Bone Marrow Diagnosis: An Illustrated Guide

By Kevin Gatter and David Brown

Bone Marrow Diagnosis, Third Edition, is an essential resource for pathologists and haematologists who need to report bone marrow trephine biopsies.

Practical and highly illustrated this edition has been comprehensively updated whilst remaining succinct and concentrating on the core information necessary to make an accurate diagnosis.

The text provides comparisons of the common methods of sample collection, fixation and staining, and a clear description of how to examine a trephine section. Applying a consistent approach, the chapters cover the range of disorders of bone marrow, discussing the clinical features, histopathology of bone marrow and diagnostic problems of each condition. Each chapter closes with a summary of key points and each diagnostic entity is accompanied by high quality images, over 900 in all, showing typical and more unusual examples of histological features.

This compact text, oriented at diagnosis and comprehensively accompanied by usable illustrations, is an invaluable reference tool for the trainee and practicing histopathologists, pathologists and haematologists.

• A practical guide aimed at allowing a busy pathologist to easily find the essential description and illustration of the most common bone marrow diseases seen in trephines
• Covers new treatment for chronic myeloid leukaemia, B-cell lymphoma and antibody treatments
• High quality colour images accompany each diagnostic entity
• Coverage of cytology in sections relating to myeloid dysplasias and acute leukaemias
• Addresses lymphoma categorization and individual lymphoma entities
• Incorporates new WHO classifications of lymphomas and leukaemias

• Language: English
• Publisher: Wiley
• Release date: Nov 10, 2014
• ISBN: 9781118952047

Book preview

Table of Contents

Title page

Copyright page

Preface to the Third Edition

Preface to the First Edition

Acknowledgements

CHAPTER 1: Introduction

Reasons for Performing Bone Marrow Biopsies

Note

How to Examine a Trephine Section

References

CHAPTER 2: The Normal Bone Marrow

Site of Haematopoiesis

Components of the Normal Bone Marrow Trephine

References

CHAPTER 3: Infections Including Human Immunodeficiency Virus

Bacterial Infection

Viral Infection

HIV Infection

Diagnostic Problems

Reference

CHAPTER 4: Anaemias and Aplasias

Anaemias

Aplasias

References

CHAPTER 5: The Myelodysplastic Syndromes

Myelodysplasia

Chronic Myelomonocytic Leukaemia

Diagnostic Problems

References

Note

CHAPTER 6: Myeloproliferative Neoplasms

Classification of MPN

Chronic Myeloid Leukaemia

Polycythaemia Vera

Essential Thrombocythaemia

Primary Myelofibrosis

Acute Myelofibrosis

Mast Cell Disease

Transient Myeloproliferative Disorder

Myeloproliferative Neoplasms with Eosinophilia and Rearrangements of PDGFRA, PDGFRB or FGFR1

References

CHAPTER 7: Acute Leukaemia

Classification

Acute Myeloid Leukaemia

Acute Lymphoblastic Leukaemia

Transplantation and Post-Transplantation Lymphoproliferative Disorders

References

CHAPTER 8: Lymphomas: an Overview

What Does the Clinician Require from the Pathologist?

B Cell Neoplasms in the WHO Classification

References

CHAPTER 9: Precursor B and T Lymphoblastic Leukaemia (Acute Lymphoblastic Leukaemia) and Lymphoblastic Lymphoma

Histopathology of the Bone Marrow

Cytogenetics of B Lymphoblastic Leukaemia/Lymphoma

Cytogenetics of T Lymphoblastic Leukaemia/Lymphoma

Diagnostic Problems

References

CHAPTER 10: Mature B Cell Neoplasms

Chronic Lymphocytic Leukaemia/Small Lymphocytic Lymphoma Incorporating B Cell and T Cell Prolymphocytic Leukaemia

References

Lymphoplasmacytic Lymphoma Including Waldenström's Macroglobulinaemia

References

Mantle Cell Lymphoma

References

Follicular Lymphoma

References

Marginal Zone B-Cell Lymphoma (Including MALT Type)

