Free ASCP MLS Exam Practice Questions Mock Test: Part 43 – Bone Marrow Examination and Disorders

• Polycythemia vera (PV) is characterized by pannyelosis – a hyperplasia (increase) of all three myeloid cell lines: erythroid, granulocytic, and megakaryocytic.

• Because all cell lines are increased, the myeloid-to-erythroid (M:E) ratio often remains within the normal range (approximately 2:1 to 4:1).

• The key diagnostic feature is the trilineage hyperplasia, not a skewed M:E ratio.

The other options are incorrect:

• b) High (>10:1) → Characteristic of chronic myeloid leukemia (CML), due to massive granulocytic hyperplasia.

• c) Low (<2:1) → Seen in pure erythroid disorders like some hemolytic anemias.

• d) Variable and unpredictable → Incorrect; the M:E ratio in PV is typically normal due to proportional increases in all lineages.

• Foam cells in the bone marrow with vacuolated cytoplasm containing sphingomyelin are characteristic of Niemann-Pick Disease (types A and B).

• This is a lysosomal storage disorder caused by a deficiency of the enzyme sphingomyelinase, leading to the accumulation of sphingomyelin in macrophages.

The other options are incorrect:

• a) Gaucher Disease → Shows Gaucher cells which have a characteristic wrinkled tissue paper appearance due to glucocerebroside accumulation, not foam cells.

• c) Multiple Myeloma → Shows plasma cell infiltration, not foam cells.

• d) Hairy Cell Leukemia → Shows lymphocytes with “hairy” projections, not foam cells.

• Dyserythropoiesis refers to abnormal and ineffective red blood cell production.

• In Myelodysplastic syndrome (MDS), dyserythropoiesis is a key feature and includes nuclear abnormalities such as:

  • Nuclear budding

  • Irregular nuclear contours

  • Multinucleation

  • Karyorrhexis (nuclear fragmentation)

• These changes reflect disordered maturation and are part of the pathologic findings in MDS bone marrow.

The other options are incorrect:

• a) Megaloblastic anemia → Shows megaloblastic changes (nuclear-cytoplasmic asynchrony) but not the same dysplastic nuclear abnormalities as MDS.

• c) Sickle cell anemia → Shows sickle-shaped RBCs due to hemoglobin S, not dyserythropoiesis with nuclear abnormalities.

• d) Leukemoid reaction → Shows increased granulocyte precursors without dysplastic features.

• Parvovirus B19 infects and lyses erythroid progenitor cells, specifically pronormoblasts.

• This leads to the appearance of giant pronormoblasts in the bone marrow—large, early red cell precursors with prominent nucleoli and viral inclusions.

• In immunocompetent individuals, this causes a transient aplastic crisis (especially in those with underlying hemolytic disorders), resulting in temporary marrow erythroid hypoplasia.

The other options are incorrect:

• a) Hypercellularity → Not typical; parvovirus B19 causes erythroid hypoplasia.

• c) Increased blasts → Seen in leukemias, not parvovirus infection.

• d) Increased megakaryocytes → Seen in myeloproliferative neoplasms like essential thrombocythemia.

• In CLL, the bone marrow is typically hypercellular and infiltrated by small, mature-looking lymphocytes (with clumped chromatin and scant cytoplasm).

• These lymphocytes are monoclonal B-cells and their accumulation in the marrow can lead to cytopenias by crowding out normal hematopoietic cells.

The other options are incorrect:

• a) ALL (Acute Lymphoblastic Leukemia) → Shows lymphoblasts (immature cells with fine chromatin and nucleoli), not small mature lymphocytes.

• c) AML (Acute Myeloid Leukemia) → Shows myeloblasts (immature myeloid cells).

• d) Multiple myeloma → Shows an increase in plasma cells, not small mature lymphocytes.

• Essential thrombocythemia (ET) is a myeloproliferative neoplasm characterized by sustained overproduction of platelets.

• The bone marrow in ET typically shows a marked increase in megakaryocytes, which are often large and clustered, with hyperlobated nuclei.

The other options are incorrect:

• b) Aplastic anemia → Shows hypocellular marrow with a marked decrease in all cell lines, including megakaryocytes.

• c) Iron deficiency anemia → May show normocellular or hypercellular marrow due to erythroid hyperplasia, but megakaryocytes are not specifically increased.

• d) Hemophilia A → A coagulation factor VIII deficiency disorder; bone marrow is normal, with no increase in megakaryocytes.

• Megaloblastic anemia (due to vitamin B12 or folate deficiency) is characterized by megaloblastoid erythropoiesis in the bone marrow.

• Key features include:

  • Large, abnormal erythroid precursors (megaloblasts) with nuclear-cytoplasmic asynchrony (immature nucleus with mature hemoglobinized cytoplasm).

  • Giant metamyelocytes and hypersegmented neutrophils.

  • Hypercellular marrow due to ineffective hematopoiesis.

The other options are incorrect:

• b) Ringed sideroblasts → Seen in sideroblastic anemia.

• c) An absence of erythroid precursors → Seen in pure red cell aplasia.

• d) An increase in small, mature lymphocytes → Seen in chronic lymphocytic leukemia (CLL).

• The normal myeloid to erythroid (M:E) ratio in a healthy adult bone marrow typically ranges from 2:1 to 4:1, with 3:1 being a standard average.

