Minimal diagnostic criteria for the myelodysplastic syndrome (MDS) in clinical practice.
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Biomedical subjects
Publications and source records attributed to R Bartl.
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In a retrospective and prospective follow-up study from 1975 to 1991, bone marrow biopsies, aspirates and clinical features of 495 patients with MDS were investigated. Sections of undecalcified plastic embedded biopsies and smears of bone marrow aspirates were stained according to Giemsa. Bone marrows with MDS were characterized by three main categories of morphologic alterations: (1) cellular abnormalities, (2) architectural disorganization in the bone marrow and (3) stromal changes; the combined use of aspirates and trephine biopsies enabled a more reliable and accurate diagnosis of MDS than either one alone. The bone marrow findings fell into one of 7 subtypes, with the frequencies and median survivals in brackets: (1) MDS sideroblastic (19%, 62 months), (2) MDS megaloblastoid (13%, 56 months), (3) MDS proliferative (22%, 31 months), (4) MDS blastic (15%, 9 months), (5) MDS hypoplastic (15%, 26 months), (6) MDS fibrotic (6%, 29 months), and (7) MDS inflammatory (10%, 42 months). In follow-up studies patients with secondary MDS were excluded and the prognosis and subsequent evolution for each of the morphologic subtypes were evaluated. The conclusion is drawn that aspirates and trephine biopsies are complementary procedures and both are required for diagnosis, classification and decisions on current treatment modalities of patients with MDS.
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In a retrospective and prospective follow-up study from 1968 to 1989, bone marrow biopsy specimens, serum beta-2-microglobulin (SB2M) levels, and the clinical features of 251 patients with multiple myeloma (MM) and 28 patients with monoclonal gammopathy of undetermined significance (MGUS) were investigated. The main histologic variables (tumor cell type, tumor growth, tumor load, and fibrosis), SB2M level, serum thymidine kinase (STK) level, and various clinical parameters were analyzed to determine factors of value in monitoring the clinical phases of activity in MM. Our recently proposed prognostic strategy combining bone marrow histologic type, SB2M level, and signs of organ failure was tested for its ability to (1) diagnose the early and smoldering variants; (2) facilitate decisions on the time of initiation, the type and duration of initial induction therapy in the pretreatment phases (active and rapidly progressive phases); and (3) characterize variations in tumor regression and tumor-host interactions during chemotherapy (early treatment, plateau, relapse, transition, and refractory phases). The results indicate that this clinicopathologic monitoring combines information both on stage and aggressivity of MM and thus facilitates therapeutic decisions in the various clinical phases of MM.
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We describe a patient with fever and multiple osteolytic bone lesions accompanied by hypercalcemia, a duodenal ulcer, anemia, and thrombocytopenia. Bone marrow showed a dense infiltration by abnormal cells characterized by small basophil granula, erythrophagocytosis and nuclear atypia. These cells were positive for toluidine blue and partly for myeloperoxidase and chloroacetate esterase, expressed myeloid differentiation markers, and exhibited multiple numerical and structural chromosome aberrations. Molecular genetic analysis showed no breakpoint cluster region rearrangement. Electron microscopy demonstrated granula both of basophil and mast cell type. Concluding, in this patient an acute hematopoietic malignancy with many features of malignant mastocytosis but also with signs of a basophil differentiation. This is further support for a hematopoietic stem cell origin of human mast cells.
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277 untreated multiple myeloma patients of stage 1 (n = 33), II (n = 106) and III (n = 138) entered the study. Patients of stage II presenting a progressive tumor (n = 64) initially or during observation (n = 14) were treated with MivP (remissions: 61%). 138 patients of stage III were randomized to receive MivP or VBAMDex treatment. 51% of MivP treated patients responded versus 70% of the VBAMDex group. 71 responders of stage II and III with stable disease were randomized on Ifn-alpha maintenance versus no maintenance treatment. The relapse rate in both groups was 50% after 7 months. 75% survival was greater than 36 months in stage II and 11 months in stage III patients.
