Session 9

Question 0

What is a Malignant Neoplasm?

Answer 0

An abnormal growth of cells that persists after the initial stimulus is removed AND invades surrounding tissue, often in a destructive manner, with potential to spread to distant sites.

Question 1

What is a Benign Neoplasm?

Answer 1

An abnormal growth of cells that persists after the initial stimulus is removed; growth is autonomous.

Question 2

What is a Tumour?

Answer 2

Any clinically detectable lump or swelling.

Note: a neoplasm is just one type of tumour. A cancer is any malignant neoplasm.

NOTE: Clinicians may use tumour and malignant neoplasm and cancer synonymously.

Question 3

What is a Metastasis?

Answer 3

A malignant neoplasm that has spread from its original site to a new non-contiguous site.

The original location is the primary site and the place to where it has spread is a secondary site.

Question 4

What is meant by Dysplasia?

Answer 4

Pre-neoplastic alteration in which cells show disordered tissue organisation (altered differentiation).

It is not neoplastic because the change is reversible.

Often dysplasia with further altered differentiation can become neoplasia.

Question 5

Describe the different behaviour benign and malignant neoplasms show

Answer 5

Benign neoplasms remain confined to their site of origin and do not produce metastases.

Malignant neoplasms have the potential to metastasise.

Benign tumours may gain further genetic alterations and become malignant.

Question 6

Describe the macroscopic features of a benign neoplasm

Answer 6

Benign neoplasms grow in a confined local area and so have a pushing outer margin (grow without destroying surrounding tissue but compress and squash surrounding tissue).

Sometimes a pseudo-capsule forms.

This is why they are rarely dangerous - non-destructive.

Question 7

Describe the macroscopic features of a malignant neoplasm

Answer 7

They have an irregular, jagged outer margin and shape and may show areas of necrosis and ulceration (if on a surface) because they tend to grow faster than their blood supply can provide.

Malignant tumours infiltrate and destroy the surrounding tissue.

Ulceration is due to the breakage of the epithelium.

As cancer spreads, tumour burden increases - a kg of tumour = very advanced disease, unlikely to be cured.

Metastasis themselves concede more metastasis.

Question 8

What do neoplasms show under the microscope?

Answer 8

Varying levels of differentiation.

A benign tumour has cells that closely resemble the parent tissue, I.e. they are well-differentiated

Malignant neoplasms range from well to poorly differentiated.

Cells with no resemblance to any tissue are called ANAPLASTIC.

Question 9

What changes can be seen with worsening differentiation?

Answer 9

Individual cells have increased nuclear size and nuclear to cytoplasmic ratio, nuclear hyperchromasia (abnormal chromatin/DNA - visible due to increased staining of the nucleus), more Mitotic figures and increasing variation in size and shape of cells and nuclei, which is called Pleomorphism.

Clinical use the term ‘grade’ to indicate differentiation, high grade being poorly differentiated.

Dysplasia also represents altered differentiation. Mild, moderate and severe dysplasia indicates worsening differentiation.

In normal tissue, cells are relatively uniform.

Question 10

What does grading mean?

Answer 10

Generally high grades tend to correlate with a poorer outcome but this is more important/relevant in some cancers e.g. Grading does not really make a difference in skin cancer but is really important in breast cancer.

Question 11

Describe differentiation in Dysplasia

Answer 11

Altered/abnormal differentiation.

Mild, moderate and severe dysplasia indicates worsening differentiation.

Severe dysplasia, under stimulus, can merge with carcinoma in situ (not yet invaded basement membrane) and then invasive carcinoma (invades basement membrane).

Dysplasia is reversible but neoplasia is irreversible.

Question 12

What is Neoplasia caused by?

Answer 12

Accumulated mutations in somatic cells.

The mutations are caused by INITIATORs, which are mutagenic agents, and PROMOTERs, which cause cell proliferation.

In combination, initiators and promoters result in an expanded, monoclonal (all derived from the same parent cell) population of mutant cells.

Chemicals, infections particularly certain viruses, and radiation are the main initiators but some of these agents can also act as promoters.

In some neoplasms, mutations can be inherited rather than from an external mutagenic agent.

A neoplasm emerges from this monoclonal population through a process called progression, characterised by the accumulation of yet more mutations.

Question 13

Which is more important, extrinsic factors (environment) or intrinsic (genetic) factors?

Answer 13

Environment plays a large role - ~85% of cancer risk is due to environment/extrinsic factors.

In a germ-line mutations, neoplastic cells get a head start because the mutation is present in all cells.

Question 14

How do we know neoplasms are monoclonal?

Answer 14

A collection of cells is monoclonal if they all originated from a single founding cell.

Evidence that neoplasms are monoclonal came from the study of the X-linked gene for the enzyme glucose-6-phosphate dehydrogenase (G6PD) in tumour tissue from women.

The gene has several alleles encoding different isoenzymes. Early in female embryogenesis one allele is randomly inactivated in each cell (Lyonisation).

