Practice question reactive white cell

Practice questions

Benign white cell disorders

© Jun Wang, MD, PhD

1. Use this case for next two questions. A 1-year-old white boy presents with recurrent pharyngitis for 4 months. His past history is otherwise unremarkable. Physical examinations reveal normal development. His weight and height are about 65 percentile. No significant abnormalities are seen except redness of his pharynx and bilateral tonsillar swollen. Laboratory tests reveal normal range hemoglobin and platelets. His absolute neutrophil count is 400/mm³ (normal > 1500/mm³). Quantity of other white cells are within normal range. Peripheral blood smear reveal no significant morphological atypia. Bone marrow biopsy reveal normal cellularity with trilineage maturation. No dysplasia is identified. What is the most likely diagnosis?

A. Autoimmune neutropenia

B. Benign ethnic neutropenia

C. Megaloblastic anemia

D. Myelodysplastic syndrome

E. Myeloproliferative neoplasm

2.  A 1-year-old white boy presents with recurrent pharyngitis for 4 months. His past history is otherwise unremarkable. Physical examinations reveal normal development. His weight and height are about 65 percentile. No significant abnormalities are seen except redness of his pharynx and bilateral tonsillar swollen. Laboratory tests reveal normal range hemoglobin and platelets. His absolute neutrophil count is 400/mm³ (normal > 1500/mm³). Quantity of other white cells are within normal range. Peripheral blood smear reveal no significant morphological atypia. Bone marrow biopsy reveal normal cellularity with trilineage maturation. No dysplasia is identified. What is the most likely causing his presentations?

A. Abnormal activation of tyrosine kinases, such as JAK2, Abl

B. Autoantibodies against human neutrophil antigen 1

C. Folate acid deficiency

D. Single nucleotide polymorphism at the Duffy antigen receptor

E.  Stem cell ineffective hematopoiesis

3. Use this case for the next three questions. A two-year-old boy presents with high-grade fever and rapid breathing for 3 days. He has history of recurrent upper respiratory infections, bilateral ear draining and high-grade fever since birth. He has an older brother who died of recurrent severe infections at age 1 month. His family history is otherwise unremarkable. Physical examination reveals skin with multiple patchy pale areas and enlarged lymph nodes at his neck, and axillae. Oral thrush is seen. Laboratory tests reveal a hemoglobin of 7 g/dL (normal 10.5-14.5 g/dL), white cells at 4 x 10⁹/L (normal 6-17 x 10⁹/L), platelet at 80 x 10⁹/L (normal 219-452 x 10⁹/L). White cell differentiation reveal 12% neutrophil, 79% lymphocytes, 6% monocytes and 3% eosinophils. Peripheral blood smear reveal large coarse granules in neutrophils and eosinophils. Red cells are morphologically unremarkable. Serum electrophrosis reveal normal level of immunoglobulins. Bone marrow aspiration reveal similar intracellular granules in neutrophils and eosinophils as seen in peripheral blood. Intracellular remnants of hematopoietic precursors are seen in histiocytes. No dysplasia is seen in all three lineages. What is the most likely diagnosis?

A. Acute immune thrombocytopenic purpura

B. Chediac Higashi disease

C. DiGeorge syndrome

D. Familial hemophagocytic lymphohistiocytosis

E. Severe combined immunodeficiency

4. A two-year-old boy presents with high-grade fever and rapid breathing for 3 days. He has history of recurrent upper respiratory infections, bilateral ear draining and high-grade fever since birth. He has an older brother who died of recurrent severe infections at age 1 month. His family history is otherwise unremarkable. Physical examination reveals skin with multiple patchy pale areas and enlarged lymph nodes at his neck, and axillae. Oral thrush is seen. Laboratory tests reveal a hemoglobin of 7 g/dL (normal 10.5-14.5 g/dL), white cells at 4 x 10⁹/L (normal 6-17 x 10⁹/L), platelet at 80 x 10⁹/L (normal 219-452 x 10⁹/L). White cell differentiation reveal 12% neutrophil, 79% lymphocytes, 6% monocytes and 3% eosinophils. Peripheral blood smear reveal large coarse granules in neutrophils and eosinophils. Red cells are morphologically unremarkable. Serum electrophrosis reveal normal level of immunoglobulins. Bone marrow aspiration reveal similar intracellular granules in neutrophils and eosinophils as seen in peripheral blood. Intracellular remnants of hematopoietic precursors are seen in histiocytes. No dysplasia is seen in all three lineages. What is the most likely causing these presentations?

