Hematopathology Practice Questions

Q: A peripheral blood smear is given, blasts count more than 60%. Immunophenotyping reveals positivity for CD13 and CD33. Negative CD19. What is the most likely diagnosis?

AML. ***AML*** - Myeloid lineage markers include **CD13** and **CD33**, which are hallmark immunophenotypic features of **Acute Myeloid Leukemia (AML)**. - A blast count greater than **20%** in the peripheral blood or bone marrow is diagnostic criteria for acute leukemia rather than a chronic process. *CML* - Typically characterized by **myeloid hyperplasia** with a full spectrum of myeloid production rather than a massive (>20%) blast crisis. - The presence of the **Philadelphia chromosome**, resulting in the **BCR-ABL1 fusion gene**, is the diagnostic driver for this condition. *ALL* - Typically positive for lymphoid markers like **CD19**, **CD10**, or **CD20** (B-cell lineage) or **CD3** (T-cell lineage). - The absence of lymphoid markers and presence of myeloid markers effectively rules out this acute leukemia subtype. *CLL* - A chronic condition characterized by the proliferation of **mature, small lymphocytes** with classic

Q: Which genetic abnormality is classically associated with Burkitt lymphoma?

t(8;14). ***t(8;14)*** - This translocation results in the **overexpression of the c-MYC oncogene** on chromosome 8 due to its placement next to the **immunoglobulin heavy chain (IgH) locus** on chromosome 14. - This specific genetic defect leads to high **cellular proliferation** rates, which is a hallmark of the diagnostically distinct **starry-sky appearance** seen in Burkitt lymphoma histology. *t(14;18)* - This translocation is characteristic of **follicular lymphoma**, resulting in the overexpression of the **BCL-2 anti-apoptotic protein**. - It prevents follicular center B-cells from undergoing apoptosis, leading to an expansion of these cells in the lymph nodes. *t(11;14)* - This translocation identifies **mantle cell lymphoma**, caused by the overexpression of **cyclin D1**. - Cyclin D1 promotes cell cycle progression from G1 to S phase, contributing to the aggressive growth of this subtype of non-Hodgkin lymphoma. *t(9;22)* - This is the famous **Philadelphia chromosome**, characterized by the formation of the **BCR-ABL fusion gene**. - It is the defining genetic abnormality in **chronic myeloid leukemia (CML)** and certain subsets of acute lymphoblastic leukemia (ALL).

Q: A peripheral blood smear is shown below. Which supravital stain was used?

New Methylene Blue. ***New Methylene Blue*** - This is a **supravital stain** used to visualize **reticulocytes** in peripheral blood by precipitating residual ribosomal RNA into distinct blue granules. - Unlike routine Romanowsky stains, it stains living red blood cells before fixation, allowing for an accurate identification of these immature cells to assess bone marrow output. *Giemsa stain* - This is a **Romanowsky stain** commonly used for identifying **malaria parasites** and other blood-borne pathogens. - It is a permanent fixative stain, not a **supravital stain**, and does not effectively visualize the ribosomal aggregates characteristic of reticulocytes. *Leishman stain* - Leishman stain is a standard **Romanowsky stain** used for routine differential counts of peripheral blood leucocytes. - It utilizes an alcohol-based fixative, prohibiting the observation of living cell processes, making it unsuitable for **supravital** staining purposes. *Diff-Quik stain* - This is a rapid, modified **Romanowsky stain** often used in cytology and hematology laboratories for quick assessment of cell morphology. - As a fixative-dependent stain, it lacks the specific chemical properties required to demonstrate **reticulocyte** RNA, which requires a vital dye.

Q: A patient diagnosed with beta-thalassemia major is being evaluated. Which of the following is characteristically associated with this condition?

Intravascular hemolysis. ***Intravascular hemolysis*** - In beta-thalassemia major, the accumulation of **unpaired alpha-globin chains** results in the formation of insoluble precipitates within red blood cell precursors. - This leads to **intramedullary hemolysis** and damage to the red cell membrane, which manifests as significant hemolysis, often both intramedullary and peripheral. *Iron overload* - While **iron overload** is a hallmark clinical complication of beta-thalassemia major, it is a **secondary phenomenon** resulting from repeated transfusions and increased intestinal absorption, rather than the primary hematologic mechanism. - It leads to **hemosiderosis** in organs like the liver, heart, and endocrine glands, but is distinct from the primary defect of effective erythropoiesis. *Leukopoiesis* - **Leukopoiesis** refers to the production of white blood cells and is not the primary process affected in beta-thalassemia major. - The bone marrow in this condition preferentially expands its **erythroid lineage** to compensate for anemia, rather than increasing leukopoiesis. *Ineffective hematopoiesis* - This refers to the **premature destruction of erythroid precursors** within the bone marrow, which is a key feature of the disease. - However, while **ineffective erythropoiesis** is a central component, the question specifically asks for a characteristic associated phenomenon; the **hemolysis** caused by globin chain imbalance is the fundamental driver of the hematologic phenotype.

Q: A patient presents with Hb 8 g/dL, MCV 62 fL, and low serum ferritin. Which type of anemia is most likely?

