Pathologic Quiz Case: A 6-Year-Old Girl With Thrombocytopenia

A 6-year-old girl presented to our hospital who had shown easy bruising since birth and was noted to have moderate thrombocytopenia. She was otherwise asymptomatic and had grown and developed normally for her age. Her prenatal history was unremarkable. She had 2 siblings who appeared healthy. The family was Jewish and of European origin with no consanguinity. There was no family history of hematologic diseases.On physical examination, she weighed 19.3 kg and measured 113 cm in height. Ecchymoses were present on both legs. There was mild hepatosplenomegaly but no lymphadenopathy. The musculoskeletal examination was unremarkable. The ultrasonography showed a homogeneously enlarged spleen and liver. A complete blood count showed a hemoglobin level of 12.3 g/dL, a leukocyte count of 7.8 × 103/mm3, a platelet count of 94 × 103/mm3, and an absolute neutrophil count of 2.11 × 103/mm3. The activated partial thromboplastin time was slightly prolonged (36.2 seconds), and the prothrombin time (international normalized ratio) was normal. Factor VIII, von Willebrand factor, and ristocetin cofactor assays were all within the reference ranges. The antiplatelet antibody immunoglobulin M (IgM) was positive. Leukocyte β-glucosidase was 0 (reference range, 8–16 nmol/mg protein/h). An evaluation of the bone marrow aspirate revealed a normocellular marrow with slightly decreased megakaryocytes that were morphologically unremarkable. Both granulopoiesis and erythropoiesis were unremarkable. An interesting finding was the presence of a number of large histiocytes containing abundant cytoplasm with bluish linear striations. These cells either formed small clusters or existed individually (Figure 1). Light microscopic examination of a trephine biopsy showed islands of normocellular hematopoietic elements interspersed with aggregates of abnormal-appearing histiocytes. Most of these histiocytes possessed eccentrically located nuclei and abundant pale pink, striated cytoplasm (Figure 2) that was positive for periodic acid–Schiff stain (Figure 3). Also noted was mild reticulin fibrosis (grade 2/4). Electron microscopy of the histiocytes performed on the deparaffinized trephine biopsy showed numerous distended elongated lysosomes with a tubular appearance (Figure 4, arrows).What is your diagnosis?Gaucher disease is the most common lipid storage disorder and is caused by the accumulation of glucocereboside in the lysosomes due to an autosomal-recessive deficiency of the enzyme glucosylceramide β-glucosidase. The phagocytic cells are predominantly involved. The most common type is type I, a nonneuronopathic form that affects both children and adults and presents with a varied clinical presentation and morbidity. It is found principally in Jewish persons with European ancestry. Progressive splenomegaly with hypersplenism, hepatomegaly, bone involvement, and hematologic abnormalities are the prominent findings with this disorder. The latter include anemia, thrombocytopenia, and, less frequently, leukopenia. Infiltrating Gaucher cells in the bone can lead to osteopenia, sclerosis, and necrosis1–5 with various suggested pathologic mechanisms. Light microscopic examination of the bone marrow aspirate and a trephine biopsy in these cases typically show Gaucher cells in small focal accumulations. These cells usually have eccentric nuclei and pale cytoplasm with a fibrillary or striated appearance similar to that of “crumpled tissue paper.”6 In addition to periodic acid–Schiff stain, Gaucher cells are also stained with tartrate-resistant acid phosphatase. Ultrastructurally, the characteristic cytoplasmic appearance is imparted by the distended elongated lysosomes, which have a tubular structure. It has been extensively reported78 that the tubular structures are composed of a bundle of 10 to 12 fibrils, 30 A thick, gently twisting into a right-handed helix along the long axis, with a periodicity of about 1700 A. The diagnosis can be confirmed by measuring leukocyte β-glucosidase from the peripheral blood. An enzyme replacement therapy is available for clinical improvement. It has been suggested that, because of a decreased level of bone marrow fat after the infiltration of Gaucher cells, a quantitative computed tomographic scan is helpful in determining the severity of marrow involvement.5 In practice, Gaucher cells should be distinguished from pseudo-Gaucher cells that are morphologically similar to Gaucher cells. Pseudo-Gaucher cells have been reported to be associated with a variety of disorders, including chronic granulocytic leukemia, thalassemia, multiple myeloma, Hodgkin disease, and lymphoplasmacytoid lymphoma as well as acquired immunodeficiency syndrome and Mycobacterium avium infection. It appears that pseudo-Gaucher cells are generated because of increased cellular turnover.2We thank Mr. Vernon Edwards for performing electron microscopy for this case and preparing the resulting report.

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