In heterogenous women that happen to have one allele encoding a heat stable isoenzyme, and one allele a heat labile isoenzyme, normal tissues will be patchwork of each type. However neoplastic tissues only express one isoenzyme indicating a monoclonal group of cells.

Question 15

Genetic alterations affect which particular types of gene?

Answer 15

Genetic alterations affect PROTO-ONCOGENES and TUMOUR SUPPRESSOR GENES which normally encode proteins in key signalling pathways.

Proto-oncogenes normally present in cells, become abnormally activated due to a mutation and then they become oncogenes, favouring neoplasm formation. The oncogene is dominant in the cell, independent of the regulation by growth factors.

Tumour suppressor genes, which normally suppress neoplasm formation, become inactivated. Both tumour suppressive genes need to be inactivated - they are recessive, they work in growth signalling pathways, angiogenesis and apoptosis amongst other signalling pathways. See session 11.

Question 16

What key differences do neoplastic cell have from normal cells?

Answer 16

Self sufficient growth signals - HER2 gene amplification

Resistance to anti-growth signals - CDKN2A gene deletion

Grow indefinitely - Telomerase gene activation

Induce new blood vessels - Activation of VEGF expression

Resistance to Apoptosis - BCL2 gene translocation

Invade and produce metastases - altered E-cadherin expression.

Question 17

Discuss how Neoplasms are classified

Answer 17

1. Benign or Malignant
2. By tissue type: Epithelial, Connective tissue, Lymphoid / haematopoietic Germ cell

Question 18

Describe naming benign epithelial neoplasms

Answer 18

Generally end in -oma

Stratified squamous: squamous papilloma (any tumour with finger-like projections) e.g. Skin, buccal, mucosa

Transitional: transitional cell papilloma e.g. bladder mucosa

Glandular: Adenoma e.g adenomatous polyp of the colon

Question 19

What is a polyp and what are the different types?

Answer 19

A polyp is anything that protrudes above a surface.

Papilloma - with finger like projections

Sessile - polyp with a broad cost base

Pedunculated - polyps on a stalk Cyst

Question 20

Describe how you would name malignant epithelial neoplasms

Answer 20

Epithelial = carcinoma, 90% of cancers are carcinomas.

Stratified squamous: squamous cell carcinoma: skin, larynx, oesophagus, lung, others

Transitional: transitional cell carcinoma: bladder, ureters

Glandular: Adenocarcinoma: stomach, colon, lung, prostate, breadth pancreas, oesophagus, others

Other: Skin: Basal cell carcinoma and melanoma

Question 21

Describe the names of benign connective tissue neoplasms

Answer 21

Smooth Muscle: Leiomyoma

Fibrous tissue: Fibroma

Bone: Osteoma

Cartilage: Chondroma

Fat: Lipoma

Nerve: Neuroma

Nerve sheath: Neurofibroma/Neurilemmoma

Glial cells: Glioma

Question 22

Describe the names of malignant connective tissue neoplasms

Answer 22

Smooth muscle: Leiomyosarcoma

Bone: Osteosarcoma

Fibrous tissue: Fibrosarcoma

Cartilage: Chondrosarcoma

Fat: Liposarcoma

Nerve sheath: Neurofibrosarcoma

Glial cells; Malignant Glioma

Question 23

Describing the naming of lymphoid and haematopoietic neoplasms

Answer 23

All regarded as malignant.

Lymphoid = Lymphoma (B and T): occurs in lymphoid tissue, usually in lymph nodes, Hodgkins Disease and Non-Hodgkins Lymphoma

Haematopoietic = Acute and Chronic Leukaemia: occurs in bone marrow and the abnormal cells then enter blood.

Question 24

What is Myeloma?

Answer 24

Sounds like a benign muscle neoplasm. But it is not! It is actually a malignant plasma cell neoplasm in bone marrow, destroying adjacent bone.

Question 25

Explain about Germ Cell Neoplasms

Answer 25

Can differentiate along all embryonic lines - into ectoderm, mesoderm and endoderm. Testis: Malignant teratoma or Seminoma (a malignant neoplasm) Ovary: Benign teratoma = Dermoid cyst - sometimes can contain teeth or skin.

