|
1
|
Book R, Ben-Ezra J, Glait Santar C, Kay S, Stemer G, Oster HS, Mittelman M. Lymphoid aggregates in the bone marrow biopsies of patients with myelodysplastic syndromes - A potential prognostic marker? Front Oncol 2023; 12:988998. [PMID: 36776361 PMCID: PMC9908947 DOI: 10.3389/fonc.2022.988998] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Accepted: 12/19/2022] [Indexed: 01/27/2023] Open
Abstract
Background Lymphoid aggregates (LA) are occasionally seen in bone marrow biopsies (BMB) of myelodysplastic syndromes (MDS) patients. Our aim was to evaluate their incidence and association with prognosis. Methods We compared BMB reports of MDS patients treated at the Tel Aviv Sourasky Medical Center (2011-2018), and controls (2015-2017, normal BMB), and examined the charts of the MDS patients (LA+ and LA-). Categorical, normally and non-normally distributed continuous variables were compared using Fisher's exact, independent t and Mann-Whitney tests respectively. Adjusted [age, gender, lymphocytes, white blood cells (WBC) and diabetes mellitus (DM)] Cox proportional hazard model examined survival at 12 and 24 months. Results MDS patients (N=140) were older than controls (N=38; 74.1 vs 69.2 years, p=0.005); 34 MDS (24.3%) and 5 controls (13.2%) had LA+ (P=0.141). CD20/CD3 staining suggested LA polyclonality. MDS/LA+ (vs MDS/LA-) patients were younger, with a trend (not statistically significant) towards poor prognostic parameters: lower Hb, WBC, and platelets, higher LDH, BM cellularity, and IPSS-R score. The incidence of cardiovascular disease was similar, but MDS/LA+ had twice the incidence of DM (38.2% vs 19.0%, p=0.022). Similar trend for cancer (26.5% vs 14.3%, p=0.102). Twelve-month survival: 24/34 (70.6%) MDS/LA+; 88/106 (83.0%) MDS/LA- (p=0.140). This trend, seen in Kaplan-Meier curves, disappeared at 24 months. The hazard ratio for LA was 2.283 (p=0.055) for 12 months. Conclusion These preliminary data suggest LA are relatively common (24%) in MDS BMB, and might indicate poor prognosis. This may reflect involvement of the immune system in MDS. Future studies will examine larger groups, to clarify the incidence, significance and the pathophysiology.
Collapse
Affiliation(s)
- Reut Book
- Department of Medicine A, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Jonathan Ben-Ezra
- Department of Pathology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Chen Glait Santar
- Hematology Laboratory, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Sigi Kay
- Hematology Laboratory, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Galia Stemer
- Hematology Institute, Galilee Medical Center, Nahariya, Israel
- Faculty of Medicine, Bar Ilan University, Safed, Israel
| | - Howard S. Oster
- Department of Medicine A, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Moshe Mittelman
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Department of Hematology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
| |
Collapse
|
|
2
|
Myeloproliferative Disorders and its Effect on Bone Homeostasis: The Role of Megakaryocytes. Blood 2021; 139:3127-3137. [PMID: 34428274 DOI: 10.1182/blood.2021011480] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Accepted: 08/11/2021] [Indexed: 11/20/2022] Open
Abstract
Myeloproliferative Neoplasms (MPNs) are a heterogeneous group of chronic hematological diseases that arise from the clonal expansion of abnormal hematopoietic stem cells, of which Polycythemia Vera (PV), Essential Thrombocythemia (ET), and Primary Myelofibrosis (PMF) have been extensively reviewed in context of clonal expansion, fibrosis and other phenotypes. Here, we review current knowledge on the influence of different forms of MPN on bone health. Studies implicated various degrees of effect of different forms of MPN on bone density, and on osteoblast proliferation and differentiation, using murine models and human data. The majority of studies show that bone volume is generally increased in PMF patients, whereas it is slightly decreased or not altered in ET and PV patients, although possible differences between male and female phenotypes were not fully explored in most MPN forms. Osteosclerosis seen in PMF patients is a serious complication that can lead to bone marrow failure, and the loss of bone reported in some ET and PV patients can lead to osteoporotic fractures. Some MPN forms are associated with increased number of megakaryocytes (MKs), and several of the MK-associated factors in MPN are known to affect bone development. Here, we review known mechanisms involved in these processes, with focus on the role of MKs and secreted factors. Understanding MPN-associated changes in bone health could improve early intervention and treatment of this side effect of the pathology.
Collapse
|
|
3
|
Tshabalala WS, Pillay S, Wilson DPK. Diagnostic outcomes of bone marrow aspirate and trephine biopsies performed at a hospital in KwaZulu-Natal, South Africa. Afr J Lab Med 2020; 9:1028. [PMID: 32158640 PMCID: PMC7057739 DOI: 10.4102/ajlm.v9i1.1028] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2019] [Accepted: 11/26/2019] [Indexed: 11/28/2022] Open
Abstract
Background Bone marrow aspiration and trephine biopsy (BMAT) are widely performed in adults to evaluate haematological and malignant conditions. However, the diagnostic yield from the procedure in unselected patients in the South African public sector has not previously been described. Objectives We identified the main indications and most common diagnoses encountered for BMAT and described the demographic and blood profiles of patients, including HIV-positive patients, who had undergone the procedure at a tertiary hospital in KwaZulu-Natal. Methods We retrospectively reviewed laboratory data from January 2016 to December 2016 for all patients aged ≥ 13 years who underwent the procedure and stratified findings by demographic data. Results Among 120 BMAT biopsies studied, 80 (67%) cases were performed to evaluate suspected malignancy and a further 40 (33%) cases for non-malignant indications. The main indications for bone marrow examination were: cytopenias 38 (32%), lymphoma 35 (29%), leukaemia 21 (18%), and multiple myeloma 17 (14%). BMAT results revealed that 60 cases (50%) were malignant in origin, 30 cases (25%) were non-malignant and 30 cases (25%) were classified as normal. The common diagnoses were: leukaemia, 24 (20%); multiple myeloma, 16 (13%) and lymphoma, 13 (11%). Cases aged ≥ 50 years were more likely to have a malignant diagnosis (odds ratio: 5.8 (95% confidence interval: 2.2–17.1) p-value < 0.001). Conclusion The diagnostic yield of BMAT was high, with significant abnormalities detected in three quarters of cases. Haematological malignancy was the more common diagnosis. Increasing age was associated with an increase in reporting of haematology malignancy.
