Bone Marrow Failure Syndromes — MCQs
What is the best treatment option for a patient aged 65 years with severe aplastic anemia who has an HLA-compatible sibling available?
An 18-year-old male presents to the OPD with gum bleeding, fever, low total leukocyte count (TLC), and low platelet count. General examination is unremarkable. Further investigations reveal a low reticulocyte count, absent megakaryocytes, and no immature cells in the bone marrow. What is the most likely diagnosis?
A 69-year-old woman, with poor dietary habits and alcoholism, is found to have a macrocytic anemia with hyper segmented neutrophils. Which of the following is the most appropriate diagnostic test?
Which of the following is not a characteristic of Fanconi's anemia?
False about Shwachman-Diamond syndrome
All are associated with malignancy except
Which of the following is not a chromosome breakage disorder?
The strongest occupational risk factor for hematological carcinoma is
Which of the following is most specific for congenital Rubella syndrome?
Exocrine pancreatic insufficiency is seen in:
Bone Marrow Failure Syndromes Indian Medical PG Practice Questions and MCQs
Question 1: What is the best treatment option for a patient aged 65 years with severe aplastic anemia who has an HLA-compatible sibling available?
- A. Antithymocyte globulin followed by cyclosporine (Correct Answer)
- B. Non-myeloablative bone marrow transplantation from the HLA identical sibling
- C. Cyclosporine monotherapy
- D. Conventional myeloablative bone marrow transplantation from the HLA identical sibling
Explanation: Antithymocyte globulin followed by cyclosporine - For patients **over 50 years** with severe aplastic anemia and an HLA-compatible sibling, **immunosuppressive therapy** with antithymocyte globulin (ATG) and cyclosporine is generally preferred over transplantation due to increased transplant-related mortality risks in older individuals. [1] - This regimen aims to suppress the immune system's attack on hematopoietic stem cells, allowing for recovery of bone marrow function. *Non-myeloablative bone marrow transplantation from the HLA identical sibling* - While generally preferred for older patients with acute myeloid leukemia, **non-myeloablative transplantation** for severe aplastic anemia is often considered for those who fail initial immunosuppressive therapy, not as a first-line option. - The goal in aplastic anemia is to remove the autoimmune attack on stem cells and foster recovery, which immunosuppression can achieve with less toxicity in older patients. *Cyclosporine monotherapy* - **Cyclosporine monotherapy** is typically less effective than combination therapy with ATG for severe aplastic anemia. - Combination therapy provides a more robust immunosuppressive effect, leading to higher response rates. *Conventional myeloablative bone marrow transplantation from the HLA identical sibling* - **Conventional myeloablative transplantation** carries significant risks, including high treatment-related mortality, particularly in patients **over 50 years**. [1] - While it offers a potential cure, the risks in this age group are generally deemed too high as a first-line therapy compared to immunosuppression.
Question 2: An 18-year-old male presents to the OPD with gum bleeding, fever, low total leukocyte count (TLC), and low platelet count. General examination is unremarkable. Further investigations reveal a low reticulocyte count, absent megakaryocytes, and no immature cells in the bone marrow. What is the most likely diagnosis?
- A. Immune Thrombocytopenic Purpura (ITP)
- B. Myelodysplastic Syndrome (MDS)
- C. Aplastic anemia (Correct Answer)
- D. Acute Myeloid Leukemia (AML)
Explanation: ***Aplastic anemia*** - This condition is characterized by **pancytopenia** (low TLC and platelet count, implied low red blood cell count by low reticulocyte count) due to **bone marrow failure**. - The absence of **megakaryocytes** and other immature cells in the bone marrow confirms the **hypocellularity** typical of aplastic anemia. *Immune Thrombocytopenic Purpura (ITP)* - While ITP presents with **low platelet count** and potential gum bleeding [1], the bone marrow typically shows **normal or increased megakaryocytes**. - ITP does not explain the **low total leukocyte count** or low reticulocyte count seen in this patient [1]. *Myelodysplastic Syndrome (MDS)* - MDS involves **ineffective hematopoiesis** and can present with cytopenias, but the bone marrow is usually **hypercellular or normocellular** with dysplastic changes. - The absence of immature cells and overall hypoplasia does not fit the typical picture of MDS. *Acute Myeloid Leukemia (AML)* - AML is characterized by an overproduction of **immature myeloid cells (blasts)** [3], which are conspicuously absent in this patient's bone marrow description. - While AML can cause pancytopenia, the presence of **immature cells** in the bone marrow is its hallmark [3]. Gum hypertrophy is also a common clinical sign in AML [2].
