A 66-year-old man comes to the physician for a 3-month history of fatigue. He has hypertension and hyperlipidemia. He had a transient ischemic attack 3 years ago. He drinks 3 beers a day, and sometimes a couple more on social occasions. He currently takes aspirin, simvastatin, hydrochlorothiazide, and metoprolol. His temperature is 37.1°C (98.8°F), pulse is 78, respirations are 19/min, and oxygen saturation on room air is 97%. He is in no distress but shows marked pallor and has multiple pinpoint, red, nonblanching spots on his extremities. On palpation, his spleen is significantly enlarged. Laboratory studies show a hemoglobin of 8.0 g/dL, a leukocyte count of 80,000/mm3, and a platelet count of 34,000/mm3. A blood smear shows immature cells with large, prominent nucleoli and pink, elongated, needle-shaped cytoplasmic inclusions. Which of the following is the most likely diagnosis?
Q2
A 35-year-old man presents with a mass on the central part of his neck. He reports it has been growing steadily for the past 2 weeks, and he has also been experiencing fatigue and recurrent fevers. No significant past medical history. The patient denies any smoking history, or alcohol or recreational drug use. He denies any recent travel in the previous 6 months. On physical examination, there are multiple enlarged submandibular and cervical lymph nodes that are firm, mobile, and non-tender. A biopsy of one of the lymph nodes is performed and shows predominantly lymphocytes and histiocytes present in a pattern ‘resembling popcorn’. A flow cytometry analysis demonstrates cells that are CD19 and CD20 positive and CD15 and CD30 negative. Which of the following is the most likely diagnosis in this patient?
Q3
A 35-year-old male presents to his physician with the complaint of fatigue and weakness for six months. His physician orders a CBC which demonstrates anemia and thrombocytopenia. During the subsequent work up, a bone marrow biopsy is performed which ultimately leads to the diagnosis of acute promyelocytic leukemia. Which of the following translocations and fusion genes would be present in this patient?
Q4
A 52-year-old postmenopausal woman seeks evaluation at a medical clinic with complaints of back pain and increased fatigue for 6 months. For the past week, the back pain has radiated to her legs and is stabbing in nature (7/10 in intensity). There are no associated paresthesias. She unintentionally lost 4.5 kg (10.0 lb) in the past 6 months. There is no history of trauma to the back. The past medical history is insignificant and she does not take any medications. The physical examination is normal. The laboratory results are as follows:
Hemoglobin 10 g/dL
Hematocrit 30%
Mean corpuscular volume 80 fL
Serum creatinine 1.5 mg/dL
Serum total protein 9 g/dL
Serum albumin 4.2 g/dL
Serum calcium 11.2 mg/dL
A peripheral blood smear shows normocytic normochromic cells. An X-ray reveals multiple osteolytic lesions in the vertebrae and long bones. Serum protein electrophoresis shows a monoclonal spike. A bone marrow biopsy shows increased plasma cells making up greater than 50% of the total cell population. Which of the following is the most likely diagnosis in this patient?
Q5
A 7-year-old boy presents to his primary care physician for a general checkup. The patient has been feeling poorly for the past several weeks and has been losing weight. He states that he often feels weak and too tired to play with his friends. He is no longer interested in many recreational activities he used to be interested in. The patient's parents state that a few of their child's friends have been sick lately. His temperature is 102°F (38.9°C), blood pressure is 77/48 mmHg, pulse is 110/min, respirations are 24/min, and oxygen saturation is 98% on room air. On exam, you note a fatigued appearing child who has lost 10 pounds since his last appointment. Left upper quadrant tenderness and a mass is noted on abdominal exam. Which of the following best describes the most likely diagnosis?
Q6
A 67-year-old man comes to the physician because of a 2-month history of generalized fatigue. On examination, he appears pale. He also has multiple pinpoint, red, nonblanching spots on his extremities. His spleen is significantly enlarged. Laboratory studies show a hemoglobin concentration of 8.3 g/dL, a leukocyte count of 81,000/mm3, and a platelet count of 35,600/mm3. A peripheral blood smear shows immature cells with large, prominent nucleoli and pink, elongated, needle-shaped cytoplasmic inclusions. Which of the following is the most likely diagnosis?