Collapse
Affiliation(s)
- Wanda S Tshabalala
- Department of Internal Medicine, Grey's Hospital, University of KwaZulu-Natal, Pietermaritzburg, South Africa
| | - Somasundram Pillay
- Department of Internal Medicine, Edendale Hospital, Pietermaritzburg complex, University of KwaZulu-Natal, Pietermaritzburg, South Africa
| | - Douglas P K Wilson
- Department of Internal Medicine, Edendale Hospital, Pietermaritzburg complex, University of KwaZulu-Natal, Pietermaritzburg, South Africa
| |
Collapse
|
|
4
|
Steer K, Stavnichuk M, Morris M, Komarova SV. Bone Health in Patients With Hematopoietic Disorders of Bone Marrow Origin: Systematic Review and Meta- Analysis. J Bone Miner Res 2017; 32:731-742. [PMID: 27787922 DOI: 10.1002/jbmr.3026] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2016] [Revised: 10/03/2016] [Accepted: 10/25/2016] [Indexed: 12/18/2022]
Abstract
Blood cell production and bone homeostasis are physically interlinked systems that exhibit active cross-talk. We examined how bone health is affected in patients with hematopoietic disorders due to abnormal proliferation of bone marrow cells. The electronic databases Medline, Embase, PubMed, BIOSIS Previews, Web of Science, and Cochrane were searched for studies presenting numerical values for trabecular bone volume or bone mineral density in control and patients with hematopoietic disorders. We identified 5 studies for beta-thalassemia, 6 for sickle cell anemia, 2 for polycythemia vera and essential thrombocythemia, 3 for chronic myelogenous leukemia, 6 for myelofibrosis, 5 for multiple myeloma, and 4 studies each for systemic mastocytosis, lymphocytic leukemia, and hemochromatosis. The effect of the disease state on bone density was significant and negative for beta-thalassemia (r = -2.00; 95% confidence interval [CI] -3.41, -0.58; p < 0.005), sickle cell anemia (-0.91; -1.36, -0.47; p < 0.00005), chronic myelogenous leukemia (-0.55; -0.88, -0.22; p < 0005), mastocytosis (-0.99; -1.16, -0.82; p < 0.00001), lymphoblastic leukemia (-0.69; -0.98, -0.40; p < 0.00001), multiple myeloma (-0.67; -0.99, -0.35; p < 0.00005), and hemochromatosis (-1.15; -1.64, -0.66; p < 0.00001). The changes were negative but not significant for polycythemia vera (-0.16; -0.38, 0.05; p = 0.069) and essential thrombocythemia (-0.33; -0.92, 0.26; p = 0.14). In myelofibrosis, disease state was associated with increased bone density (0.74; 0.12, 1.36; p < 0.05). Bone density change significantly and negatively correlated with the level of ferritin and bone marrow cellularity but not with hemoglobin or erythropoietin. Thus, independent of hematopoietic lineage, abnormal proliferation of bone marrow cells appears to be associated with bone loss. Iron metabolism may independently contribute to bone homeostasis. © 2016 American Society for Bone and Mineral Research.
Collapse
Affiliation(s)
- Kieran Steer
- Shriners Hospital for Children-Canada, Montreal, Canada.,Department of Pharmacology and Therapeutics, Faculty of Medicine, McGill University, Montreal, Canada
| | - Mariya Stavnichuk
- Shriners Hospital for Children-Canada, Montreal, Canada.,Department of Anatomy and Cell Biology, Faculty of Medicine, McGill University, Montreal, Canada
| | - Martin Morris
- Schulich Library of Physical Sciences, Life Sciences and Engineering, McGill University, Montreal, Canada
| | - Svetlana V Komarova
- Shriners Hospital for Children-Canada, Montreal, Canada.,Department of Anatomy and Cell Biology, Faculty of Medicine, McGill University, Montreal, Canada.,Faculty of Dentistry, McGill University, Montreal, Canada
| |
Collapse
|
|
5
|
Islam A. Indications for and Value of Bone Marrow Trephine Biopsy in Haematological Disorders. Hematology 2016; 1:167-72. [DOI: 10.1080/10245332.1996.11746301] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022] Open
Affiliation(s)
- Anwarul Islam
- Division of Hematology/Oncology, Department of Medicine, Buffalo General Hospital, Buffalo, New York
| |
Collapse
|
|
6
|
Michiels JJ, Valster F, Wielenga J, Schelfout K, Raeve HD. European vs 2015-World Health Organization clinical molecular and pathological classification of myeloproliferative neoplasms. World J Hematol 2015; 4:16-53. [DOI: 10.5315/wjh.v4.i3.16] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2014] [Revised: 11/15/2014] [Accepted: 04/30/2015] [Indexed: 02/05/2023] Open
Abstract
The BCR/ABL fusion gene or the Ph1-chromosome in the t(9;22)(q34;q11) exerts a high tyrokinase acticity, which is the cause of chronic myeloid leukemia (CML). The 1990 Hannover Bone Marrow Classification separated CML from the myeloproliferative disorders essential thrombocythemia (ET), polycythemia vera (PV) and chronic megakaryocytic granulocytic myeloproliferation (CMGM). The 2006-2008 European Clinical Molecular and Pathological (ECMP) criteria discovered 3 variants of thrombocythemia: ET with features of PV (prodromal PV), “true” ET and ET associated with CMGM. The 2008 World Health Organization (WHO)-ECMP and 2014 WHO-CMP classifications defined three phenotypes of JAK2V617F mutated ET: normocellular ET (WHO-ET), hypercelluar ET due to increased erythropoiesis (prodromal PV) and ET with hypercellular megakaryocytic-granulocytic myeloproliferation. The JAK2V617F mutation load in heterozygous WHO-ET is low and associated with normal life expectance. The hetero/homozygous JAK2V617F mutation load in PV and myelofibrosis is related to myeloproliferative neoplasm (MPN) disease burden in terms of symptomatic splenomegaly, constitutional symptoms, bone marrow hypercellularity and myelofibrosis. JAK2 exon 12 mutated MPN presents as idiopathic eryhrocythemia and early stage PV. According to 2014 WHO-CMP criteria JAK2 wild type MPL515 mutated ET is the second distinct thrombocythemia featured by clustered giant megakaryocytes with hyperlobulated stag-horn-like nuclei, in a normocellular bone marrow consistent with the diagnosis of “true” ET. JAK2/MPL wild type, calreticulin mutated hypercellular ET appears to be the third distinct thrombocythemia characterized by clustered larged immature dysmorphic megakaryocytes and bulky (bulbous) hyperchromatic nuclei consistent with CMGM or primary megakaryocytic granulocytic myeloproliferation.
Collapse
|
|
7
|
|
|
8
|
|
|
9
|
Krenacs T, Bagdi E, Stelkovics E, Bereczki L, Krenacs L. How we process trephine biopsy specimens: epoxy resin embedded bone marrow biopsies. J Clin Pathol 2005; 58:897-903. [PMID: 16126867 PMCID: PMC1770834 DOI: 10.1136/jcp.2004.023788] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
Improved cytomorphology of semithin resin sections over paraffin wax embedded sections may be important in diagnostic haematopathology. However, resin embedding can make immunohistochemical antigen detection or DNA isolation for clonal gene rearrangement assays difficult. This review describes the processing of bone marrow biopsies using buffered formaldehyde based fixation and epoxy resin embedding, with or without EDTA decalcification. Traditional semithin resin sections are completely rehydrated after etching in home made sodium methoxide solution. Resin elimination allows high resolution staining of tissue components with common histological stains. Efficient antigen retrieval and the Envision-HRP system permit the immunohistological detection of many antigens of diagnostic relevance, with retention of high quality cytomorphology. Furthermore, DNA can be extracted for clonality analysis. The technique can be completed within a similar time period to that of paraffin wax processing with only approximately 30% increase in cost. This technique has been used for diagnosis in over 4000 bone marrow biopsies over the past 14 years. By meeting traditional and contemporary demands on the haematopathologist, it offers a powerful alternative to paraffin wax processing for diagnosis and research.