Question 3: A 69-year-old woman, with poor dietary habits and alcoholism, is found to have a macrocytic anemia with hyper segmented neutrophils. Which of the following is the most appropriate diagnostic test?
- A. serum folate levels
- B. bone marrow
- C. RBC folate levels (Correct Answer)
- D. Schilling test
Explanation: RBC folate levels - **RBC folate levels** reflect **tissue folate stores** and are less susceptible to daily dietary fluctuations than serum folate. - This test is considered a more reliable indicator for diagnosing **chronic folate deficiency**, which is consistent with poor dietary habits and alcoholism. *serum folate levels* - **Serum folate levels** are easily influenced by recent dietary intake, making them less indicative of long-term folate stores [1]. - A normal serum folate level can be seen in patients with **tissue folate deficiency** if they have recently ingested folate-rich foods [1]. *bone marrow* - A **bone marrow biopsy** might show megaloblastic changes, but it is an invasive procedure and is usually reserved for cases where the diagnosis remains unclear after less invasive tests [2]. - While it can confirm **megaloblastic anemia**, it does not specifically differentiate between **folate** and **B12 deficiencies** as the primary diagnostic tool. *Schilling test* - The **Schilling test** is used to diagnose **vitamin B12 malabsorption** (pernicious anemia or other causes), not folate deficiency. - This patient's clinical picture points more towards a **folate deficiency** given the poor dietary habits and alcoholism, although B12 deficiency can also cause macrocytic anemia [3].
Question 4: Which of the following is not a characteristic of Fanconi's anemia?
- A. Skeletal anomalies
- B. Pancytopenia
- C. Chromosome fragility
- D. Bone marrow failure in infancy (Correct Answer)
Explanation: ***Bone marrow failure in infancy*** - Fanconi anemia patients are typically **asymptomatic at birth** with normal blood counts. - **Progressive bone marrow failure** develops gradually, with median age of onset around **7 years** (range 5-10 years). - While subtle hematologic changes (macrocytosis, elevated HbF) may appear earlier, clinically significant **pancytopenia does not occur in infancy**. - This delayed hematologic presentation distinguishes Fanconi anemia from other congenital bone marrow failure syndromes. *Pancytopenia* - **Pancytopenia** is the hallmark hematologic feature of Fanconi anemia, but develops in **mid-childhood**, not infancy. - Results from progressive bone marrow failure affecting all three cell lines: **red blood cells, white blood cells, and platelets**. - Thrombocytopenia is often the first manifestation, followed by anemia and neutropenia. *Skeletal anomalies* - **Skeletal anomalies** are common congenital malformations present in approximately **60-75%** of patients. - Include **radial ray defects** (absent or hypoplastic thumbs, absent radius), **short stature**, and other limb abnormalities. - These are present from birth and often lead to early clinical suspicion. *Chromosome fragility* - **Chromosome fragility** is the **diagnostic hallmark** of Fanconi anemia due to defective DNA repair mechanisms. - Diagnostic test uses **diepoxybutane (DEB)** or **mitomycin C (MMC)** to induce DNA crosslinks, revealing increased chromosomal breaks and rearrangements. - This test is positive regardless of age or hematologic status.