A. Abnormal heavy chain switching

B. Autoantibodies against human neutrophil antigen 1

C. Lysosomal dysfunction

D. Proliferation of hyperactive macrophages

E. Stem cell ineffective hematopoiesis

5. A two-year-old boy presents with high-grade fever and rapid breathing for 3 days. He has history of recurrent upper respiratory infections, bilateral ear draining and high-grade fever since birth. He has an older brother who died of recurrent severe infections at age 1 month. His family history is otherwise unremarkable. Physical examination reveals skin with multiple patchy pale areas and enlarged lymph nodes at his neck, and axillae. Oral thrush is seen. Laboratory tests reveal a hemoglobin of 7 g/dL (normal 10.5-14.5 g/dL), white cells at 4 x 10⁹/L (normal 6-17 x 10⁹/L), platelet at 80 x 10⁹/L (normal 219-452 x 10⁹/L). White cell differentiation reveal 12% neutrophil, 79% lymphocytes, 6% monocytes and 3% eosinophils. Peripheral blood smear reveal large coarse granules in neutrophils and eosinophils. Red cells are morphologically unremarkable. Serum electrophrosis reveal normal level of immunoglobulins. Bone marrow aspiration reveal similar intracellular granules in neutrophils and eosinophils as seen in peripheral blood. Intracellular remnants of hematopoietic precursors are seen in histiocytes. No dysplasia is seen in all three lineages. Abnormality of what gene is the most likely associated with these presentations?

A. Bruton tyrosine kinase

B. Common gamma-chain of interleukin receptors

C. LYST

D. Perforin

E. WASp

6. A 57-year-old man presents with chills, chest pain after 3 days of fever and coughing with rusty colored sputum. He has type II diabetes since age 42. He has been smoking cigarette, 1 pack a day for 40 years. Physical examination reveals rales in the right lower lobe. No lymph adenopathy is seen. Chest X-ray reveals infiltrate of right lower lobe, but no discrete mass is seen. CBC reveals white cell count of 56 x 10⁹/L, with 60% mature neutrophils, 20% bands, 10% lymphocytes, 7% monocytes and 3% eosinophils. Some neutrophils and bands have dark coarse intracytoplasmic granules. No hypersegmentation is noted. No significant morphological abnormality is seen in eosinophils and monocytes. The red cells and platelets are unremarkable in quantity and morphology. His leukocyte alkaline phosphatase score is 125 (normal 20-100). What is the most likely cause of his peripheral blood findings?

A. Acute myelocytic leukemia

B. Chronic myelocytic leukemia

C. Chronic lymphocytic leukemia

D. Leukemoid reaction

E. Myelodysplastic syndrome

7. Use this case for the next two questions. A 64-year-old woman presents with fatigue and left upper abdomen discomfort. She has a history of left breast ductal carcinoma 5 years ago and was treated lumpectomy and left axillary lymph node dissection, followed by chemotherapy. She has type II diabetes for 15 years. Her past medical history is otherwise unremarkable. Physical examination reveals a spleen 5 cm below costal margin. No other significant abnormality is seen except findings associated with her previous surgery. Laboratory test reveals a hemoglobin of 9.5 g/dL (normal 11-15 g/dL), white cell count 12.1 x 10⁹/L (normal 4.7–11 × 10⁹/L) with normal differential, platelet 820 × 10⁹/L (normal 150-450 × 10⁹/L). Peripheral blood reveal markedly increased number of platelets. There are giant platelets and immature myelocytic series including myelocytes and metamyelocytes. No blast is seen. Nucleated red cells and teardrop-shaped red cells are seen. Bone marrow aspirate is not successful. Bone marrow biopsy reveal isolated megakaryocytic hyperplasia with reticulin fibrosis. No dysplasia is seen in all three lineages. Molecular studies reveal JAK2 V617F mutation. What is the best description of her peripheral blood findings?

