Working classification of chronic myeloproliferative disorders based on histological, haematological, and clinical findings.

Bone marrow biopsies of 850 patients with chronic myeloproliferative disorders were taken at initial diagnosis; and 169 sequential biopsies over periods of one to 188 months. Three micron sections of all biopsies were evaluated semiquantitatively with reference to the proliferating cell lines, anomalies of megakaryocytes, and fibrosis or osteosclerosis. Correlations between initial histological findings, clinical, haematological, and survival data were analysed statistically. The predominant cell lines distinguished the classical entities of polycythaemia vera, primary thrombocythaemia, and chronic myeloid leukaemia and correlated with their different prognoses, while megakaryocytes characterised subgroups that were prone to fibrotic or blastic transformation. Based on the initial histological, clinical, and haematological data analysed a working classification of chronic myeloproliferative disorders was proposed that permits recognition of both typical and atypical cases of chronic myeloproliferative disorders.

Chronic myeloproliferative disorders (CMPD).

The wide clinical range of CMPD can be understood as leukaemia of pluripotent stem cells according to the pathogenic concepts reviewed above. Blastic metamorphoses of CMPD are regressions to a more primitive level of cellular differentiation. The predominant proliferative cell line characterizes the classical entities of PV, PT and CML, and their different prognoses. Pure erythrocytic and megakaryocytic proliferations are more compatible with sustained physiologic bone marrow functions than granulocytic proliferations. The combinations of granulocytic and megakaryocytic growth are especially prone to develop MF/OMS, in which participation of immune reactions, of granulocytic and of platelet factors is probable. An etiologic role for ineffective thrombocytopoiesis is supported by experimental as well as by histologic evidence. Myelofibrosis and osteomyelosclerosis may have similar causes, but develop independently. The prevalence of the female sex among thrombocythaemic patients was proven statistically also for the increase of giant type megakaryocytes in the form of clusters in the bone marrow, and for longer median survival of females in CMPD, especially when there is megakaryocytosis in the bone marrow. It is assumed that females may be better protected against the detrimentous effects of abnormal platelet production. An arbitrary classification according to haematologic and histologic criteria was applied to PV, PT and CML, and groups with typical and atypical haematologic and histologic signs were distinguished. The latter cannot be separated from each other by their various haematologic manifestations, but by histology and their different propensity to progress into more immature and/or fibrotic stages. Three major groups are characterized by histology: mixed granulocytic-megakaryocytic myelosis with giant megakaryocytic clusters, a similar variant with diffuse distribution of giant megakaryocytes, and immature and/or pleomorphic megakaryocytic myelosis. Transitions from each of these groups have been observed as well as transitions from each of the typical CMPD-entities into these less typical forms. CML, frequently accompanied by dwarf-megakaryocytes, often develops into pleomorphic megakaryocytic or blastic myelosis. Blastic dedifferentiation and myelofibrosis manifest themselves as closely related end stages, to which principally all groups proceed after a longer or shorter period of time, modified by the proliferating cell lines in each group. Clinical, experimental and histologic evidence of this natural history has been reviewed, with special emphasis on the re-evaluation of technically optimal bone marrow biopsies of untreated patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Scope and value of bone marrow biopsies in metastatic cancer.

The results of examination of 1,810 bone marrow biopsies of 1,725 patients with known or suspected carcinomas are presented. The frequency of positive biopsies was 72% for unknown primaries, 42% for mammary, 32% for prostatic, 14% for pulmonary and 19% for other cancers; the overall rate of detection of metastases was 35%. The mode of spread, the grade of tumour cell differentiation and the host response to the presence of the metastases were investigated by light and electron microscopic studies and by means of antibody reactions on fresh-frozen sections. The results are presented and their relevance to the fundamental understanding of the metastatic process is outlined. Implications for clinical oncology and patient management are discussed.

Bone marrow histology in Waldenström's macroglobulinaemia. Clinical relevance of subtype recognition.

Bone marrow biopsies of 137 patients with Waldenström's macroglobulinaemia (WM), 26 with non-secretory immunocytoma and 32 with benign monoclonal gammopathy were processed for histologic evaluation. Bone marrow involvement was found in 110 (80%) initially, and in 24 (18%) in sequential biopsies. 3 types were distinguished: lymphoplasmacytoid (47%), lymphoplasmacytic (42%) and polymorphous (11%) with median survivals of 74, 25 and 12 months, respectively. When grouped according to the tumour cell mass in the biopsies, the median survivals were 55, 21 and 8 months for less than 20 vol%, 20-50 vol% and greater than 50 vol% respectively; in each subtype, the tumour cell mass correlated with the disease progression. 6 clinical variables were also found prognostically significant. These results demonstrate that (i) 98% of patients with WM have bone marrow involvement; (ii) the lymph node sub-classification is applicable to the bone marrow and has both clinical and prognostic significance; (iii) patients may be staged according to the tumour cell burden in the bone marrow biopsy.

Assessment of bone marrow histology in the malignant lymphomas (non-Hodgkin's): correlation with clinical factors for diagnosis, prognosis, classification and staging.

Bone marrow biopsies of 678 untreated patients with established malignant non-Hodgkin's lymphomas (ML) were investigated. The bone marrow was involved in 468 cases, an overall frequency of 69%. The Kiel classification of the ML (based on lymph node histology) was applied and the biopsies were classified: ML lymphocytic 36%, ML 'hairy cell' 24%, ML lymphoplasmacytic/cytoid 24%, ML centrocytic 6%, ML centroblastic/centrocytic 4%, ML lymphoblastic (without ALL) 3%, ML centroblastic 2% and ML immunoblastic 1%. The life tables of the patients were similar whether classified according to the histology of the lymph node or the bone marrow. A multivariate computer based analysis of both clinical and histological data was performed to test their prognostic relevance. The cell type, the proliferation pattern and the extent of infiltration in the bone marrow all proved to be factors of prognostic significance. The results indicate that classification of the ML based on lymph node histology is applicable to the bone marrow, is reproducible and has prognostic significance. Consequently, a bone marrow biopsy is a useful clinical tool for staging and for histological classification of patients with ML.

Bone marrow histology in myeloma: its importance in diagnosis, prognosis, classification and staging.

A study has been made of 420 bone marrow biopsies from patients with multiple myeloma (220), idiopathic monoclonal gammapathy (50), reactive plasmacytosis (42) and solitary plasmacytoma (22). Histology and immunohistological parameters were more reliable than cytology in distinguishing a reactive from a neoplastic plasmacytosis. Histological variables were correlated with the clinical features of the patients to determine the factors which were of value in predicting prognosis. Plasma cell maturity and the extent of infiltration in the biopsy by myeloma cells proved to be highly significant in predicting the duration of survival. On the basis of these criteria multiple myeloma was classified into two types: plasmacytic of low-grade malignancy and plasmablastic of high-grade malignancy; and into three stages which accurately reflected the progression of the disease. We conclude that a bone biopsy provides useful information for the diagnosis, classification and staging of patients with multiple myeloma.

Imitation in the family: a study of older parents and their adult sons.

Older parents and their adult sons (fifteen father-mother-son triads) participated in this study which investigated whether imitative behavior is prominent in these families and whether interpersonal perceptions are related to the degree of imitation. Both perceptual and moral imitation tasks were used and personality descriptions were obtained on dimensions of activity, potency, and evaluation. Adult sons were found to imitate their parents on both tasks and particularly their fathers on moral issues. Older parents also were found to imitate their sons in a possible "reversal" of the direction of identification. Differential patterns of interpersonal perceptions were related to imitation for the three groups. Potential theoretical explanations are discussed.