A morphometric study of bone marrow angiogenesis in hairy cell leukaemia with clinicopathological correlations

Abstract

Summary. Bone marrow angiogenesis has recently been implicated in the pathophysiology and course of various haematological malignancies. Little is known, however, about the significance of this phenomenon in hairy cell leukaemia (HCL). We evaluated various morphometric characteristics of microvessels, highlighted by means of anti-CD34 immunohistochemistry, in the bone marrow of 44 patients with typical HCL, before and after treatment with interferon-a (IFN-a). Overall, bone marrow from 103 HCL patients and 20 controls was examined. Microvessel density (MVD) and several size-and shape-related parameters were quantified in the region of most intense vascularization using image analysis. MVD, size-related parameters and the percentage of branching microvessels were higher in HCL than in controls. Likewise, perimeter counts were higher in partial/non-responders than in complete responders.Achievement of complete response was accompanied by smaller calibre microvessels. IFN-a induced a decrease in MVD and branching values in cases with diffuse marrow involvement. In univariate analysis, progression-free survival was adversely affected by MVD, branching and major axis length. Multivariate analysis indicated that MVD/ branching independently affected progression-free survival and the likelihood of complete response. Our data suggest that the generation of bone marrow microvessels indicated an increased risk of progression and IFN-a treatment failure in HCL. Furthermore, the prognostic significance of angiogenesis requires the concomitant assessment of MVD and the complexity of the microvascular network.

Morphology of angiogenesis in human cancer: a conceptual overview, histoprognostic perspective and significance of neoangiogenesis

“…In most current studies, the measurements are made by image analysis using appropriate software programs 25–28 . The hotspot images are scanned into the computer, which is calibrated with the use of a micrometer slide.…”

“…In MDS, larger calibre vessels were seen in refractory anaemia (RA) compared with refractory anaemia with excess blasts (RAEB), and correlated with prognosis 8 . In hairy cell leukaemia, complete response to interferon (IFN)‐α was correlated with small‐calibre microvessels 27 . In a recent study of astrocytic brain tumours, it was found that although MVD, TVA and branching counts were adversely related to DFS in univariate analysis, only TVA remained statistically significant in multivariate analysis 53 .…”

Angiogenesis in Hodgkin's lymphoma: a morphometric approach in 286 patients with prognostic implications

“…5 A plethora of investigations support the intuitive notion that solid tumors progress in concert with an induction of neovascular response (for a review see Hlatky et al 6 ). Evidence of the importance of angiogenesis in hematologic malignancies is rapidly accruing, indirectly implicating bone marrow angiogenesis in the pathophysiology and course of acute leukemias, 7 chronic myeloid and lymphoid leukemias, [8][9][10] myelodysplastic syndromes 11 and multiple myeloma. 12,13 In non-Hodgkin's lymphomas (NHL) and B chronic lymphocytic leukemia, microvessel counts correlate with histologic grade and clinical stage, respectively.…”

Practical Approaches to Microvessel Analysis: Hotspots, Microvessel Density, and Vessel Proximity

“…These have included major axis length, minor axis length, perimeter, compactness (perimeter/area), and more esoteric measurements like shape factor and Feret diameter [13,14].…”