Histologic findings in bone marrow biopsies of patients with thrombocythemic cell counts

Abstract

Histologic diagnoses from bone marrow biopsies were analyzed in a total of 1165 patients presenting with thrombocythemic platelet counts at initial examination. Two cut-off points suggested by the Polycythemia Vera Study Group to define thrombocythemia by platelet counts were compared: the former limiting value of 1000 x 10(9)/l platelets versus the recently proposed value of 600 x 10(9)/l. The percentage of all nonproliferative disorders was 41% under the lower, dropping to 11% under the high cut-off point. The respective figures for myeloproliferative disorders increased from 49% under the lower to 74% under the high limiting value. Primary thrombocythemia was included in 72% by the lower, and in only 40% by the high limiting value when classified by its histologic pattern in bone marrow biopsy. A striking decrease of platelet counts occurs, related to fiber increase, among each of three main groups of myeloproliferative disorders: in CML with megakaryocytic predominance from 40% down to 25%, in megakaryocytic-granulocytic myelosis (primary, i.e., agnogenic myelofibrosis) from 36.6% to 10%, and in primary thrombocythemia from 72.6% to 28.6% in cases with reticulin sclerosis.

Prodromal myeloproliferative neoplasms: The 2008 WHO classification

“…An important feature is the large to giant cell forms with extensively folded (hyperlobulated) nuclei (Fig. 1C,D) surrounded by well differentiated (mature) cytoplasm [96,97,99,100]. Any increase in the reticulin fibers, i.e., myelofibrosis (MF) is not compatible with early stage ET [98,101].…”

“…Concerning BM morphology, a conflict of opinion is evident, whether an untrained pathologist or hematologists would be able to recognize the relevant features of distinctive value in ET versus early PMF on routinely processed, i.e., Hematoxylin and Eosin stained BM biopsy specimens and whether these parameters as defined by the WHO classification [1,2] are reproducible to an acceptable extent. This certainly raises a very critical point, because this controversy is significantly related to the experience and training of the investigator, particularly when standardized means of BM evaluation to recognize characteristic histological patterns are not used [62,100]. Referring in this context to the diagnosis and classification of malignant lymphomas we are facing the same problem that has only be more or less resolved by establishing reference centers and by setting up relevant training courses for the interested pathologists and clinicians.…”

“…It has to be realized that reproducibility of histological features endorsed by the WHO persists to be a critical issue. However, several groups confirmed their ability to discriminate between the thrombocythemic manifestations of early stage PMF versus ET [96,97,99,100,114]. On the other hand, in a blinded study among three hematologists/pathologists partially using BM specimens from the UK-PT 1 trial [27], the reproducibility and validity of distinguishing so-called true ET according to the WHO classification [1,2] from prefibrotic PMF [122] was questioned.…”

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

“…Conflict and discussion still persist regarding characteristic bone marrow (BM) features as reliable criteria for diagnosis [5][6][7]. These should facilitate a clear-cut recognition of ET without knowledge of clinical data and especially a distinction of this disorder from reactive causes [8][9][10].…”

“…The updated guidelines of the Polycythemia Vera Study Group (PVSG) consider histopathology only marginally because these include, in addition to stainable iron, a minor degree of collagen fibrosis [3,4]. Considering the latter point, it seems to be difficult to differentiate ET from early stages of idiopathic (primary) myelofibrosis (IMF) accompanied by severe thrombocytosis [6,7]. Therefore, a revision of the original and updated criteria of the PVSG [1,3] suggested that certain features of megakaryocyte morphology have to be included in the set of relevant diagnostic requirements and that collagen fibrosis has to be discarded [11].…”