Question 5: False about Shwachman-Diamond syndrome
- A. Bone marrow dysfunction
- B. Exocrine pancreatic insufficiency
- C. Leucocytosis (Correct Answer)
- D. Short stature
Explanation: ***Leucocytosis*** - **Leucocytosis** (an increase in white blood cells) is generally **not** a feature of Shwachman-Diamond syndrome (SDS); rather, patients typically experience **neutropenia** (low neutrophils) due to bone marrow dysfunction. - This persistent or intermittent neutropenia is a hallmark of the immune deficiency seen in SDS, making leucocytosis an incorrect finding. *Bone marrow dysfunction* - **Bone marrow dysfunction** is a defining characteristic of Shwachman-Diamond syndrome, leading to various **cytopenias**, most notably **neutropenia**. - This dysfunction can also manifest as anemia or thrombocytopenia, contributing to the overall morbidity of the disease. *Exocrine pancreatic insufficiency* - **Exocrine pancreatic insufficiency** is a primary clinical feature of Shwachman-Diamond syndrome, leading to **malabsorption** and **failure to thrive**. - This insufficiency is due to abnormal pancreatic development and is distinct from the more severe pancreatic involvement seen in cystic fibrosis. *Short stature* - **Short stature** is a common finding in children with Shwachman-Diamond syndrome, often resulting from a combination of **growth plate abnormalities** and **malnutrition** due to pancreatic insufficiency. - It is considered a key **skeletal manifestation** of the disease, along with metaphyseal chondrodysplasia.
Question 6: All are associated with malignancy except
- A. Fragile - X syndrome (Correct Answer)
- B. Down's syndrome
- C. Fanconi's anaemia
- D. Bloom syndrome
Explanation: ***Fragile - X syndrome*** - While Fragile-X syndrome is a common cause of **inherited intellectual disability**, it is **not directly associated with an increased risk of malignancy**. - Its pathology involves a mutation in the **FMR1 gene**, leading to an altered protein required for normal neuronal development, rather than a predisposition to cancer. *Down's syndrome* - Individuals with Down's syndrome have a **significantly increased risk of developing certain malignancies**, most notably **acute lymphoblastic leukemia (ALL)**. - The abnormal chromosome 21 dosage is thought to disrupt normal cell growth and differentiation, predisposing to cancer. *Fanconi's anaemia* - Fanconi's anaemia is a **genetic disorder characterized by bone marrow failure** and a **high predisposition to various cancers**, particularly **acute myeloid leukemia (AML)** and solid tumors. - It involves defects in **DNA repair pathways**, leading to genomic instability and increased oncogenic mutations. *Bloom syndrome* - Bloom syndrome is a rare genetic disorder characterized by **growth deficiency**, a **photosensitive rash**, and a **markedly increased risk of developing various cancers** at an early age. - It is caused by a mutation in the **BLM gene**, which plays a crucial role in maintaining genomic stability and DNA repair.
Question 7: Which of the following is not a chromosome breakage disorder?
- A. Bloom syndrome
- B. Ataxia telangiectasia
- C. Duchenne muscular dystrophy (Correct Answer)
- D. Fanconi anemia
Explanation: ***Duchenne muscular dystrophy*** - Duchenne muscular dystrophy is primarily a **muscle degeneration disorder** caused by mutations in the **dystrophin gene**, not a chromosome breakage disorder. - It does not involve issues with **chromosomal stability** or breakage, unlike the others listed. *Ataxia telangiectasia* - Ataxia telangiectasia is associated with defects in **DNA repair mechanisms**, leading to **chromosome breakage** and instability [1]. - Patients exhibit progressive **ataxia**, **telangiectasia**, and increased sensitivity to radiation. *Fanconi anemia* - Fanconi anemia is characterized by a defect in the **DNA repair pathway**, resulting in increased **chromosome breakage** [1]. - It is associated with **bone marrow failure** and development of various malignancies. *Bloom syndrome* - Bloom syndrome results from defects in the **BLM gene**, leading to **genomic instability** and an increased rate of chromosome breakage [1]. - This condition causes symptoms like **short stature**, **facial lesions**, and a predisposition to cancer. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 322-323.
Question 8: The strongest occupational risk factor for hematological carcinoma is
- A. Benzene (Correct Answer)
- B. Lithium
- C. Radiation exposure
- D. Cigarette smoke
Explanation: ***Benzene*** - Benzene exposure is recognized as a potent **carcinogen** linked to various hematological malignancies, including **leukemia** [1]. - It affects the **bone marrow**, leading to dysplastic changes and ultimately malignancy. *Nicotine* - Although nicotine is associated with **smoking-related cancers**, it is not directly linked to **hematological carcinomas**. - Its primary role is in causing **lung cancer**, rather than blood cancers. *Lithium* - Lithium is primarily used for **bipolar disorder** and does not have a known link to causing hematological malignancies. - Side effects are more related to **nephrotoxicity** rather than carcinogenic effects. *Alcohol* - Alcohol consumption is primarily associated with **liver cancers** and not specifically linked to hematological carcinomas [2]. - It can contribute to general malignancy development but is not a direct cause of blood cancers. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, p. 286. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. (Basic Pathology) introduces the student to key general principles of pathology, both as a medical science and as a clinical activity with a vital role in patient care. Part 2 (Disease Mechanisms) provides fundamental knowledge about the cellular and molecular processes involved in diseases, providing the rationale for their treatment. Part 3 (Systematic Pathology) deals in detail with specific diseases, with emphasis on the clinically important aspects., pp. 217-218.