References

Hairy Cell Leukaemia

References

Multiple Myeloma

References

Diffuse Large B Cell Lymphoma

References

Burkitt Lymphoma

CHAPTER 11: Mature T and NK Cell Neoplasms

T-cell Large Granular Lymphocytic Leukaemia

Aggressive NK Cell Leukaemia

References

Cutaneous T Cell Lymphoma

Reference

Peripheral T Cell Lymphomas, Not Otherwise Specified

Hepatosplenic T Cell Lymphoma

Angio-immunoblastic T Cell Lymphoma

Adult T Cell Lymphoma/Leukaemia

Anaplastic Large Cell Lymphoma

References

CHAPTER 12: Hodgkin Lymphoma

Clinical Features

CHAPTER 13: Metastatic Disease

Clinical Features

Histopathology of the Bone Marrow

Diagnostic Problems

Reference

CHAPTER 14: Bone, Stroma and Miscellaneous Changes

Bone

Stroma

Miscellaneous Changes

References

CHAPTER 15: Technical Considerations

Preparation of Bone Marrow Biopsies

Fixation and Decalcification

Staining of Bone Marrow Biopsies

The Value of Immunostaining Methods

Index

End User License Agreement

List of Tables

Table 1.1  Comparison of the relative advantages and disadvantages of paraffin and plastic embedding of bone marrow trephine biopsies.

Tables 1.2–1.5  A scheme for assessing the bone marrow trephine with some common pathological conditions as examples.

Table 2.1  Bone marrow cellularity.

Table 2.2  Causes of erythroid hyperplasia.

Table 2.3  Megakaryocyte morphology in haematological conditions.

Table 2.4  A comparison of the features which may help discriminate between benign lymphoid aggregates in bone marrow and neoplastic involvement.

Table 2.5  Causes of a reactive plasmacytosis.

Table 2.6  A comparison of the histological features of reactive plasmacytosis and multiple myeloma.

Table 2.7  Causes of mast cell hyperplasia.

Table 3.1  Summary of features seen in HIV-positive bone marrow biopsies.

Table 4.1  Drugs which may cause aplasia.

Table 6.1  Histological features helpful in distinguishing early chronic myeloid leukaemia (CML) from leukaemoid reaction.

Table 6.2  Histological features of polycythaemia vera (PV) not found in CML.

Table 6.3  Causes of megakaryocytic hyperplasia.

Table 6.4  Distinction between essential thrombocythaemia (ET) and reactive thrombocytosis.

Table 6.5  Causes of secondary diffuse fibrosis in the bone marrow.

Table 6.6  Comparison of MDS with MPN.

Table 6.7  Immunocytochemical distinction of systemic mastocytosis (SM) and Hodgkin lymphoma (HL).

Table 8.1  Historical perspective of the development of lymphoma classification.

Table 10.1  Differential diagnosis of small B cell lymphoma.

Table 10.2  A comparison of the histological and immunophenotypic features of reactive plasmacytosis and multiple myeloma.

Table 10.3  Differential diagnosis of diffuse large B cell lymphomas and carcinomas.

Table 13.1  Immunocytochemical identification of carcinomas and paediatric tumours.

Table 13.2  Patterns of expression of keratins CK7 and CK 20 in epithelial malignancies.

Table 14.1  Causes of fibrosis in the bone marrow.

Table 14.2  Causes of granulomas.

Table 14.3  Causes of serous atrophy (gelatinous transformation of the marrow).

Table 14.4  Conditions in which foamy macrophages may be seen.

Table 14.5  Pathological conditions often associated with erythrophagocytosis.

Table 14.6  Semiquantitative grading scheme for haemosiderin in tissue section. After Krause et al. (1979)³.

Table 14.7  Conditions affecting iron stores.

Table 15.1  Suggested antibody types for identifying normal cells.

Table 15.2  Causes and diagnoses of dry taps.

Table 15.3  Some causes of focal disease in bone marrows.