• This means there are normally about three myeloid cells (granulocytes and their precursors) for every one erythroid cell (red blood cell precursors).

The other options are incorrect:

• a) 1:1 → Suggests erythroid hyperplasia, seen in conditions like hemolytic anemia or blood loss.

• b) 1:3 → Indicates a marked reversal, seen in pure red cell aplasia or severe erythroid expansion.

• d) 10:1 → Indicates myeloid hyperplasia, seen in chronic myeloid leukemia or severe infections.

• Marrow fibrosis (reticulin or collagen deposition) is best detected and evaluated on a bone marrow core biopsy.

• Special stains, particularly the reticulin stain (and trichrome stain for collagen), are used to visualize and grade the extent of fibrosis.

• A core biopsy provides the structural integrity needed to assess fiber density and pattern, which is lost in an aspirate smear.

The other options are incorrect:

• a) Aspirate smear → Often results in a “dry tap” in fibrosis, and fibers are not visible on a smear.

• c) Flow cytometry → Used for immunophenotyping, not fibrosis detection.

• d) Peripheral smear → May show teardrop cells and leukoerythroblastosis as indirect signs, but cannot directly detect marrow fibrosis.

• Chronic Myeloid Leukemia (CML) is characterized by a massive increase in myeloid cells at all stages of development.

• The bone marrow is hypercellular due to granulocytic hyperplasia (marked increase in neutrophils and their precursors).

• There is a left shift, meaning an increased number of immature granulocytes (myelocytes, promyelocytes), but blasts are <20% (if ≥20%, it suggests transformation to acute leukemia).

The other options are incorrect:

• a) Increased blasts >20% → Indicates blast crisis (accelerated or acute phase) of CML, not the chronic phase.

• c) Fatty replacement → Seen in aplastic anemia.

• d) Pure erythroid hyperplasia → Seen in polycythemia vera (early) or hemolytic anemias.

• In hemolytic anemia, the premature destruction of red blood cells leads to compensatory erythropoiesis in the bone marrow.

• This results in erythroid hyperplasia, meaning a significant increase in erythroid precursors (normoblasts) in the marrow.

• The M:E (myeloid-to-erythroid) ratio is often decreased (e.g., 1:1 or even reversed) due to the expansion of the erythroid series.

The other options are incorrect:

• b) Decreased erythroid activity → Seen in aplastic anemia or bone marrow failure.

• c) Fatty replacement → Characteristic of aplastic anemia.

• d) Fibrosis → Seen in myelofibrosis.

• Acute Myeloid Leukemia (AML) with inv(16)(p13.1q22) or t(16;16)(p13.1;q22) is a specific genetic subtype of AML (formerly known as M4Eo in the FAB classification).

• This abnormality disrupts the CBFB-MYH11 fusion gene and is characteristically associated with a significant increase in abnormal eosinophil precursors in the bone marrow.

• These eosinophils often contain a mixture of eosinophilic and basophilic granules, which are a distinctive morphological clue to this diagnosis.

The other options are incorrect:

• b) Chronic Lymphocytic Leukemia (CLL) → Shows an increase in small, mature lymphocytes, not eosinophils.

• c) Iron deficiency anemia → Shows microcytic, hypochromic red cells and decreased iron stores; no increase in eosinophils.

• d) Multiple Myeloma → Shows an increase in plasma cells, not eosinophils.

• Reed–Sternberg cells are the pathognomonic malignant cells of Hodgkin lymphoma.

• These are large, binucleated or multilobated cells with prominent eosinophilic nucleoli, giving an “owl-eye” appearance.

• Their presence in a bone marrow biopsy indicates marrow involvement by Hodgkin lymphoma, which is typically seen in advanced-stage disease.

The other options are incorrect:

• b) Non-Hodgkin lymphoma → Involves the marrow with lymphoma cells specific to the subtype (e.g., small lymphocytes in CLL), but not Reed–Sternberg cells.

• c) Multiple myeloma → Involves plasma cells, not Reed–Sternberg cells.

• d) AML → Involves myeloblasts, not Reed–Sternberg cells.

• The myeloid-to-erythroid (M:E) ratio is assessed by performing a manual morphologic differential count on a bone marrow aspirate smear under the microscope.

• This involves counting and categorizing at least 500 nucleated cells into myeloid precursors, erythroid precursors, lymphocytes, monocytes, and other cells to determine the ratio of granulocytic to erythroid cells.

The other options are incorrect:

• a) Flow cytometry → Used for immunophenotyping, not for determining M:E ratio.

• c) Hemoglobin electrophoresis → Used to identify hemoglobin variants (e.g., in thalassemia or sickle cell disease).

• d) Reticulocyte count → Measures red blood cell production in peripheral blood, not bone marrow M:E ratio.

• The Prussian blue stain (also known as Perls’ stain) is the standard histochemical stain used to detect iron stores in bone marrow aspirate or biopsy specimens.

• It specifically stains ferric iron (Fe³⁺) as a blue color, allowing for the visualization and grading of iron stores in marrow macrophages and erythroid precursors.

The other stains have different uses:

• a) PAS stain → Used to detect glycogen, mucins, and other carbohydrates; helpful in diagnosing certain leukemias (e.g., erythroleukemia) and storage diseases.

