Hematology and Oncology Board Review Sample Questions

The correct answer is A. MYH9 protein aggregates

Explanations: This case has four features suggestive of May-Hegglin anomaly (MH). The first feature of this disorder being the characteristic large platelets. The larger platelets may cause an abnormally low platelet count on the hematology analyzer. Thrombocytopenia is the second feature in this case which is consistent with MH and because the patient’s platelet count is likely higher than the value given by the analyzer it makes sense that she did not have any bleeding episodes in the past (even in relation to her surgeries). The third feature consistent with MH is Dohle body-like inclusions as shown above by arrows. These paracrystalline inclusions consist of MYH9 protein aggregates in neutrophils.

Finally, the fourth feature is the patient’s clinical history of sensorineural hearing loss. MH and related disorders (Epstein syndrome, Fechtner syndrome, and Sebastian syndrome) are associated with varying degrees of progressive high-frequency sensorineural hearing loss, presenile cataract and renal disease. These four conditions are now regarded as one disorder, MYH9-related disorders. Immunofluorescence detection of MYH9 protein aggregates in neutrophils may be used to screen for MYH9-RD with reported sensitivity and specificity of 100% and 95%, respectively.

Molecular genetic testing of MYH9 is used to confirm the diagnosis in those with a positive immunofluorescence test. B: Lysosomal aggregates may be observed in Chédiak-Higashi syndrome, during which the basic defect is in microtubules resulting in fusion of Lysosomal granules, seen as giant azurophilic granules in the neutrophils. In addition, the clinical history in cases of Chédiak-Higashi syndrome would consist of things such as chronic infections or oculocutaneous albinism, which are not present here. C: Intracellular Ehrlichia organisms may aggregate intracellularly to form large, mulberry-shaped aggregates referred to as morula.

Though the patient is from the northeast, the morphology and clinical presentation is not consistent with Ehrlichia. D: Inclusions comprised of mucopolysaccharides is consistent with Alder-Reilly anomaly, which is associated with the genetic mucopoly- saccharidoses. Dense azurophilic granules, resembling toxic granulation in neutrophils, are seen. E: Inclusions consisting of nuclear material may be found in multiple scenarios such as dysgranulopoiesis, cancer chemotherapy, or HIV.