Table 15.4  Immunocytochemical aids in lymphoma and leukaemia diagnosis.

Table 15.5  Antigens identifiable in routine trephine sections by commercially available antibodies.

List of Illustrations

Figure 2.1  Examples of bone marrow cellularity at different ages.

Figure 2.2  Lamellar bone showing parallel lines of ossification. Giemsa.

Figure 2.3  Osteoblasts (arrow) along the endosteal surface. Giemsa.

Figure 2.4  Osteoclast (arrow) housed in a Howship's lacuna. Giemsa.

Figure 2.5  Cartilage (arrow) undergoing ossification. Osteocytes (arrowheads) are present within the lacunae. Giemsa.

Figure 2.6  (a) and (b) Necrotic bone. Note the absence of osteocytes in the lacunae. There is a small focus of viable bone where osteocytes are present (arrowheads).

Figure 2.7  Typical example of thin trabeculae in the osteoporotic bone of an elderly patient. Such trephines are often rather shattered in appearance as they tend to crumple up on biopsy due to the weakness of the bone. Giemsa.

Figure 2.8  Small capillary (arrowhead) surrounded by a thin layer of mature plasma cells. Giemsa.

Figure 2.9  Semiquantitative grading system of marrow reticulin content.

(a) Grade 0. Focal fine reticulin. Normal. Gomori.

(b) Grade 1. Diffuse fine reticulin. Normal. Gomori.

(c) Grade 2. Diffuse and dense reticulin with only occasional collagen fibres. Abnormal. Gomori.

(d) Grade 3. Diffuse coarse reticulin including collagen, i.e. fibrosis. Osteosclerosis is often present. Abnormal. Gomori.

Figure 2.10  Marrow from elderly patient showing increased fat. Giemsa.

Figure 2.11  Single layer of fat cells separating marrow from the endosteal surface ‘first fat space’. Giemsa.

Figure 2.12  Post blood transfusion marrow showing how well Giemsa staining highlights iron in macrophages ( arrows).

Figure 2.13  Schematic illustration of granulocytic cell differentiation.

Figure 2.14  Crush artefact mimicking fibrosis. H&E.

Figure 2.15  Paratrabecular arrangement of granulocytic series immuno-stained for myeloperoxidase.

Figure 2.16  Arteriole with adjacent granulopoiesis. (a) Giemsa. (b) Immunoperoxidase for elastase.

Figure 2.17  Schematic illustration of erythroid differentiation.

Figure 2.18  Small erythroid island with central macrophage immunostained for CD68. Immunoperoxidase.

Figure 2.19  Erythroid colony showing distinct blueness of erythroblasts (arrow). Giemsa.

Figure 2.20  Normoblast (arrows) showing ‘halo’ artefact. Giemsa.

Figure 2.21  Neonatal marrow showing erythroid colonies which should not be confused with metastatic disease. (a) Giemsa. (b) Immunostaining for red cell glycophorin. APAAP.

Figure 2.22  Schematic illustration of megakaryocytic differentiation.

Figure 2.23  Distribution of megakaryocytes stained for CD61 in normal marrow a) low power view immunoperoxidase and b) higher power showing two megakaryocytes lying in close proximity to a venous sinusoid (arrow). APAAP.

Figure 2.24  Megakaryocyte showing emperipolesis. A neutrophil (arrow) is present within the megakaryocyte. Giemsa.

Figure 2.25  Megakaryocyte showing mitosis. H&E.

Figure 2.26  Distribution of B cells (immunostaining for CD20 and CD79a) and T cells (immunostaining for CD3 and CD5) in normal marrow. Immunoperoxidase.

Figure 2.27  Reactive lymphoid nodules in normal marrow (H&E) showing the distribution of B (CD20) and T (CD3) cells and the polyclonal nature of the B cells (k and λ).

Figure 2.28  (a) A low power view of normal marrow showing scattered mast cells (arrowheads). (b) and (c) High power views showing (b) how Giemsa staining highlights mast cells which are often difficult to identify on (c) H&E (arrow).