• c) Wright–Giemsa stain → The routine stain for peripheral blood and bone marrow smears to assess overall cell morphology.

• d) Sudan black stain → Used to stain myeloid granules; helpful in classifying acute myeloid leukemia (AML).

Refractory Anemia with Excess Blasts (RAEB) is a well-defined category within the WHO classification of Myelodysplastic Syndromes (MDS).

It is subdivided into:

RAEB-1: 5–9% blasts in the bone marrow.

RAEB-2: 10–19% blasts in the bone marrow (or Auer rods present with <20% blasts).

The other options are not classified as MDS:

• a) Chronic Myelomonocytic Leukemia (CMML) → Classified under MDS/MPN overlap syndromes.
• c) Essential Thrombocythemia (ET) → A myeloproliferative neoplasm (MPN).
• d) Juvenile Myelomonocytic Leukemia (JMML) → Also classified under MDS/MPN overlap syndromes.

• The Prussian blue stain (also known as Perls’ stain) is the gold standard for evaluating iron stores in the bone marrow.

• It specifically detects ferric iron (Fe³⁺) in hemosiderin within macrophages and erythroid precursors, staining it a blue color.

• This allows for the assessment of both storage iron (in macrophages) and functional iron (in erythroid precursors), and is essential for diagnosing iron deficiency, iron overload, and sideroblastic anemias.

The other stains have different uses:

• a) Wright stain → Routine stain for cellular morphology.

• b) Myeloperoxidase stain → Used to identify myeloid lineage in acute leukemias.

• c) Periodic acid-Schiff (PAS) stain → Used to detect glycogen and mucopolysaccharides; helpful in diagnosing certain leukemias and storage diseases.

• Multiple myeloma is a malignancy of plasma cells.

• The bone marrow in multiple myeloma shows a significant increase in plasma cells, typically making up more than 10% of the marrow cellularity (often much higher), with sheets or clusters of abnormal plasma cells.

• These malignant plasma cells produce monoclonal immunoglobulin, which appears as an M-spike on serum protein electrophoresis.

The other options are incorrect:

• a) Lymphoblasts → Increased in acute lymphoblastic leukemia (ALL).

• c) Erythroblasts → Increased in erythroid hyperplasia (e.g., hemolytic anemia).

• d) Myeloblasts → Increased in acute myeloid leukemia (AML).

According to the WHO classification, Refractory Anemia with Ringed Sideroblasts (RARS) is defined by:

• ≥15% ringed sideroblasts in the bone marrow erythroid series.

• <5% blasts in the bone marrow.

• Dysplasia primarily restricted to the erythroid lineage.

• Presence of refractory anemia (anemia that does not respond to usual treatments).

The other options are incorrect:

• b) >50% ringed sideroblasts with >20% blasts → This would suggest an overlap with acute leukemia or MDS/MPN, not RARS.

• c) <5% ringed sideroblasts with single lineage dysplasia → This would fall under MDS with single lineage dysplasia, not RARS.

• d) Presence of Auer rods with any number of ringed sideroblasts → Auer rods indicate MDS with excess blasts or acute myeloid leukemia, not RARS.

• The presence of ≥20% blasts in the bone marrow is the defining diagnostic criterion for acute leukemia according to the World Health Organization (WHO) classification.

• This applies to both acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL).

The other options are incorrect:

• a) Leukemoid reaction → Shows increased mature and immature granulocytes, but blasts are not increased to ≥20%.

• c) Aplastic anemia → Characterized by marrow hypocellularity and a decrease in all cell lines, including blasts.

• d) Myelodysplasia only → Myelodysplastic syndromes (MDS) have <20% blasts. If blasts reach ≥20%, the diagnosis changes to acute leukemia.

• The normal myeloid-to-erythroid (M:E) ratio in adult bone marrow is approximately 2:1 to 4:1.

• This means there are normally about 2 to 4 myeloid cells (granulocytes and their precursors) for every 1 erythroid cell (red blood cell precursors).

The other options are incorrect:

• a) 1:1 → This would indicate erythroid hyperplasia (e.g., in hemolytic anemia or blood loss).

• c) 10:1 → This indicates myeloid hyperplasia (e.g., in chronic myeloid leukemia or infection).

• d) 20:1 → This is markedly elevated and suggests a significant increase in myeloid cells or a severe reduction in erythroid precursors.

• Primary myelofibrosis is a myeloproliferative neoplasm characterized by bone marrow fibrosis (reticulin and collagen deposition), which is its hallmark feature.

• This fibrosis disrupts normal hematopoiesis, leading to:

  • Extramedullary hematopoiesis (in the spleen and liver)

  • A characteristic peripheral blood picture with teardrop cells (dacrocytes) and a leukoerythroblastic reaction

The other options are incorrect:

• a) Pannyelosis → Characteristic of polycythemia vera (increase in all myeloid cell lines).

• c) Ringed sideroblasts → Seen in sideroblastic anemia.

• d) Decreased megakaryocytes → Incorrect; primary myelofibrosis often shows increased and atypical megakaryocytes in clusters.

In infants and young children, the proximal tibia is a commonly used site for bone marrow aspiration because:

• It contains active hematopoietic (red) marrow.

