Practice questions answers benign wbc

Practice questions answers

Benign white cell disorders

© Jun Wang, MD, PhD

1. A. This case is characterized by neutropenia with increased risk of infection, as shown in this patient with recurrent pharyngitis. Benign ethnic neutropenia is seen in some African descendent and does not carry an increased risk for infection. Absence of morphological atypia, dysplasia and anemia make it unlikely to be megaloblastic anemia, or myelodysplastic syndrome (MDS). Myeloproleferative neoplasms (MPN) are characterized by peripheral cytosis, not cytopenia.

2. B. Autoimmune neutropenia is likely associated with autoantibodies againt human neutrophil antigen 1. Abnormal activation of tyrosine kinases can be associated with variable disorders, including MPN. Folate acid and vitamin B12 deficiency are associated megaloblastic anemia. Single nucleotide polymorphism at Duffy antigen receptor is seen in benign ethnic neutropenia. Ineffective hematopoiesis of stem cells are associated with MDS.

3. B. Abnormal immune function associated with neutropenia and coarse granules in neutrophils and eosinophils is compatible with Chediak Higashi syndrome. Acute immune thrombocytopenia usually present with bleeding and isolated thrombocytopenia, even with a preceding viral infection. DiGeorge syndrome and severe combined immunodeficiency usually have lymphocytopenia. Familial hemophagocytic lymphohistiocytosis may have similar presentations, but intracellular coarse granules are less likely seen.

4. C. Chediak Higashi syndrome is associated with abnormal lysosomal function, due to mutation at LYST gene. Abnormal heavy chain switch is seen in hyper IgM syndrome, due to mutation of CD40 ligand. Autoantibodies against human neutrophil antigen is associated with autoimmune neutropenia. Proliferation of hyperactive macrophages is seen in hemophagocytic lymphohistiocytosis. Ineffective hematopoiesis of stem cells are associated with MDS.

5. C. LYST/CHS1 mutation is seen in Chediak Higashi syndrome. Bruton tyrosine kinase mutation is seen in X-linked agammaglobulinemia. Mutation of common gamma chain of interleukin receptor is associated with X-linked SCID. Perforin mutation may be seen in hemophagocytic lymphohistiocytosis. WASp mutation is seen in Wiskott-Aldrich syndrome, a primary immune deficiency characterized by triad of recurrent bacterial sinopulmonary infections, eczema and bleeding diathesis.

6. D. Elevated LAP score and leukocytosis is compatible with leukemoid reaction. Diagnosis of AML requires either more than 20% blasts, or specific genetic abnormalities. CML has low LAP scores. CLL has lymphocytosis. Both MDS and AML will presents with dysplasia.

7. B. Presence of immature myelocytes and nucleated red cells is leukoerythroblastosis. Megaloblastic changes are associated with impaired DNA synthesis and present with hypersegmented neutrophils and eosinophils. MDS is characterized by dysplastic changes of one of myelocytic lineages. 

 

8. B. Leukoerythroblastosis is usually associated with bone marrow disruption, including conditions such as MPN. Autoimmune hemolysis usually has spherocytes. JAK2 V617F mutation with fibrosis in bone marrow is most likely to be primary myelofibrosis, not metastatic cancers. Myelocytic maturation arrest is seen in MDS and AML. Blastic phase of CML has more than 20% blasts in circulation or bone marrow.

9. E. This is most likely a parasitic gastroenteritis, as characterized by eosinophilia without features of other hematopoietic neoplasms. MDS and AML have dysplastic changes or certain amount of blasts. CML usually presents with leukocytosis with basophilia. Drug may induce eosinophilia but usually has history of usage.

10. E. The difference between CLL and monoclonal B cell lymphocytosis is the quantity of absolute monoclonal lymphocytes. Monoclonal B cell lymphocytosis is believed to be precursor lesion for CLL. Both acute lymphoblastic leukemia and infectious mononucleosis have related clinical symptoms. Adult T cell leukemia/lymphoma is characterized by multilobulated nuclei (cloverleaf/flower cells).