Figure 2.29  The distribution of macrophages throughout the normal marrow CD68 immunoperoxidase.

Figure 2.30  Fragment of epidermis introduced into the marrow during the biopsy procedures.

Figure 2.31  Bone dust filling the marrow cavity is an artefact of trephining. H&E.

Figure 2.32  Small lymph node present within the marrow. H&E.

Figure 2.33  The space left by tearing out the bone trabecular (T) can look like a sinus (S) but lacks red cells and an endothelial lining. H&E.

Figure 3.1  Case of gram-negative sepsis pre-treatment showing a hypercellular packed marrow with granulocytic and erythroid hyperplasia. The latter is highlighted by glycophorin C immunostaining. After successful therapy the marrow returned to normal.

Figure 3.2  Typical case of tuberculosis with a Langhans giant cell at 7 o'clock in the H&E stain. These granulomas are composed of macrophages as demonstrated by CD68 immunostaining. In this case a few scattered ZN-positive bacilli were detected.

Figure 3.3  Reactive haemophagocytosis showing a large number of macrophages (CD68 positive) throughout the marrow containing numerous nucleated cells and erythrocytes (glycophorin C positive).

Figure 3.4  EBV demonstrated in a severe case of infectious mononucleosis (top row) and parvovirus giving rise to giant erythroblasts (bottom row). The parvovirus is highlighted by immunostaining.

Figure 3.5  Typical hypercellular marrow seen in uncomplicated HIV infection. H&E.

Figure 3.6  Examples of hypocellularity seen in HIV infection. (a) H&E. (b) Giemsa.

Figure 3.7  Dyserythropoiesis in HIV infection. Binucleate normoblast (arrow). Giemsa.

Figure 3.8  Megaloblastic precursors (arrows) in HIV infection. Giemsa.

Figure 3.9  Micromegakaryocytes in HIV infection. (a) H&E (b) CD31. (c) CD61.

Figure 3.10  Naked megakaryocyte nuclei. Giemsa and immunostains for CD61.

Figure 3.11  Increased numbers of (a) plasma cells immunostained with antibody VS38 and (b) macrophages immunostained for CD68 in HIV-infected marrow.

Figure 3.12  Macrophages demonstrating erythrophagocytosis. The cytology is Giemsa, histology H&E and immunostains for glycophorin C showing the red cells (erythrocytes) and CD68 for macrophages.

Figure 3.13  Increased numbers of plasma cells. (a) Giemsa. (b) Antibody VS38.

Figure 3.14  Lymphohistiocytic aggregates in HIV. (a) H&E. (b) CD3 for T cells. (c) CD68 for macrophages. (d) CD79a for B lymphocytes and plasma cells.

Figure 3.15  Serous atrophy in HIV. (a) Low power. (b) High power. Both H&E.

Figure 3.16  TB-infected HIV marrow. The top row shows a case with well-formed granulomas and many tubercle bacilli whereas the lower row is a case with ill-formed granulomas and very few tubercle bacilli (shown in inserts). TB stained by ZN and macrophages immunostained for CD68.

Figure 3.17  Atypical tuberculosis in HIV marrow not associated with granulomata. ZN stain.

Figure 3.18  HIV-associated cryptococcal infection. (a) H&E. (b) Mucicarmine.

Figure 3.19  HIV-associated histoplasmosis. (a) H&E. (b) Grocott.

Figure 3.20  Leishmania donovani bodies in macrophage cytoplasm. (a) H&E. (b) Giemsa.

Figure 3.21  Histoplasmosis associated with granuloma formation. H&E.

Figure 3.22  CMV infection showing typical inclusions in both endothelial cells and macrophages. H&E and immunoperoxidase for CMV.

Figure 3.23  Diffuse Large B cell lymphoma in HIV-infected marrow.

Figure 3.24  Burkitt's lymphoma in HIV-infected marrow.

Figure 3.25  B cell lymphoblastic lymphoma. (a) Giemsa. (b) B cell marker CD79a. (c) Immunoperoxidase for proliferation associated marker JC1.

