Classification and Staging of Ph-negative Myeloproliferative Disorders by Histopathology from Bone Marrow Biopsies

Abstract

The present study illustrates characteristic features of histopathology in the 3 non-leukemic, Ph-negative groups of chronic myeloproliferative diseases (CMPD). Attention is paid to the final outcome of CMPD, especially its transformation into acute leukemias and the occurrence of myelofibrosis from bone marrow biopsies (BMB) in a total of 1,716 CMPD patients. Essential thrombocythemia (ET), polycythemia vera (P. vera), and chronic megakaryocytic granulocytic myelosis (CMGM) can readily be distinguished by histopathology from BMB in the great majority of patients without regarding laboratory data, leaving a compartment of about 12% unclassifiable cases. Histologic patterns of staging are the increase in number and pleomorphism of megakaryocytes (MK), increase in number and density of reticulin fibers and collagen fibrosis, and excess of blasts. These 3 criteria are each graded from 0 to 3 in every biopsy. From these, a staging results by means of the histology of BMB in each of the Ph-negative CMPD. This staging provides a classification by defined criteria which permits comparative studies, the possibility of monitoring the individual patients by follow-up histology, and offers a baseline for reliable evaluation of results from therapy protocols.

Follow‐up examinations including sequential bone marrow biopsies in essential thrombocythemia (ET): A retrospective clinicopathological study of 120 patients

“…According to a reference center, a critical evaluation of BM features in ET patients revealed an initial frequency of reticulin and collagen fibrosis of less than 3% in specimens derived from more than 900 patients [13]. After excluding explicitly early stages of IMF, evolution into manifest myelofibrosis was found to range between 6% and 10% after a mean observation time of about 5 years [14,31]. When BM morphology is regarded more thoroughly in the set of diagnostic criteria for ET [11,12], the stringent postulate of a definite platelet limit (Ն600 × 10 9 /L) should be abandoned.…”

Bone Marrow Features and Natural History of BCR/ABL-Positive Thrombocythemia and Chronic Myeloid Leukemia Compared to BCR/ABLNegative Thrombocythemia in Essential Thrombocythemia and Polycythemia Vera

“…Prefibrotic CMGM is dominated by primary megakaryocyticgranulocytic myeloproliferation (PMGM) and increase of clustered atypical dysmorphic megakaryocytes due to increases of cellular and nuclear sizes. In CMGM/PMGM, the nuclei of dysmorphic megakaryocytes are bulky with clumsy lobuli and irregular roundish shaped form (so-called cloud-like nuclei), which are never seen in ET, PV and CML [16][17][18][19][20][21][22][23][24][25][26]. CMGM/PMGM is not preceded or followed by normocellular ET, PV or MDS and can be regarded as the third distinct prefibrotic primary MPD (Table 1) [19][20][21][22][23][24][25][26][27][28][29].…”

“…Michiels et al and the German pathologists Georgii and Thiele recognized that small mono-or bi-nucleated megakaryocytes are diagnostic for the Ph-positive diseases ET and CML. In contrast, large megakaryocytes with hyper-lobulated nuclei are pathognomonic for Ph-negative essential thrombocythemia (Figures 1 and 2) [13][14][15][16][17][18][19][20][21][22][23][24]. The Hannover Bone Marrow Classification of CML and MPD regarded myelofibrosis (MF) as a reactive secondary feature of myeloproliferative disease.…”

“…The terms agnogenic myeloid metaplasia (AMM), myeloid metaplasia with myelofibrosis (MMM), and chronic idiopathic myelofibrosis (CIMF) and primary myelofibrosis (PMF) lack accuracy because it is applied to both the early prefibrotic hypercellular stage and the advanced fibrotic stages [15,16]. Secondary MF in ET, PV and CMGM is classified as reticulin fibrosis (RF) grade 0 and 1 (=MF 0), RF grade 2 (=MF 1), RF 3 with minor collagen fibrosis (=MF 2) and advanced reticulin-collagen fibrosis (RCF) with or without osteosclerosis (=MF 3) [17,18]. In the Hannover Bone Marrow Classification the megakaryocytes in BRC/ABL-positive thrombocythemia and CML are small containing uni-or bi-lobulated nuclei (Figures 1 and 2) but large and mature with hyperlobulated nuclei in ET [16][17][18][19][20][21][22][23][24][25][26].…”

Essential Thrombocythemia

“…The diagnostic target of histopathology in patients presenting an elevated platelet count according to this classification may be twofold: 1) To confirm the presence of a Ph-negative MPD and exclude long lasting reactive thrombocytoses (Rth). This step can be achieved through a systematic analysis of: a) megacaryocytopoiesis, focusing especially on the proportion of giant vs. small forms, nuclear lobulation, maturation defects, cluster formation by megacaryocytes; b) BM cellularity; c) degree of expansion and of left shifting of granulocyte and erythrocyte lineages; d) densification of the reticulin network and presence of collagen fibrosis in the BM stroma [7,21,22].…”