Question 9: Which of the following is most specific for congenital Rubella syndrome?
- A. Blueberry muffin rash is seen
- B. Triad of CRS are cataract, cardiac defects, sensorineural deafness (Correct Answer)
- C. Infection is most serious in the first trimester of pregnancy
- D. Virus can be isolated up to 12 months after birth
Explanation: ***Triad of CRS are cataract, cardiac defects, sensorineural deafness*** - The **classic Gregg triad** of **cataracts**, **cardiac defects** (especially patent ductus arteriosus and pulmonary artery stenosis), and **sensorineural deafness** is the **most specific and pathognomonic** feature of **congenital Rubella syndrome**. - While individual components can occur in other conditions, the **combination of this triad** is highly specific for CRS and distinguishes it from other congenital infections. - This triad was first described by **Norman Gregg** in 1941 and remains the hallmark diagnostic feature of congenital rubella syndrome. *Blueberry muffin rash is seen* - The **blueberry muffin rash** (dermal erythropoiesis) presents as purpuric lesions or small dark blue papules and can be seen in congenital rubella syndrome. - However, this finding is **NOT specific to rubella** and occurs in multiple congenital infections including **CMV, toxoplasmosis, parvovirus B19**, and can also be seen in neonatal malignancies like neuroblastoma. - While characteristic, it is less specific than the Gregg triad for diagnosing CRS. *Infection is most serious in the first trimester of pregnancy* - Maternal rubella infection during the **first trimester** carries the highest risk (up to 85% if infected before 12 weeks) of severe multi-organ abnormalities due to rapid organogenesis. - While true, this describes the **timing and severity** of infection rather than a specific clinical feature that distinguishes rubella from other congenital infections. - Many congenital infections (CMV, toxoplasmosis, HSV) are also more severe when acquired in early pregnancy. *Virus can be isolated up to 12 months after birth* - Infants with **congenital Rubella syndrome** can shed virus in bodily fluids (urine, nasopharyngeal secretions) for **12 months or longer** after birth. - This prolonged viral shedding is important for **infection control** and isolation precautions but is a virological characteristic rather than a specific diagnostic clinical feature. - Other congenital infections (CMV) can also demonstrate prolonged viral shedding in infants.
Question 10: Exocrine pancreatic insufficiency is seen in:
- A. Shwachman-Diamond syndrome (Correct Answer)
- B. Rubinstein-Taybi syndrome
- C. Seckel syndrome
- D. Diamond-Blackfan syndrome
Explanation: ***Shwachman-Diamond syndrome*** - This syndrome is characterized by **exocrine pancreatic insufficiency**, neutropenia, skeletal abnormalities, and growth retardation. - The pancreatic insufficiency leads to **malabsorption** and **steatorrhea** due to insufficient production of digestive enzymes. *Rubinstein-Taybi syndrome* - This syndrome is characterized by broad thumbs and great toes, intellectual disability, and distinctive facial features, but not primarily by exocrine pancreatic insufficiency. - It is caused by mutations in the **CREBBP** or **EP300** genes, which are not directly involved in pancreatic function. *Seckel syndrome* - This is a rare genetic disorder characterized by **primordial dwarfism**, microcephaly, and intellectual disability. - While it affects growth and development, it is not typically associated with exocrine pancreatic insufficiency. *Diamond-Blackfan syndrome* - This syndrome primarily involves **pure red cell aplasia**, leading to severe anemia. - Although it can have various congenital anomalies, **exocrine pancreatic insufficiency** is not a characteristic feature of this condition.
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