Figure 3.26  Hodgkin lymphoma in HIV-infected marrow. (a) H&E. (b) Giemsa. (c) CD30 immunostain.

Figure 3.27  Kaposi sarcoma deposit in an HIV-positive bone marrow showing the typical co-involvement with HHV8 virus.

Figure 4.1  Iron deficiency anaemia. Hypercellular marrow at low and high power showing increased erythropoiesis. Giemsa. Immunostained for glycophorin C to outline erythroid colonies.

Figure 4.2  Anaemia of chronic disease. Normal cellularity for age shown at low and higher powers H&E. Iron may be seen in macrophages staining green on Giemsa.

Figure 4.3  Autoimmune haemolytic anaemia. (a) Hypercellular marrow. (b) Erythroid hyperplasia. Giemsa.

Figure 4.4  Typical megaloblastic anaemia. (a) Cytology (b) Low power. (c&d) High power. Note the characteristic elongated ‘coin slot’ nucleoli of the megaloblasts (arrow) (e&f) immunostains for glycophorin C to highlight erythroid cells.

Figure 4.5  Megaloblastic anaemia with extreme hypercellularity with many blast cells simulating acute leukaemia. (a) Low power. H&E. (b) High power. H&E. (c) High power. Giemsa. (d) Immunostain for red cell glycophorin. Peroxidase.

Figure 4.6  Megaloblastic anaemia with extreme myeloblastic proliferation. Histology shown at low power with H&E and at higher powers with H&E and Giemsa respectively. Immunostains for myeloperoxidase and CD10 highlight the paratrabecular aggregations of blasts. This case resolved with vitamin B12 administration.

Figure 4.7  Drug-induced macrocytosis. (a) Low power. (b) High power. Giemsa.

Figure 4.8  Congenital dyserythropoietic anaemia in a child's marrow shows disrupted erythroid colonies with marked pleomorphic features in all cell types (a) low power (b) Giemsa.

Figure 4.9  Aplastic anaemia. (a) Low power. Giemsa. (b) Vessel surrounded by reactive plasma cells showing polyclonal light chain production. (c) Kappa immunostain. (d) Lambda immunostain.

Figure 4.10  (a) Marrow appearances one year after successful treatment for typical aplastic anaemia. (b) High power view shows dysplastic changes (reduced granulocyte differentiation, dyserthropoiesis) which should not be interpreted as preleukaemic. Giemsa.

Figure 4.11  Severely hypocellular marrow as seen in Fanconi's anaemia. Giemsa.

Figure 4.12  Blackfan-Diamond syndrome. Although the marrow shows good cellularity for a child it can be seen that the red cell population is severely restricted (Giemsa and Glycophorin C immunostains) whereas granulocytes (myeloperoxidase) and megakaryocytes (CD31) are normal.

Figure 4.13  Schwachman-Diamond syndrome showing normal cellularity for age but with greatly reduced granulocytic maturation. Note that the myeloid population is relatively preserved and that it is the polymorph maturation which is heavily reduced.

Figure 5.1  Typical jumbled appearance of cell types in myelodysplasia. Giemsa.

Figure 5.2  Increased numbers of megakaryocytes in myelodysplastic syndrome (MDS). (a) H&E. (b) Highlighted by immunostaining for CD61.

Figure 5.3  Typical micromegakaryocyte (arrowhead) next to a monolobated form (arrow) in MDS. H&E.

Figure 5.4  Monolobated megakaryocyte (arrow) in MDS. Giemsa.

Figure 5.5  Megakaryoblast (arrow) with 2 micromegakaryocytes. H&E.

Figure 5.6  Enlarged irregular erythroid colony in MDS highlighted by immunostaining for glycophorin C. (a) Giemsa. (b) Immunoperoxidase.

Figure 5.7  Clusters of immature erythroid precursors in MDS. Giemsa.

Figure 5.8  A small cluster of precursor cells of uncertain origin which the authors believe represent abnormally located immature precursors (ALIPs). Giemsa.