Collapse
Affiliation(s)
- T Krenacs
- Laboratory of Tumour Pathology and Molecular Diagnostics, Institute for Biotechnology, Bay Zoltan Foundation for Applied Research, H-6726 Szeged, Derkovits fasor 2, Hungary.
| | | | | | | | | |
Collapse
|
|
10
|
Ozgüroglu M, Esen Ersavasti G, Demir G, Aki H, Demirelli F, Kanberoglu K, Mandel N, Büyükünal E, Serdengeçti S, Berkarda B. Magnetic resonance imaging of bone marrow versus bone marrow biopsy in malignant lymphoma. Pathol Oncol Res 1999; 5:123-8. [PMID: 10393364 DOI: 10.1053/paor.1999.0183] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Bone marrow involvement is a frequent finding in malignant lymphoma. Bone marrow biopsy of the posterior iliac crest is routinely performed for staging. Abnormal magnetic resonance imaging (MRI) signals of bone marrow was also reported to be indicative of bone marrow involvement. This study included 60 patients with malignant lymphoma. Unilateral bone marrow biopsy of the posterior iliac crest was performed. MRI of lumbar spine was studied within 24 hours of bone marrow biopsy. 22 healthy controls were used for the detection of MRI objectivity during visual evaluation. In 83% of patients (50/60), biopsy and MRI results agreed completely. In two patients, histologic sections failed to show any evidence of bone marrow involvement despite abnormal MRI signals suggestive of involvement. In three patients, MRI was completely normal despite biopsy proven bone marrow infiltration. False negativity (3/60) and false positivity (2/60) rates were very low. Negative biopsy findings with positive or equivocal MRI results should not exclude bone marrow involvement and needs further evaluation with bilateral or guided biopsy. Thus, we conclude that MRI of bone marrow is a fairly sensitive, noninvasive modality and might be of potential value in detecting bone marrow infiltration in malignant lymphoid neoplasms which can be utilized as a useful adjunct to standard staging procedures.
Collapse
Affiliation(s)
- M Ozgüroglu
- Cerrahpasa Medical School, Istanbul University, Department of Internal Medicine Yogurtçu Basi Sokagi, Akçira apt. 20/3 , Istanbul, 81030, Turkey.
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
11
|
Le Bousse-Kerdilès MC, Martyré MC. Myelofibrosis: pathogenesis of myelofibrosis with myeloid metaplasia. French INSERM Research Network on Myelofibrosis with Myeloid Metaplasia. SPRINGER SEMINARS IN IMMUNOPATHOLOGY 1999; 21:491-508. [PMID: 10945038 DOI: 10.1007/bf00870307] [Citation(s) in RCA: 20] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
|
|
12
|
Martyré MC. TGF-beta and megakaryocytes in the pathogenesis of myelofibrosis in myeloproliferative disorders. Leuk Lymphoma 1995; 20:39-44. [PMID: 8750621 DOI: 10.3109/10428199509054751] [Citation(s) in RCA: 58] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Myeloproliferative disorders are clonal disorders of the hematopoietic stem cell and comprise a spectrum of more or less well-defined clinical entities: polycythaemia vera, chronic myeloid leukemia, essential thrombocythaemia, and agnogenic myeloid metaplasia. Myelofibrosis, which contributes substantially to the impaired hematopoiesis, is commonly observed in myeloproliferative disorders but it represents the criterion of agnogenic myeloid metaplasia also termed idiopathic myelofibrosis. Although progress has been made in the elucidation of the pathogenesis of myelofibrosis, it still remains unclear. The aim of this review is to address the new insights that outline the potential role of TGF-beta in the promotion of myelofibrosis, through its release from megakaryocytes/platelets, particularly in agnogenic myeloid metaplasia.
Collapse
Affiliation(s)
- M C Martyré
- Section de Biologie, Unité 365 INSERM Interférons et Cytokines, Institut Curie, Paris, France
| |
Collapse
|
|
13
|
Martyré MC, Romquin N, Le Bousse-Kerdiles MC, Chevillard S, Benyahia B, Dupriez B, Demory JL, Bauters F. Transforming growth factor-beta and megakaryocytes in the pathogenesis of idiopathic myelofibrosis. Br J Haematol 1994; 88:9-16. [PMID: 7803262 DOI: 10.1111/j.1365-2141.1994.tb04970.x] [Citation(s) in RCA: 113] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Although the disease is well described, the pathogenesis of bone marrow fibrosis in idiopathic myelofibrosis still remains unclear. We previously reported elevated intraplatelet transforming growth factor-beta (TGF-beta) levels in patients with this myeloproliferative disorder, compared with healthy subjects. Here, in a series of 16 patients, we show that TGF-beta expression is also increased in patients' peripheral blood mononuclear cells (PBMC): (i) at the mRNA level analysed by Northern blot hybridization and/or reverse transcription-polymerase chain reaction (RT-PCR); (ii) and/or at the secreted peptide level as evaluated in conditioned media from patients' mononuclear cells by a growth inhibition assay on CC164 cells. By immunostaining with a polyclonal anti-TGF-beta 1 antibody, TGF-beta was localized in morphologically heterogenous cells; these cells were characterized as megakaryocytes by labelling with a gpIIbIIIa monoclonal antibody. Thus we provide evidence that both TGF-beta and megakaryocytes are linked in the pathogenesis of idiopathic myelofibrosis.
Collapse
Affiliation(s)
- M C Martyré
- Unité 365 INSERM, Institut Curie, Section de Biologie, Paris, France
| | | | | | | | | | | | | | | |
Collapse
|
|
14
|
Hasselbalch HC. Idiopathic myelofibrosis--an update with particular reference to clinical aspects and prognosis. INTERNATIONAL JOURNAL OF CLINICAL & LABORATORY RESEARCH 1993; 23:124-38. [PMID: 8400333 DOI: 10.1007/bf02592297] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
Idiopathic myelofibrosis (IMF) is characterized by excessive accumulation of connective tissue in the bone marrow as part of a clinical syndrome which in its classical form is featured by leukoerythroblastic anemia and huge splenomegaly at the time of diagnosis. An acute variant of the disease exists being featured by pancytopenia, nor or minimal splenomegaly and a rapidly fatal clinical course. This review describes the relationship of IMF to other chronic myeloproliferative disorders and highlights current concepts of the pathogenesis of bone marrow fibrosis, implicating the intramedullary release of various growth factors, including platelet-derived growth factor beta. In a subgroup of patients bone marrow fibrosis may develop consequent to autoimmune bone marrow damage. The clinical and laboratory findings in some of the larger series of patients are presented and the reasons for the highly variable clinical presentation and prognosis are critically discussed. It is proposed that studies on prognosis in IMF are based upon simple prognostic staging systems, which should include the Hb-concentration, platelet count, spleen size and the presence/absence of osteomyelosclerosis on X-ray. Using these parameters the patients are easily categorized into three prognostic groups with highly different survival times.
