Hereditary leukocyte anomalies

5 ASCP MLS practice questions on Hereditary leukocyte anomalies, part of Hematology. The first 5 are below; the first 5 with answers and explanations (tap Show answer after you have chosen), the rest in Learn with a free account.

1. Question 1 · Easy

   Partial albinism, recurrent pyogenic infections and giant cytoplasmic granules in neutrophils and lymphocytes point to which disorder?

   1. AChédiak-Higashi syndrome
   2. BAlder-Reilly anomaly
   3. CPelger-Huët anomaly
   4. DMay-Hegglin anomaly

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   Answer: A · Chédiak-Higashi syndrome

   Chédiak-Higashi syndrome is an autosomal recessive defect of the LYST gene, which controls lysosome trafficking. Lysosomes fuse into giant granules in granulocytes, monocytes and lymphocytes, and the cells kill bacteria poorly. Melanosomes are also abnormal, causing partial albinism, and platelets lack dense granules, so bruising is common. Many patients later develop an accelerated phase resembling hemophagocytic lymphohistiocytosis.

   • B: Alder-Reilly granules are dark and coarse, but the cells work normally and there is no albinism.
   • C: Pelger-Huët anomaly changes nuclear shape, not granules, and causes no illness.
   • D: May-Hegglin anomaly shows Döhle-like inclusions and giant platelets, not giant granules.

2. Question 2 · Easy

   Alder-Reilly anomaly is associated with which group of disorders?

   1. APartial albinism and immune deficiency
   2. BMyelodysplasia and cytopenias
   3. CGiant platelets and mild thrombocytopenia
   4. DHurler and other mucopolysaccharidoses

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   Answer: D · Hurler and other mucopolysaccharidoses

   In Alder-Reilly anomaly, leukocytes contain large, dark purple-to-lilac granules made of partly digested mucopolysaccharides (glycosaminoglycans). It occurs in inherited mucopolysaccharidoses such as Hurler, Hunter and Maroteaux-Lamy syndromes. The granules resemble toxic granulation, but they also appear in lymphocytes and monocytes and do not fade as an infection settles. Leukocyte function is normal.

   • A: Albinism with immune deficiency is Chédiak-Higashi syndrome.
   • B: Myelodysplasia causes acquired pseudo-Pelger cells and hypogranular neutrophils, not Alder-Reilly granules.
   • C: Giant platelets with thrombocytopenia point to May-Hegglin anomaly and other MYH9 disorders.

3. Question 3 · Medium

   A film shows pale blue, Döhle-like inclusions in many neutrophils. The finding that best supports May-Hegglin anomaly rather than a reactive response to infection is:

   1. AGiant platelets with a low platelet count
   2. BA neutrophil count of 18 × 10^3/µL (18 × 10^9/L)
   3. CA left shift with many band neutrophils
   4. DToxic granulation and cytoplasmic vacuoles

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   Answer: A · Giant platelets with a low platelet count

   May-Hegglin anomaly is an autosomal dominant MYH9-related disorder. Abnormal non-muscle myosin heavy chain IIA clumps into large, spindle-shaped, Döhle-like inclusions in granulocytes, and megakaryocytes release giant platelets in reduced numbers. Infection causes true Döhle bodies, which come with toxic granulation, vacuoles and a left shift. Analyzers may undercount giant platelets, so the count should be checked on the film.

   • B: Neutrophilia is a reactive feature; leukocyte counts are normal in May-Hegglin anomaly.
   • C: A left shift points to a reactive response to infection.
   • D: Toxic granulation and vacuoles accompany Döhle bodies in infection.

4. Question 4 · Easy

   In heterozygous Pelger-Huët anomaly, most neutrophils have nuclei that are:

   1. ABilobed, with coarse clumped chromatin
   2. BRound, like a myelocyte nucleus
   3. CHypersegmented, with 6 or more lobes
   4. DBand-shaped, with fine chromatin

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   Answer: A · Bilobed, with coarse clumped chromatin

   Pelger-Huët anomaly is an autosomal dominant defect of the lamin B receptor (LBR) gene that stops normal nuclear segmentation. In heterozygotes, most neutrophils have two round lobes joined by a thin strand (the pince-nez form) or a peanut-shaped nucleus, with coarse, mature chromatin. Granules and function are normal, so the person is healthy. Counting these cells as bands gives a false left shift.

   • B: Round nuclei are seen in the rare homozygous form.
   • C: Six or more lobes is hypersegmentation, seen in megaloblastic anemia.
   • D: The chromatin is coarse and mature; mistaking these cells for bands causes a false left shift.

5. Question 5 · Medium

   A 74-year-old man has new pancytopenia with an MCV of 104 fL. Many neutrophils are bilobed and hypogranular. A blood film from a year ago showed normally segmented neutrophils. What is the best interpretation of the bilobed cells?

   1. AHypersegmentation from B12 deficiency
   2. BInherited Pelger-Huët anomaly
   3. CAcquired pseudo-Pelger-Huët change
   4. DA left shift from infection

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   Answer: C · Acquired pseudo-Pelger-Huët change

   Bilobed neutrophils that appear late in life with cytopenias, macrocytosis and hypogranular cytoplasm are an acquired pseudo-Pelger-Huët change. This is a dysplastic feature, most often of a myelodysplastic neoplasm, and certain drugs can also cause it. In the inherited anomaly, nearly all neutrophils are affected, granules and blood counts are normal, and relatives share the finding. A bone marrow examination is the next step here.

   • A: B12 deficiency causes hypersegmented neutrophils, not bilobed ones.
   • B: The inherited anomaly is present from birth, with normal granules and normal counts.
   • D: Infection raises the neutrophil count and causes toxic changes, not pancytopenia with hypogranular cells.