Figure 5.9  Blast cells identified by either cKIT (CD117) or CD34 can be useful in identifying those cases of MDS with either excess blast cells or frank transformation into AML. Pathologists often have difficulty in distinguishing the normal background pattern of cKIT and CD34 staining from blast cells so a normal marrow is included in this portfolio of images to offer assistance.

Figure 5.10  The bone marrow smear cytology shows increased numbers of poorly differentiated myeloid precursors and monocytes. Note the paucity of polymorphs and the hypogranular nature of the monocytic cells.

Figure 5.11  In chronic myelomonocytic leukaemia (CMML) the marrow is hypercellular and is characterized by an increased number of myelocytes with a lack of more mature granulocytes. Top row H&E and Giemsa. Bottom row shows the granulocytic precursors (myeloperoxidase) and immature monocytes (KP1 positive PGM1 negative – these are two CD68 switch variants, the former being absent on mature monocytes and macrophages). Glycophorin C immunostaining outlines the frequently accompanying dyserythropoiesis.

Figure 6.1  The Philadelphia chromosome.

Figure 6.2  (a) Typical low power appearances of CML. Note lack of fat spaces. H&E. (b) High power. Giemsa.

Figure 6.3  Atypical megakaryocytes in CML. Giemsa.

Figure 6.4  Examples of two pseudo-Gaucher cells in CML. Giemsa.

Figure 6.5  Typical reticulin pattern in CML. Silver stain.

Figure 6.6  Blast crisis in CML. (a) Low power. (b) High power. Giemsa.

Figure 6.7  Polycythaemia vera. (a) Low power. H&E. (b) Low power. Giemsa. (c) Erythroid differentiation. Giemsa. (d) Confirmed by immunostaining for glycophorin C.

Figure 6.8  Abnormal megakaryocytes in PV. (a) H&E. (b) Giemsa. (c) Immunostains for CD31 and CD61 highlight the megakaryocytes. Note the heterogeneity of the immunostaining which is a feature of the abnormal megakaryocytes in these myeloproliferative disorders.

Figure 6.9  Large dilated sinus in PV. H&E.

Figure 6.10  Increased reticulin in PV.

Figure 6.11  Two cases of PV with associated myelofibrosis. In the first case the clinical pattern was still that of PV whereas the second had developed chronic myelofibrosis (so-called post-polycythaemic myelofibrosis). Giemsa.

Figure 6.12  Major clinical features of essential thrombocythaemia.

Figure 6.13  Typical histological appearances of ET shown by Giemsa (left and centre) and HE (right) on top row. The abnormal megakaryocytes are highlighted by immunostaining for CD31 (middle row) and CD61 (bottom row). Note in both the high power Giemsa and immunostains that abnormal megaplatelets can be detected within the cytoplasm of the larger megakaryocytes. This is a feature rarely seen in reactive megakaryocytes.

Figure 6.14  Megakaryocytes clustering around dilated sinuses. Giemsa.

Figure 6.15  Fibrosis associated with abnormal megakaryocytes in ET. Giemsa.

Figure 6.16  Philadelphia chromosome positive CML with the clinical features of ET.

Figure 6.17  MPN – myelofibrosis.

Figure 6.18  Dense fibrosis in primary myelofibrosis. (a) Giemsa. (b) Reticulin.

Figure 6.19  Abnormal megakaryocytic proliferation in osteomyelofibrosis. The bone remodelling is well shown by Giemsa staining whereas immunostaining for CD61 (here) or CD31 will be needed to give a clear picture of the megakaryocytes. Note the increased vascularity associated with this condition which is best seen by immunostaining for CD34 in this case.

Figure 6.20  PRV-like area in primary myelofibrosis. Giemsa.

Figure 6.21  Prefibrotic PMF. This patient had all the clinical features of primary myelofibrosis though the marrow shows only cellular myeloproliferative disease highlighted here by myeloperoxidase (MPO) and CD61 immunostaining. The reticulin stain is unremarkable.