Q7
A 67-year-old man presents to the emergency department with increased fatigue. He states that he has been feeling very tired lately but today lost consciousness while walking up the stairs. He reports mild abdominal distension/discomfort, weight loss, a persistent cough, and multiple episodes of waking up drenched in sweat in the middle of the night. The patient does not see a primary care physician but admits to smoking 2 to 3 packs of cigarettes per day and drinking 1 to 3 alcoholic beverages per day. He recently traveled to Taiwan and Nicaragua. His temperature is 99.5°F (37.5°C), blood pressure is 177/98 mmHg, pulse is 100/min, respirations are 17/min, and oxygen saturation is 98% on room air. On physical exam, you note a fatigued appearing elderly man who is well-groomed. Cardiopulmonary exam reveals mild expiratory wheezes. Abdominal exam is notable for a non-pulsatile mass in the left upper quadrant. Laboratory values are ordered as seen below.
Hemoglobin: 12 g/dL
Hematocrit: 36%
Leukocyte count: 105,500/mm^3
Platelet count: 197,000/mm^3
Serum:
Na+: 139 mEq/L
Cl-: 100 mEq/L
K+: 4.3 mEq/L
HCO3-: 25 mEq/L
BUN: 20 mg/dL
Glucose: 92 mg/dL
Creatinine: 1.4 mg/dL
Ca2+: 10.2 mg/dL
Leukocyte alkaline phosphatase score: 25 (range 20 - 100)
AST: 12 U/L
ALT: 17 U/L
Which of the following is the most likely diagnosis?
Q8
A 59-year-old man presents to his primary care physician for fatigue. In general, he has been in good health; however, he recently has experienced some weight loss, abdominal pain, and general fatigue. He has a past medical history of anxiety, diabetes, a fracture of his foot sustained when he tripped, and a recent cold that caused him to miss work for a week. His current medications include metformin, insulin, buspirone, vitamin D, calcium, and sodium docusate. His temperature is 99.5°F (37.5°C), blood pressure is 150/100 mmHg, pulse is 90/min, respirations are 18/min, and oxygen saturation is 98% on room air. Physical exam reveals a calm gentleman. A mild systolic murmur is heard in the left upper sternal region. The rest of the physical exam is within normal limits. Laboratory values are ordered as seen below.
Hemoglobin: 12 g/dL
Hematocrit: 36%
Leukocyte count: 66,500/mm^3 with normal differential
Platelet count: 177,000/mm^3
Leukocyte alkaline phosphatase: elevated
Serum:
Na+: 139 mEq/L
Cl-: 100 mEq/L
K+: 4.3 mEq/L
BUN: 20 mg/dL
Glucose: 120 mg/dL
Creatinine: 1.1 mg/dL
Ca2+: 10.9 mEq/L
AST: 12 U/L
ALT: 10 U/L
Which of the following is the most likely diagnosis?
Q9
A 31-year-old female undergoing treatment for leukemia is found to have a frontal lobe abscess accompanied by paranasal swelling. She additionally complains of headache, facial pain, and nasal discharge. Biopsy of the infected tissue would most likely reveal which of the following?
Q10
A 24-year-old woman complains of intermittent fever and joint pain. She says that these symptoms have been present for the past month. Before that, she had no signs or symptoms and was completely healthy. She has also lost her appetite and some weight. A complete blood count (CBC) showed severe pancytopenia. What is the next best step in evaluating this patient?
Hematologic malignancies overview US Medical PG Practice Questions and MCQs
Question 1: A 66-year-old man comes to the physician for a 3-month history of fatigue. He has hypertension and hyperlipidemia. He had a transient ischemic attack 3 years ago. He drinks 3 beers a day, and sometimes a couple more on social occasions. He currently takes aspirin, simvastatin, hydrochlorothiazide, and metoprolol. His temperature is 37.1°C (98.8°F), pulse is 78, respirations are 19/min, and oxygen saturation on room air is 97%. He is in no distress but shows marked pallor and has multiple pinpoint, red, nonblanching spots on his extremities. On palpation, his spleen is significantly enlarged. Laboratory studies show a hemoglobin of 8.0 g/dL, a leukocyte count of 80,000/mm3, and a platelet count of 34,000/mm3. A blood smear shows immature cells with large, prominent nucleoli and pink, elongated, needle-shaped cytoplasmic inclusions. Which of the following is the most likely diagnosis?
A. Cirrhosis
B. Acute lymphoblastic leukemia
C. Chronic lymphocytic leukemia
D. Myelodysplastic syndrome
E. Acute myelogenous leukemia (Correct Answer)
Explanation: **Acute myelogenous leukemia**
- The presence of **fatigue**, **marked pallor**, **splenomegaly**, **petechiae** (pinpoint, red, nonblanching spots), and **pancytopenia** (anemia, leukocytosis with immature forms, thrombocytopenia) are highly suggestive of acute leukemia.
