Neoplasia

Question 1

What is a neoplasm?

Answer 1

Disordered cell growth that is triggered by a series of acquired mutations affecting a single cell and its clonal progeny

Question 2

What makes a tumour benign?

Answer 2

A tumour is said to be benign when its gross and microscopic appearances are considered relatively innocent, implying that it will remain localised, will not spread to other sites and is amenable to local surgical removal

Question 3

What makes a tumour malignant?

Answer 3

Malignant tumours can invade and destroy adjacent structures and spread to distant sites (metastasise) to cause death

Question 4

What is a hamartoma?

Answer 4

Hamartomas are disorganised but benign masses composed of cells indigenous to the involved site

Question 5

The great majority of neoplasms, even mixed tumours, are composed of cells from a single germ layer. An exception is a teratoma - what is it?

Answer 5

A teratoma contains recognisable mature or immature cells or tissues belonging to more than one germ cell layer (and sometimes all three).

They originate from totipotential germ cells that are normally present in the ovary and testis and sometimes also found in abnormal midline embryonic rests.

Question 6

What is a choristoma?

Answer 6

Choristoma is the term applied to a heterotypic rest of cells. Eg. a small nodule of well-developed and normally organised pancreatic tissue may be found in the submucosa of the stomach, duodenum or small intestine.

Question 7

What are the morphologic hallmarks of malignancy?

Answer 7

Anaplasia
Pleomorphism
Abnormal nuclear morphology
Mitoses
Loss of polarity
Central ischaemic necrosis

Question 8

What is anaplasia?

Answer 8

Lack of differentiation

Question 9

What is pleomorphism?

Answer 9

Variation in cellular shape and size

Question 10

What do the nuclei of cancerous cells look like?

Answer 10

Nuclei are disproportionately large for the cell with a nuclear-to-cytoplasm ration approaching 1:1 instead of the normal 1:4 or 1:6

Variable and irregular nuclear shape

Clumped chromatin distributed along the nuclear membrane

Darkly stained chromatin (hyperchromatic)

Abnormally large nucleoli

Question 11

What are mitoses?

Answer 11

Many cells are in mitosis in undifferentiated tumours, reflecting the high proliferative activity of the parenchymal cells.

Mitoses are indicative of rapid cell growth (not necessarily indicative that a tumour is malignant or that the tissue is neoplastic).

More important as a morphologic feature of malignancy are atypical, bizarre mitotic figures, sometimes with tripolar, quadripolar or multipolar spindles

Question 12

What is loss of polarity?

Answer 12

In addition to the cytologic abnormalities, the orientation of anaplastic cells is markedly disturbed. Sheets or large masses of tumour cells grow in an anarchic, disorganised fashion

Question 13

Why do malignant tumours develop central necrosis?

Answer 13

Growing tumour cells obviously require a blood supply, but often the vascular stroma is insufficient and as a result many rapidly growing malignant tumours develop large central areas of ischaemic necrosis

Question 14

What is metaplasia?

Answer 14

Metaplasia is the replacement of one type of cell with another type. Nearly always found in association with tissue damage, repair and regeneration.

Often the replacing cell type is better suited to some alteration in the local environment.

Eg. gastro-oesophageal reflux damages the squamous epithelium of the oesophagus, leading to its replacement by glandular (gastric or intestine) epithelium more suited to an acidic environment

Question 15

What is dysplasia?

Answer 15

Disordered growth, principally encountered in epithelia.
Characterised by:
- Loss of uniformity and loss of architectural orientation
- Considerable pleomorphism and large hyperchromatic nuclei with a high nuclear-to-cytoplasmic ratio
- Disordered architecture
- More abundant mitotic figures

Question 16

What is carcinoma in situ?

Answer 16

When dysplastic changes are marked and involve the full thickness of the epithelium, but the lesion does not penetrate the basement membrane, it is considered a pre -invasive neoplasm and is referred to as carcinoma in situ.

Once the tumour cells breach the basement membrane, the tumour is said to be invasive.

Question 17

Does dysplasia progress to cancer?

Answer 17

Dysplastic changes are often found adjacent to foci of invasive carcinoma and in some circumstances such as long-term cigarette smokers and persons with Barrett oesophagus, severe epithelial dysplasia frequently antedates the appearance of cancer.

Thus, although dysplasia may be a precursor to malignant transformation, it does not always progress to cancer.

Question 18

With regards to expansion and invasion, how do benign and malignant tumours differ?

Answer 18

The growth of cancer is accompanied by progressive infiltration, invasion and destruction of the surrounding tissue, whereas nearly all benign tumours grow as cohesive expansile masses that remain localised to their site of origin and lack the capacity to infiltrate, invade or metastasise to distant sites

Question 19

What is the capsule surrounding a benign tumour made of? What are some examples of unencapsulated benign tumours?

Answer 19

Because benign tumours grow and expand slowly, they usually develop a rim of compressed fibrous tissue called a capsule that separates them from the host tissue.

This capsule consists largely of extracellular matrix deposited by stromal cells such as fibroblasts, which are activated by hypoxic damage resulting from the pressure of the expanding tumour.

Such encapsulation does not prevent tumour growth, but it creates a tissue plane that makes the tumour discrete, readily palpable, moveable (non-fixed) and easily excisable by surgical enucleation.

Haemangiomas (neoplasms composed of tangled blood vessels) are one of the few exceptions - they are unencapsulated and permeate the site in which they arise. When such lesions are extensive, they may be unresectable.

Question 20

Next to the development of metastases, _______ is the most reliable feature that differentiates cancers from benign tumours.

Answer 20

Invasiveness.

Most malignant tumours do not recognise normal anatomic boundaries and can be expected to penetrate the wall of the colon or uterus, for example, or fungal though the surface of the skin.

Question 21

What is metastasis?

Answer 21

Metastasis is the spread of a tumour to sites that are physically discontinuous with the primary tumour and unequivocally marks a tumour as malignant, as by definition benign neoplasms do not metastasise.

The invasiveness of cancers permits them to penetrate into blood vessels, lymphatics and body cavities, providing the opportunity for spread.

Question 22

All malignant tumours can metastasise, but some do so very infrequently. Give two examples of malignant neoplasms which invade early in their course but rarely metastasise.

Answer 22

Gliomas

Basal cell carcinomas of the skin

Question 23

Excluding skin cancers other than melanomas, what percentage of newly diagnosed solid tumours present with metastases?

Answer 23

30%

Question 24

What are the three pathways of cancer dissemination?

Answer 24

Direct seeding of body cavities or surfaces
Lymphatic spread
Haematogeneous spread

Question 25

What are some examples of cavities being directly seeded?

Answer 25

Peritoneal cavity, pleural cavity, pericardial sac, subarachnoid space, joint space.

Peritoneal seeding is very characteristic of ovarian malignancies and mucus-secreting appendices carcinomas → gelatinous neoplastic mass (pseudomyxoma peritonei)

Question 26

What is the most common pathway for the initial dissemination of carcinomas?

Answer 26

Lymphatic spread

Question 27

What is a sentinel lymph node?

Answer 27

The first node in a regional lymphatic basic that receives lymph flow from the primary tumour

Question 28

Haematogeneous spread is typical of what broad type of malignant neoplasms?

Answer 28

Sarcomas, but is also seen with carcinomas