FIGURE 8.1

Diagrammatic structure of a lymph node. Material enters the sinus network of the lymph node via the afferent lymphatics. The phagocytic cells which line the sinuses entrap the antigenic material and deliver it to antigenpresenting cells within the B- and T-cell areas. A B-cell reaction results in germinal centre formation within the cortex, which leads to the production of plasma cells and memory cells which re-circulate. T-cell reactions occur mainly within the deep paracortical areas.

FIGURE 8.2

A lymph node displaying follicular hyperplasia. GC = germinal centre; MZ = mantle zone; SS = subcapsular sinus; PC = paracortex.

FIGURE 8.3

Schematic diagram of the cellular composition of classical Hodgkin lymphoma. The Reed–Sternberg and mononuclear Hodgkin cells are the neoplastic component and may account for only 5% of the total cellularity. The Hodgkin/Reed–Sternberg (HRS) cells secrete cytokines (e.g. interleukins, tumour necrosis factor) which invoke the inflammatory cellular reaction.Cytokine production is also likely to account for the fever and sweats experienced by some patients.

FIGURE 8.4

A typical Reed–Sternberg cell surrounded by a mixed infiltrate of small lymphocytes, a single histiocyte and eosinophils.

FIGURE 8.5

Immunocytochemistry for EBV latent membrane protein 1 (LMP1) in CHL. Numerous HRS cells are positive.

FIGURE 8.6

In-situ hybridization using an oligonucleotide probe to EBV-encoded RNA (EBER) in a case of CHL. The nuclei of Reed–Sternberg and mononuclear Hodgkin cells contain large amounts of EBERs. The surrounding reactive T cells are negative.

FIGURE 8.7

In-situ hybridization for EBV EBER in a case of Burkitt lymphoma. The nucleus of every tumour cell is positive.

FIGURE 8.8

Photograph of the cut surface of the excised lymph node (3 cm maximum) which has a nodular architecture with fibrotic bands between the nodules.

FIGURE 8.9

Low-power view of the nodal histology. Thick bands of collagen divided the node into cellular nodules. There is also a thickened capsule.

FIGURE 8.10

Immunohistochemistry for CD30. Several HRS cells display membrane and perinuclear dot positivity for CD30.

FIGURE 8.11

Computed tomography scan of the thorax, showing a large mediastinal mass.

FIGURE 8.12

Computed tomography scan of the thorax after treatment; the mass is no longer apparent.

FIGURE 8.13

Relative frequency of lymphoma types in Great Britain.

FIGURE 8.14

Immunostaining for bcl2. (A) Reactive follicle: the germinal centre (GC) cells are negative. A small number of intrafollicular T-cells are positive. (B) In contrast, the GC cells in the neoplastic follicle in follicular lymphoma are strongly positive. Overexpression is a consequence of the t(14;18) translocation where the promoters on the IgH gene on chromosome 14 cause transcription of the bcl2 gene on chromosome 18 and is a useful tool to distinguish between reactive and malignant follicular lesions.

FIGURE 8.15

(A) Low-power view of the lymph node biopsy: the node is replaced by numerous follicular structures. At high power (B), there is a mixture of germinal centre-type cells comprising large cells (centroblasts) and smaller cells with a cleaved nucleus (centrocytes). Tingible body macrophages are absent. This pattern is characteristic of follicular lymphoma. The number of large cells is less than 5 per high-power field and therefore the lesion is regarded as grade 1.

FIGURE 8.16

The bone marrow is extensively involved by follicular lymphoma. (A) This low-power H&E view shows a band of small lymphoid cells involving the area immediately adjacent to the bony trabecula (paratrabecular). (B) A parallel section is stained for CD20 (a B-lymphocyte marker) by immunocytochemistry, thus confirming the B-cell nature of the infiltrate.

FIGURE 8.17

(A) H&E staining of colonic biopsy. There is a lymphomatous infiltrate within the mucosa and submucosa which is composed of a diffuse infiltrate of lymphoid cells resembling centrocytes. (B) Immunocytochemistry for cyclinD1. There is nuclear expression of cyclinD1 in the neoplastic lymphoid population (not normally seen in other types of lymphoma).

FIGURE 8.18

Fluorescence in-situ hybridization (FISH) for the t(11;14) translocation is performed on a 1 µm paraffin section from the biopsy. Red and green signals indicate the 11 and 14 chromosomes, respectively. In a cell containing a t(11;14) reciprocal translocation (arrowed), one red and one green signal (corresponding to the normal chromosomes) and two fusion signals (where the red and green probes are brought together bythe translocation giving rise to emission of yellow light) are seen.

FIGURE 8.19

Diffuse large B-cell lymphoma. The lymph node is completely replaced by a diffuse infiltrate of large lymphoid blast cells.

FIGURE 8.20

Burkitt lymphoma. (A) Diffuse infiltrate of small blast cells in addition to numerous macrophages with abundant pale cytoplasm phagocytosing cellular debris. (B) Almost 100% of tumour cells display nuclear positivity for the proliferation marker Ki67.

FIGURE 8.21

Cross-section of small bowel and mesentery in enteropathy-type T-cell lymphoma complicating coeliac disease. The patient presented with small bowel obstruction and malabsorption. Note the markedly narrowed bowel lumen (short arrow) and the involved lymph node within the mesentery (long arrow).

