Title: The Dark Side of Growth: Neoplasia and Its Consequences

Authors: Jina Kum (Author)
Licence: CC BY-NC-SA 4.0

Neoplasia

The Dark Side of Growth:

NEOPLASIA

Courtesy of Farres Obeidin, M.D. and PathologyOutlines.com, see URL.

Funded by the Government of Ontario.
The views expressed in this publication are the views of the author(s) and do not necessarily reflect those of the Government of Ontario or the Ontario Online Learning Consortium.

Overview

Click on the audio button for narration.

OVERVIEW

- Benign vs Malignant Tumours
- Case Study: Armin Iravani
  - Physical Examination
  - Imaging
  - Histology
  - Risk Factors for Cancer

Introduction

Neoplasia refers to a new, abnormal growth of tissue. A neoplasm’s growth surpasses and is uncoordinated with the growth of surrounding normal tissue. Neoplasms can be either benign or malignant.

BENIGN TUMOUR

MALIGNANT TUMOUR

Localized

Rapid, uncontrolled growth

Well-differentiated cells

Cancerous cells; may be life-threatening

Do not invade surrounding tissues or metastasize to other sites

Invasive and able to metastasize to distant sites

Case Study

PATIENT PROFILE

1 pack year = Smoking 20 cigarettes (1 pack) per day for a year

- Name: Armin Iravani
- Age: 72
- Sex: Male
- Lifestyle Factors: Smoker
(40 pack years)
- Medical History: Type 2 diabetes, obesity, hypertension

Photo by Ali Ehyaei (Pexels, a Canva Germany GmbH). See URL.

Case Study - Narration

Hi Mr. Iravani, I’m Dr. Lee. What brings you to the clinic today?

[Image: Family doctor]

[Image: Patient]

Hi Dr. Lee. I have this lump on my left shin that I'm worried about. It doesn't hurt, but it's been growing slowly for the past 6 months.

[Image: Family doctor]

How did you notice the lump? Did you have any trauma, infection, or exposure to radiation or chemicals that could have caused it?

[Image: Patient]

No, I haven’t. I just felt it one day while I was changing my clothes. I thought it was nothing at first, but then I realized it was getting bigger.

[Image: Family doctor]

Do you have any other signs or symptoms, such as fever, weight loss, or fatigue?

[Image: Patient]

No, nothing like that.

[Image: Family doctor]

Do you have any medical history or family history of cancer or other diseases?

Smoking and obesity are risk factors for some types of cancer.

[Image: Patient]

I have hypertension and diabetes, and I take medication for them. I also smoke about a pack a day and am overweight. But no one in my family has ever had cancer, as far as I know.

Photo by Kindel Media (Pexels, a Canva Germany GmbH). See URL.

Photo by Ayşe İpek (Pexels, a Canva Germany GmbH). See URL.

Case Study - Physical Examination

Physical Examination

Mr. Iravani's left shin shows a firm, irregular, and non-tender mass about 10 cm in diameter. The overlying skin is normal, and there is no evidence of lymphadenopathy (swelling of lymph nodes caused by some malignancies) or edema (swelling caused by excessive interstitial fluid at the affected site). His vital signs and blood test results appear normal.

[Image: CT scanner]

I'm worried about the mass. I'm going to order more tests and imaging (either an MRI or a CT scan) to see how big it is, how clear its edges are, and if it affects any other parts of Mr. Iravani's body.

I also want to take a tissue biopsy and observe it under the microscope to see what type of cells make up the mass.

[Image: Family doctor]

Photo by MART PRODUCTION (Pexels, a Canva Germany GmbH). See URL.

Case Study - Findings from Imaging

Findings from Imaging

Imaging results reveal a large, irregular mass in the left shin with evidence of invasion into adjacent tissues. This prompts Dr. Lee to suspect a malignant neoplasm.

Figure 1: Clinical appearance and magnetic resonance imaging (MRI) features of a sarcoma (malignant tumour originating from mesenchymal cells, including connective tissues like bones, cartilage, and muscle) of the leg.
Figure from Riouallon, G., Larousserie, F., Pluot, E. & Anract, P. Superficial myxofibrosarcoma: assessment of recurrence risk according to the surgical margin following resection. A series of 21 patients. Orthop Traumatol Surg Res 99, 473-477 (2013). https://doi.org/10.1016/j.otsr.2012.11.020

Case Study - Histological Analysis

Histological Analysis

A core needle biopsy is performed, and microscopic examination reveals a proliferation of atypical, hyperchromatic cells with abundant cytoplasm. The cells show invasive growth patterns and appear to be originating from the mesenchymal (connective) tissues. Dr. Lee discusses these findings with the patient, explaining that the features are suggestive of a malignant tumour, specifically a sarcoma.

