Splenic extramedullary hematopoietic proliferation in Philadelphia chromosome-negative myeloproliferative neoplasms: heterogeneous morphology and cytological composition

Abstract

We studied 24 spleens with extramedullary hematopoietic proliferation, a key feature of advanced stage Philadelphia chromosome-negative myeloproliferative neoplasms, obtained from 24 patients (14 primary myelofibrosis, 7 polycythemia vera, and 3 unclassifiable). Hematoxylin and eosin, reticulin and trichrome stains and immunohistochemical stains for myeloperoxidase, glycophorin-C, CD42b, CD34, CD117, CD8, nerve growth factor receptor and smooth muscle actin were evaluated. Clinical information was correlated with the morphologic findings. Three distinct histological patterns of extramedullary hematopoietic proliferation were recognized: diffuse (12), nodular (5), and mixed-nodular and diffuse (7). The preponderant lineage was granulocytic in diffuse, trilineage in nodular and erythroid in mixed extramedullary hematopoietic proliferation. Erythropoiesis was largely intravascular, granulopoiesis was within the splenic cords and megakaryopoiesis was observed in both locations. The stromal changes paralleled the histological pattern with preservation of the splenic stromal and vascular architecture in the diffuse areas as opposed to areas of nodular extramedullary hematopoietic proliferation. The morphologic features of splenic extramedullary hematopoietic proliferation did not correlate with specific subtypes of myeloproliferative neoplasms. The mean duration of follow-up from initial diagnosis was 80 months. Fifteen of the 24 patients died of disease: 8 of 12 (67%) with diffuse, 2 of 5 (40%) with nodular and 5 of 7 (71%) with mixed growth patterns. The mean duration from diagnosis to splenectomy was shorter in patients with diffuse (83 months) as compared to those with nodular extramedullary hematopoietic proliferation (127 months). Our study demonstrates that splenic extramedullary hematopoietic proliferation in Philadelphia chromosome-negative myeloproliferative neoplasms shows distinct histological patterns that do not correlate with disease subtypes but appear to suggest a trend between the histologic patterns and clinical behavior. These results suggest a different biology of the disease in the nodular and diffuse extramedullary hematopoietic proliferation groups.

Chronic psychological stress activates BMP4‐dependent extramedullary erythropoiesis

“…Additionally, the spleen has been recognized as a microenvironment that accelerates the expansion of erythroleukaemic cells [44]. The fact that acute leukaemic transformation in myeloproliferative neoplasms can occur in the spleen [10] further support a role of splenic microenvironment in creating conditions favourable to leukaemic transformation.…”

Splanchnic vein thrombosis in myeloproliferative neoplasms

“…This non‐obstructive PHT may be reversed by splenectomy. Extramedullary haemopoiesis (EMH) occurs in the myelofibrotic spleen; the histological patterns of EMH do not correlate with disease subtypes or clinical events such as SVT (Prakash et al , ). Splenic CD34 + cells but not peripheral blood CD34 + cells from V617F + MF patients can successfully sustain haemopoiesis in primary and secondary transplantation into immunodeficient mice.…”

JAK2-V617F promotes venous thrombosis through β1/β2 integrin activation

“…We hypothesized that abnormal function of integrins on leukocytes, in particular neutrophils, may induce abnormal leukocyte-endothelium interaction and thus may contribute to pathologic thrombosis in CMN. In addition, abnormal trafficking of hematopoietic progenitors from bone marrow into the bloodstream and abnormal homing of hematopoietic cells including leukocytes to the spleen have been described as a prominent feature of JAK2-V617F-positive CMN (4,5,(31)(32)(33)(34)(35). Using in vitro and in vivo experimentation, we sought to elucidate the role of abnormal β 1 /β 2 integrin activity in the JAK2-V617F kinase-induced prothrombotic state and in aberrant homing of leukocytes to the spleen.…”