A. Leukocytosis

B. Leukoerythroblastosis

C. Leukemoid reaction

D. Megaloblastic changes

E. Myelodysplastic changes

8. A 64-year-old woman presents with fatigue and left upper abdomen discomfort. She has a history of left breast ductal carcinoma 5 years ago and was treated lumpectomy and left axillary lymph node dissection, followed by chemotherapy. She has type II diabetes for 15 years. Her past medical history is otherwise unremarkable. Physical examination reveal a spleen 5 cm below costal margin. No other significant abnormality is seen except findings associated with her previous surgery. Laboratory test reveals a hemoglobin of 9.5 g/dL (normal 11-15 g/dL), white cell count 12.1 x 10⁹/L(normal 4.7–11 × 10⁹/L) with normal differential, platelet 820 × 10⁹/L (normal 150-450 × 10⁹/L). Peripheral blood reveal markedly increased number of platelets. There are giant platelets and immature myelocytic series including myelocytes and metamyelocytes. No blast is seen. Nucleated red cells and teardrop-shaped red cells are seen. Bone marrow aspirate is not successful. Bone marrow biopsy reveal isolated megakaryocytic hyperplasia with reticulin fibrosis. No dysplasia is seen in all three lineages. Molecular studies reveal JAK2 V617F mutation. What is the cause of her peripheral blood findings?

A. Autoimmune hemolysis

B. Disruption of marrow

C. Metastatic breast cancer to bone marrow

D. Myelocytic maturation arrest

E. Transformation to acute myelocytic leukemia (blastic phase of CML)

9. A 19-year-old man presents with mild periumbilical pain and diarrhea after a hiking trip to Rocky mountains. His past medical history is unremarkable. Physical examination reveal mild tenderness around central abdomen. No other abnormalities are seen. CBC reveals a hemoglobin of 14 g/dL (normal 11-15 g/dL), white cell count 10.1 x 10⁹/L (normal 4.7–11 × 10⁹/L), platelet 420 × 10⁹/L (normal 150-450 × 10⁹/L). He has an absolute eosinophils count of 820 /mm³ (normal <500). No morphological abnormality is seen. Other blood cells are unremarkable. No immature myelocytes are seen. What is the most likely diagnosis?

A. Acute myelocytic leukemia with eosinophilia

B. Chronic myelocytic leukemia

C. Drug induced eosinophilia

D. Myelodysplastic syndrome with eosinophilia

E. Parasitic gastroenteritis

10. Use this case for the next two questions. A 50-year old man presents for physical check up as required by a life insurance carrier. His past history is unremarkable. Physical examination reveals no significant abnormality. CBC reveals a hemoglobin of 13.5 g/dL (normal 11-15 g/dL), white cell count 15.3 x 10⁹/L (normal 4.7–11 × 10⁹/L), platelet 397 × 10⁹/L (normal 150-450 × 10⁹/L). White cell differential reveals 50% neutrophils, 40% lymphocytes, 8% monocytes and 2% eosinophils. No immature white cells are identified. Peripheral blood reveal presence of monotonous small lymphocytes. Flow cytometry reveals a CD20 positive monoclonal lymphocytic population at a level of 4.5 x 10⁹/L. Immunofixation reveal no evidence of monoclonal immunoglobulin. His other lab tests are unremarkable. What is the most likely diagnosis?