• It is easily accessible and relatively safe, with no major nerves or blood vessels in the immediate vicinity.

• The bone is still soft and easier to penetrate.

The other options are less common or not used:

• a) Sternum → Can be used in older children and adults, but carries more risk and is generally avoided in young children.

• c) Radius and d) Ulna → Not standard sites for bone marrow aspiration, as they are primarily cortical bone with little marrow space.

• Auer rods are slender, needle-shaped cytoplasmic inclusions formed by the fusion of primary (azurophilic) granules.

• They are pathognomonic for myeloid lineage and are found in myeloblasts or promyelocytes.

• Their presence is a definitive feature of Acute Myeloid Leukemia (AML) and helps distinguish it from Acute Lymphoblastic Leukemia (ALL).

The other options are incorrect:

• a) Acute Lymphoblastic Leukemia (ALL) → Lymphoblasts do not contain Auer rods.

• b) Chronic Lymphocytic Leukemia (CLL) → Involves mature lymphocytes, not blasts, and no Auer rods.

• d) Hairy Cell Leukemia → Involves mature B-lymphocytes with “hairy” projections, not Auer rods.

• Myelofibrosis is characterized by:

  • “Dry tap” during bone marrow aspiration due to marrow fibrosis, making it difficult to aspirate marrow particles.

  • Tear-drop cells (dacrocytes) in the peripheral blood smear, caused by the extrusion of red blood cells through the fibrotic marrow.

  • Other features include extramedullary hematopoiesis and leukoerythroblastosis (presence of immature myeloid and erythroid precursors in the blood).

The other options are incorrect:

• a) Polycythemia vera → Shows hypercellular marrow (easy aspiration) and increased red cell mass, not tear-drop cells.

• c) Aplastic anemia → Shows hypocellular marrow but no tear-drop cells; dry tap may occur but is due to empty marrow, not fibrosis.

• d) Leukemoid reaction → Shows immature myeloid cells in blood but no dry tap or tear-drop cells.

• The Philadelphia chromosome is a shortened chromosome 22 resulting from a reciprocal translocation between chromosomes 9 and 22, denoted as t(9;22)(q34;q11).

• This translocation creates the BCR-ABL1 fusion gene, which produces a constitutively active tyrosine kinase that drives uncontrolled myeloid cell proliferation.

• It is the pathognomonic genetic abnormality found in over 95% of Chronic Myelogenous Leukemia (CML) cases.

The other options are incorrect:

• a) Acute Promyelocytic Leukemia → Associated with t(15;17).

• b) Polycythemia Vera → Often associated with JAK2 V617F mutation.

• d) Myelodysplastic Syndrome → Has various cytogenetic abnormalities, but not the Philadelphia chromosome.

The description of >80% erythroid precursors in the bone marrow, with >30% of the nucleated cells being proerythroblasts (early erythroid blasts), is the diagnostic hallmark of Acute Erythroid Leukemia (according to the WHO classification).

This specific subtype of AML (formerly known as AML-M6) is characterized by a predominant erythroid population and a high percentage of immature erythroblasts.

The other options are incorrect:

• a) Myelodysplastic Syndrome (MDS) → Has dysplastic features and <20% blasts; it does not show such a high percentage of proerythroblasts.

• b) Acute Myeloid Leukemia (AML) with minimal differentiation → Myeloblasts are the dominant population, not erythroid precursors.

• d) Aplastic Anemia → Shows a hypocellular marrow with fat replacement and a severe reduction of all hematopoietic cells, not an expansion of erythroblasts.

• Hairy cell leukemia (HCL) is characterized by:

  • A “dry tap” during bone marrow aspiration due to increased marrow fibrosis and infiltration by hairy cells.

  • The bone marrow biopsy shows a diffuse or interstitial infiltrate of characteristic hairy cells with abundant pale cytoplasm and well-defined borders.

  • Immunophenotyping (e.g., CD103, CD25, CD11c positivity) on peripheral blood or marrow confirms the diagnosis.

The other options are incorrect:

• b) Reticulocyte count → Assesses erythropoietic activity, not diagnostic for HCL.

• c) Hemoglobin electrophoresis → Used for hemoglobinopathies (e.g., sickle cell, thalassemia).

• d) Coombs test → Detects antibodies in immune hemolytic anemia.

• Erythroleukemia (a subtype of acute myeloid leukemia, specifically AML-M6 in the older FAB classification) is defined by:

  • ≥50% erythroid precursors of all nucleated cells in the bone marrow.

  • ≥20% myeloblasts of the non-erythroid cells.

  • This results in a low M:E ratio due to the massive expansion of the erythroid series.

The other options are incorrect:

• a) Chronic Myelogenous Leukemia (CML) → Shows granulocytic hyperplasia and a high M:E ratio.

• c) Aplastic Anemia → Shows a hypocellular marrow, not hypercellular.

• d) Essential Thrombocythemia → Shows increased megakaryocytes, not a predominance of erythroid precursors.

• Megaloblastic bone marrow, caused by vitamin B12 or folate deficiency, is characterized by megaloblastic erythropoiesis.

• The key feature is nuclear–cytoplasmic asynchrony: the nucleus remains immature and large (with open, lacy chromatin) while the cytoplasm matures normally, leading to large, developing red blood cells (megaloblasts).

