Agnogenic myeloid metaplasia (AMM)—correlation of bone marrow lesions with laboratory data: A longitudinal clinicopathological study on 114 patients

Abstract

A clinicopathological study was performed on 114 patients (46 male/68 female, median age 67 years) with the diagnosis of agnogenic myeloid metaplasia (AMM) respectively primary osteo-myelofibrosis which was not preceded by any other or allied subtype of chronic myeloproliferative disorders. On admission patients revealed a striking variability of laboratory data as well as different histopathological features of initial bone marrow biopsies. For this reason discrimination was done into two groups based on bone marrow findings: group I patients (n = 46, 19 male/27 female) showed a hypercellular marrow without or only borderline (n = 24) to slight (n = 22) reticulin fibrosis and group II cases (n = 68, 27 male/41 female) displayed coarse bundles of collagen fibres (n = 18) frequently accompanied by osteosclerosis (n = 50). Statistical analysis of the corresponding initial hematological findings resulted in significant differences. These differences concerned also the complications occurring during the lengthy course of disease, which included a higher incidence of pancytopenia and severe marrow failure with hemorrhage and blast crisis in group II patients. However, overall survival time was not different in both groups. This may be related to the similarity of age distribution (64 resp. 65 years) and its significant association with arteriosclerotic vascular lesions. Consequently acute myocardial infarction and congestive heart failure were frequent causes of death in addition to infections due to marrow failure and blast crisis. Repeated bone marrow biopsies in 24 patients revealed an insidious transition from hypercellular lesions (group I) into advanced fibro-osteosclerotic changes (group II) concurring with laboratory data. Therefore our discrimination into two groups of patients represents variable stages or static histological and corresponding hematologic features in the evolution of a dynamic disease process in AMM.

Prodromal myeloproliferative neoplasms: The 2008 WHO classification

“…Wide ranges of clinical parameters on first sight were paralleled by corresponding BM features that may very initially present a hypercellular BM without or only slight reticulin MF [102,104,106,[109][110][111]. Additionally, scrutinized evaluations of follow-up studies including BM examinations were in keeping with a stepwise evolution of the disease process starting with a prefibrotic precursor stage and progressing over many years into overt MMM [103,106,107,109,110,[112][113][114]. Concerning the dynamics of disease process in PMF, the former gold standard for the diagnosis of MMM [6,22,23,89,115,116] or agnogenic myeloid metaplasia (AMM) should be avoided, because these criteria include only the advanced or overt stages of a wide spectrum of clinical and morphological disease manifestations [102].…”

“…Clinicians are aware that in large series a striking variability in the hematological findings of patients may be observed at the time of first presentation [90,[102][103][104][105][106][107][108]. Wide ranges of clinical parameters on first sight were paralleled by corresponding BM features that may very initially present a hypercellular BM without or only slight reticulin MF [102,104,106,[109][110][111].…”

“…A remarkable point is that progression of prodromal PMF into MMM/AMM [6,22,115,116] is not triggered by the JAK2V617F mutation status, but by a number of relevant target genes that are involved in matrix modeling and regulation of fibrillogenesis [119]. Clinical data in these prodromal stages of PMF are usually characterized by only minimal abnormalities as borderline to slight anemia, minimal splenomegaly, a very low or missing peripheral blast count but often a conspicuous thrombocytosis [93,98,102,103,106,107,[109][110][111]120] as shown in Table III.…”

“…Histopathology of BM biopsy samples in prodromal PMF reveals a hypercellularity by a prominent neutrophil granulocytic and megakaryocytic proliferation often associated with a concomitant reduction of nucleated red cell precursors [62,102,103,109,110,[112][113][114] in the absence or only minor reticulin MF (Fig. 2A).…”

The 2006 → 2008 European Clinical, Molecular and Patholobiogical (2008 ECMP) Classification and the 2007 WHO Revised Criteria for Myeloproliferative Neoplasms

“…This difference in bone marrow smears observed by Michiels et al in 1987 is reproducible in bone marrow biopsies by pathologists to distinguish between small mononucleated megakaryocytes in Ph + diseases versus clustered large megakaryocytes with hyperlobulated nuclei in Phnegative MPDs [14,[18][19][20][21][22][23][24][25][26]. Georgii et al defined in 1990 [22] the Hannover Bone Marrow classification of the MPDs, which had the great advantage to pick up the early stages of prefibrotic MPD ET,PV and PMGM, which are overlooked by the PVSG criteria.…”