A. Acute lymphoblastic leukemia

B. Adult T cell leukemia

C. Chronic lymphocytic leukemia

D. Infectious mononucleosis

E. Monoclonal B cell lymphocytosis

11. A 50-year old man presents for physical check up as required by a life insurance carrier. His past history is unremarkable. Physical examination reveals no significant abnormality. CBC reveals a hemoglobin of 12 CBC reveals a hemoglobin of 13.5 g/dL (normal 11-15 g/dL), white cell count 15.3 x 10⁹/L (normal 4.7–11 × 10⁹/L), platelet 397 × 10⁹/L (normal 150-450 × 10⁹/L). White cell differential reveals 50% neutrophils, 40% lymphocytes, 8% monocytes and 2% eosinophils. No immature white cells are identified. Peripheral blood reveal presence of monotonous small lymphocytes. Flow cytometry reveals a CD20 positive monoclonal lymphocytic population at a level of 4.5 x 10⁹/L. Immunofixation reveal no evidence of monoclonal immunoglobulin. His other lab tests are unremarkable.What condition he is at risk to develop into?

A. Acute myeloid leukemia

B. Chronic lymphocytic leukemia

C. Hairy cell leukemia

D. Hodgkin lymphoma

E. Multiple myeloma

12. Use this case for the next three questions. A 17-year-old female high school student presents with sore throat for 3 days and 40°C fever. Her past history is unremarkable. Physical examination reveals enlarged tonsils with whitish exudates, swollen adenoids, and a few enlarged posterior cervical lymph nodes. A spleen is palpated 3 cm below costal margin. Her CBC reveal a white count of 17 x 10⁹/L (normal 4.5-10.5 x 10⁹/L). Peripheral smear reveals presence of enlarge cells with moderate amount of basophilic agranular cytoplasm with peripheral darkening, and slight irregular nuclear contour. Neutrophils, eosinophils, red cells and platelets are normal in quantity and morphology. No immature cells are seen. However, there are smashed nuclear remnant (smudge cells). Her liver function tests are slightly elevated. She is positive for monospot test. Flowcytometry studies reveal polyclonal lymphocytic population. No blast is detected. What is the most likely diagnosis?

A. Acute lymphocytic leukemia

B. Acute myeloid leukemia

C. Chronic lymphocytic leukemia

D. Infectious mononucleosis

E. Myeloproliferative neoplasm

13. A 17-year-old female high school student presents with sore throat for 3 days and 40°C fever. Her past history is unremarkable. Physical examination reveals enlarged tonsils with whitish exudates, swollen adenoids, and a few enlarged posterior cervical lymph nodes. A spleen is palpated 3 cm below costal margin. Her CBC reveal a white count of 17 x 10⁹/L (normal 4.5-10.5 x 10⁹/L). Peripheral smear reveals presence of enlarge cells with moderate amount of basophilic agranular cytoplasm with peripheral darkening, and slight irregular nuclear contour. Neutrophils, eosinophils, red cells and platelets are normal in quantity and morphology. No immature cells are seen. However, there are smashed nuclear remnant (smudge cells). Her liver function tests are slightly elevated. She is positive for monospot test. Flowcytometry studies reveal polyclonal lymphocytic population. No blast is detected. What is the most likely causing her disorder?

A. EB virus

B. Human herpes virus 8

C. Human papilloma virus

D. Staphylococcus aureus

E. Streptococcus pyogenes

14. A 17-year-old female high school student presents with sore throat for 3 days and 40°C fever. Her past history is unremarkable. Physical examination reveals enlarged tonsils with whitish exudates, swollen adenoids, and a few enlarged posterior cervical lymph nodes. A spleen is palpated 3 cm below costal margin. Her CBC reveal a white count of 17 x 10⁹/L (normal 4.5-10.5 x 10⁹/L). Peripheral smear reveals presence of enlarge cells with moderate amount of basophilic agranular cytoplasm with peripheral darkening, and slight irregular nuclear contour. Neutrophils, eosinophils, red cells and platelets are normal in quantity and morphology. No immature cells are seen. However, there are smashed nuclear remnant (smudge cells). Her liver function tests are slightly elevated. She is positive for monospot test. Flowcytometry studies reveal polyclonal lymphocytic population. No blast is detected. What is her most likely complication?