Figure 6.22  Acute myelofibrosis (of M7 type). (a–c) H&E. (d) Reticulin.

Figure 6.23  Hypercellular bone marrow in mastocytosis. H&E.

Figure 6.24  So-called ‘mast cell granulomas’ in systemic mastocytosis. (a, b) H&E. (c, d) Giemsa.

Figure 6.25  Cytological appearances of mastocytosis. (a) H&E. (b, c) Giemsa. Note how spindle-shaped these cells can be (c).

Figure 6.26  Granulation in mast cells. (a) H&E. (b) Giemsa.

Figure 6.27  Cytological appearances of systemic mastocytosis showing the atypical mononuclear cells with irregular granulation (next to a mature mast cell in the high power Giemsa [arrowhead] for comparison). These cells are characteristically immunostained for c-kit (CD117) and CD68.

Figure 6.28  Another typical case of sytemic mastocytosis showing the granuloma fromation with Giemsa and H&E. Toluidine blue staining will also identify the mast cells but immunostaining for c-kit (CD117) is much superior. Normal mast cells are myeloperoxidase negative though neoplastic ones may occasionally express it weakly.

Figure 6.29  Typical immunostaining of systemic mastocytosis for CD68 (antibody PGM1) myeloperoxidase, mib1 and c-kit (CD117).

Figure 6.30  Neoplastic mast cells are positive for CD2 and CD25 which are not present on normal mast cells.

Figure 6.31  A case of transient myeloproliferative disorder in a neonate with Down's syndrome. The marrow is hypercellular, even allowing for age, with a prominent population of primitive blast cells. Some of these can be identified in this case as megakaryocytic (CD31) but others are clearly myeloid (myeloperoxidase). This case resolved after a few weeks and the child has been well for the past 14 years.

Figure 7.1  Primitive case of AML positive only for TdT.

Figure 7.2  Typical case of AML positive for myeloperoxidase and c-kit (CD117). Note for interest the weak positivity for CD31 which is not lineage specific and glycophorin C; such so-called anomalous findings are common in AML.

Figure 7.3  Acute promyelocytic leukaemia with abnormal granulated promyelocytes being plentiful in the marrow smear. Note an Auer rod (arrowhead) in the high power view. The histology can be confusing at times. This case has a lymphoplasmacytic appearance but is negative for plasma cell markers (VS38) and other lymphoid antigens but positive for myeloperoxidase.

Figure 7.4  Case of AML with a patchy distribution in the marrow that was inconclusive on aspirate examination. The biopsy is diagnostic, showing large numbers of blasts immunostaining for myeloperoxidase, CD34, CD56 and c-kit (CD117).

Figure 7.5  AML arising from a dysplastic marrow (well demonstrated by the megakaryoctic pattern with CD61). Myeloperoxidase and c-kit (CD117) immunostains outline the substantial blast cell population.

Figure 7.6  An unusual case of AML that was positive for CD30 and CD7, raising the question whether it was lymphoid in origin. Myeloperoxidase and to a lesser extent c-kit (CD117) positivity on the blasts reveals its true nature.

Figure 7.7  Secondary AML positive only for CD68, suggesting a monoblastic lineage. This case arose two years after therapy for ALL, which is shown at the bottom of the figure and has an entirely different immunophenotpye.

Figure 7.8  Secondary AML arising five years after treatment for myeloma. The AML though negative for myeloperoxidase is identified by staining for c-kit (CD117), CD56, CD34, glycophorin C and CD61. As well as this complex AML there is also present a relapse of the myeloma demonstrated by staining for VS38 and light chains (κ and λ).

Figure 7.9  The first four images are of an acute monoblastic leukaemia identified by positivity for CD68 and lysozyme. Most cases are negative for myeloperoxidase though this one shows that exceptions occur. The second case (bottom three images) illustrates the value of CD163 in highlighting infiltration by monoblastic leukaemia.

Figure 7.10  M6 erythroleukaemia. The histology is shown