Collapse
|
|
15
|
Reverter JC, Feliu E, Climent C, Rozman M, Berga L, Rozman C. Stereological study of human bone marrow adipocytes. A comparison of four methods for estimating size distributions. Pathol Res Pract 1993; 189:1215-20. [PMID: 8183743 DOI: 10.1016/s0344-0338(11)80846-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
Several methods are available for estimating size distributions of spherical objects in tissue sections. In this article a comparative study of four stereological techniques applied to human bone marrow adipocytes was carried out. In the first part, four stereological methods (Giger-Riedwyl, Saltykov, Wicksell, and Cruz-Orive) were used for the evaluation of adipocyte size in a set of 50 human bone marrow specimens (20 normal controls, 10 aplastic, 10 hyperplastic and 10 dysplastic bone marrows). In the second part, a computer simulation model was employed for generating both control and test populations. The latter were analyzed by means of the four stereological methods and compared to the control. When applied to bone marrow specimens, no statistically significant differences were seen among the four methods. Results were very close between the Giger-Riedwyl and Saltykov methods, and between the Wicksell and Cruz-Orive methods. In the simulation model, Saltykov's method was the most accurate stereological technique for the studied conditions. Additional advantages of this method are that the assumption of Gaussian distribution is not required, and that a higher relative weight is assigned to the largest classes, in which accurate definition is easier in the microphotographs. However, since the differences among the four methods are very small, they may all be considered as valid for the stereological study of human bone marrow adipocytes.
Collapse
Affiliation(s)
- J C Reverter
- Postgraduate School of Haematology Farreras Valenti, Hospital Clínic, University of Barcelona, Spain
| | | | | | | | | | | |
Collapse
|
|
16
|
Buhr T, Georgii A, Choritz H. Myelofibrosis in chronic myeloproliferative disorders. Incidence among subtypes according to the Hannover Classification. Pathol Res Pract 1993; 189:121-32. [PMID: 8321741 DOI: 10.1016/s0344-0338(11)80081-6] [Citation(s) in RCA: 59] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
The distribution and the development of fibrosis were evaluated from bone marrow biopsies of patients with chronic myeloproliferative disorders (CMPD), regarding two groups of patients: (1) 564 with follow-up biopsies over a period of up to twelve years observation time, and (2) 1.787 diagnostic bone marrow biopsies from CMPD patients. Fibrosis was divided into three grades of fiber increase: early myelosclerosis, myelofibrosis, and advanced myelofibrosis. The first group of sequential BMB showed a significant progress to myelofibrosis in so-called "Chronic Megakaryocytic-Granulocytic Myelosis"--CMGM-, which corresponds to Agnogenic Myeloid Metaplasia-AMM-in 72.4% (21/29 patients), as well as in CML with megakaryocytic increase-CML.MI-in 39.2% (20/51). In the second group of diagnostic biopsies, only 30% of CMGM cases showed no fibrosis. In P. vera, 16.2% (18/111) developed myelofibrosis up to twelve years later. This figure was 4.3% (2/46) in Primary Thrombocythemia. Increase of megakaryocytes in CML indicates a high risk for developing fibrosis, combined with reduced life expectancy.
Collapse
Affiliation(s)
- T Buhr
- Pathologisches Institut, Medizinische Hochschule Hannover, FRG
| | | | | |
Collapse
|
|
17
|
Affiliation(s)
- C Schmid
- Institute of Pathology, University of Graz Medical School, Austria
| | | |
Collapse
|
|
18
|
Lambertenghi-Deliliers G, Annaloro C, Soligo D, Oriani A, Pozzoli E, Quirici N, Luksch R, Polli EE. Incidence and histological features of bone marrow involvement in malignant lymphomas. Ann Hematol 1992; 65:61-5. [PMID: 1324741 DOI: 10.1007/bf01698130] [Citation(s) in RCA: 26] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Bone marrow biopsy (BMB) is a routine investigation in the diagnosis and staging of Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL), and there is evidence supporting its prognostic importance in some histological varieties. The histological characteristics of BMB in 433 NHL and 155 HD patients were reviewed for clinicopathological correlations; 36 of these cases were also studied by means of immunohistochemistry. BM infiltrates were discovered in 171 NHL patients. In 36 cases, the diagnosis of NHL was directly established by BMB; a discordance between lymph node and BM histology was observed in 38 of the other 135 cases. BM-positive centroblastic and immunoblastic NHL were significantly associated with larger infiltrates, BM fibrosis, and megakaryocytic hyperplasia. Leukemization at diagnosis was more frequent in low-malignancy NHL. No correlation was found between histology and prognosis, although immunohistochemistry revealed a B-cell phenotype in all but two cases. BMB was positive in 18 of the 155 HD patients and directly diagnostic in two; Reed-Sternberg and Hodgkin cells were CD-30 positive and surrounded by T-cell infiltration. The concordance between BM and lymph node histology was fairly satisfactory, although the relationships between BM infiltration and other histological parameters may reflect peculiar interactions with BM microenvironmental factors. The usefulness of BMB in the diagnosis of malignant lymphomas has been demonstrated, and further progress can be expected from the availability of reliable immunohistochemical markers of clonality reacting on paraffin-embedded BM sections.
Collapse
|
|
19
|
Thaler J, Dietze O, Denz H, Demuth R, Nachbaur D, Stauder R, Huber H. Bone marrow diagnosis in lymphoproliferative disorders: comparison of results obtained from conventional histomorphology and immunohistology. Histopathology 1991; 18:495-504. [PMID: 1879809 DOI: 10.1111/j.1365-2559.1991.tb01475.x] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
In this study we have investigated 313 bone marrow biopsies from 280 patients with lymphoproliferative disorders. Trephines were sectioned transversely to obtain one cylinder for cryostat sectioning and immunostaining and a second for histomorphological evaluation using a plastic-embedding technique. The results obtained by histomorphological and immunohistological evaluation were compared for their contribution to staging and classification. Using both techniques, bone marrow involvement was seen in 3/43 (7.0%) biopsies from patients with Hodgkin's disease and in 193/270 (71.5%) cases with non-Hodgkin's lymphoma, including multiple myeloma and acute lymphocytic leukaemia. Immunohistology proved superior in detecting minimal mainly interstitial bone marrow infiltration in 15 leukaemia/lymphoma cases. Biopsies showing infiltration with both methods (n = 157) were re-examined for classification of lymphomatous infiltrates. Whereas immunohistology did not provide additional information in cases with Hodgkin's disease and myeloma, this method was crucial for establishing the definitive diagnosis in a number of cases with acute lymphocytic leukaemia and non-Hodgkin's lymphoma. In all of six leukaemia cases, in which no or inadequate material was available for immunophenotyping of cell suspensions, immunohistology clearly defined the subtype. In the 140 cases of non-Hodgkin's lymphoma the majority of cases (76.4%) were identically classified. In some cases, with important prognostic and therapeutic implications, immunohistology alone provided the definitive diagnosis: T-cell lymphoma (n = 2), hairy cell leukaemia (n = 2) and centrocytic non-Hodgkin's lymphoma (n = 3). Bone marrow immunohistology is, therefore, an important supplement for classical lymphoma/leukaemia diagnosis. The differences observed between histomorphology and immunohistology emphasize the importance of lymph node biopsy in lymphoma classification.
