Growth Disorders

When I saw this lecture on the schedule, I thought we were going to be learning about gigantism, dwarfism, and so on. However, it turns out that "growth disorder" also means an abnormal proliferation of cells and tissue. What are these abnormal proliferations of cells and tissue? Read on...

Understand terminology of the common growth disorders and how this relates to biological behavior (reactive vs benign vs malignant processes)

• Mass- An aggregate of tissue that normally has a name ending in -oma (e.g. lipoma, haematoma, etc.)
• Tumour- A solid proliferation of cells. May or may not be a neoplasm- hernias and abscesses can be tumours, but they are not neoplasms.
• Neoplasia/neoplasm- Abnormal and excessive tissue growth from proliferating abnormal cells, due to underlying cellular and genetic alterations. Can be benign or malignant. Note that not all neoplasms are tumours: a leukaemia is a neoplasm, but since it is made of circulating cells and not a solid proliferation of cells, it is not a tumour.
• Hamartoma- A mass formed of cells that are native to the tissue, but are found in a disorganised arrangement. NOT a neoplasm.
• Ectopia- Normal tissue that is found at the wrong site. NOT a neoplasm.
• Benign- A "well-formed" neoplasm made up of specific cell types with an abnormal architecture. Benign tumours are not cancer and are generally not fatal, but they can be incredibly harmful if they press against vital structures (e.g. the brain stem). Benign neoplasms may or may not progress to malignancy.
• Malignant- A neoplasm that is able to invade other tissues, able to metastasise (spread to other sites in the body), and has unconstrained proliferation.
• Cancer- Proliferation of a malignant neoplasm.
• Dysplasia- A lesion with atypical features. May or may not progress to malignancy.
• Metastasis- Spread of a malignant neoplasm to another site in the body.

In addition to the above, make sure that you are familiar with the terms described at the end of the post on Cell Injury and Adaptations.

Understand principles of how neoplastic tumours are recognised and classified based on macroscopic, microscopic and genetic features

As mentioned in the definitions above, neoplasms can be benign or malignant. A benign neoplasm is more "well-formed" and tends to stay put whereas a malignant neoplasm can invade, metastasise, and/or proliferate uncontrollably. Many neoplasms are named after their tissue type, with a suffix of -oma for most benign neoplasms, a suffix of -carcinoma for malignant neoplasms that are epithelial-derived, and a suffix of -sarcoma for malignant neoplasms that are mesenchymal-derived. There are, however, exceptions: melanoma and myeloma (plasma cell malignancy) may both end in -oma, but they are both malignant tumours. Leukaemia is another malignant neoplasm that doesn't fit standard naming conventions.

Understand the basic principles behind development of neoplastic disease, including interactions between genetic and environmental factors

Cancer is thought to arise from an interaction between genetic susceptibility and exposure to initiating factors, such as carcinogens (something that can increase the risk of cancer). Note that exposure to a carcinogen doesn't mean that you will definitely get cancer- it just increases the risk. That is why some people like to say, "I smoked for XX years and I didn't get cancer!!!!"

Cancer also generally doesn't develop all at once. The Knudson hypothesis states that cancer is a multi-step process. At each step, there are mutations that affect important functions of the cell, such as cell growth, cell division, etc. As these mutations accumulate, cell growth and proliferation can get out of control.

There are four broad phases for the development of cancer. In the initiation phase, there are changes in a single cell. In the promotion phase, this cell proliferates in a process known as clonal expansion. As it divides and expands, some of the daughter cells acquire new mutations of their own. Eventually, during the conversion phase, there are critical new mutations that transform these abnormal cells into an invasive malignancy. Finally, during the progression phase, there are further mutations that may confer treatment resistance, metastastis, and loads of other fun things.

List the intrinsic barriers that exist to prevent cancer development and the capabilities that cancer cells acquire to overcome these barriers

Part of the reason why cancer doesn't happen all at once is because cells and tissues have ways to prevent cancer development. For instance, DNA repair mechanisms can prevent mutations from taking hold. Cancer eventually takes off when the cells have acquired mechanisms to bypass these barriers to development and proliferation. For instance, cancer cells can acquire the ability to survive without external growth signals, insensitivity to growth inhibition, resistance to apoptosis, increased activity of telomerases (enzymes that keep our telomeres from shrinking, thus preventing cellular aging), ensure their own nutrient supply by promoting angiogenesis (growth of new blood vessels), and so on.

Metastasis itself requires many mechanisms to bypass defences that would otherwise prevent spread of cells. Tumour cells might have proteinases that can degrade physical barriers or can gain the ability to attach to extracellular matrix proteins. There are many ways in which tumours can spread: directly, haematogenous (via blood), lymphatic (via lymph), or transcoelomic (via body cavities such as the peritoneum).

Understand the local and systemic effects of neoplastic disease

As mentioned earlier, even benign neoplasms can cause problems by pressing against other structures. Aside from this, there are many ways in which neoplasms can be problematic: they can result in weight loss, unexplained symptoms such as fever and night sweats, an increased risk of thrombosis, and so on. There are also paraneoplastic syndromes, which are basically the result of hormone-like substances being produced by tumour cells. For instance, a neoplasm that secretes renin (part of the system involved in regulating blood pressure) might cause hypertension. Note that neoplastic disease can manifest differently in different individuals, according to individual characteristics such as age. Furthermore, neoplasms in different locations (i.e. liver vs. lung) can manifest very differently.

Understand general principles of diagnosis and treatment of neoplasms

Ultimately, we want to be able to identify neoplastic disease earlier as that usually results in better treatment outcomes. This may be done through screening the population and/or identifying individuals at high risk. In terms of treatment, curative treatment is obviously ideal, but where that is not possible, treatment aims to slow the progression of the illness and/or alleviate symptoms.

There are several features of cells that can suggest malignancy. Malignant cells may have dark nuclei with irregular outlines and large nucleoli. The cytoplasm may have more mitochondria, glycogen, or other substances in it. Tissues may also show features of malignancy, such as necrosis, infarction (as the tumour outgrows the blood supply), invasion of other tissues, or abnormal architecture. There may also be symptoms that can be detected, such as weight loss, shortness of breath, or the paraneoplastic syndromes as mentioned earlier. Finally, genetic sequencing might be able to detect mutations that are common to particular tumours.

The severity of a neoplastic disease can be assessed by either grading or staging. Grading is a subjective assessment of how much the tumour cells look like normal cells (differentiation). (A complete loss of differentiation is called anaplasia.) Unfortunately, since grading is quite subjective, it only has a fair correlation with the outcome. Staging is a more objective assessment as it assesses how far a tumour has spread from the original site. Since it is more objective, it is good for research purposes and for ensuring consistency of care.