The other options are incorrect:

• b) Hypocellularity → Characteristic of aplastic anemia, not megaloblastic anemia.

• c) Abundant iron stores → May be present but is not specific to megaloblastic anemia.

• d) Predominance of lymphoblasts → Seen in acute lymphoblastic leukemia (ALL).

• Chronic Lymphocytic Leukemia (CLL) is characterized by a progressive accumulation of monoclonal, mature-looking B lymphocytes in the bone marrow, blood, and lymphoid tissues.

• In the bone marrow, these cells are typically small, mature lymphocytes with clumped chromatin and scant cytoplasm. The infiltration can be nodular, interstitial, or diffuse, and as the disease progresses, it can replace normal marrow elements, leading to cytopenias.

The other options are incorrect:

• a) An increase in myeloblasts → This is seen in acute myeloid leukemia (AML).

• c) An increase in megakaryocytes → This is a feature of myeloproliferative neoplasms like essential thrombocythemia.

• d) A depletion of all cell lines → This describes aplastic anemia.

• Aplastic anemia is characterized by bone marrow failure leading to pancytopenia (low red blood cells, white blood cells, and platelets) in the peripheral blood.

• The defining bone marrow finding is marked hypocellularity (usually < 25–30% cellularity) with replacement by fat.

• There is an absence of significant fibrosis, infiltrates, or increased blasts.

The other options are incorrect:

• a) Hypercellular marrow → Seen in leukemias, myeloproliferative neoplasms, or hemolytic anemias.

• c) Normal cellularity → Not characteristic of aplastic anemia.

• d) Increased blasts → Seen in acute leukemias or myelodysplastic syndromes.

• Ringed sideroblasts are abnormal erythroid precursors (normoblasts) in which iron-laden mitochondria form a perinuclear ring, visualized with Prussian blue stain.

• This finding is the hallmark of sideroblastic anemia, a disorder of ineffective erythropoiesis due to impaired heme synthesis.

• Causes can be hereditary (e.g., ALAS2 gene mutations) or acquired (e.g., myelodysplastic syndromes, alcohol, drugs).

The other options are incorrect:

• a) Iron deficiency anemia → Shows absent marrow iron stores and no ringed sideroblasts.

• b) Anemia of chronic inflammation → Shows normal or increased iron stores, but not ringed sideroblasts.

• d) Thalassemia → May show erythroid hyperplasia and increased iron, but not the characteristic ringed sideroblasts.

• According to the WHO classification, MDS with ringed sideroblasts (MDS-RS) is defined by:

  • ≥15% ringed sideroblasts in the bone marrow erythroid series (or ≥5% if accompanied by an SF3B1 mutation).

  • Dysplasia primarily in the erythroid lineage.

  • <5% blasts in the bone marrow and <1% in the peripheral blood.

The other options are incorrect:

• a) MDS with single lineage dysplasia → Defined by dysplasia in one cell line and <15% ringed sideroblasts.

• b) MDS with excess blasts → Defined by 5–19% blasts, not by ringed sideroblasts.

• d) MDS with isolated del(5q) → Defined by the specific cytogenetic abnormality del(5q), regardless of ringed sideroblast count.

The posterior superior iliac crest is the most common and preferred site for bone marrow aspiration and biopsy in adults because it is:

• Safely accessible

• Contains abundant marrow

• Involves minimal risk to nearby structures

The other options are less common or not preferred:

• a) Sternum → Can be used for aspiration in some cases, but carries higher risk due to proximity to major vessels and the heart.

• b) Tibia → Used primarily in infants and young children, not adults.

• d) Femur → Not a standard site for marrow aspiration; typically involved in procedures like bone

• In severe iron deficiency anemia, the body’s iron stores are depleted.

• When a Prussian blue stain is performed on a bone marrow aspirate or biopsy, it demonstrates the amount of storage iron (as hemosiderin) in macrophages.

• In uncomplicated, established iron deficiency anemia, these iron stores are absent (a result of 0 on the Gale scale).

The other options are incorrect:

• a) Markedly increased → Seen in conditions like hemochromatosis or transfusion overload.

• b) Normal → Inconsistent with severe iron deficiency.

• d) Ringed sideroblasts → Seen in sideroblastic anemia, where iron is present but improperly utilized in the mitochondria of erythroid precursors.

A “dry tap” occurs when no bone marrow particles or fluid can be aspirated into the syringe during a bone marrow aspiration procedure. This is most commonly associated with:

1. Myelofibrosis: Replacement of normal marrow with fibrous tissue, making aspiration difficult or impossible.

2. Aplastic anemia: Marked hypocellularity (empty marrow) with very few cells to aspirate.

3. Marrow infiltration: By tumor cells (e.g., metastatic cancer, lymphoma) or other abnormal tissue.

The other options are incorrect:

• a) Iron deficiency anemia → Usually yields good marrow aspirate with erythroid hyperplasia.

• c) Megaloblastic anemia → Typically yields hypercellular marrow.

• d) Hemolytic anemia → Usually yields good aspirate with erythroid hyperplasia.

• Gaucher cells are enlarged, lipid-laden macrophages found in the bone marrow (and other organs) of patients with Gaucher disease.

• They contain undegraded glucocerebroside due to a deficiency of the enzyme glucocerebrosidase.

