Frequency of pseudo-Gaucher cells in diagnostic bone marrow biopsies from patients with Ph-positive chronic myeloid leukaemia.

Pseudo-Gaucher cells (PGC) are a characteristic finding in Ph-positive CML, and prolongation of survival was observed when PGC were detected within the bone marrow. However, the conspicuous variation in the reported frequencies indicates the necessity for analysis of their natural occurrence in the bone marrow from untreated CML patients. A total of 833 diagnostic bone marrow biopsies from patients with Ph-positive CML were examined for PGC by 7 observers. Proof of PGC was based on systematic examination of Giemsa-stained slides with and without polarization at high magnification. Birefringence within the cytoplasm turned out to be highly specific for PGC. The risk of overlooking PGC was at least 80% when the number of these storing histiocytes was 70 per slide or less, and at least 50% when the total amount per slide was < or = 250. This high risk of failure explained the disagreement among the authors. An intensive investigation by at least two observers is mandatory if results are to be evaluated in research. Under the conditions used in this study, the natural frequency of PGC within the bone marrow from untreated patients with a Ph-positive CML is much higher than assumed to date, amounting to about 70%. On the basis of these findings, the prognostic importance of PGC in CML must be evaluated critically.

Prognostic relevance of a histologic classification system applied in bone marrow biopsies from patients with multiple myeloma: a histopathological evaluation of biopsies from 153 untreated patients.

A total of 153 diagnostic bone marrow biopsies from patients with advanced stages of multiple myeloma corresponding to stages II and III according to the Durie/Salmon classification were evaluated prior to any treatment in a prospective therapy trial of the German Myeloma Treatment Group. Histologic sections were analyzed according to a pre-defined system of criteria microscopically by 2 observers, determining three criteria: 1) grading by histopathology, regarding the cytologic differentiation of neoplastic cells and quantifying the percentage of plasmacytic, pleomorphic, and plasmablastic myeloma cells distributed within the sections; 2) the volume of infiltration; and 3) the pattern of neoplastic growth. Furthermore, four other criteria, namely hematopoiesis, fiber increase, osteomalacia, and micro-osteo-lesions, were evaluated. A cluster analysis using the three histological criteria revealed three groups of patients with significantly different survival times based on histological criteria only; the three criteria were mentioned above. It is concluded from these results that bone marrow biopsies, when evaluated histologically by grading and staging according to the three criteria, provide most valuable prognostic parameters in myeloma patients.

Cytogenetics of chronic myelogenous leukemia (CML) correlated to the histopathology of bone marrow biopsies.

Cytogenetic findings were correlated to histopathological bone marrow findings evaluated simultaneously in 103 patients with chronic myelogenous leukemia (CML). CML was subtyped histologically according to the number of megakaryocytes and increase of fibers or blasts within the bone marrow. The Philadelphia chromosome (Ph 1) was found in 88.3% of all patients (91/103). Chromosome aberrations additional to the Ph 1-chromosome were noticed in 20 of 91 (22%) cases. The additional karyotype changes occurred significantly more frequently among patients with increase of fibers in the bone marrow compared with patients without increase of fibers or blasts (p less than 0.05). Karyotype changes associated with increase of fibers in Ph 1-positive cases of CML were trisomy 8 and 19, +Ph1, t (1; 11), and i (17q). Ph 1-positive CML patients with additional karyotype changes had a significantly shorter survival (p less than 0.04) than Ph 1-positive patients without additional chromosome aberrations. Our results suggest that histopathological examination of the bone marrow should be considered in the evaluation of cytogenetic markers in chronic myeloproliferative disorders.

Chronic myeloproliferative disorders in bone marrow biopsies.