- The blood smear findings of **immature cells with large, prominent nucleoli** and **pink, elongated, needle-shaped cytoplasmic inclusions** (likely **Auer rods**) are pathognomonic for **acute myelogenous leukemia (AML)**.
*Cirrhosis*
- While **splenomegaly** and **pancytopenia** can occur in cirrhosis due to portal hypertension and hypersplenism, the specific blood smear findings of **immature cells** and **Auer rods** are not characteristic of cirrhosis.
- The patient's alcohol intake could contribute to cirrhosis, but the hematological picture points definitively away from liver disease as the primary diagnosis.
*Acute lymphoblastic leukemia*
- Although acute lymphoblastic leukemia (ALL) presents with **fatigue**, **pallor**, and **pancytopenia**, the **immature cells** in ALL are lymphoblasts, which **lack Auer rods**.
- The specific morphology described (large, prominent nucleoli, needle-shaped cytoplasmic inclusions) is inconsistent with ALL.
*Chronic lymphocytic leukemia*
- CLL typically presents with **lymphocytosis** (extremely high leukocyte count composed of mature-appearing lymphocytes) and often **splenomegaly**, but usually **without significant anemia or thrombocytopenia** at presentation.
- The presence of **immature cells** and **Auer rods** is inconsistent with CLL, which involves mature B-lymphocytes.
*Myelodysplastic syndrome*
- MDS can cause **cytopenias** and may involve **immature blast forms**, but the blast count is typically less than 20% in the bone marrow (or periphery) and it does **not typically present with Auer rods** in circulating blasts.
- The profound leukocytosis with highly immature cells and specific inclusions points beyond MDS to an acute leukemia.
Question 2: A 35-year-old man presents with a mass on the central part of his neck. He reports it has been growing steadily for the past 2 weeks, and he has also been experiencing fatigue and recurrent fevers. No significant past medical history. The patient denies any smoking history, or alcohol or recreational drug use. He denies any recent travel in the previous 6 months. On physical examination, there are multiple enlarged submandibular and cervical lymph nodes that are firm, mobile, and non-tender. A biopsy of one of the lymph nodes is performed and shows predominantly lymphocytes and histiocytes present in a pattern ‘resembling popcorn’. A flow cytometry analysis demonstrates cells that are CD19 and CD20 positive and CD15 and CD30 negative. Which of the following is the most likely diagnosis in this patient?
A. Nodular sclerosis classical Hodgkin lymphoma
B. Nodular lymphocyte-predominant Hodgkin lymphoma (Correct Answer)
C. Lymphocyte depleted Hodgkin lymphoma
D. Mixed cellularity classical Hodgkin lymphoma
E. Lymphocyte rich classical Hodgkin lymphoma
Explanation: ***Nodular lymphocyte-predominant Hodgkin lymphoma***
- The key features are **lymphohistiocytic (L&H) cells**, also known as **popcorn cells**, which are large, multilobed Hodgkin-Reed-Sternberg (HRS) cell variants.
- Immunophenotypically, these cells are typically **CD19+, CD20+, CD45+, and CD30-, CD15-**, consistent with the flow cytometry findings.
*Nodular sclerosis classical Hodgkin lymphoma*
- Characterized by **lacunar cells** (a variant of HRS cells) and broad bands of **collagen fibrosis**, which are not described.
- HRS cells in classical Hodgkin lymphoma (cHL) are typically **CD15+ and CD30+**, and usually **CD20-**, which contradicts the flow cytometry results.
*Lymphocyte depleted Hodgkin lymphoma*
- This is a rare form of cHL with **few lymphocytes** and abundant atypical HRS cells, often seen in older, immunosuppressed patients.
- The flow cytometry profile (CD15+, CD30+) and the histological description of "popcorn cells" do not fit this subtype.
*Mixed cellularity classical Hodgkin lymphoma*
- This subtype of cHL features a heterogeneous cellular infiltrate and classic **HRS cells (CD15+, CD30+)**, which differ from the described immunophenotype.
- It lacks the "popcorn cell" morphology and the nodal sclerosis seen in other cHL subtypes.
*Lymphocyte rich classical Hodgkin lymphoma*
- While it has abundant lymphocytes, the characteristic cells are still **classic HRS cells (CD15+, CD30+)**, not the popcorn cells described.
- The immunophenotype **CD20+ and CD15-, CD30-** is inconsistent with any form of classical Hodgkin lymphoma.