FIGURE 8.22

A deposit of metastatic adenocarcinoma is present in the subcapsular sinus of this lymph node (between arrows). GC = germinal centre.

FIGURE 8.23

Microanatomy and function of the spleen. (A) High-power view of the spleen (this field is 2 mm in diameter). (B) Immunocytochemical staining of spleen for CD8, highlighting the CD8+ splenic sinusoidal lining cells. The spleen contains white pulp (WP) which consists of periarteriolar lymphoid sheaths (PALS) comprising both T and B lymphocytes, and the red pulp (RP) which acts as a filter for the blood. Blood leaves the arterioles, enters sinusoids (Si), flows through fenestrae in the sinusoidal lining cells, percolates through the cellular splenic cords (SC) containing macrophages and fibroblasts, and eventually reaches the efferent capillaries. Effete and damaged red cells are removed from the circulation within the splenic cords.

FIGURE 8.24

Massively enlarged spleen surgically removed from patient with chronic idiopathic myelofibrosis.

FIGURE 8.25

Cut surface of spleen showing expansion of periarteriolar lymphoid sheaths by splenic marginal zone lymphoma.

FIGURE 8.26

Simplified diagram of normal haemopoiesis. The pluripotent stem cell in the marrow gives rise to a number of progenitor cells that in turn proliferate and differentiate to produce all the cellular constituents of blood, including lymphoid cells. This process is controlled by various growth factors, produced by a range of cells including lymphocytes and endothelial cells, the secretion of which is partially dependent on environmental factors; for example hypoxia induces erythropoietin secretion, resulting in increased red cell production. The marrow stroma provides the appropriate environment for stem cells to grow and proliferate. The stem cell, which is capable of producing approximately 106 mature blood cells, is also capable of self renewal.

FIGURE 8.27

Trephine biopsy of ileum from a normal adult. The cellular haemopoietic red marrow accounts for 40–50% of the marrow space. The remainder consists of fat cells.

FIGURE 8.28

The normal blood film. Contrast this with the abnormal smears on the following pages.

FIGURE 8.29

Blood film in iron-deficiency anaemia. Note the hypochromic and microcytic red blood cells and pencil-shaped poikilocytes.

FIGURE 8.30

Blood film in megaloblastic anaemia due to vitamin B₁₂ deficiency. Poikilocytosis and oval macrocytes are prominent. A single hypersegmented neutrophil polymorph is also present.

FIGURE 8.31

Blood film in hereditary spherocytosis. The spherocytes are small and round with a reduction in the degree of central pallor. The larger cells are reticulocytes which reflect the reactive hyperplasia within the marrow.

FIGURE 8.32

Microangiopathic haemolytic leukaemia. Fragmented red blood cells are prominent.

FIGURE 8.33

Blood film in β-thalassaemia. Numerous hypochromic microcytic red blood cells and circulating normoblasts (red cell precursors) are prominent. Transfused normal erythrocytes are also present.

FIGURE 8.34

Bone marrow trephine biopsy in metastatic prostatic carcinoma. (A) Haematoxylin and eosin staining; (B) immunocytochemistry for prostatespecific antigen is positive, confirming an origin from the prostate.

FIGURE 8.35

Leucoerythroblastic blood film: a nucleated red blood cell precursor (short arrow) and an immature granulocyte (long arrow) are present. Immature precursors are not normally seen in the peripheral blood but, when present, indicate replacement of the normal marrow and consequent extramedullary haemopoiesis. Tear-drop poikilocytes are also a feature.

FIGURE 8.36

Bone marrow trephine biopsy in Gaucher’s disease. The marrow is replaced by macrophages filled with glucocerebroside.

FIGURE 8.37

Blood film in acute myeloid leukaemia. A single blast cell containing an Auer rod (cytoplasmic crystalline structure specific for myeloid differentiation) is depicted.

FIGURE 8.38

Trephine biopsy of bone marrow in acute lymphoblastic leukaemia. (A) The marrow cellularity is almost 100% and is replaced by an infiltrate of small blast cells. (B) Nuclear positivity for terminal deoxynucleotidyl transferase (TdT) is identified in the majority of cells by immunocytochemistry.

FIGURE 8.39

Blood film from patient with chronic myelogenous leukaemia (CML). There is a marked increase in the number of granulocytes compared to the normal blood film (see Figure 8.28).

FIGURE 8.40

Cytogenetic abnormality in chronic myelogenous leukaemia (CML). This diagram depicts the classical t(9;22)(q34;q11) translocation associated with CML. This was the first cytogenetic abnormality ever detected in a human malignancy. There is a reciprocal translocation between the long arms of Ch 9 and Ch 22 bringing together the abl and bcr genes in the derivative Ch 22 (the Philadelphia chromosome).

FIGURE 8.41

Bone marrow trephine biopsy in multiple myeloma. (A) Haematoxylin and eosin staining shows confluent sheets of atypical plasma cells. (B) The neoplastic plasma cells stain only for kappa light chain using immunocytochemistry and are therefore monoclonal. (C) The same population of cells is negative for lambda light chain.