Collapse
Affiliation(s)
- J Thaler
- Department of Internal Medicine, University Hospital, Innsbruck, Austria
| | | | | | | | | | | | | |
Collapse
|
|
20
|
Thiele J, Fischer R. Megakaryocytopoiesis in haematological disorders: diagnostic features of bone marrow biopsies. An overview. VIRCHOWS ARCHIV. A, PATHOLOGICAL ANATOMY AND HISTOPATHOLOGY 1991; 418:87-97. [PMID: 1899960 DOI: 10.1007/bf01600283] [Citation(s) in RCA: 32] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Affiliation(s)
- J Thiele
- Institute of Pathology, University of Cologne, Federal Republic of Germany
| | | |
Collapse
|
|
21
|
Thiele J, Langohr J, Skorupka M, Fischer R. Reticulin fibre content of bone marrow infiltrates of malignant non-Hodgkin's lymphomas (B-cell type, low malignancy)--a morphometric evaluation before and after therapy. VIRCHOWS ARCHIV. A, PATHOLOGICAL ANATOMY AND HISTOPATHOLOGY 1990; 417:485-92. [PMID: 2125386 DOI: 10.1007/bf01625728] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
A morphometric study was performed on bone marrow infiltrates of non-Hodgkin's lymphomas (B-cell type, low malignancy) to evaluate the content of argyrophilic (reticulin) fibres in the various subtypes before and after therapy. In congruence with the corresponding lymph node lesions, subtypes consisted of lymphocytic lymphoma--chronic lymphocytic leukaemia (CLL, n = 39), centroblastic-centrocytic lymphoma (CB-CC, n = 35), lymphoplasmacytoid immunocytoma (LPI, n = 22) and finally hairy cell leukaemia (HCL, n = 21). In comparison with control specimens, morphometric measurements on trephine biopsies (initial staging procedure) disclosed a borderline or minimal increase in reticulin in CLL and moderate fibrosis in CB-CC and LPI, whereas HCL had the greatest increase in fibres. The marrow surrounding focal or patchy lymphoma infiltrates of CLL and CB-CC displayed no relevant changes in fibre density with respect to the control samples. Following chemotherapy, repeated trephine biopsies (restaging procedure) were obtainable from 38 patients. There was no significant decrease in the fibre content of CLL, CB-CC and LPI infiltrates. In HCL an incomplete reduction was recorded after interferon treatment. So-called benign lymphoid lesions may be distinguished from focal-patchy infiltrates of CB-CC and LPI not only by showing a central localization, but also by the absence of significant amounts of reticulin. However, considering the density of the reticulin fibres, a clear-cut discrimination of these lymphoid aggregates from an early nodal-central growth pattern of CLL is not feasible in many cases.
Collapse
Affiliation(s)
- J Thiele
- Institute of Pathology, University of Cologne, Federal Republic of Germany
| | | | | | | |
Collapse
|
|
22
|
Abstract
To date, various models have been proposed to explain the diversification of haemopoietic stem cells along one of at least six pathways of differentiation. Consideration of evidence for and against particular models leads to the conclusion that a precise lineage map for the haemopoietic system is, as yet, unavailable. However, recently available cell and molecular biology techniques provide the means to resolve this problem.
Collapse
Affiliation(s)
- G Brown
- Department of Immunology, University of Birmingham, U.K
| | | | | |
Collapse
|
|
23
|
Islam A, Frisch B, Henderson ES. Plastic embedded core biopsy: a complementary approach to bone marrow aspiration for diagnosing acute myeloid leukaemia. J Clin Pathol 1989; 42:300-6. [PMID: 2649520 PMCID: PMC1141873 DOI: 10.1136/jcp.42.3.300] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Bone marrow aspirates and biopsy specimens were taken at diagnosis from 51 patients with acute myeloid leukaemia (AML). The diagnosis was based on morphological and cytochemical analyses, and the leukaemias were classified by FAB criteria. A considerable difference was observed between the results of bone marrow aspirates and the findings of plastic-embedded bone marrow biopsy specimens, particularly in marrow cellularity, extent of blast cell infiltration, and cell type involved in the leukaemic process. The myelomonocytic cell type seemed to predominate in the sections. In four cases there was considerable marrow infiltration with maturing, but dysplastic, granulocytic cells in the sections, but not in the aspirate smears. Features of potential prognostic importance, such as bone marrow infiltration with inflammatory cells, were easily recognised and quantified in the sections. These results indicate that plastic embedded bone marrow biopsy sections complement the findings of bone marrow aspiration in the diagnosis of AML and may also provide information of independent prognostic importance that cannot be obtained by other means.
Collapse
Affiliation(s)
- A Islam
- Department of Medical Oncology, Roswell Park Memorial Institute, Buffalo, New York
| | | | | |
Collapse
|
|
24
|
Cervantes F, Pereira A, Marti JM, Feliu E, Rozman C. Bone marrow lymphoid nodules in myeloproliferative disorders: association with the nonmyelosclerotic phases of idiopathic myelofibrosis and immunological significance. Br J Haematol 1988; 70:279-82. [PMID: 3207625 DOI: 10.1111/j.1365-2141.1988.tb02482.x] [Citation(s) in RCA: 24] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
The presence of lymphoid nodules in bone marrow biopsy was investigated at diagnosis in 200 patients with chronic myeloproliferative disorders (MPD). Twelve out of 51 patients with idiopathic myelofibrosis (IM) showed such a feature (23.5%), versus two out of 100 with Ph1-positive chronic myeloid leukaemia, two of 32 with polycythaemia vera, and one of 17 with essential thrombocythaemia, the difference between IM and the remaining MPD being statistically significant (P less than 0.0001). When IM patients were compared for their initial characteristics according to the presence or not of bone marrow lymphoid nodules, patients with such a histological finding showed significantly lower values for either WBC counts, number of primitive cells in the blood, and serum lactic dehydrogenase levels. Moreover, it was observed that virtually all patients with lymphoid nodules were in the nonmyelosclerotic phases of IM. Finally, among the 14 of 32 IM patients (44%) investigated for circulating immune complexes who gave a positive test, a significant association between this immunological abnormality and bone marrow lymphoid nodules was found. The above results reinforce the immunological significance of the finding of bone marrow lymphoid nodules in IM and give support to the hypothesis of an immune component in the pathogenesis of the disorder.
