Morphologic and immunohistochemical evaluation of splenic hematopoietic proliferations in neoplastic and benign disorders

Abstract

Spleen is a common site of extramedullary hematopoiesis. Extramedullary hematopoiesis seen in nonneoplastic conditions can occasionally be extensive and raise concerns for a myeloid neoplasm. We compared the morphologic and immunohistochemical features of splenic hematopoietic proliferations seen in neoplastic myeloid disorders (eg chronic myeloproliferative disorders, myelodysplastic/myeloproliferative disorders and acute myeloid leukemias) to extramedullary hematopoiesis seen in a variety of reactive conditions. In all, 80 spleen specimens were reviewed. The presence of each marrow-derived lineage, dysplasia and immunohistochemical results were evaluated (CD34, CD117, myeloperoxidase, CD68, p53, TdT, CD42b and hemoglobin). Neoplastic hematopoietic proliferations in chronic myeloproliferative disorders are characterized by trilineage hematopoiesis with significant dysplasia in all cell lineages. Acute myeloid leukemia showed an increase in immature forms, which were highlighted by immunohistochemistry. Reactive extramedullary hematopoiesis showed variability in histologic features. Post-bone marrow transplant and thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome spleens showed extramedullary hematopoiesis with some morphologic features of immaturity, which could simulate chronic myeloproliferative disorder. However, they lacked characteristic immunohistochemical features of neoplastic myeloid disorders such as positivity for CD34 or CD117. Modern Pathology (2005) 18, 1550-1561.

The role of Janus Kinase 2 V617F mutation in extramedullary hematopoiesis of the spleen in neoplastic myeloid disorders

“…30 These precursor cells may then circulate to and become trapped within the spleen, leading to a clonal extramedullary hematopoietic expansion. O'Malley et al 3,4 recently reported that EMH cases associated with neoplastic myeloid disorders showed concordant loss-of-heterozygosity (LOH) lesions and X-chromosome inactivation patterns in the respective bone marrow and spleen specimens. Furthermore, additional LOH abnormalities were identified in the spleen, suggesting evolution of the original clone.…”

“…It has been hypothesized that EMH cells are derived from either circulating neoplastic stem cells, which undergo terminal differentiation within the spleen as part of the neoplastic process or reactivated embryonic remnants of fetal hematopoiesis as compensation for marrow failure. [1][2][3][4][5] The former concept is more strongly favored, as hematopoietic elements in EMH have histomorphological and molecular findings similar to those of the corresponding marrow biopsies. [1][2][3][4][5] However, the clonal relationship between splenic EMH cells and neoplastic bone marrow cells remains unconfirmed.…”

Analysis of loss of heterozygosity and X chromosome inactivation in spleens with myeloproliferative disorders and acute myeloid leukemia

“…The nature and evolution of neoplastic myeloid proliferations in the spleen, particularly in chronic myeloproliferative disorder, is a potentially rich area of future research. 16 Although it is unlikely to be used as a primary diagnostic method, LOH studies may be of benefit in understanding nature of evolution of clonal cells and the detection of abnormal genetic findings in chronic myeloproliferative disorder and other hematopoietic disorders.…”

The myelodysplastic/myeloproliferative neoplasms: myeloproliferative diseases with dysplastic features

“…31 The spleen enlargement in CMML is usually due to infiltration of the red pulp by leukemic cells. [32][33] It is important to remember, however, that in CMML, the spleen may be the initial site of acute extramedullary transformation. In these instances, because of the myeloid-rich cellular background, it is often difficult to identify the accumulation of blasts which characterize early acute transformation.…”