A. Autoimmune hemolysis

B. Disseminated intravascular coagulation

C. Severe aplastic anemia

D. Spontaneous splenic rupture

E. Transformation into blastic phase

15. A 9-year-old previously healthy boy presents for routine medical examination. Physical examination is unremarkable. His CBC is within normal range. However, peripheral blood smear reveal presence of neutrophils with bi-lobed nuclei. No morphological abnormalities are seen in eosinophils, monocytes and lymphocytes. What is the most likely diagnosis?

A. Acute myelocytic leukemia

B. Megaloblastic anemia

C. Myelodysplastic syndrome

D. Pelger-huet anomaly

16. Use this case for the next two questions. A 40-year-old woman presents with fatigue and shortness of breath after exercise for 3 weeks. She had a history of autoimmune gastritis. Her past history is otherwise unremarkable. Physical examination reveals a heart rate at 110 /minute. Heart sound is unremarkable. She appears to be pale, but no jaundice is noted. Her tongue is beefy red and smooth, and painful. She has unsteady gait. No other abnormalities are found. Laboratory tests reveal a hemoglobin at 6.5 g/dL (normal 11-15 g/dL), white cell count 3.3 x 10⁹/L (normal 4.7–11 × 10⁹/L) with normal differential, platelet 92 × 10⁹/L (normal 150-450 × 10⁹/L). Peripheral blood smear reveal large pale red cells. Many neutrophils have 5 to 6 lobed nuclei. A few eosinophils with 3 and more lobed nuclei are seen. No blast nor other myeloid precursors are found. Her aPTT and PT are within normal range. What is the most likely diagnosis?

A. Acute promyelocytic leukemia with PML-RARA

B. Bone metastasis of gastric adenocarcinoma

C. Iron deficiency anemia

D. Myelodysplastic syndrome

E. Pernicious anemia

17. A 40-year-old woman presents with fatigue and shortness of breath after exercise for 3 weeks. She had a history of autoimmune gastritis. Her past history is otherwise unremarkable. Physical examination reveals a heart rate at 110 /minute. Heart sound is unremarkable. She appears to be pale, but no jaundice is noted. Her tongue is beefy red and smooth and painful. She has unsteady gait. No other abnormalities are found. Laboratory tests reveal a hemoglobin at 6.5 g/dL (normal 11-15 g/dL), white cell count 3.3 x 10⁹/L (normal 4.7–11 × 10⁹/L) with normal differential, platelet 92 × 10⁹/L (normal 150-450 × 10⁹/L). Peripheral blood smear reveal large pale red cells. Many neutrophils have 5 to 6 lobed nuclei. A few eosinophils with 3 and more lobed nuclei are seen. No blast nor other myeloid precursors are found. Her aPTT and PT are within normal range. What is the most likely causing her peripheral blood findings?

A. Folate deficiency

B. Hemoglobin alpha subunit abnormality

C. Iron deficiency

D. Spectrin abnormality

E. Vitamin B12 deficiency

18. A 29-year-old man presents with a non healing painful penile ulcer for 3 days. He had unprotected sex with a sex worker two weeks before the ulcer developed. He has been HIV positive for 6 years. He has a history of infectious mononucleosis at age 21. Physical examination reveal an ulcer with irregular border at the left side of his penile shaft. A 2 cm tender lymph node is found at his left inguinal area. No other abnormality is seen. His CBC reveal slightly increase white cell count, but are otherwise unremarkable. Microbiology studies of the ulcer reveal chains of Gram-negative rod. Biopsy of the ulcer reveal ulcerated skin with marked lymphoplasmacytic infiltrate. No significant epithelial atypia is seen. Biopsy of the lymph node reveal hyperplastic appearing follicles with neutrophilic infiltration and microabscess formation. No atypical cells are seen. What is the most likely diagnosis of the lymph node findings?