Question 3: A 35-year-old male presents to his physician with the complaint of fatigue and weakness for six months. His physician orders a CBC which demonstrates anemia and thrombocytopenia. During the subsequent work up, a bone marrow biopsy is performed which ultimately leads to the diagnosis of acute promyelocytic leukemia. Which of the following translocations and fusion genes would be present in this patient?
A. t(15;17) - PML/RARalpha (Correct Answer)
B. t(9;22) - PML/RARalpha
C. t(9;22) - BCR/Abl1
D. t(14;18) - PML/RARalpha
E. t(8;14) - BCR/Abl1
Explanation: ***t(15;17) - PML/RARalpha***
- **Acute Promyelocytic Leukemia (APL)** is uniquely characterized by the **t(15;17) translocation**, which fuses the **PML (promyelocytic leukemia)** gene on chromosome 15 with the **RARalpha (retinoic acid receptor alpha)** gene on chromosome 17.
- This specific genetic alteration is crucial for diagnosis and dictates treatment with **all-trans retinoic acid (ATRA)**, which targets the aberrant RARalpha fusion protein.
*t(9;22) - PML/RARalpha*
- The **t(9;22) translocation** is associated with **Chronic Myeloid Leukemia (CML)**, forming the **BCR-ABL1 fusion gene**, not PML/RARalpha.
- This option incorrectly pairs the translocation with a fusion gene specific to APL.
*t(9;22) - BCR/Abl1*
- While **t(9;22)** and the **BCR/Abl1 fusion gene** are correctly paired, this is the hallmark of **Chronic Myeloid Leukemia (CML)**, not acute promyelocytic leukemia.
- CML typically presents with a different clinical picture and bone marrow findings than APL, primarily **leukocytosis with a left shift** and **basophilia**.
*t(14;18) - PML/RARalpha*
- The **t(14;18) translocation** is characteristic of **follicular lymphoma**, not any form of acute leukemia.
- It results in the overexpression of the **BCL-2 gene**, promoting cell survival, and is not associated with the PML/RARalpha fusion.
*t(8;14) - BCR/Abl1*
- The **t(8;14) translocation** is associated with **Burkitt lymphoma**, leading to the translocation of the **MYC oncogene** close to immunoglobulin heavy chain enhancers.
- This option also incorrectly pairs the translocation with the **BCR/Abl1 fusion gene**, which is characteristic of CML, and is not relevant to APL.
Question 4: A 52-year-old postmenopausal woman seeks evaluation at a medical clinic with complaints of back pain and increased fatigue for 6 months. For the past week, the back pain has radiated to her legs and is stabbing in nature (7/10 in intensity). There are no associated paresthesias. She unintentionally lost 4.5 kg (10.0 lb) in the past 6 months. There is no history of trauma to the back. The past medical history is insignificant and she does not take any medications. The physical examination is normal. The laboratory results are as follows:
Hemoglobin 10 g/dL
Hematocrit 30%
Mean corpuscular volume 80 fL
Serum creatinine 1.5 mg/dL
Serum total protein 9 g/dL
Serum albumin 4.2 g/dL
Serum calcium 11.2 mg/dL
A peripheral blood smear shows normocytic normochromic cells. An X-ray reveals multiple osteolytic lesions in the vertebrae and long bones. Serum protein electrophoresis shows a monoclonal spike. A bone marrow biopsy shows increased plasma cells making up greater than 50% of the total cell population. Which of the following is the most likely diagnosis in this patient?
A. POEMS syndrome
B. Monoclonal gammopathy of unknown significance
C. Waldenstrom macroglobulinemia
D. Metastatic bone disease
E. Multiple myeloma (Correct Answer)
Explanation: ***Multiple myeloma***
- The patient's presentation with **back pain**, **fatigue**, **anemia**, **elevated creatinine**, **hypercalcemia**, **osteolytic lesions**, and a **monoclonal spike** on serum protein electrophoresis, along with **>50% plasma cells** in bone marrow, is classic for **multiple myeloma**.
- These findings fulfill the criteria for active multiple myeloma, characterized by end-organ damage (e.g., **CRAB criteria**: **C**alcium elevation, **R**enal failure, **A**nemia, **B**one lesions) and significant plasma cell infiltration.
*POEMS syndrome*
- While POEMS syndrome involves **monoclonal plasma cell proliferation**, it presents with features like **Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, and Skin changes**, which are not described in this patient.
- The dominant symptoms of **bone pain**, **anemia**, **hypercalcemia**, and **renal failure** are not typical primary manifestations of POEMS syndrome.
*Monoclonal gammopathy of unknown significance*
- **MGUS** is characterized by the presence of a **monoclonal protein** without evidence of end-organ damage (**CRAB criteria**) or significant bone marrow plasma cell infiltration (typically <10%).