During embryonic development, mesenchyme differentiates into virtually all types of connective tissue, including bone, cartilage, and skeletal muscle.

A.

B.

Sheets of well-differentiated (mature) fat cells known as adipocytes, excessively proliferating

Multivacuolated lipoblasts (immature fat cells) with hyperchromatic, scalloped nuclei

A vacuole is a membrane-bound organelle. Vacuoles in adipocytes and lipoblasts are filled with lipids (fat).

Figure 2: A microscopic examination of the mass in the leg revealed abnormal proliferation of mature adipocytes and lipoblasts.
Figure from Raza, M., Vinay, H. G., Ali, M. & Siddesh, G. Bilateral paratesticular liposarcoma - a rare case report. J Surg Tech Case Rep 6, 15-17 (2014). https://doi.org/10.4103/2006-8808.135140

Case Study - Narration

[Image: Family doctor]

Mr. Iravani, I have the results of your biopsy and imaging tests. I'm afraid you have liposarcoma, which is a type of cancer that grows from fat cells.

[Image: Patient]

Oh no, that sounds serious. How bad is it?

Liposarcomas can be very aggressive and may spread to other parts of your body. The good news is that your tumor is localized to your leg and has not reached any vital organs. The bad news is that it is quite large and has invaded some of your muscles and blood vessels.

[Image: Family doctor]

[Image: Patient]

How do you treat it?

The best option is to surgically remove the tumor as soon as possible. This will reduce the risk of recurrence and metastasis. However, surgery alone may not be enough, as some tumor cells may remain in the surrounding tissues or escape into the bloodstream. So, you may also need additional therapies, such as radiation or chemotherapy, to kill any remaining or hidden cancer cells.

[Image: Family doctor]

Case Study - Narration & Grade vs Stage

[Image: Patient]

What are the chances of survival and recovery?

That depends on many factors, such as the grade and stage of your liposarcoma, age, general health, and your response to treatment. In general, the earlier the diagnosis and treatment, the better the prognosis. However, liposarcomas are unpredictable and can recur or metastasize even after successful treatment. Therefore, you will need regular follow-up and monitoring to check for any signs of recurrence or progression. I will refer you to a specialist who will discuss the details of your treatment plan and answer any questions you may have.

[Image: Family doctor]

GRADE

Describes the appearance of cancerous cells; the higher the grade, the more aggressive and faster cancer cells grow, and the less they resemble normal cells.

STAGE

Describes the size of a tumour and how far it has spread from its site of origin.

Case Study - Risk Factors

Risk Factors

Smoking: While there is not a direct link between smoking and liposarcomas, tobacco use can contribute to overall health issues that may impact the body's ability to resist and combat tumour growth.

Obesity: Associated with increased risk of various cancers, including sarcomas. The excess adipose tissue may create a pro-inflammatory environment, potentially promoting the development of certain tumours.

Note: In hematoxylin and eosin (H&E)-stained sections, the lipids stored in adipocyte vacuoles are washed away during tissue preparation, resulting in the white, empty space seen in histology slides.

Figure 3: Histology of adipose tissue. Image from the University of Leeds, https://www.virtualpathology.leeds.ac.uk/.

Case Study - Narration

[Image: Family doctor]

I have some more information about your condition. Reviewing your imaging and biopsy results more closely, I have noticed something unusual in the muscle tissue near your liposarcoma.

[Image: Patient]

What is it?

[Image: Family doctor]

Some of your muscle cells have changed their appearance and function. They have become more like cartilage cells, which are the cells that make up your joints. This is called metaplasia, which means that one type of cell transforms into another type of cell.

[Image: Patient]

How does that happen?

Metaplasia can happen when a cell is exposed to chronic irritation or inflammation, which makes it adapt to a different environment. In your case, it might be a reaction to the presence of the liposarcoma, which is causing damage and stress to the surrounding tissues. Metaplasia is not necessarily a bad thing, as it can help protect the cells from further harm. However, it can also affect the normal function and structure of the tissue, and sometimes it can progress to dysplasia or malignancy if the stimulus is not removed.

[Image: Family doctor]

Case Study - Narration

[Image: Patient]

What does that mean in terms of treatment?

It means that we need to be more careful and thorough when we remove your liposarcoma. We need to make sure that we get rid of all the tumor cells, as well as any metaplastic or dysplastic cells that may be present. We also need to monitor your condition closely after the surgery to check for any signs of recurrence or progression.

[Image: Family doctor]

Dr. Lee refers Mr. Iravani to an oncologist and a surgeon for a more comprehensive treatment plan and prognosis.