Iron deficiency anemia. ***Iron deficiency anemia*** - The combination of **microcytic anemia** (low MCV) and **low serum ferritin** is diagnostic for iron deficiency anemia, representing the body's depleted iron stores. - This is the most common cause of microcytic anemia, typically resulting from chronic blood loss, poor dietary intake, or malabsorption. *Sideroblastic anemia* - Characterized by inadequate utilization of iron for heme synthesis, usually leading to **high serum ferritin** and iron overload, rather than low, due to iron deposition in mitochondria. - Often shows **ringed sideroblasts** in the bone marrow, a classic feature that distinguishes it from iron deficiency. *Megaloblastic anemia* - Presents with **macrocytic anemia** (high MCV), not microcytic, due to impaired DNA synthesis (e.g., Vitamin B12 or folate deficiency). - The presence of **hypersegmented neutrophils** on a peripheral blood smear is a hallmark feature, which is not present in microcytic cases. *Aplastic anemia* - A **normocytic (or macrocytic)** anemia caused by bone marrow failure and pancytopenia, not typically microcytic. - Serum ferritin levels in aplastic anemia are usually **elevated** due to ineffective erythropoiesis and frequent blood transfusions.

Question 1

A peripheral blood smear is given, blasts count more than 60%. Immunophenotyping reveals positivity for CD13 and CD33. Negative CD19. What is the most likely diagnosis?

Accepted Answer

AML

Answer

CML

Answer

ALL

Answer

CLL

Question 2

Which genetic abnormality is classically associated with Burkitt lymphoma?

Accepted Answer

t(8;14)

Answer

t(14;18)

Answer

t(11;14)

Answer

t(9;22)

Question 3

A peripheral blood smear is shown below. Which supravital stain was used?

Accepted Answer

New Methylene Blue

Answer

Giemsa stain

Answer

Leishman stain

Answer

Diff-Quik stain

Question 4

A patient diagnosed with beta-thalassemia major is being evaluated. Which of the following is
characteristically associated with this condition?

Accepted Answer

Intravascular hemolysis

Answer

Iron overload

Answer

Leukopoiesis

Answer

Ineffective hematopoiesis

Question 5

A patient presents with Hb 8 g/dL, MCV 62 fL, and low serum ferritin. Which type of anemia is
most likely?

Accepted Answer

Iron deficiency anemia

Answer

Sideroblastic anemia

Answer

Megaloblastic anemia

Answer

Aplastic anemia

Question 6

A 45-year-old male presents with fatigue, weight loss, and a dragging sensation in the left upper abdomen for 3 months. Examination reveals massive splenomegaly. CBC shows WBC 1,20,000/µL with haemoglobin 9 g/dL. The peripheral blood smear is shown in Image 1. Which cytogenetic abnormality is most directly responsible for the constitutively active tyrosine kinase driving this disease?

Accepted Answer

A. t(9;22)(q34;q11) producing a BCR-ABL1 fusion protein with persistent RAS/MAPK and JAK-STAT signalling

Answer

B. t(15;17)(q22;q12) producing a PML-RARA fusion protein that blocks myeloid differentiation

Answer

C. t(8;14)(q24;q32) producing a MYC-IGH fusion protein with uncontrolled cell cycle entry

Answer

D. del(5q) producing haploinsufficiency of RPS14 with dysregulated erythroid maturation

Question 7

A 53-year-old male presents with an enlarged supraclavicular lymph node. Examination reveals enlargement of the Waldeyer ring of oropharyngeal lymphoid tissue. There is no hepatosplenomegaly. Lymph node biopsy reveals replacement by a monomorphous population of large lymphoid cells with enlarged nuclei and prominent nucleoli. The CBC is normal except for mild anemia. Immunohistochemical staining and flow cytometry of the node reveals that most lymphoid cells are CD19+, CD10-, CD3-, CD15-, and TdT negative. What is the most likely diagnosis?

Accepted Answer

Diffuse large B-cell lymphoma

Answer

Chronic lymphadenitis

Answer

Hodgkin disease

Answer

Lymphoblastic lymphoma

Question 8

The nucleotide triplet CTC in the sixth position of the beta-globin chain in DNA forms the complementary nucleotide on mRNA that codes for glutamic acid. A point mutation on the beta-globin chain resulting in the nucleotide triplet CAC forms a complementary nucleotide on mRNA that codes for valine. In sickle cell anemia, what is the expected complementary nucleotide triplet on mRNA, read 5' to 3'?

Accepted Answer

GUG

Answer

GAG

Answer

CTC

Answer

GTG

Question 9

Purpura fulminans is seen in?

Accepted Answer

Protein C deficiency

Answer

Protein S deficiency

Answer

AT III deficiency

Answer

Factor 5 Leiden mutation

Question 10

What is the cause of alpha thalassemia?

Accepted Answer

Deletion of alpha genes

Answer

Deletion of beta genes

Answer

Excess of alpha genes

Answer

Single amino acid substitution in alpha chain

Hematopathology — MCQs

Hematopathology — MCQs

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