• Microscopically, they have a characteristic wrinkled tissue paper appearance in the cytoplasm.

The other options are incorrect:

• a) DNA remnants → This describes Howell-Jolly bodies in red blood cells.

• c) Iron deposits → This describes Pappenheimer bodies or hemosiderin-laden macrophages.

• d) Hemoglobin crystals → Seen in certain hemoglobinopathies like HbC disease.

• Bone marrow cellularity refers to the percentage of the marrow space occupied by hematopoietic cells (as opposed to fat).

• In healthy adults, normal bone marrow cellularity is approximately 30–70%, with the remaining being fat.

• Cellularity decreases with age; in younger adults, it may be closer to 50–70%, while in older adults it may be lower (around 30–50%).

The other options are incorrect:

• a) 10% → This would indicate severe hypocellularity, as seen in aplastic anemia.

• c) 90% → This indicates hypercellularity, which can be seen in leukemia, myeloproliferative neoplasms, or severe hemolytic anemias.

• d) 100% → This is not seen in normal marrow and would indicate complete replacement by abnormal cells (e.g., solid tumor metastasis or extensive fibrosis).

• Myelofibrosis (especially primary myelofibrosis, a type of myeloproliferative neoplasm) is characterized by:

  • Bone marrow fibrosis: Replacement of normal marrow with collagen and reticulin fibers.

  • Extramedullary hematopoiesis (EMH): Blood cell production occurring outside the marrow, typically in the spleen and liver, causing hepatosplenomegaly.

The other options are incorrect:

• a) Increased bone marrow cellularity → May occur early in the disease, but the hallmark is progressive fibrosis leading to eventual hypocellularity.

• c) Increased iron stores → Not specific to myelofibrosis; can be seen in many conditions.

• d) Pure erythroid hyperplasia → Characteristic of conditions like polycythemia vera (early) or hemolytic anemias, not myelofibrosis.

• The defining feature of acute myeloid leukemia (AML) is the presence of ≥20% blasts (myeloblasts) in the bone marrow or peripheral blood, according to the World Health Organization (WHO) classification.

• This replacement of normal hematopoietic cells by a clonal population of immature blasts leads to bone marrow failure, resulting in cytopenias.

The other options are incorrect:

• a) Chronic Lymphocytic Leukemia (CLL) → Characterized by an accumulation of mature-looking lymphocytes, not blasts.

• b) Myelodysplastic Syndromes (MDS) → Defined by dysplasia and cytopenias with <20% blasts. If blasts reach ≥20%, the diagnosis is changed to AML.

• d) Polycythemia Vera (PV) → A myeloproliferative neoplasm characterized by overproduction of mature red cells, white cells, and platelets; it does not show increased blasts.

• The isolated del(5q) abnormality defines the MDS with isolated del(5q) subtype in the WHO classification.

• Patients with this abnormality typically have a more favorable prognosis and a stable clinical course compared to other MDS subtypes.

• They often present with refractory macrocytic anemia, normal or elevated platelet counts, and hypolobated megakaryocytes in the bone marrow.

• They also have a lower risk of transformation to acute myeloid leukemia (AML) and often respond well to treatment with lenalidomide.

The other options are associated with a poorer or intermediate prognosis:

• a) Monosomy 7 → Associated with a poor prognosis and higher risk of AML transformation.

• c) Trisomy 8 → Generally an intermediate-risk abnormality.

• d) del(20q) → Considered an intermediate-risk abnormality.

• Multiple myeloma is a malignant plasma cell disorder. Key bone marrow findings that distinguish it from a reactive plasmacytosis include:

  • Sheets or clusters of immature/atypical plasma cells (replacing normal marrow architecture).

  • Monoclonal plasma cell population (confirmed by flow cytometry or immunohistochemistry).

  • Significant percentage of plasma cells (usually >10%, often much higher).

The other options can be seen in both reactive and neoplastic conditions:

• a) Presence of occasional flame cells → Can be seen in both reactive states and myeloma.

• b) Plasmacytic satellitesis → An artifact of smear preparation, not diagnostic.

• d) Presence of Russell bodies → Can be found in both benign and malignant plasma cells.

• In a normal bone marrow aspirate, the typical range is 5 to 10 megakaryocytes per low power field (10x objective).

• This count helps assess whether megakaryopoiesis is normal, increased (as in myeloproliferative neoplasms like essential thrombocythemia), or decreased (as in aplastic anemia or certain drug toxicities).

The other options are incorrect:

• a) 1-2 → Indicates megakaryocytic hypoplasia.

• c) 15-20 and d) 25-30 → Indicate megakaryocytic hyperplasia.

• Myelodysplastic syndromes (MDS) are a group of clonal hematopoietic stem cell disorders.

• They are characterized by:

  • Dysplasia (abnormal morphology) in one or more myeloid cell lines (erythroid, granulocytic, megakaryocytic).

  • Cytopenias (low blood counts) in the peripheral blood.

  • Ineffective hematopoiesis (the bone marrow is often hypercellular, but blood cell production is defective).

  • An increased risk of progression to acute myeloid leukemia (AML).

The other options are incorrect:

• a) Purely erythroid disorders → Incorrect, as MDS involves multiple cell lines.