- This patient exhibits **hypercalcemia**, **renal dysfunction**, **anemia**, **bone lesions**, and **>50% plasma cells**, all of which rule out MGUS.
*Waldenstrom macroglobulinemia*
- This is a **lymphoplasmacytic lymphoma** often associated with **hyperviscosity syndrome**, **lymphadenopathy**, and a **monoclonal IgM spike**, none of which are highlighted in this patient's presentation.
- While it involves elevated protein and sometimes anemia, the **osteolytic lesions** and **hypercalcemia** are not characteristic of Waldenstrom macroglobulinemia; it rarely causes destructive bone lesions.
*Metastatic bone disease*
- Although metastatic bone disease can cause **osteolytic lesions** and **back pain**, it typically does not present with a **monoclonal protein spike** or **elevated plasma cells** in the bone marrow.
- The detailed laboratory findings, including **monoclonal gammopathy** and **high plasma cell percentage**, are highly specific to plasma cell dyscrasias rather than solid tumor metastases.
Question 5: A 7-year-old boy presents to his primary care physician for a general checkup. The patient has been feeling poorly for the past several weeks and has been losing weight. He states that he often feels weak and too tired to play with his friends. He is no longer interested in many recreational activities he used to be interested in. The patient's parents state that a few of their child's friends have been sick lately. His temperature is 102°F (38.9°C), blood pressure is 77/48 mmHg, pulse is 110/min, respirations are 24/min, and oxygen saturation is 98% on room air. On exam, you note a fatigued appearing child who has lost 10 pounds since his last appointment. Left upper quadrant tenderness and a mass is noted on abdominal exam. Which of the following best describes the most likely diagnosis?
A. Smudge cells on peripheral smear
B. TdT positive cells (Correct Answer)
C. Infection sensitive to oseltamivir
D. Auer rods on peripheral smear
E. Parental mistreatment of the child
Explanation: ***TdT positive cells***
- This patient's symptoms, including **fever**, **weight loss**, **fatigue**, and **splenomegaly** (left upper quadrant tenderness and mass), are highly suggestive of **Acute Lymphoblastic Leukemia (ALL)**.
- **Terminal deoxynucleotidyl transferase (TdT)** is a DNA polymerase found in immature lymphocytes (blasts) and is a key marker for diagnosing ALL.
- ALL is the **most common childhood malignancy**, particularly prevalent in children aged 2-10 years.
*Smudge cells on peripheral smear*
- **Smudge cells** are characteristic of **Chronic Lymphocytic Leukemia (CLL)**, which predominantly affects older adults and is rare in children.
- The clinical picture of rapid decline and significant systemic symptoms in a child is inconsistent with CLL.
*Infection sensitive to oseltamivir*
- Oseltamivir is an **antiviral medication for influenza**, and while the child has a fever, the profound **weight loss**, **fatigue**, and **abdominal mass** point towards a hematologic malignancy, not a typical viral infection.
- Viral infections rarely present with such a significant abdominal mass or sustained constitutional symptoms for several weeks.
*Auer rods on peripheral smear*
- **Auer rods** are cytoplasmic inclusions pathognomonic for **Acute Myeloid Leukemia (AML)**.
- While AML can occur in children, **ALL is far more common in this age group** (85% of childhood leukemias), and the presentation is highly classic for ALL, making TdT positivity the best diagnostic marker.
*Parental mistreatment of the child*
- While some symptoms (weight loss, fatigue) could potentially be seen in neglect, the presence of **fever**, **splenomegaly** (abdominal mass), and **hypotension** points strongly to a severe underlying medical condition.
- Objective signs of systemic illness necessitate a thorough medical workup rather than suspicion of abuse.
Question 6: A 67-year-old man comes to the physician because of a 2-month history of generalized fatigue. On examination, he appears pale. He also has multiple pinpoint, red, nonblanching spots on his extremities. His spleen is significantly enlarged. Laboratory studies show a hemoglobin concentration of 8.3 g/dL, a leukocyte count of 81,000/mm3, and a platelet count of 35,600/mm3. A peripheral blood smear shows immature cells with large, prominent nucleoli and pink, elongated, needle-shaped cytoplasmic inclusions. Which of the following is the most likely diagnosis?
A. Acute lymphoblastic leukemia
B. Myelodysplastic syndrome
C. Hairy cell leukemia
D. Acute myelogenous leukemia (Correct Answer)
E. Chronic myelogenous leukemia
Explanation: ***Acute myelogenous leukemia***
- The presence of immature cells with **large, prominent nucleoli** and **pink, elongated, needle-shaped cytoplasmic inclusions** (**Auer rods**) on peripheral blood smear is pathognomonic for **acute myeloid leukemia (AML)**.