Question 26

Explain about Neuroendocrine tumours

Answer 26

System of cells distributed throughout the body, have various sites. Carcinoid tumours (various organs) Phaeochromocytoma (adrenal) Small cell carcinoma of bronchus (often secretes hormones e.g. ACTH)

Question 27

Describe the classification of Benign Epithelial Tumours

Answer 27

They are either: - Papilloma: benign tumour of non-glandular or non-secretory epithelium, such as transitional or stratified squamous epithelium, - Adenoma: benign tumour of glandular or secretory epithelium. The name of a papilloma or adenoma is incomplete unless prefixed by the name of the specific epithelial cell type or glandular origin e.g. Squamous cell papilloma, transitional cell papilloma, colonic adenoma, thyroid adenoma

Question 28

Describe the classification of Malignant Epithelial Tumours

Answer 28

Always called carcinomas. Carcinomas of non-glandular epithelium are always prefixed by the epithelial cell type e.g. squamous cell carcinoma, transitional cell carcinoma Malignant tumours of glandular epithelium are always designated adenocarcinomas coupled with the name of the tissue of origin e.g. Adenocarcinoma of the breast, Adenocarcinoma of the prostate and Adenocarcinoma of the stomach

Question 29

Describe how benign connective tissue and mesenchymal tumours are named

Answer 29

They are named after the cell or tissue of origin suffixed by '-oma' as follows: Lipoma: benign tumour of the lipocytes of adipose tissue Rhabdomyoma: benign tumour of striated muscle Leiomyoma: benign tumour of smooth muscle cells Chrondroma: benign tumour of cartilage Osteoma: benign tumour of bone Angioma: benign vascular tumour

Question 30

Describe how malignant connective tissue and mesenchymal tumours are named

Answer 30

Known as sarcomas Liposarcoma: malignant tumour of lipocytes Rhabdomyosarcoma: malignant tumour of striated muscle Leiomyosarcoma: malignant tumour of smooth muscle Chondrosarcoma: malignant tumour of cartilage Osteosarcoma: malignant tumour of bone Angiosarcoma: malignant vascular tumour As with carcinomas, sarcomas can be further categorised to their grade or degree of differentiation

Question 31

Explain about Gliomas

Answer 31

Tumours arising from glial cells and may occur in the spinal cord or the brain. Gliomas are graded according to their likely rate of growth. Grades 1 and 2 are considered low-grade, are well-differentiated and usually associated with a better outcome. Grades 3 and 4 are undifferentiated or anaplastic and have a worse prognosis. Gliobastoma multiforme (GBM) is the most common and most aggressive type of primary brain tumour. It involves glial cells and has small areas of necrotising tissue surrounded by anaplastic cells. There are also hyperplastic blood vessels.

Question 32

Explain about Lymphomas

Answer 32

Cancer that starts in the lymph glands or other organs of the lymphatic system. There are many different types. Hodgkins disease Non-Hodgkins Lymphoma

Question 33

Explain about Hodgkins Disease

Answer 33

Principally a disease of the lymph nodes. Affected lymph nodes show partial or complete effacement (reduction) of normal features by a mixed infiltrate containing lymphocytes, macrophages, plasma cells and eosinophils as well as neoplastic cells. Typical classical Hodgkins Disease: large cells, heterogenous in appearance which may be mononuclear (Hodgkin cells) or bi- or multi-nucleated (Reed-Sternbeg cells). Collectively termed HRS cells, these share characteristic nuclear details with scanty chromatin and one or more prominent eosinophilic nucleolus.

Question 34

Explain about Non-Hodgkins Lymphoma

Answer 34

Group of lymphomas that are not Hodgkins lymphomas, they can vary from indolent (very slow growing) to very aggressive.

Question 35

Explain about Germ Cell tumours (teratomas)

Answer 35

A teratoma forms cells representing all three germ cell layers of the embryo. In their benign form, these cellular types are often easily recognised; the tumour may contain teeth and hair and on histology, respiratory epithelium, cartilage, muscle, neural tissue etc. In their malignant form, these representatives of ectoderm, mesoderm and endoderm may appear more immature and can be less easily identifiable. Teratomas occur most often in the gonads where germ cells are abundant. Ovarian teratomas are almost always benign and cystic. In the testis, teratomas are almost always malignant and relatively solid. As germ cells in the embryo originate at a site remote from developing gonadal teratomas arise occasionally elsewhere in the body, usually in the midline, possibly from germ cells that have been arrested in their migration. These extragonadal sites for teratomas include the mediastinum and sacroccygeal regions.

Question 36

Explain about Leukaemias

Answer 36

Neoplastic proliferations of white blood cell precursors, this proliferation results in the common features of leukaemia. Diffuse replacement of normal bone marrow by leukaemic cells with variable accumulation of abnormal cells in the peripheral blood. Infiltration of organs such as liver, spleen, lymph nodes, meninges and gonads by leukaemic cells.

Question 37

Compare Acute versus Chronic Leukaemia

Answer 37

Acute: Leukaemic cells do not differentiate, bone marrow failure, rapidly fatal if untreated, potentially curable Chronic: cells retain ability to differentiate, proliferation without bone marrow failure, survival for a few years, not presently curable without stem cell transplant.

Question 38

Explain about Multiple Myeloma

Answer 38

Malignant proliferation of plasma cells in bone marrow, Occurs in older age groups. Usually associated with the accumulation of monoclonal intact immunoglobulin or light chains in plasma and urine. The plasma cells synthesise a monoclonal immunoglobulin of light chain referred to as the M- component or paraprotein in plasma.