• c) Reactive conditions → MDS are neoplastic, not reactive.

• d) Autoimmune marrow suppression → This describes conditions like some cases of aplastic anemia, not MDS.

• The megakaryocyte is the largest cell normally found in the bone marrow, typically ranging from 50 to 100 micrometers in diameter.

• It is responsible for producing platelets and is easily identified by its enormous size and multilobulated nucleus.

The other options, while notable, are not the largest:

• a) Osteoblast → A bone-forming cell, large but generally smaller than a megakaryocyte.

• b) Histiocyte (macrophage) → Can be large, especially when activated, but not typically as large as a megakaryocyte.

• d) Mast Cell → Generally smaller and rounder, with granules that obscure the nucleus.

• The finding of ≥20% blasts in the bone marrow is the defining criterion for a diagnosis of acute leukemia.

• A marrow that is hypercellular with 95% blasts far exceeds this threshold.

• The presence of Auer rods (needle-shaped inclusions composed of fused primary granules) specifically indicates a myeloid lineage, confirming Acute Myeloid Leukemia (AML).

The other options are incorrect:

• a) Chronic Myelogenous Leukemia (CML) → Shows a full spectrum of myeloid maturation with <10% blasts in the chronic phase.

• c) Myelodysplastic Syndrome (MDS) → Defined by <20% blasts.

• d) Aplastic Anemia → Characterized by a hypocellular marrow, not a hypercellular one filled with blasts.

• Pannyelosis refers to the hyperplasia (overgrowth) of all three myeloid cell lines in the bone marrow: erythroid, granulocytic, and megakaryocytic.

• This is a hallmark histological finding in Polycythemia Vera (PV), a Philadelphia chromosome-negative myeloproliferative neoplasm.

• The bone marrow in PV is typically hypercellular with increased red blood cell precursors, white blood cell precursors, and megakaryocytes (which often appear in clusters).

The other options are incorrect:

• a) Aplastic Anemia → Shows hypocellular marrow with fatty replacement.

• b) Myelodysplastic Syndrome (MDS) → May be hypercellular or normocellular, but shows dysplasia in one or more cell lines, not balanced pannyelosis.

• c) Paroxysmal Nocturnal Hemoglobinuria (PNH) → Shows normocellular or hypocellular marrow, not pannyelosis.

• Multiple myeloma is characterized by the overproduction of monoclonal immunoglobulins (M-proteins).

• These abnormal proteins coat red blood cells, reducing their normal negative surface charge repulsion and causing them to stack together in chains, a phenomenon known as rouleaux formation.

• This is a classic and frequently observed finding on the peripheral blood smear of patients with multiple myeloma.

The other options are incorrect:

• b) Target cells → More characteristic of liver disease or hemoglobinopathies like thalassemia.

• c) Howell–Jolly bodies → Seen in hyposplenism or megaloblastic anemia.

• d) Bite cells → Seen in oxidative hemolysis, such as in G6PD deficiency.

• Aplastic anemia is defined by bone marrow failure resulting in:

  • Hypocellularity (marked reduction in hematopoietic cells).

  • Fatty replacement of the normal marrow space.

  • Pancytopenia (low red blood cells, white blood cells, and platelets) in the peripheral blood.

The other options are incorrect:

• a) Hypercellular with increased blasts → Characteristic of acute leukemia.

• b) Hypercellular with dysplastic changes → Seen in myelodysplastic syndromes (MDS).

• d) Normocellular with ringed sideroblasts → Seen in sideroblastic anemia.

• In a normal adult bone marrow aspirate, the most abundant granulocyte precursor is the metamyelocyte.

• Maturation sequence of granulocytes:

  1. Myeloblast → 2. Promyelocyte → 3. Myelocyte → 4. Metamyelocyte → 5. Band → 6. Segmented neutrophil.

• Myeloblasts and promyelocytes are less numerous.

• Segmented neutrophils are mainly found in peripheral blood rather than in marrow.

• Aplastic anemia is defined by:

  • Hypocellular bone marrow (marked reduction in hematopoietic cells, replaced by fat).

  • Pancytopenia (low counts of all three blood cell lines: red blood cells, white blood cells, and platelets).

The other options are incorrect:

• b) Iron deficiency anemia → Shows microcytic, hypochromic anemia, but the bone marrow is usually normocellular or hypercellular (due to erythroid hyperplasia), and pancytopenia is not present.

• c) Thalassemia minor → Shows mild microcytic anemia, but bone marrow is hypercellular (due to ineffective erythropoiesis) and pancytopenia is absent.

• d) CML (Chronic Myeloid Leukemia) → Shows hypercellular bone marrow (due to massive granulocytic proliferation) and elevated white blood cell counts, not pancytopenia.

• Polycythemia vera (PV) is a myeloproliferative neoplasm characterized by overproduction of red blood cells, and often white blood cells and platelets as well.

• The bone marrow biopsy typically shows:

  • Hypercellularity (increased cellularity for the patient’s age)

  • Pannyelosis: Increase in all myeloid cell lines (erythroid, granulocytic, and megakaryocytic)

  • Prominent erythroid precursors and megakaryocytes (which may be clustered and pleomorphic)

The other options are incorrect:

• a) Hypocellularity → Seen in aplastic anemia.