Collapse
Affiliation(s)
- F Cervantes
- Postgraduate School of Haematology Farreras Valenti, Hospital Clínico y Provincial, University of Barcelona, Spain
| | | | | | | | | |
Collapse
|
|
25
|
Faulkner-Jones BE, Howie AJ, Boughton BJ, Franklin IM. Lymphoid aggregates in bone marrow: study of eventual outcome. J Clin Pathol 1988; 41:768-75. [PMID: 3410973 PMCID: PMC1141586 DOI: 10.1136/jcp.41.7.768] [Citation(s) in RCA: 27] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
The practical importance of finding a morphologically benign lymphoid aggregate in the bone marrow of patients without known lymphoproliferative disease was assessed in 786 consecutive patients who had had 951 iliac crest bone marrow biopsies performed. Of these, 430 patients known to have lymphoproliferative disease at the time of biopsy were excluded. Of 356 patients, 86 (aggregate group) had at least one lymphoid aggregate in their biopsy specimen biopsy specimen (82 morphologically benign, three suspicious, and one malignant). Another 86 patients without aggregates (control group) were matched by age and sex. Both groups were followed up until death, or for a mean of 21.9 and 22.9 months, respectively, to assess their outcome. Eighteen (22%) of the 82 patients with morphologically benign lymphoid aggregates were later proved to have lymphoproliferative disease compared with none of the 86 control patients. Another 12 patients in the aggregate group and seven in the control group were suspected of having a lymphoproliferative disease on clinical grounds, so that altogether 30 (37%) and seven (8%), respectively, developed confirmed or suspected lymphoproliferative disease. In both cases the differences were highly significant (p less than 0.001). It is suggested that lymphoid aggregates in clinical biopsy material may not be a physiological finding and should alert pathologists or haematologists to the possibility of lymphoproliferative disease.
Collapse
|
|
26
|
Abstract
A series of 256 bone marrow biopsy specimens was obtained at different times from a group of patients with acute myeloid leukaemia, chronic granulocytic leukaemia and acute lymphoblastic leukaemia, and was analysed in parallel with peripheral blood smears and bone marrow aspirate samples. In five of these biopsy specimens the bone marrow lesion was discrete, deeply seated within the marrow cavity and detected only in long-core biopsies. Neither peripheral blood nor bone marrow aspirates obtained at the same time established the correct diagnosis. This suggests that when peripheral blood and bone marrow aspirate samples fail to indicate the diagnosis a long-core biopsy may yield positive results.
Collapse
Affiliation(s)
- A Islam
- Department of Medical Oncology, Roswell Park Memorial Institute, Buffalo, NY 14263
| | | |
Collapse
|
|
27
|
Abstract
Myelonecrosis is a rare antemortem finding in acute leukemia and its clinical significance is uncertain. The clinical events in nine patients with acute leukemia whose bone marrow biopsies after induction therapy revealed myelonecrosis were reviewed. No patient gained a complete remission and four patients achieved a partial remission. The median duration of survival was 2 months (range, less than 1 month to 8.5 months) from the start of therapy. Myelonerosis after induction therapy in acute leukemia indicates a very poor prognosis.
Collapse
Affiliation(s)
- P A Cassileth
- Department of Pathology, University of Pennsylvania School of Medicine, Philadelphia
| | | |
Collapse
|
|
28
|
Thaler J, Denz H, Gattringer C, Glassl H, Lechleitner M, Dietze O, Huber H. Diagnostic and prognostic value of immunohistological bone marrow examination: results in 212 patients with lymphoproliferative disorders. BLUT 1987; 54:213-22. [PMID: 3103722 DOI: 10.1007/bf00594196] [Citation(s) in RCA: 24] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Cryostat sections of 246 consecutive bone marrow biopsies from 212 patients with lymphoproliferative disease were investigated using a panel of monoclonal antibodies (MOAb's) and an immunoperoxidase technique. Bone marrow involvement was demonstrated by immunohistological examination in 121/160 patients (76%) with non-Hodgkin lymphomas (NHL) and 16/23 patients (70%) with plasma cell malignancies; the definite immunological diagnosis could be performed in 77% and 88%, respectively. Reactivity with the MoAb Ki-67 correlated with clinical parameters: in all cases exhibiting more than 5% positive cells an unfavourable course was seen, independent of the histological subtype. Another MoAb of potential prognostic relevance is KiM 4 b, which reacts with follicular dendritic cells (FDC). Besides the presence of FDC in germinal center tumors (CB/CC and CC-NHL) we found FDC in a minority of cases with B-CLL (5/44) and IC lymphoma (4/18). In the latter group 3/4 patients showed a favourable clinical course (vs 2/14 without FDC). The MoAb Tü 1 could discriminate between the lymphoplasmocytoid (11/12 positive) and the lymphoplasmocytic (0/6 positive) subtype of IC lymphoma and has proven of diagnostic importance. Expression of IL-2 receptors, detected by MoAb anti-Tac (CD 25), was demonstrated on leukemic cells from patients with hairy cell leukemia (100%), B-CLL (82%), IC (61%), CC (50%) and CB/CC lymphoma (50%). A considerable number of reactive T-lymphocytes (5%-60% of tissue cells) were identified among the neoplastic B cells with a predominance of CD4+ cells in most cases with NHL, whereas the CD4+/CD8+ ratio was significantly lower in myelomas and non-infiltrated bone marrows. The potential meaning of these findings is discussed. The immunohistological bone marrow analysis represents an important additional method in the diagnostic procedures of lymphoproliferative diseases involving the bone.
Collapse
MESH Headings
- Antibodies, Monoclonal
- Antigens, Differentiation, T-Lymphocyte
- Antigens, Neoplasm/analysis
- Antigens, Neoplasm/classification
- Antigens, Surface/analysis
- B-Lymphocytes/immunology
- Bone Marrow/immunology
- Bone Marrow/pathology
- Bone Marrow Cells
- Bone Marrow Examination/methods
- Cell Division
- Dendritic Cells/immunology
- Dendritic Cells/pathology
- Histocytochemistry
- Hodgkin Disease/diagnosis
- Hodgkin Disease/pathology
- Humans
- Immunoenzyme Techniques
- Lymphoma, Non-Hodgkin/diagnosis
- Lymphoma, Non-Hodgkin/pathology
- Lymphoproliferative Disorders/diagnosis
- Prognosis
- Receptors, Immunologic/physiology
- Receptors, Interleukin-2
- T-Lymphocytes/immunology
Collapse
|
|
29
|
Lazzarino M, Morra E, Castello A, Inverardi D, Coci A, Pagnucco G, Magrini U, Zei G, Bernasconi C. Myelofibrosis in chronic granulocytic leukaemia: clinicopathologic correlations and prognostic significance. Br J Haematol 1986; 64:227-40. [PMID: 3465364 DOI: 10.1111/j.1365-2141.1986.tb04115.x] [Citation(s) in RCA: 67] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
We performed 221 marrow trephine biopsies in 139 patients with Ph1-positive (Ph1+) chronic granulocytic leukaemia (CGL) in order to assess the incidence, degree and prognostic significance of marrow fibrosis (MF) at various stages of the disease. We also attempted to elucidate the relationship between development of MF and the various clinical and haematological features of CGL. A significant correlation was found between the amount of fibrosis (graded from 0 to 3) and the stage of CGL, indicating that major fibrotic changes are associated with accelerated or blastic disease. Survival studies performed to assess the prognostic significance of the various degrees of MF, showed a progressively worse life-expectancy from grade 0 to grade 3 fibrosis. Multivariate regression analysis indicated Hb level, age, number of marrow megakaryocytes (MKs), time from diagnosis as the features most significantly correlated with the degree of MF. This study demonstrates that the natural history of CGL involves a progressive increase in reticulin deposition towards severe MF, although the rate of this progression varies widely. Monitoring changes of fibrosis with sequential biopsies could give a measure of the rate of progression of the disease and help in prognostic assessment of CGL patients. Our findings also confirm that among marrow features the number of MKs is the cytological variable most significantly correlated with MF.