- The pancytopenia (anemia, thrombocytopenia) and extreme leukocytosis, along with generalized fatigue and pale appearance, are consistent with the presentation of AML.
*Acute lymphoblastic leukemia*
- Characterized by the proliferation of **lymphoblasts** (immature lymphocytes) in the bone marrow and peripheral blood, which typically lack Auer rods.
- While it can present with fatigue, pallor, and cytopenias, the specific morphologic features of the blast cells are different.
*Myelodysplastic syndrome*
- Involves ineffective hematopoiesis leading to **cytopenias** and dysplastic features in mature blood cells, but typically features less aggressive proliferation of immature cells than acute leukemias and **lacks Auer rods**.
- While it can progress to AML, the current description points to actively proliferating immature cells.
*Hairy cell leukemia*
- Characterized by **B lymphocytes with cytoplasmic projections** ("hairy cells") and is typically associated with **massive splenomegaly** and **pancytopenia**, but the characteristic Auer rods are absent.
- The cell morphology described (large nucleoli, needle-shaped inclusions) is inconsistent with hairy cells.
*Chronic myelogenous leukemia*
- Characterized by the **Philadelphia chromosome (BCR-ABL1 fusion gene)** and a marked increase in mature and immature myeloid cells, including granulocytes at various stages of maturation, but typically **lacks Auer rods** and usually has a higher proportion of mature rather than acutely immature cells.
- While it presents with leukocytosis and splenomegaly, the prominent immature cells with nucleoli and Auer rods are not features of CML.
Question 7: A 67-year-old man presents to the emergency department with increased fatigue. He states that he has been feeling very tired lately but today lost consciousness while walking up the stairs. He reports mild abdominal distension/discomfort, weight loss, a persistent cough, and multiple episodes of waking up drenched in sweat in the middle of the night. The patient does not see a primary care physician but admits to smoking 2 to 3 packs of cigarettes per day and drinking 1 to 3 alcoholic beverages per day. He recently traveled to Taiwan and Nicaragua. His temperature is 99.5°F (37.5°C), blood pressure is 177/98 mmHg, pulse is 100/min, respirations are 17/min, and oxygen saturation is 98% on room air. On physical exam, you note a fatigued appearing elderly man who is well-groomed. Cardiopulmonary exam reveals mild expiratory wheezes. Abdominal exam is notable for a non-pulsatile mass in the left upper quadrant. Laboratory values are ordered as seen below.
Hemoglobin: 12 g/dL
Hematocrit: 36%
Leukocyte count: 105,500/mm^3
Platelet count: 197,000/mm^3
Serum:
Na+: 139 mEq/L
Cl-: 100 mEq/L
K+: 4.3 mEq/L
HCO3-: 25 mEq/L
BUN: 20 mg/dL
Glucose: 92 mg/dL
Creatinine: 1.4 mg/dL
Ca2+: 10.2 mg/dL
Leukocyte alkaline phosphatase score: 25 (range 20 - 100)
AST: 12 U/L
ALT: 17 U/L
Which of the following is the most likely diagnosis?
A. Tuberculosis
B. Leukemoid reaction
C. Acute myelogenous leukemia
D. Acute lymphoblastic leukemia
E. Chronic myeloid leukemia (Correct Answer)
Explanation: ***Chronic myeloid leukemia***
- The patient presents with **fatigue, weight loss, night sweats, and a persistent cough**, which are common symptoms of CML. The **extreme leukocytosis (105,500/mm^3)**, **non-pulsatile LUQ mass (splenomegaly)**, and a **low-normal leukocyte alkaline phosphatase (LAP) score of 25** are highly indicative of CML.
- CML characteristically shows a **low LAP score (typically <20)**, which distinguishes it from a leukemoid reaction. This patient's LAP of 25, while technically within the normal range (20-100), is at the lower end and consistent with CML.
- CML is a myeloproliferative disorder characterized by the **Philadelphia chromosome (BCR-ABL fusion gene)**, leading to uncontrolled proliferation of myeloid cells.
*Tuberculosis*
- While **fatigue, weight loss, night sweats, and cough** can be present in tuberculosis, the **dramatically elevated leukocyte count** and **splenomegaly** are not characteristic findings of TB.
- Tuberculosis would typically show a more prominent respiratory symptomology (e.g., hemoptysis) and imaging findings consistent with lung involvement, and its diagnosis would be confirmed by microbiologic studies.
