islands are missing, separate normoblasts are sparsly dispersed. Lymphocytosis and plasmocytosis are usually reactive, the number of mast cells and macrophages with abundant iron deposits is increased.

  • dysplastic changes in at least 10% of cells from two or more hematopoietic lineages
  • the number of myeloblasts in bone marrow is 5 – 19%
  • rAEB-1: 5 – 9% myeloblasts
  • rAEB-2: 10 – 19% myeloblasts
  • prognosis: 25% of patients with RAEB-1 and 33% of patients with RAEB-2 develop AML, median survival time is 18 months(RAEB-1) and 10 months (RAEB-2)
3.3.2.3  Agranulocytosis

Introduction:

Agranulocytosis rarely occures on its own, more often it exists as part of aplastic anemia.

Etiology, pathogenesis:

Autoimmune myelopoiesis inhibition, autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus), tumorous diseases (systemic mastocytosis), drugs, toxins.

Histology:

Bone marrow is hypocellular, with normal megakaryocytes and normal erythropoiesis. Myelopoiesis is significantly decreased or missing completely. Reactive lymphocytosis and plasmocytosis is usually present.

3.3.2.4  Amegakaryocytic thrombocytopenia

Introduction:

Amegakaryocytic thrombocytopenia is either congenital or acquired (amegakaryocytic thrombocytopenic purpura).

Introduction:

Autoimmune diseases, drugs, toxins, hepatic cirrhosis, lymphoproliferative disorders and other malignacies.

Histology:

Bone marrow is normocellular, erythropoiesis and myelopoiesis are normal. Megakaryocytes are substantially decreased in number or sometimes even completely missing.

3.3.3  Anemias

Introduction:

Anemia is an abnormally low number of circulating erythrocytes leading to low hemoglobin levels in peripheral blood (less than 130 g/l in men or 120 g/l in women).

The classification of anemias is complex and since it is a part of hematology, this text will focus on basic types of anemias and the morphological changes they cause in the bone marrow.

Clinical signs:

  • fatigue
  • dyspnea
  • tachycardia with palpitations
  • pale skin
  • neurologic symptoms (dizziness, faintness, headache)
  • other

Classification:

  • Anemia resulting from an increased peripheral blood loss
    • acute posthemorrhagic anemia
    • chronic posthemorrhagic anemia
  • Anemia resulting from a decreased erythrocyte production
    • megaloblastic anemia
    • sideropenic anemia
    • myelodysplastic syndrome
    • aplastic anamia
    • anemia caused by hematopoietic depression
    • chronic kidney disease anemia
    • anemias of chronic disorders
  • Anemia resulting from an increased erythrocyte destruction
    • hemolytic anemia
3.3.3.1  Posthemorrhagic anemias

Introduction:

Posthemorrhagic anemia is caused by a sudden massive blood loss for example in severe injury (acute posthemorrhagic anemia) or repeated or prolonged blood losses (chronic posthemorrhagic anemia).

3.3.3.1.1  Acute Posthemorrhagic Anemia

Histology:

  • Peripheral blood: normochromic normocytic anemia
  • Bone marrow: normocellular with a temporary increase in normoblastic erythropoiesis
3.3.3.1.2  Chronic Posthemorrhagic Anemia

Histology:

  • Peripheral blood: normochromic normocytic or hypochromic microcytic anemia
  • Bone marrow: normocellular or slightly hypercellular bone marrow with increased normoblastic erythropoiesis, if iron depletion occures, the morphological changes match those of sideropenic anemia.
3.3.3.2  Megaloblastic Anemia

Introduction:

Anemia which arises from abnormal DNA synthesis caused by vitamin B12 or folate deficiencis. This leads to abnormal nuclear maturation of the hematopoietic cells and ineffective erythropoiesis. The anemia caused by B12 deficiency is also called pernicious anemia (apart from anemia, other symptoms such as atrophic glossitis, atrophic gastritis and neurologic disorders are often present).

Clinical signs:

  • macrocytic normochromic anemia
  • pernicious anemia: also atrophic glossitis, atrophic gastritis, neurologic disorders

Histology:

  • Peripheral blood: normochromic macrocytic anemia, often pancytopenia, significant anisocytosis, poikilocytosis, polychromasia is absent, neutrophilic hypersegmentation, Howell-Jolly bodies, nuclei-containing erythrocytes, basophilic stippling.
  • Bone marrow: hypercellular with inreased erythropoiesis, which usually dominates (M:E ratio is lower than 1:1). There is an erythropietic left shift and more immature cells are present —  proerythroblasts and basophilic erythroblasts, which contain abnormally large nuclei with finer chromatin. Megakaryocytes are usually larger with hyperlobated nuclei. Mature granulopoietic cells contain hypersegmented nuclei. Giant metamyelocytes are also present.

Pictures

Megaloblastic anemia, bone marrow:
Megaloblastic anemia, bone marrow, HE 100x (72608)

3.3.3.3  Sideropenic Anemia

Introduction:

Anemia caused by inadeqaute iron deposits resulting from insufficient iron intake or increased loss (repeated or prolonged bleeding).

Clinical signs:

Microcytic hypochromic anemia.

Histology:

  • Peripheral blood: hypochromic microcytic anemia, anisocytosis, polychromasia is absent, poikilocytosis.
  • Bone marrow: normocellular or slightly hypercellular with increased normoblastic erythropoiesis. More mature normoblasts contain light cytoplasm with decreased hemoglobin levels. Stainable stromal iron is missing.
3.3.3.4  Chronic Kidney Disease Anemia

Introduction:

Anemia caused by decreased erythropoietin production in chronic kidney disorders.

  • Peripheral blood: normochromic normocytic anemia, minimal polychromasia, sporadic poikilocytes.
  • Bone marrow: normocellular or slightly hypocellular with normal or slightly decreased normoblastic erythropoiesis. Bone changes matching renal osteodystrophia may also be present.
3.3.3.5  Anemias of Chronic Disorders

Introduction:

Anemias caused by chronic diseases (chronic infection, chronic non-infectius inflammation, malignancies, chronic kidney and hepatic diseases).

Clinical signs:

Normocytic normochromic anemia.

Histology:

  • Peripheral blood: normochromic normocytic or hypochromic microcytic anemia, no significant anisocytosis or polychromasia.
  • Bone marrow: normocellular or only slightly hypocellular with normal or slightly decreased normoblastic erythropoiesis. Stainable stromal iron is significantly increased, the number of sideroblasts is decreased or there are none at all.
3.3.3.6  Hemolytic Anemias

Introduction:

Anemias caused by excesive hemolysis. Hemolytic anemias are either congenital or acquired.

Clinical signs:

Normocytic normochromoc anemias.

Histology:

  • Peripheral blood: normochromic normocytic anemia.
  • Bone marrow: is hypercellular with increased normoblastic erythropoiesis, usually with a left shift.
3.3.3.7  Other anemias

Other anemias caused by reduction of erythropoiesis or ineffective erythropoiesis were discussed in other chapters.



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