Collapse
|
|
30
|
De Wolf-Peeters C, Stessens R, Desmet V, Tricot G, Verwilghen RL. The histological characterization of ALIP in the myelodysplastic syndromes. Pathol Res Pract 1986; 181:402-7. [PMID: 3763479 DOI: 10.1016/s0344-0338(86)80075-9] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Bone marrow biopsies of patients with a myelodysplastic syndrome (MDS) may, in the absence of an increased number of blasts in the bone marrow smears, contain small clusters of immature precursors. The presence of these cell nests, previously described as "abnormal localized immature precursors" or ALIP, bears a strong prognostic value predisposing patients to early death with an increased risk to develop myeloid leukaemia. In order to describe and delineate this histological characteristic more precisely, we compared bone biopsies of patients with MDS, used in these previous studies, with bone marrow biopsies performed for staging procedures in patients with Hodgkin's disease, non-Hodgkin's lymphoma and carcinoma. From this comparison we conclude that immature precursors are readily differentiated from proerythroblasts, myeloblasts and small-sized megakaryocytes, and that they most probably represent precursors of the myelo-monocytic-erythroid series. A clearcut increase in their number, mostly resulting in the formation of small clusters, is only found in biopsies from patients with MDS.
Collapse
|
|
31
|
Islam A, Frisch B. Plastic embedding in routine histology. I: Preparation of semi-thin sections of undecalcified marrow cores. Histopathology 1985; 9:1263-74. [PMID: 2420695 DOI: 10.1111/j.1365-2559.1985.tb02809.x] [Citation(s) in RCA: 35] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
The preparation of sections of bone marrow cores in a routine histology laboratory requires decalcification and paraffin embedding, which produces shrinkage and considerable loss of cellular detail. This may be avoided by using plastic embedding procedures. This report describes a simplified routine procedure for using methylmethacrylate as a plastic embedding medium for the preparation of semi-thin sections of undecalcified bone marrow cores. A modification of the May-Grunwald-Giemsa stain is also given which provides good colour differentiation of various haematopoietic cells in the marrow. The method is simple, reproducible, requires no expensive equipment, and is suitable for routine processing of bone marrow biopsy cores in any histopathology laboratory.
Collapse
|
|
32
|
Brown G, Bunce CM, Rose PE, Howie AJ. Progenitor cells and classification of myelodysplastic and myeloproliferative disorders. Lancet 1985; 2:885. [PMID: 2864593 DOI: 10.1016/s0140-6736(85)90145-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
|
|
33
|
Islam A, Catovsky D, Goldman JM, Galton DA. Bone marrow biopsy changes in acute myeloid leukaemia. I: Observations before chemotherapy. Histopathology 1985; 9:939-57. [PMID: 3864727 DOI: 10.1111/j.1365-2559.1985.tb02879.x] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Pretreatment bone marrow trephine biopsy sections (BMB) from 34 patients with acute myeloid leukaemia (AML) were studied in parallel with bone marrow aspiration smears and peripheral blood films. In four cases marrow aspiration was inadequate and in five cases it was unsatisfactory. In two other cases hypoplastic AML was diagnosed, the aspirate in one suggested hypercellularity and in another it was unsatisfactory. Trephine biopsy was superior to aspiration for the evaluation of fat and marrow cellularity, pattern and extent of blast cell infiltration, homogeneity of the leukaemic infiltrate, frequency of mitoses, residual haemopoietic activity and presence of inflammatory cells. Of the various features studied in the sections, the presence of an increased number of plasma cells and considerable myelodysplasia (MD) appeared to be unfavourable prognostic features. We conclude that trephine biopsies are essential for the diagnosis of hypoplastic AML and are most useful when marrow aspiration is either inadequate or unsatisfactory. They also provide additional information about the bone marrow changes in AML and suggest that some histological features may also have prognostic significance.
Collapse
|
|
34
|
Krech R, Thiele J. Histopathology of the bone marrow in toxic myelopathy. A study of drug induced lesions in 57 patients. VIRCHOWS ARCHIV. A, PATHOLOGICAL ANATOMY AND HISTOPATHOLOGY 1985; 405:225-35. [PMID: 3918387 DOI: 10.1007/bf00704374] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Following the introduction of numerous highly effective drugs in recent decades, haematologists are confronted with a panmyelopathy or "toxic myelopathy" originating from the exhibition of certain therapeutic regimens. Among 16,711 trephines referred to us in the last 5 1/2 years, 57 cases or 0.34 percent were found to have clear evidence of lesions caused by the ingestion of potentially toxic agents. The evaluation of the histopathology shows two groups of alterations which concern the haematopoietic parenchyma as well as the mesenchyme of the bone marrow. Different degrees of cellularity ranging from aplasia to regenerative hyperplasia and a pronounced mesenchymal reaction with proteinaceous oedema, perivascular plasmacytosis and frequent necrobiosis of neutrophilic granulocytes or cellular debris are the most conspicuous features. However, the histopathology of the bone marrow described gives no indication of the specific drug responsible and no specific suggestion of any group of drugs. Generally the histopathology allows the recognition of lesions which are induced by the toxicity of these agents. Therefore a bone marrow biopsy should be included in the diagnostic procedures whenever a toxic lesion is suspected of causing haematological disorders, particularly in all cases of uncertain pancytopenia.
Collapse
|
|
35
|
Hoff B, Lumsden JH, Valli VE. An appraisal of bone marrow biopsy in assessment of sick dogs. CANADIAN JOURNAL OF COMPARATIVE MEDICINE : REVUE CANADIENNE DE MEDECINE COMPAREE 1985; 49:34-42. [PMID: 3986679 PMCID: PMC1236113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Dogs were classified into a number of disease categories according to hematological, cytological and serochemical changes. Aspiration and core bone marrow biopsies were examined in 128 dogs in the various disease categories and compared to marrow samples in 36 dogs which appeared clinically normal. Differential cell counts on bone marrow smears were examined in relation to the blood variables in all animals. Blood and bone marrow data (group means) were compared among the normal and disease groups. Anemia, responsive and poorly responsive was the most frequent blood abnormality. Most dogs in the thrombocytopenia group had increased numbers of megakaryocytes in the marrow but two dogs had a marked decrease. The frequency of serious alteration of marrow production of the erythroid, myeloid and megakaryocytic series was less than anticipated. Marrow hemopoiesis was not significantly compromised in dogs with lymphoma or in dogs with other types of cancer. Bone marrow examination was necessary for the diagnosis of myelofibrosis and pancytopenia and was very helpful in the groups with insufficient change in the blood to permit a definitive diagnosis to be made. The myeloid-erythroid ratio was a useful indicator of marrow response while the erythroid maturation index and the myeloid maturation index were useful for identification of altered patterns of maturation (ineffective hemopoiesis). The reticulocyte response in absolute numbers is the most efficient and clinically relevant measure of erythroid response.