*Leukemoid reaction*
- A leukemoid reaction is a **reactive leukocytosis (>50,000/mm^3)** often triggered by severe infection or inflammation, but it would present with an **elevated leukocyte alkaline phosphatase (LAP) score (typically >100)**, which contradicts the patient's low-normal LAP score of 25.
- Unlike CML, a leukemoid reaction does not typically cause **splenomegaly** to the extent that it forms a palpable mass.
*Acute myelogenous leukemia*
- AML typically presents with **malignant myeloid blasts** in the peripheral blood (often >20%) and bone marrow, and patients are usually more acutely ill with symptoms related to **pancytopenia** (e.g., severe anemia, thrombocytopenia with bleeding), which are not present in this case.
- While AML can cause leukocytosis, it is characterized by a **predominance of immature blast cells** rather than the mature granulocytes seen in CML.
*Acute lymphoblastic leukemia*
- ALL is primarily a disease of **lymphoid progenitor cells** and is more common in children, though it can occur in adults. It is characterized by the presence of **lymphoblasts** in the blood and bone marrow.
- While it can cause fatigue and weight loss, the **extremely high leukocyte count composed primarily of mature myeloid cells** and **prominent splenomegaly** are inconsistent with ALL.
Question 8: A 59-year-old man presents to his primary care physician for fatigue. In general, he has been in good health; however, he recently has experienced some weight loss, abdominal pain, and general fatigue. He has a past medical history of anxiety, diabetes, a fracture of his foot sustained when he tripped, and a recent cold that caused him to miss work for a week. His current medications include metformin, insulin, buspirone, vitamin D, calcium, and sodium docusate. His temperature is 99.5°F (37.5°C), blood pressure is 150/100 mmHg, pulse is 90/min, respirations are 18/min, and oxygen saturation is 98% on room air. Physical exam reveals a calm gentleman. A mild systolic murmur is heard in the left upper sternal region. The rest of the physical exam is within normal limits. Laboratory values are ordered as seen below.
Hemoglobin: 12 g/dL
Hematocrit: 36%
Leukocyte count: 66,500/mm^3 with normal differential
Platelet count: 177,000/mm^3
Leukocyte alkaline phosphatase: elevated
Serum:
Na+: 139 mEq/L
Cl-: 100 mEq/L
K+: 4.3 mEq/L
BUN: 20 mg/dL
Glucose: 120 mg/dL
Creatinine: 1.1 mg/dL
Ca2+: 10.9 mEq/L
AST: 12 U/L
ALT: 10 U/L
Which of the following is the most likely diagnosis?
A. Chronic myeloid leukemia
B. Acute lymphoblastic leukemia
C. Multiple myeloma
D. Leukemoid reaction (Correct Answer)
E. Chronic lymphocytic leukemia
Explanation: ***Leukemoid reaction***
- The **highly elevated leukocyte count** (66,500/mm^3) with **normal differential** and **elevated leukocyte alkaline phosphatase (LAP)** are classic features of a leukemoid reaction.
- This condition is a reactive increase in white blood cells, often triggered by **severe infections, inflammation, or malignancy**, rather than a primary hematologic malignancy.
- The patient's **recent cold/infection** provides a clear trigger for this reactive process.
*Chronic myeloid leukemia*
- While CML also presents with marked leukocytosis, it is typically characterized by a **low or normal LAP score** and a left shift with immature myeloid forms (e.g., myelocytes, metamyelocytes).
- The patient's **normal differential** and **elevated LAP score** argue strongly against CML.
*Acute lymphoblastic leukemia*
- ALL is characterized by the presence of a large number of **lymphoblasts** (immature lymphocytes) in the blood and bone marrow, which is not suggested by the normal differential.
- It usually presents with symptoms of **bone marrow failure** (anemia, thrombocytopenia, infection) and often affects children, though it can occur in adults.
*Multiple myeloma*
- Multiple myeloma is a plasma cell malignancy characterized by **monoclonal gammopathy**, bone lesions, renal failure, and hypercalcemia; **marked leukocytosis is not a primary feature**.
- Although the patient has mildly elevated calcium, the absence of other myeloma features (renal dysfunction, anemia, bone pain) and the **very high WBC count with elevated LAP** make this diagnosis unlikely.
*Chronic lymphocytic leukemia*
- CLL is characterized by a **profound lymphocytosis** (elevated lymphocytes) with mature-appearing cells, which is not described by the "normal differential" of the leukocyte count.