A. Chronic lymphadenopathy

B. Follicular lymphoma

C. Hodgkin lymphoma, classic type

D. Suppurative lymphadenitis

19. A 68-year-old farmer presents with a 1.5 cm non healing ulcer of his right forehead. He has a history of multiple skin cancers, including basal cell carcinoma and squamous cell carcinoma, all removed by surgery. He has a history of chronic lymphocytic leukemia for 3 years and is currently being monitored. Physical examination reveals a 1 cm tender lymph node at his right upper neck. The ulcer is resected and microscopic examination reveal irregular nests of polygonal cells with abundant cytoplasm and markedly pleomorphic nuclei. Intercellular bridges are seen. Some of the cells aggregate with concentric layers and central keratinization. Biopsy of the lymph nodes reveal irregularly enlarged follicles with abundant tingible body macrophages. The architecture of these follicles appear to be normal. No epithelial cells are seen. No monoclonal lymphocytic population is detected per flow cytometry. What is the most likely diagnosis concerning the lymph node?

A. Chronic lymphadenopathy

B. Follicular lymphoma

C. Metastatic squamous cell carcinoma

D. Small lymphocytic lymphoma

E. Suppurative lymphadenopathy

20. Use this case for the next two questions. A 65-year-old woman presents with fever, gum bleeding and a few left axillary nodules. She was diagnosed with left breast invasive ductal carcinoma 1 year ago, and was treated with lumpectomy. Sentinel lymph node biopsy at the time of lumpectomy reveal reactive lymph node without evidence of metastatic cancer. Physical examination reveal a fever of 103 degrees, swollen gum with multiple petechial bleeding sites, and 3 slightly enlarged left axillary lymph nodes up to 1 cm in greatest dimension. Her spleen is 4 cm below costal margin and soft. Her CBC reveals hemoglobin at 7.2 g/dL (normal 11-15 g/dL), white cell count 4.5 x 10⁹/L (normal 4.7–11 × 10⁹/L) with normal differential, platelet 52 × 10⁹/L (normal 150-450 × 10⁹/L). Peripheral blood smear reveals no morphological abnormality. Her ferritin is 7000 ng/ml (normal 12 to 150 ng/mL). Radiology studies reveal a few nodules in lungs. Biopsy of the lymph nodes reveal irregularly enlarged follicles with normal appearing architecture and diffuse infiltration of histiocytes, some histiocytes have intracellular red cells. No nuclear grooves are seen. No epithelial cells are seen in the lymph nodes. What is the most likely diagnosis?

A. Chediak-Higashi syndrome

B. Follicular lymphoma

C. Hemophagocytic lymphohistiocytosis

D. Langerhans cell histiocytosis

E. Metastatic ductal carcinoma

21. A 65-year-old woman presents with fever, gum bleeding and a few left axillary nodules. She was diagnosed with left breast invasive ductal carcinoma 1 year ago, and was treated with lumpectomy and chemotherapy. Sentinel lymph node biopsy at the time of lumpectomy reveal reactive lymph node without evidence of metastatic cancer. Physical examination reveal a fever of 103 degrees, swollen gum with multiple petechial bleeding sites, and 3 slightly enlarged left axillary lymph nodes up to 1 cm in greatest dimension. Her spleen is 4 cm below costal margin and soft. Her CBC reveals hemoglobin at 7.2 g/dL (normal 11-15 g/dL), white cell count 4.5 x 10⁹/L (normal 4.7–11 × 10⁹/L) with normal differential, platelet 52 × 10⁹/L (normal 150-450 × 10⁹/L). Peripheral blood smear reveals no morphological abnormality. Her ferritin is 7000 ng/ml (normal 12 to 150 ng/mL). Radiology studies reveal a few nodules in lungs. Biopsy of the lymph nodes reveal irregularly enlarged follicles with normal appearing architecture and diffuse infiltration of histiocytes, some histiocytes have intracellular red cells. No epithelial cells are seen in the lymph nodes. What is the most likely cause of the lymph node finding?

A. Abnormal hematopoiesis due to JAK2 mutation

B. Acute myeloid leukemia associated with previous chemotherapy

C. Lysosomal dysfunction due to LYST mutation

D. Over activation of macrophages associated with underlying malignancy

E. Over expression of bcl2 due to 14:18 translocation

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