• c) Increased lymphocytes only → Seen in chronic lymphocytic leukemia.

• d) Increased blasts only → Seen in acute leukemia.

• Sea-blue histiocytes are macrophages in the bone marrow (and other organs) whose cytoplasm is filled with lipid-containing granules that stain a distinctive sea-blue or blue-green color with Wright-Giemsa stain.

• They are associated with lipid storage disorders, particularly:

  • Niemann-Pick disease (sphingomyelinase deficiency)

  • Other inborn errors of lipid metabolism

• They can also be seen in certain acquired conditions like chronic myelogenous leukemia (CML) or after splenectomy, but they are classically linked to inherited lipid storage diseases.

The other options are incorrect:

• b) Megaloblastic anemia → Shows megaloblastic changes, not sea-blue histiocytes.

• c) Iron deficiency → Shows microcytic, hypochromic RBCs and absent iron stores.

• d) Aplastic anemia → Shows hypocellular marrow, not sea-blue histiocytes.

• Ring sideroblasts are abnormal erythroid precursors (normoblasts) in the bone marrow in which iron-laden mitochondria form a ring or collar around the nucleus.

• They are visualized using Prussian blue stain, which shows blue granules encircling at least one-third of the nucleus.

• This finding is the hallmark of sideroblastic anemia, a disorder characterized by defective heme synthesis and ineffective erythropoiesis.

The other options are incorrect:

• a) Iron deficiency anemia → Shows absent iron stores and no ring sideroblasts.

• c) Thalassemia → May have increased iron stores and sideroblasts, but not the characteristic ring form.

• d) Pernicious anemia → A type of megaloblastic anemia due to B12 deficiency; shows megaloblastic changes, not ring sideroblasts.

• Giant, vacuolated, multinucleated erythroid precursors are a hallmark dysplastic finding in erythroleukemia (a subtype of acute myeloid leukemia, specifically AML-M6 in the FAB classification).

• This subtype is characterized by a predominant erythroid population (>50% of nucleated cells in the marrow) and significant dysplastic changes in the erythroid series, including these abnormal, giant forms.

The other options are incorrect:

• a) Chronic Myelogenous Leukemia (CML) → Shows a full spectrum of granulocytic maturation without prominent erythroid dysplasia.

• b) Primary Myelofibrosis → Shows megakaryocytic proliferation and fibrosis, not giant multinucleated erythroid precursors.

• d) Acute Lymphoblastic Leukemia (ALL) → Involves lymphoblasts, not dysplastic erythroid cells.

• A high myeloid to erythroid (M:E) ratio indicates a relative increase in myeloid cells (granulocytes and their precursors) compared to erythroid cells.

• This is caused by granulocytic hyperplasia, which is an expansion of the granulocytic series.

• Common causes include:

  • Chronic myeloid leukemia (CML)

  • Myeloproliferative neoplasms

  • Severe infections or inflammatory states

The other options are incorrect:

• a) Lymphoid hyperplasia → Would increase lymphocytes, not the myeloid series, and would not typically raise the M:E ratio.

• c) Normoblastic hyperplasia → Would increase erythroid precursors, lowering the M:E ratio.

• d) Myeloid hypoplasia → Would result in a hypocellular marrow with a low M:E ratio.

The WHO classification includes a specific category for Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPN), which are conditions featuring both dysplastic and proliferative features. Chronic Myelomonocytic Leukemia (CMML) is a classic example within this group.

• CMML is characterized by:

  • Persistent peripheral blood monocytosis (≥1 × 10⁹/L).

  • Features of myelodysplasia in one or more myeloid lineages.

The other options are classified elsewhere:

• a) Acute Myelomonocytic Leukemia (AMML) → A subtype of Acute Myeloid Leukemia (AML).

• b) Chronic Myelogenous Leukemia (CML) → Classified as a Myeloproliferative Neoplasm (MPN).

• c) Refractory Anemia with Excess Blasts (RAEB) → A category within Myelodysplastic Syndromes (MDS).

• “Dwarf” or micromegakaryocytes are small, hypolobated megakaryocytes that are a characteristic dysplastic feature seen in certain myeloproliferative neoplasms (MPNs), particularly primary myelofibrosis.

• They can also be seen in myelodysplastic syndromes (MDS) and MDS/MPN overlap disorders.

• Their presence reflects abnormal megakaryopoiesis and is a clue to an underlying clonal marrow disorder.

The other options are incorrect:

• a) Reactive thrombocytosis → Shows normal or increased mature, large megakaryocytes without dysplasia.

• c) Iron deficiency anemia → No specific abnormality in megakaryocytes.

• d) Vitamin B12 deficiency → Shows megaloblastic changes in erythroid and granulocytic series, not abnormal megakaryocytes.

In adults, the bone marrow is the primary site of hematopoiesis (production of blood cells), specifically the axial skeleton (pelvis, sternum, vertebrae, ribs, and skull) and proximal ends of long bones.

The other options are incorrect:

• a) Liver → A major site of hematopoiesis during fetal development, but not in healthy adults.

• b) Spleen → Involved in filtering blood and immune functions, not primary hematopoiesis in adults (except in certain diseases like myelofibrosis, where extramedullary hematopoiesis may occur).

• d) Thymus → Site of T-cell maturation, not general blood cell production.