FIGURE 5.1

This bronchial biopsy shows islands of large tumour cells which are cohesive and have long cell-to-cell borders. Keratin production is not, however, prominent.

FIGURE 5.2

This section of left lung shows a large white tumour which extends to the pleural surface to which parietal pleura is attached. Two peribronchial lymph nodes contain what appears to be white tumour.

FIGURE 5.3

(A) Benign tumours are well circumscribed and the surrounding tissue often forms a capsule of fibrous tissue. (B) The cells of benign tumours closely resemble those of the normal tissue in which they arise. The nuclei are normal. As growth is slow, mitoses are uncommon, and as division is normal mitotic figures are of normal appearance. (C) Malignant tumours have infiltrative margins both on naked eye and on microscopic examination. (D) The nuclei are usually enlarged and the nucleoli active, indicating that the cell is active. The nuclei are often darkly staining – hyperchromatic – and variable in size and shape – pleomorphic – as the DNA content of the nucleus is frequently increased. Mitoses are often numerous and they are frequently abnormal in form indicating that the process of cell division may be abnormal. A tripolar mitosis is one in which the chromosomes are attempting to segregate towards three daughter cells.

FIGURE 5.4

Squamous papilloma, larynx. This lesion consists of finger-like projections of squamous epithelium with central connective tissue cores.

FIGURE 5.5

Adenoma of colon. Several gland-like structures are present, mimicking the structure of normal colonic mucosa.

FIGURE 5.6

Tubular adenoma of colon. This is a small pedunculated polyp on a slender stalk.

FIGURE 5.7

Squamous carcinoma. This is an example of a well-differentiated tumour with irregular islands of squamous epithelium, and one showing central keratinization.

FIGURE 5.8

Adenocarcinoma. The tumour cells form an acinar structure. The nuclei contain prominent nucleoli.

FIGURE 5.9

Signet-ring cell cancer of stomach. The tumour cells have eccentric nuclei, pushed to the side by a central globule of mucus.

FIGURE 5.10

Leiomyosarcoma. This tumour consists of elongated cells with a cigar-shaped nucleus and eosinophilic cytoplasm. There are several mitoses in this field.

FIGURE 5.11

Hodgkin lymphoma. A typical Reed–Sternberg cell is present in the middle of the field. It is binucleate with an ‘owl’s eye’ appearance due to the large eosinophilic nucleoli.

FIGURE 5.12

Benign cystic teratoma of ovary. This cyst is lined by squamous epithelium and is filled with sebaceous material and hair.

FIGURE 5.13

Early invasive squamous carcinoma. Small groups of tumour cells have broken free from the overlying epithelium and have invaded the underlying connective tissue.

FIGURE 5.14

Local invasion by breast carcinoma. The tumour cells have spread along paths of least resistance, here through adipose tissue.

FIGURE 5.15

Lymphatic spread. This malignant melanoma has spread extensively through the lymphatics (outlined in black by melanin) in the leg.

FIGURE 5.16

Early involvement of a lymph node by metastatic carcinoma. A nodule of white tumour is present under the subcapsular sinus.

FIGURE 5.17

Breast carcinoma showing lymph node involvement. The tumour lies just lateral to the nipple. The largest arrow indicates the first node in the chain. This and the node marked by the next arrow are both involved by metastatic carcinoma. The third node is free from tumour.

FIGURE 5.18

This large yellow renal carcinoma is seen invading along the opened renal vein. Tumour can propagate via the inferior vena cava and reach the heart.

FIGURE 5.19

Paget’s disease of the nipple. The mechanism of development is shown in (A) and the resulting eczema-like appearance of the overlying skin in (B).

FIGURE 5.20

The process of tumour spread (metastasis). This diagram outlines the basic process of blood-borne metastasis. More detail is provided in the accompanying Special Study Topic 5.1.

FIGURE 5.21

Cirrhotic liver on left with large spleen (due to portal hypertension) on right. A large hepatocellular carcinoma has arisen in the cirrhotic liver.

FIGURE 5.22

Central necrosis is a feature of many highly malignant tumours such as this large soft tissue sarcoma.

FIGURE 5.23

This carcinoma of the oesophagus had caused a tight stricture, resulting in dysphagia.

FIGURE 5.24

Metastatic melanoma in the liver. Note the numerous deposits of tumour, some deeply pigmented and others more pale. The liver was greatly enlarged. The patient had had an eye removed for a malignant melanoma many years before.

FIGURE 5.25

Needle biopsy of mass in thigh shows a highly cellular tumour. There was enough tissue for immunohistochemistry to confirm the diagnosis of Ewing’s sarcoma (see Chapter 12).

FIGURE 5.26

This needle biopsy is from the paraspinal tissue of a 40-year-old woman. The H&E-stained section (A) shows an adenocarcinoma. Strongly positive immunostaining for thyroid transcription factor 1 in the nuclei (B), and cytokeratin 7 in the cytoplasm (C), indicate that the likely primary is in the lung.

FIGURE 5.27

Immunocytochemistry is a powerful tool in determining the histogenesis of poorly differentiated tumours. Here, the nuclei stain strongly for myoD₁, a marker of skeletal muscle differentiation, allowing the diagnosis of rhabdomyosarcoma to be made with confidence.

FIGURE 5.28

(1) A genotoxin may directly interact with DNA or do so following metabolic activation, e.g. by one of the cytochrome P450 enzymes. DNA adducts are formed or direct DNA strand breakage occurs. (2) Defective DNA repair may result in mutations which affect key genes such as those involved in regulating the cell cycle, apoptosis or differentiation leading to tumour formation. (3) Non-genotoxins do not have direct effects on DNA but cause cell proliferation by deregulating normal cell cycle activity. (4) Many of the enzymes involved are polymorphic, that is there is a sequence variation in the gene that may reflect a change in expression, inducibility of the gene or function. At each stage of metabolism there is variability between individuals in terms of exposure levels and also the metabolic activity determined both by the genotype of the individual and level of expression and function of the enzymes. GST = glutathione S-transferase.

FIGURE 5.29

Familial adenomatous polyposis coli. This patient had a pancolectomy at the age of 25. Innumerable polyps are present throughout the colon. Fortunately no invasive carcinomas were identified. The patient’s mother was less fortunate and died at the age of 43 from metastatic carcinoma of the colon.

FIGURE 5.30

Inheritance of retinoblastoma. The retinoblastoma gene lies on the long arm of chromosome 13. (A) The sporadic form of retinoblastoma occurs in individuals who have two normal Rb genes. Loss of both alleles is required before a tumour will develop, therefore the risk of this is very small and the tumour, which is unilateral, often occurs in older children. (B) In contrast, in patients with familial retinoblastoma one Rb allele is mutated in the germ line, and therefore in every cell in the body. Only one mutation in the remaining normal Rb gene is required for a tumour to develop. Accordingly, this almost invariably occurs, and most patients develop bilateral tumours at an early age. Unfortunately, they also develop a variety of other tumours in later life.