- The elevated LAP would also be unusual in CLL, as CLL cells typically have low LAP activity.
Question 9: A 31-year-old female undergoing treatment for leukemia is found to have a frontal lobe abscess accompanied by paranasal swelling. She additionally complains of headache, facial pain, and nasal discharge. Biopsy of the infected tissue would most likely reveal which of the following?
A. Yeast with pseudohyphae
B. Septate hyphae
C. Irregular non-septate hyphae (Correct Answer)
D. Spherules containing endospores
E. Budding yeast with a narrow base
Explanation: ***Irregular non-septate hyphae***
- The clinical presentation of a **leukemic patient** with a **frontal lobe abscess** and **paranasal swelling**, along with headache, facial pain, and nasal discharge, strongly suggests **mucormycosis**.
- Mucormycosis is characterized by **broad, ribbon-like, irregular non-septate hyphae** with **right-angle branching** on tissue biopsy, making this the most likely finding.
*Yeast with pseudohyphae*
- This morphology is characteristic of **Candida species**, which can cause opportunistic infections but typically manifest as candidemia, esophagitis, or vulvovaginitis in immunocompromised patients, not usually a frontal lobe abscess with paranasal involvement.
- While Candida can cause severe systemic infections, the specific combination of a frontal lobe abscess and paranasal swelling points away from Candida as the primary cause in this context.
*Septate hyphae*
- **Septate hyphae** are typical of **Aspergillus species**, which can cause invasive aspergillosis, including sinopulmonary infections and CNS involvement in immunocompromised hosts.
- However, Aspergillus hyphae are typically **narrow (3-6 µm)** with **acute-angle (45-degree) branching**, differentiating them from the broad, irregular hyphae seen in mucormycosis.
*Spherules containing endospores*
- This morphology is characteristic of **Coccidioides immitis**, the causative agent of coccidioidomycosis.
- Coccidioidomycosis is geographically restricted to endemic areas (e.g., southwestern US) and typically presents with pulmonary symptoms, disseminated disease, or meningitis, which does not fit the described paranasal and frontal lobe presentation.
*Budding yeast with a narrow base*
- This morphology is characteristic of **Cryptococcus neoformans**, an encapsulated yeast that commonly causes **meningitis** and **pneumonia** in immunocompromised individuals.
- While Cryptococcus can cause CNS infections, the presence of paranasal swelling and the specific description of a frontal lobe abscess make mucormycosis a more fitting diagnosis.
Question 10: A 24-year-old woman complains of intermittent fever and joint pain. She says that these symptoms have been present for the past month. Before that, she had no signs or symptoms and was completely healthy. She has also lost her appetite and some weight. A complete blood count (CBC) showed severe pancytopenia. What is the next best step in evaluating this patient?
A. Repeated CBCs for several weeks and reassess
B. Treatment with corticosteroids
C. Treatment with antibiotics
D. Treatment for acute leukemia
E. Bone marrow examination (Correct Answer)
Explanation: ***Bone marrow examination***
- The combination of **fever**, **joint pain**, **weight loss**, and **pancytopenia** in a previously healthy young woman raises suspicion for serious hematologic conditions like **aplastic anemia** or **acute leukemia**.
- A **bone marrow examination** is crucial for definitive diagnosis by evaluating the cellularity, morphology, and presence of abnormal cells.
*Repeated CBCs for several weeks and reassess*
- This approach is inappropriate given the **severe pancytopenia** and progressive symptoms, which indicate an urgent underlying pathology.
- Delaying diagnosis could worsen the patient's condition and compromise treatment outcomes due to the potential for severe infections or bleeding.
*Treatment with corticosteroids*
- While corticosteroids might be used in some autoimmune conditions causing pancytopenia, initiating treatment without a definitive diagnosis is premature and could mask the underlying cause, especially in cases of malignancy.
- There is no specific indication for corticosteroid use in this scenario without further diagnostic information.
*Treatment with antibiotics*
- Although **fever** is present, there's no clear evidence of an infection (like localized symptoms or positive cultures), and **pancytopenia** is not primarily managed with antibiotics.
- Administering antibiotics empirically without a confirmed infection addresses a symptom rather than the underlying progressive hematological disorder.
*Treatment for acute leukemia*
- While **acute leukemia** is a strong possibility, definitive treatment should only commence after a confirmed diagnosis through **bone marrow examination**, as misdiagnosis can lead to inappropriate and harmful therapy.
- Other conditions like severe aplastic anemia also present with similar features but require different management strategies.
Want unlimited practice?
Get full access to all questions, explanations, and performance tracking.