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For years, brown tumors have been considered to be a characteristic of primary hyperparathyroidism. However, since 1963 several reports indicate the incidence of brown tumors in patients with renal secondary hyperparathyroidism to be 1.5%-1.7%. The appearance of multiple brown tumor lesions is rather uncommon in secondary hyperparathyroidism which is also true for malabsorption as its cause. We report on a 56-year-old man presenting with pain in the bones and multiple osteolyses. A bone biopsy specimen and the laboratory examinations were indicative of secondary hyperparathyroidism caused by malabsorption most likely due to Billroth's II/I gastric resection. Thus, the patient's osteolyses represent brown tumors which have been induced by nutritional secondary hyperparathyroidism.
Bone marrow biopsies of 720 patients with multiple myeloma (MM) were investigated from 1968-1989. Histologic variables were correlated with clinical parameters and survivals to determine prognostic factors. In 207 of these patients initial levels of serum beta 2 microglobulin (SB2M) were also measured for prognostic evaluation. Four tumour growth patterns were distinguished: interstitial (56%), interstitial/sheets (13%), nodular (15%) and packed marrow (16%) with median survivals of 46, 31, 22 and 16 months. When grouped according to the tumour cell mass in the biopsy, four histologic stages were recognized. Cellular characteristics were used to classify MM into 6 histologic types which were subsequently combined into 3 grades of malignancy: low, intermediate and high, analogous to the malignant lymphomas. With respect to tumour products, only SB2M proved to be a valuable prognostic indicator for staging and follow-up. Complications of MM such as anaemia, azotaemia, osteolytic lesions, hypercalcaemia and hypoalbuminaemia all predicted a poor prognosis, highly significant in the test statistics. We propose a new prognostic approach in MM, comprising 1) parameters defining the tumour itself, 2) the tumour products (SB2M) and 3) the tumour complications. This prognostic strategy combines information both on stage and malignancy of MM and enables definition of smouldering and of aggressive variants of MM at an early stage.
Lymph node and bone marrow biopsies of 226 patients with malignant lymphomas were available for evaluation and comparison. 120 of the 226 lymphoma patients had classifiable infiltration in both lymph node and bone marrow and these were used for comparison. Congruence in the histologic subtypes in lymph node and bone marrow was found in 91 patients (76%). The majority of the 29 cases with divergent histologies showed ML of low grade malignancy in the bone marrow even with long time intervals between the two biopsies. The most notable in this group were seven cases who had ML centroblastic/centrocytic in the lymph node biopsy and ML immunocytic in the bone marrow, although none had a serum M-component. 65 of the 106 patients excluded from comparison had involvement in only one organ, the others had unclassifiable or equivocal histologies in either lymph node or bone marrow or in both. The findings are discussed with respect to the histologic behaviour of the lymphomas. The results show that comparison between lymph node and bone marrow findings in patients with ML is feasible and clinically relevant.
Bone marrow biopsies of 503 untreated patients with chronic lymphocytic leukemia (CLL) were processed for diagnostic evaluation. Histologic variables were correlated with the initial clinical features registered when the biopsies were taken, to determine factors of value in predicting prognosis. Four cellular characteristics (small round nuclei, notched nuclei, large round nuclei and presence of nucleoli) were used to classify CLL into the following three histologic types: (1) small round, (2) notched and (3) mixed. Patients classified according to these types had significantly different median survival times: 53, 26 and 28 months, respectively. CLL showed three growth patterns in the bone marrow: nodular, interstitial and packed, and these patterns had outstanding prognostic significance at all clinical stages (median survivals of 90, 46 and 28 months, respectively). The results are discussed in relation to the various growth patterns and their significance previously reported in the literature. In addition, the quantity of lymphoid cell burden in the bone marrow served as a useful criterion for histologic staging of CLL, thus supplementing any clinical staging system in use. All three histologic parameters--cell type, growth pattern and tumor cell burden--provide information on prognosis and thus provide a basis for decisions on treatment modalities in CLL.
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