A 68-Year-Old Man With Thrombocytosis and Ringed Sideroblasts

Archives of Pathology & Laboratory Medicine,  Jul 2004  by Jani, Jigna C,  Gaitonde, Sujata,  Saunthararajah, Yogen,  Ni, Hongyu

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A 68-year-old white man was referred to our institute for evaluation of anemia. The patient was scheduled for hernia repair surgery. On routine blood work, he was found to have anemia and thrombocytosis. He had no complaints except mild intermittent right lower quadrant pain, which was thought to be caused by his hernia. He had experienced mild dizziness when waking up in the morning during the past 1 to 2 months. He reported no loss of consciousness and no falls. He was not taking any medications. His past medical history was significant for a small myocardial infarction 30 years earlier, but he had not had problems since. Family history revealed no history of cancer or any hematologic disorders.

Physical examination demonstrated no lymphadenopathy, no bruises, and no purpura. His liver was palpated 1 cm below the right costal margin. The spleen was not palpable.

Peripheral blood examination demonstrated a hemoglobin level of 9.3 g/dL; red blood cell count, 3.3 × 10^sup 6^/µL; mean corpuscular volume, 84.2 × 10^sup -15^ L; mean corpuscular hemoglobin, 27.9 pg; mean corpuscular hemoglobin concentration, 33.2 g/dL; red cell distribution width, 29.9%,; white blood cell count, 10.3 × 10^sup 3^/µL; and platelets, 988 × 10^sup 3^/µL. Differential count of the peripheral blood showed neutrophils at 51%; monocytes, 4%; and lymphocytes, 41%. There were no circulating blasts. Platelets were markedly increased and occasional giant platelets were seen (Figure 1).

The patient's serum iron level was normal (55 µg/dL), and his total iron binding capacity was slightly decreased (191 µg/dL). He had increased an serum ferritin level (517 ng/mL). His serum folate and serum B12 levels were within normal limits.

Bone marrow biopsy was performed, which revealed a hypercellular marrow with 70% cellularity (Figure 2). The myeloid series showed orderly maturation. The erythroid series showed mild hyperplasia with megaloblastoid changes and mild dyserythropoiesis, as manifest by irregular nuclei and nuclear budding of ervthroid precursors.

There was megakaryocytic hyperplasia with clusters of megakaryocytes consisting predominantly of large, hyperlobulated forms (Figure 3). Rare, small, hypolobulated megakaryocytes were seen. Megakaryocytic emperipolesis and platelet clumps were present.

The differential count demonstrated blasts at 2%; promyelocytes, 4%; myelocytes, 10%; metamyelocytes, 6%; bands, 5%; neutrophils, 15%; erythroid precursors, 32%; monocytes, 3%; lymphocytes, 15%; plasma cells, 2%; basophils, 0%; and eosinophils, 6%. There was mild erythroid hyperplasia with a myeloid-erythroid ratio of 1.6:1.

Iron staining of the bone marrow aspirate revealed increased storage iron. Ring sideroblasts were present (Figure 4) and accounted for approximately 6O0X. of the erythroid precursors.

Cytogenetic analysis of the bone marrow showed normal male karyotype.

What is your diagnosis?

Pathologic Diagnosis: Essential Thrombocythemia With Ringed Sideroblasts

Chronic clonal disorders of hematopoiesis are usually classified as either myeloproliferative disorder or myelodysplastic syndrome. Both groups are clonal hematopoietic stem cell disorders and both are characterized by increased numbers of proliferating cells in the bone marrow.1,2 In myeloproliferative disorders, hematopoiesis is effective, and there is overproduction of end cells of at least 1 hematopoietic lineage.2 In contrast, hematopoiesis is ineffective in myelodysplastic syndrome, which is usually manifest by cytopenia.1

Essential thrombocythemia is a chronic myeloproliferative disorder characterized by sustained thrombocytosis in the blood and increased numbers of large, mature megakaryocytes in the bone marrow.3 Essential thrombocythemia usually is associated with decreased marrow iron and does not show increased ringed sideroblasts.4

The increase in ringed sideroblasts in the bone marrow is consistent with dysplasia. The abnormality of ringed sideroblasts with typical perinuclear, coarsely granulated iron deposits in more than 15% of the erythroid precursors has been recognized as refractory anemia with ringed sideroblasts.1 This disorder is generally considered to be a clonal expansion of abnormal hematopoietic progenitor cells in the context of a myelodysplastic syndrome.

In the current case, the patient had marked thrombocytosis and hypercellular marrow with megakaryocytic proliferation. The megakaryocytes were large. Chromosome analysis demonstrated normal male karyotype. These features support the diagnosis of essential thrombocythemia. However, the bone marrow showed increased sideroblasts (60% of erythroid precursors). Therefore, the case is best characterized as essential thrombocythemia with sideroblastic erythropoiesis. This disorder could also be regarded as refractory anemia with ringed sideroblasts with thrombocytosis.5,6

According to the recently published World Health Organization classification, essential thrombocythemia with ringed sideroblasts remains an ambiguous category, which may be considered as myelodysplastic/myeloproliferative disease, unclassifiable.7 The presence of increased ringed sideroblasts indicates a dysplasia associated with a disturbance of iron metabolism.