This Diagnostic Seminar intends to announce that CMPDs can be classified from BMB histologically by a rather simple system, which can be applied by interested histopathologists successfully. The rationale of this classification is to stay within the groups of diseases which are outlined by clinical findings including the peripheral blood and bone marrow smears. The concept of traditional classification as given by the WHO and textbooks, however, has to be revised as follows (1) Primary diseases of CMPDs must be distinguished from advanced disorders. Primary diseases are CML, P. vera, Thrombocythemia, CMGM, and unclassifiable CMPD. (2) Idiopathic, primary myelosclerosis of the bone marrow is a reactive feature consecutive to neoplastic transformation of hematopoiesis, i.e. myeloproliferation. (3) Advanced disorders comprise (3.1.) excess of blasts and blast crisis, and (3.2.) early myelosclerosis, myelosclerosis and myelofibrosis, advanced myelofibrosis. Advanced disorders are designated by a composed term classifying them among the groups of primary disease and specifying the advanced stage by a suffix, so that the underlying disease remains coining the term, even in unclassifiable cases in which only CMPDs can be applied. (4) The CML group must be subtyped into CML of common type versus that with increase or predominance of megakaryocytes. By this system of classification, it seems possible to classify and type the spectrum of variations occurring among CMPDs to a satisfying result.

The differential diagnosis of juvenile digital fibromatosis.

Juvenile digital fibromatosis is a rare condition in which distinctive benign soft tumours occur in the hands and feet of children and adolescents. If bony involvement is found at presentation a malignant soft tissue tumour must be excluded and extensive investigation is required using plain x-rays, scintigraphy and angiography. Histological examination, however, is the only definitive diagnostic measure. In this paper a case of juvenile digital fibromatosis is presented with a discussion of the differential diagnosis.

Autopsy and clinical findings in acute leukemia and chronic myeloproliferative diseases--an evaluation of 104 patients.

In acute myeloid leukemia (AML-46 patients) and various entities of chronic myeloproliferative diseases (CMPD-58 patients) an evaluation and comparison of clinical and postmortem findings has been performed. This study included also aspirates and core biopsies of the bone marrow which were initially taken on admission of those patients. Classification of CMPD was done following the concept of Georgii et al. (1984) into CGL -24-, CMGM-6-, E-MS-13- and MS/OMS-15 cases. There was a significant increase in blastic crisis in CGL compared with the other entities and in the latter a prolongation of the total course of disease due to a long period between symptoms--clinical diagnosis. As revealed by the autopsies causes of death were mostly infections (pneumonia, septicemia-50%) and lethal hemorrhages (gastrointestinal and cerebral--about 30%) in both AML and CMGM patients. Rare causes comprised fatal pulmonary embolism due to a peripheral thrombocytosis in CMPD, acute rupture of the spleen and extensive leukemic infiltrates of the myocard in AML. In addition to the well known giant enlargement of the spleen in MS/OMS, the relatively high frequency of a meningeal involvement (meningeosis leukemica) in AML (about 35%) and during an acute transformation in CMPD (up to 30%) was conspicuous. The examination of the bone marrow at various sites became feasible during the postmortem procedure and thus provided the opportunity to investigate the development and extent of a myelosclerosis evolving in CMPD. In contrast to the a- or hypoplasia and regeneration of the hematopoiesis following chemotherapy, the evolution of myelosclerotic lesions showed a very uniform pattern throughout the skeleton and obviously no reversal of a manifest MS/OMS after cytotoxic treatment.

Malignant (acute) myelosclerosis--a clinical and pathological study in 6 patients.

Clinical and morphological findings are described in 6 patients with malignant (acute) myelosclerosis/fibrosis (MMS). Haematological data are characterized by severe anaemia and thrombocytopenia, frequently accompanied by a leucopenia with an increase in myeloblasts and promyelocytes in the peripheral blood count. There is an absence of, or a minimal hepatosplenomegaly and the survival times after onset of clinical symptoms to death range from 4-12 months. The histopathology of the bone marrow shows a conspicuous proliferation of blasts (myeloblasts, promyelocytes and megakaryoblasts) in a variable amount, besides a fibrosclerosis consisting of reticulin and collagen fibrils. A comparison of MMS with ordinary myelofibrosis/osteomyelosclerosis (MF/OMS) of a chronic course implicates two important facts: (a) evolution of fibrosclerosis takes a considerable period of time for manifestation, which ranges between 20-30 months; (b) the histopathology of MMS is identical with those features observable in the rare event of a terminal stage, i.e. blastic transformation of chronic MF/OMS. Consequently MMS should be designated as an accelerated variant of MF/OMS with a rather early occurrence of a blastic crisis. The insidious onset with the dominant clinical finding of anaemia is probably responsible for the relatively late appearance of symptoms, while the progressive course prevents an overt myeloid metaplasia with a massive hepatosplenomegaly.