Collapse
|
|
36
|
Thiele J, Laubert A, Vykoupil KF, Georgii A. Autopsy and clinical findings in acute leukemia and chronic myeloproliferative diseases--an evaluation of 104 patients. Pathol Res Pract 1985; 179:328-36. [PMID: 3856835 DOI: 10.1016/s0344-0338(85)80142-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
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.
Collapse
|
|
37
|
Burkhardt R, Bartl R, Jäger K, Frisch B, Kettner G, Mahl G, Sund M. Chronic myeloproliferative disorders (CMPD). Pathol Res Pract 1984; 179:131-86. [PMID: 6395125 DOI: 10.1016/s0344-0338(84)80124-7] [Citation(s) in RCA: 59] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
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)
Collapse
|
|
38
|
Thiele J, Krech R, Vykoupil KF, Georgii A. Malignant (acute) myelosclerosis--a clinical and pathological study in 6 patients. SCANDINAVIAN JOURNAL OF HAEMATOLOGY 1984; 33:95-109. [PMID: 6611583 DOI: 10.1111/j.1600-0609.1984.tb02217.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
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.
Collapse
|
|
39
|
Bartl R, Frisch B, Burkhardt R, Jäger K, Pappenberger R, Hoffmann-Fezer G. Lymphoproliferations in the bone marrow: identification and evolution, classification and staging. J Clin Pathol 1984; 37:233-54. [PMID: 6699189 PMCID: PMC498694 DOI: 10.1136/jcp.37.3.233] [Citation(s) in RCA: 74] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
Bone marrow biopsies from 3229 patients with lymphoproliferative disorders and 1156 patients with benign or reactive lymphoproliferations were investigated and criteria for distinguishing between them are given. Bone marrow involvement was found in 89% of multiple myeloma, 64% of non-Hodgkin's lymphomas and 8% of Hodgkin's disease. According to the predominant proliferative cell type there were five major entities in multiple myeloma and non-Hodgkin's lymphomas: (1) plasmacytic; (2) lymphocytic; (3) hairy cell; (4) immunocytic; (5) centrocytic. These were further classified into distinct subtypes each of which had independent prognostic significance. The mode of spread of the lymphoproliferative disorders in the bone marrow showed one of six architectural patterns, which together with the quantity of infiltration in the biopsy (reflecting the tumour cell burden) had significant predictive value. These results demonstrate the value of bone marrow biopsies in the identification, classification and staging of lymphoproliferative disorders, as well as in monitoring the course of disease and the response to therapy.
Collapse
|
|
40
|
Falini B, Martelli MF, Tarallo F, Moir DJ, Cordell JL, Gatter KC, Loreti G, Stein H, Mason DY. Immunohistological analysis of human bone marrow trephine biopsies using monoclonal antibodies. Br J Haematol 1984; 56:365-86. [PMID: 6365152 DOI: 10.1111/j.1365-2141.1984.tb03968.x] [Citation(s) in RCA: 48] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
This paper describes the use of a recently developed immuno-alkaline phosphatase method (the 'APAAP' technique) for labelling frozen sections of undecalcified bone marrow biopsies with monoclonal antibodies, including reagents reactive with T cells and their subsets, B cells, glycophorin, HLA-DR antigen, common ALL antigen, epithelial cells and megakaryocytes. Use of an immuno-alkaline phosphatase technique avoids problems due to endogenous enzyme activity encountered when staining bone marrow by immunoperoxidase procedures. Immunohistological labelling of frozen trephine biopsies is of particular value when it is impossible to aspirate marrow particles and for identifying cells which do not readily enter suspension (e.g. dendritic reticulum cells or stromal cells). Details are given of cases in which immunohistological analysis was used for the phenotyping of acute leukaemias, for the differential diagnosis of intramedullary T and B cell proliferations, and for identifying bone marrow metastases.
Collapse
|
|
41
|
Kuto F, Nagaoka T, Watanabe Y, Hayashi M, Horasawa Y, Hirasawa Y, Tokuhiro H. Chronic myelocytic leukemia: ultrastructural histopathology of bone marrow from patients in the chronic phase. Ultrastruct Pathol 1984; 6:307-17. [PMID: 6592869 DOI: 10.3109/01913128409018589] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
We investigated the ultrastructural changes in the hematopoietic microenvironment of the bone marrow obtained from 15 untreated patients with chronic myelocytic leukemia (CML) in the chronic phase by transmission and scanning electron microscopy using the cryofracture technique. Examination of the undecalcified bone marrow specimens confirmed extensive hyperplastic granulopoiesis. In the stroma, fat cells were scarce or absent. Macrophages were increased and scattered throughout the marrow. The cytoplasm contained abundant cellular debris and crystals of the Charcot-Leyden type. Slender reticular cells were inconspicuously located between proliferating myeloid cells. A few foci of fibrosis were occasionally observed. The sinus endothelium generally retained its continuity, and no features suggesting complete deterioration of the sinus were evident. However, certain alterations in the sinus wall were noted in the process of leukemia cell migration. Many cells migrated transcellularly into the circulation through transient large openings in the sinus endothelium.
Collapse
|
|
42
|
Chilosi M, Pizzolo G, Fiore-Donati L, Bofill M, Janossy G. Routine immunofluorescent and histochemical analysis of bone marrow involvement of lymphoma/leukaemia: the use of cryostat sections. Br J Cancer 1983; 48:763-775. [PMID: 6360192 PMCID: PMC2011562 DOI: 10.1038/bjc.1983.265] [Citation(s) in RCA: 51] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
Enzyme histochemical and immunohistological (immuno-fluorescence and -peroxidase) techniques have been routinely used for investigating over 70 normal and pathological bone marrow samples. This recently standardized diagnostic procedure is very quick and can be performed in a few hours. In 6 cases the clinical diagnosis of leukaemia/lymphoma has become apparent only after the immunohistological analysis of the bone marrow. In 6 other cases the information about the staging of B cell malignancies was superior in the frozen biopsies to the paraffin embedded preparations. Amongst many other features the monoclonality of B CLL/lymphomas, the special features of B CLL infiltrates (RFA-1+, Leu-1+, HLA-DR+, SmIg+), follicular lymphoma deposits (containing follicular dendritic cells) and non-T, non-B acute lymphoblastic leukaemic blasts (terminal transferase+, HLA-DR+) as well as the sometimes conspicuous presence of infiltrating normal T cells could be clearly and reproducibly demonstrated.
Collapse
|
|
43
|
Krause JR. An appraisal of the value of the bone marrow biopsy in the assessment of proliferative lesions of the bone marrow. Histopathology 1983; 7:627-44. [PMID: 6578999 DOI: 10.1111/j.1365-2559.1983.tb02276.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
The diagnostic value of the bone marrow needle biopsy has proved impressive in a variety of disorders. As a complementary procedure to the aspiration smear it adds an invaluable dimension to the examination of haematopoietic tissue. The procedure is easily learned and safe and should be utilized routinely in haematological practice. The usefulness of the bone marrow biopsy is examined in assessing proliferative lesions of the bone marrow.
Collapse
|
|
44
|
Correction. Clin Mol Pathol 1982. [DOI: 10.1136/jcp.35.7.796] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
|