11. B. See answer to question 10.

12. D. Infectious mononucleosis is characterized by a triad of fever, tonsillar pharyngitis, and lymphadenopathy. AML and ALL have circulating blasts. Lymphocytes in CLL and monoclonal B cell lymphocytosis are monoclonal small lymphocytes. Usually if no monoclonal lymphocytes are detected by flow cytometry, it is likely to be reactive, although flow cytometry is not helpful in diagnosis of Hodgkin lymphoma. MPNs usually have increased myelocytic series, not lymphocytes.

13. A. Infectious mononucleosis is associated with EBV infection. HHV 8 is seen in primary effusion lymphoma and Kaposi sarcoma. HPV is well known to be associated with cervical cancers including endocervical adenocarcinoma, and squamous cell carcinoma is various locations. Bacterial infection usually cause neutrophilia, not lymphocytosis.

14. D. Spontaneous splenic rupture is a severe complication for infectious mononucleosis. The risk of splenic rupture caused by exercise need to be addressed. Transformation to blastic phase can be seen in low grade hematopoietic neoplasms, including CML.

15. D. Pelger-Huet anomaly is an autosomal dominant condition characterized by round (homozygote) or bilobed nuclei (heterozygote) in neutrophils. It usually have normal function. Pseudo Pelger-Huet changes can be seen in MDS and AML, usually accompanied with other clinical presentations. Megaloblastic anemia has hypersegmentation of granular cells.

16. E. This is a case of autoimmune gastritis associated pernicious anemia, due to vitamin B12 deficiency, as a result of lack of intrinsic factor. The classic triad of weakness, sore tongue, and paresthesias may be elicited but usually is not the chief symptom complex. Although both folate and vitamin B12 deficiency may present with megaloblastic anemia, characterized by macrocytic anemia and granulocytes hypersegmentation, neurological presentations are more compatible with vitamin B12 deficiency. MDS may be associated with hyposegmented neutrophils (pseudo Pelger-Huet changes). AMLs have blasts and other immature myelocytes. Metastatic cancer usually has a history of malignancy. Iron deficiency anemia is characterized by microcytic, hypochromic red blood cells.

17. E. Autoimmune gastritis is characterized by loss of parietal cells, therefore with a subsequent lack of intrinsic factor, and results in vitamin B12 deficiency due to lack of absorption. Folate deficiency may present with megaloblastic anemia, but usually without neurological abnormalities. Hemoglobin alpha subunit abnormality is seen in thalassemia. Spectrin abnormality is associated with hereditary spherocytosis, but usually with normal morphology of white cells. Iron deficiency anemia is characterized by microcytic, hypochromic red blood cells.

18. D. Presence of neutrophils with microabscess formation is most compatible with suppurative lymphadenitis. This case is most likely a chancroid, a sexually transmitted disease caused by Gram negative rod Haemophilus ducreyi. Chronic lymphadenopathy (chronic lymphadenitis) is characterized by follicular hyperplasia with normal architecture, but not neutrophilic infiltration. Follicular lymphomas usually have packed follicles without normal architecture. Hodgkin lymphomas have Reed-Sternberg cells if classic type, and pop-corn cells, if NLPHL.

19. A. Chronic inflammation in drainage area may cause chronic lymphadenitis. Morphologically it is characterized by follicular hyperplasia with tingible body macrophages.  Follicular lymphomas usually have packed follicles without normal architecture. Lack of epithelial cells in lymph nodes rules out mets. Suppurative lymphadenitis has neutrophil infiltration. SLL is characterized by sheets of small lymphocytes with soccer ball like nuclei.

20. C. Hemophagocytic lymphohistiocytosis can be familial, due to mutation of various genes, including perforin, MUNC13-4, etc, or acquired, associated with infection, malignancy etc. Chediak Higashi syndrome presents with coarse granules in granulocytes, due to abnormal lysosomal function. Lack of epithelial cells in lymph nodes rules out mets. Follicular lymphomas usually have packed follicles without normal architecture. Langerhans histiocytosis has solid infiltration of histiocytes with elongated nuclei with nuclear grooves.

21. D. Acquired hemophagocytic lymphohistiocytosis is caused by over activation of macrophages, resulted from either certain infections or underlying malignancy. JAK2 mutation is associated with MPN. AMLs have blasts and other immature myelocytes. LYST mutation is seen in Chediak Higashi syndrome. Over expression of bcl2 due to 14:18 translocation is seen in follicular lymphoma.

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