Acute Panmyelosis with Myelofibrosis: An Evaluation of Distinctive Clinicopathological Features Including Bone Marrow Stroma.
Authors: Schmitt-Graeff Annette , Thiele Juergen , Kvasnicka Hans M. , Lübbert Michael 
Published: October 2019

Abstract
Acute panmyelosis with myelofibrosis (APMF) is a rare AML category of the current WHO-classification. The main clinical characteristics are an acute onset of disease, no splenomegaly, few blasts in the blood and an aggressive clinical course. Differentiation of APMF from hyperfibrotic high-grade myelodysplastic syndromes with excess blasts or acute megakaryoblastic leukaemia may be difficult because of the actual lack of molecular markers. As a consequence of myelofibrosis and dry tap, bone marrow cytology and cytogenetic analyses are only available in a minority of cases. Therefore, histopathology and immunohistochemistry of trephine bone marrow biopsies may offer further clues to the biology of APMF.
Our study focused on the clinicopathological features of 52 patients meeting the criteria of APMF. Cases with any other category of MDS or AML, a history of preceding chronic myeloproliferative disorder, especially idiopathic myelofibrosis, autoimmune disorders, and cytotoxic or radiation therapy were excluded. All patients presented with anemia, granulocytopenia, low to normal platelets and low peripheral blast counts (≤5%). Cytogenetic abnormalities included monosomy 7, del (7p), del (17p) and trisomy 8 or complex karyotypic abnomalities. The median survival was <12 months. The lethal outcome was due to severe pancytopenia or overt leukaemia. Multilineage maturation defects associated with a strikingly increased atypical megakaryopoiesis and slight to marked degrees of fibrosis were the characteristic features common to all bone marrow trephines. Abnormalities of megakaryocytes included loose grouping or prominent clusters of medium sized to small cells with nuclear hypolobulation and dwarf cells and occasionally scattered bizarre forms. By confocal laser scanning microscopy (CLSM) we observed heterogeneous megakaryocyte c-Mpl signals using a polyclonal rabbit antibody kindly provided by Dr. J. Spivak, Baltimore, MG, USA.
Cytoplasmic immunolabeling ranged from weak in larger polymorphous forms to moderate or strong in smaller megakaryocytes. The predominantly membraneous c-Mpl localization of normal megakaryocytes was generally downregulated.
In contrast to acute megakaryoblastic leukaemia, blasts rarely expressed CD61 or CD41, but predominantly myeloid or myelomonocytic antigens. In accordance with the data recently published by Orazi et al. (Mod Pathol2005; 18: 603–14) blasts were less numerous than in acute megakaryoblastic leukaemia. Bone marrow stroma contained increased microvessels, CD4 and CD8+ T-cell subsets, B-cell rich lymphoid nodules and CD68+ macrophages. By CLSM, myofibroblastic cells coexpressing alpha-smooth muscle actin and cellular retinol-binding protein 1, a key molecule of retinoid metabolism, could be visualized ín the stromal compartment.
In conclusion, refined in situ imaging techniques of bone marrow trephines improve the diagnostic impact of the WHO criteria for the diagnosis of APMF. Our study provides further evidence that both hematopoietic and stromal components of the bone marrow are conspicuously modulated in this uncommon disorder in keeping with the designation as a panmyelosis.