Knowledge Check

Neoplasms MCQ

Q: Which of the following is TRUE about neoplasms?
- A. The higher the stage of a tumour, the better the prognosis (patient outcome).
- B. Benign tumours can infiltrate adjacent tissues.
- C. Malignant tumours grow in coordination with surrounding tissue.
- D. The higher the grade of a tumour, the more abnormal cells are. (correct) (The answer is D. A higher stage of tumour indicates greater size and further extent of metastasis (spread). Benign tumours remain localized and are incapable of infiltrating adjacent tissues (by definition, only malignant tumours can invade). All neoplasms, both benign and malignant, grow out of coordination with surrounding tissue. Metaplasia is a reversible process and not necessarily indicative of malignancy, but can sometimes progress to malignancy.) (if not chosen: The answer is D. A higher stage of tumour indicates greater size and further extent of metastasis (spread). Benign tumours remain localized and are incapable of infiltrating adjacent tissues (by definition, only malignant tumours can invade). All neoplasms, both benign and malignant, grow out of coordination with surrounding tissue. Metaplasia is a reversible process and not necessarily indicative of malignancy, but can sometimes progress to malignancy.)
- E. Metaplasia is always characteristic of malignancies.

Knowledge Check

Malignant Tumour MCQ

Q: Which of the following is NOT a characteristic of an aggressive malignant tumour?
- A. Lack of differentiation
- B. Lymphadenopathy
- C. Localization (correct) (The answer is C because, by definition, malignant tumours invade other surrounding tissue and can even metastasize to distant parts of the body through lymphatics or vasculature. Cells of a high-grade malignant tumour would not resemble normal cells and likely show a lack of differentiation. Lymphadenopathy (swelling of lymp nodes) results from some malignancies, indicating metastasis. Edema may also result if a tumour blocks the lymphatic system, preventing the normal circulation of lymph throughout the body. Tumour cells originating from the leg being found in the liver indicates metastasis, which is characteristic of malignancy.) (if not chosen: The answer is C because, by definition, malignant tumours invade other surrounding tissue and can even metastasize to distant parts of the body through lymphatics or vasculature. Cells of a high-grade malignant tumour would not resemble normal cells and likely show a lack of differentiation. Lymphadenopathy (swelling of lymp nodes) results from some malignancies, indicating metastasis. Edema may also result if a tumour blocks the lymphatic system, preventing the normal circulation of lymph throughout the body. Tumour cells originating from the leg being found in the liver indicates metastasis, which is characteristic of malignancy.)
- D. Edema
- E. Tumour cells originating from the leg being found in the liver

Knowledge Check

Definition MCQ

Q: What is the change from one type of normal adult tissue into another type called?
- A. Atrophy
- B. Neoplasia
- C. Hyperplasia
- D. Sarcoma
- E. Metaplasia (correct) (The answer is E. Changing from one type of normal adult tissue into another (not necessarily abnormal) type of tissue is known as metaplasia. Atrophy refers to a decrease in cell size. Neoplasia refers to the development or presence of new, abnormal tissue growth. Hyperplasia refers to an increase in the number of cells in a tissue. Sarcoma refers specifically to a malignant tumour originating from mesenchymal cells (e.g., connective tissue).) (if not chosen: The answer is E. Changing from one type of normal adult tissue into another (not necessarily abnormal) type of tissue is known as metaplasia. Atrophy refers to a decrease in cell size. Neoplasia refers to the development or presence of new, abnormal tissue growth. Hyperplasia refers to an increase in the number of cells in a tissue. Sarcoma refers specifically to a malignant tumour originating from mesenchymal cells (e.g., connective tissue).)

Knowledge Check

Definition MCQ

Q: What is the most important feature to distinguish a malignant tumour from a benign tumour?
- A. The size of the tumour
- B. The site of the tumour
- C. Patient symptoms
- D. The extent of metastasis (correct) (The correct answer is D because only malignant tumours are capable of metastasis; benign tumours are not. The size and site of the tumour are insufficent to determine whether the growth is benign or malignant. Both benign and malignant tumours can grow large enough to press on other bodily tissues, resulting in similar patient symptoms, such as hemorrhage (bleeding), headaches, and localized pain or discomfort. By definition, any neoplasm (benign or malignant) shows abnormal growth patterns relative to normal tissue.) (if not chosen: The correct answer is D because only malignant tumours are capable of metastasis; benign tumours are not. The size and site of the tumour are insufficent to determine whether the growth is benign or malignant. Both benign and malignant tumours can grow large enough to press on other bodily tissues, resulting in similar patient symptoms, such as hemorrhage (bleeding), headaches, and localized pain or discomfort. By definition, any neoplasm (benign or malignant) shows abnormal growth patterns relative to normal tissue.)
- E. Abnormal growth patterns