Malignant degeneration in Madelung's disease (benign lipomatosis of the neck): case report.

Although not a common condition, benign lipomatosis of the neck (Madelung's disease) is well documented in the literature and to date we have failed to trace any reference to malignant change developing in this tissue. We wish therefore to report the case of a patient with benign lipomatosis of the neck in which malignant degeneration appeared after an interval of 6 years and in which this transformation from a benign to a malignant lesion was verified by histological examination.

[Comparative clinical and histological investigations in chronic myeloid leukaemias ]. / Vergleichende klinisch-histologische Untersuchungen bei 76 chronischen Myelosen.

76 cases of CML were divided according to clinical parameters (duration of illness prior to diagnosis, size of spleen, leucocyte and platelet counts, ALP index, bone marrow cytology and others) into groups showing a classical or an atypical course of the disease. All patients were submitted to bone marrow biopsy, using the method of Jamshidi and Swaim. The histological subtypes of CML, i.e. chronic granulocytic leukaemia and chronic megakaryocytic granulocytic myelosis were correlated with the two clinical types of disease. The classical form of CML was histologically inhomogeneous and was subdivided into 40% cases of chronic granulocytic leukaemia and 60% cases of chronic megakaryocytic granulocytic myelosis. At the time of bone marrow biopsy 20% of patients with classical leukaemia were already found to have myelofibrosis. The atypical myeloses consisted of chronic megakaryocytic granulocytic myelosis only and myelofibrosis was present initially in 50% of patients. In view of these findings agnogenic myeloid metaplasia is considered to be merely a variant of chronic myeloid leukaemia and the term "atypical myelosis" is preferred.

Chronic megakaryocytic granulocytic myelosis-CMGM. A subtype of chronic myeloid leukemia.

In 1,083 core biopsies of the bone marrow with myeloproliferative diseases 454 cases or 42% were found to have neoplastic megakaryopoiesis. Neoplasia of megakaryocytes was assumed from the conspicuous cytological atypicality revealed by light microscopy, extending and confirming earlier ultrastructural findings. Histopathology of the bone marrow in these patients was described as chronic megakaryocytic-granulocytic myelosis - CMGM - since neutrophilic granulopoiesis is also apparently neoplastic and both cell lineages showed a complete differentiation to mature forms. CMGM should be separated from the chronic granulocytic leukemia - CGL - which consists of only a single line proliferation. The incidence of CGL in our total of 1,083 patients was 25%. Both entities are included in chronic myeloid leukemia - CML - because of the demonstration of the Philadelphia chromosome in the hematopoietic cells of these two groups of patients. Primary or idiopathic thrombocythemia has to be differentiated from CMGM since there is no evidence for malignancy of the granulocytic series.

Ultrastructure of blastic crisis in osteomyelofibrosis. A report of 2 cases with some unusual features.

The clinical and morphological findings are presented in two patients suffering from myelofibrosis and osteomyelosclerosis which terminated in an acute blastic crisis. Clinical follow-up data and light microscopy of the bone marrow however, revealed a chronic megakaryocytic-granulocytic myelosis (CMGM) with progression into myelofibrosis during the course of disease. In one patient the blastic transformation involved predominantly basophils, and in the other, neutrophils, with an accompanying abnormal proliferation of megakaryocytes in both cases. Electron microscopy of this cell population demonstrated remarkable atypicalities of the neutrophilic, basophilic and megakaryocytic cell lines. These abnormalities consisted of a nuclear-cytoplasmic asynchrony and a partial arrest of maturation, sometimes resulting in bizarre cell forms. Our investigations support the hypothesis of a mixed cellularity type of myelosis with a gradual and insiduous progression into osteomyelofibrosis/-sclerosis and a potential blastic crisis. In the evolution of blastic crisis all cell lines may be transformed, but with predominance of one population - basophils and neutrophils in our two cases - in addition to atypicalities of megakaryocytes.