Help! What Are They Talking About? (Part 3)

This is the third and final article in a series of three aimed at breaking down and defining some of the more common terms and concepts used in veterinary oncology.

The terms selected for this article all center around treatment and prognosis (how well a patient will do and how long they may live with a certain type of cancer or treatment). 

If you haven't had a chance to read the previous articles in this series, you may want to do so now. Here are the links: Part 1, Part 2.

I hope you find this article helpful. 

Part 3 - 

(1) Margins:
When a tumor is removed surgically, the surgeon should remove the tumor, plus a rim of (usually) 1-3 cm of normal-looking tissue around the tumor, in order to have a chance at removing all cancer cells in the area. Each type of tumor has a suggested measured margin (the surgeon can measure with a ruler) that the surgeon should achieve in order to obtain complete tumor removal. For benign tumors, 1 cm should be adequate. For soft tissue sarcomas, removing 3 cm of normal-looking skin around the tumor should be adequate.  This is why it is crucial for the surgeon to know what type of tumor is being removed PRIOR to the surgery.

The margins that we're specifically referring to in this definition are the margins that the pathologist measures when they're evaluating a tumor that's been removed and submitted to the lab. The pathologist's job is to measure the rim of tissue that the surgeon removed around the tumor. Specifically, they're measuring the distance between the edge of the tissue submitted and the nearest tumor cell they see.

Picture a circular tumor surrounded by an inch or so of skin. The pathologist will pick a few areas to evaluate from this sample and measure the distance between the edge and nearest tumor cells. If the distance is only 1 mm or less than, we would worry that the tumor may grow back (because there are probably still cancer cells left in the dog's skin). For most tumors, if the margin is at least 5 mm, it probably won't grow back locally. 

So what do we do if the margin is incomplete (tumor cells actually extend to the edge of the tissue evaluated by the pathologist) or narrow (tumor cells extend to 1 or 2 mm of evaluated margins)? In these cases, if we want to prevent the tumor from growing back at the surgery site, we could offer (1) a second surgery if we think there is more skin that can be removed, (2) local radiation to kill remaining cancer cells in the area, (3) electrochemotherapy to kill remaining cancer cells in the area. 

(2) Tumor recurrence:
When a tumor returns locally at the site of previous surgical removal. This happens when cancer cells were left behind after surgery, due to an incomplete surgery (the margins were narrow or incomplete). Over time, the cancer cells divide and multiply, forming a new tumor.

[Note that this is different than metastasis. Metastasis is when cancer cells spread to a distant location or organ. Metastasis can occur even after a complete and successful surgery has been performed. In these cases, the tumor cells have already entered blood vessels or lymphatics prior to surgery and have begun to travel elsewhere; these microscopic cancer cells are too few in number and too small to detect when a patient is evaluated for metastasis prior to surgery. This is why chemotherapy is recommended for patients (after surgery) that have highly metastatic tumors such as osteosarcoma; chemotherapy is meant to kill most of the cells that are traveling around the body in blood vessels and lymphatics.]

(3) Mitotic index:
The ratio of cells undergoing mitosis (viewed in metaphase under a microscope by a pathologist) in a tumor or biopsy sample vs those not in mitosis. It is customary to report this number as an average "per 10 high power fields". The mitotic index is a prediction of tumor behavior. The higher the number, the more aggressive we would expect a tumor to behave (more likely to metastasize, more likely to recur after narrow surgical removal). Oncologists use the mitotic index to help determine prognosis (how long a patient may live) and/or tumor grade for many types of tumors.

(4) Grade
In pathology, the grade is a measure of the cellular appearance of tumors. In veterinary oncology, different types of tumors are graded differently, but not all tumors are given a grade. The grade of the tumor is associated with prognosis (how long the patient may live after diagnosis).

If a tumor is assigned a low grade (1), it would suggest that the cells appear more organized and close to normal; these tumors typically grow slowly. Higher grade tumors (grade 3) have cell features that are disorganized; these cells appear very abnormal. Grade 3 tumors are more likely to metastasize, grow quickly and lead to the death of the patient. 

(5) Stage:
Stage refers to where cancer is located in the body. I wouldn't get hung up on learning the TNM staging system that they use in human oncology. In veterinary oncology, we typically just name the location where the tumor is located and/or has spread, instead of using a fancy number system. 

The "primary tumor" is the location where cancer started. If a dog develops a mast cell tumor in the skin on the left front leg (for example), that is the primary tumor. If the tumor spreads beyond the skin (to the lymph node in the left armpit), you would say that the patient has a mast cell tumor with axillary lymph node metastasis.

Typically, the further from the primary tumor cancer has spread, the worse the prognosis (and the more advanced the stage). 

(6) Chemotherapy:
Chemotherapy typically refers to the use of a drug (medication) to treat cancer. Traditional chemotherapy works by killing the rapidly dividing cells in the body. These include cancer cells but also cells in the bone marrow, gastrointestinal tract, and hair follicles (in some dogs). This is why we can see transient decreases in certain blood cells (neutrophils and platelets in particular) after chemotherapy, and also why some dogs will develop nausea or diarrhea a few days after treatment. Dogs that have continuously growing hair (those that need routine grooming) may develop a thin coat if they receive certain types of chemotherapeutics such as doxorubicin.  

Newer types of chemotherapeutics target certain markers on cells. These drugs often cause fewer side effects because they are more targeted and specialized.

Chemotherapy is used to treat cancers that can metastasize and those that are considered systemic (such as lymphoma) because it can access and kill cancer cells throughout the body.

Dogs are treated with significantly lower dosages of chemotherapy than humans. This is largely because the goal of veterinary oncology is to lengthen life but to improve or preserve the quality of life. The trade-off is that we cure fewer dogs than we do people with cancer.

(7) Radiation:
A type of cancer treatment that uses focused beams of energy to treat a localized area containing tumor cells. 

In order to ensure that a precise and localized area is treated, a CT scan in conjunction with 3D radiation planning software is used. This software helps the radiation oncologist create a radiation plan that only treats tissue suspected to contain tumor cells and spares "normal" tissue from receiving treatment, limiting side effects. 

(8) Electrochemotherapy:
A method of killing cancer cells and providing localized tumor control employing the use of an electroporator and intralesional chemotherapy. 

In most cases, chemotherapy is injected under the skin where we suspect there are tumor cells. An electroporator is then used to deliver electrical pulses to the heavily sedated (or anesthetized) patient, which causes cancer cell membranes to temporarily become leaky and allow a flood of chemotherapy inside the cell, killing it. 

If you are interested in learning more about electrochemotherapy (ECT), read our recent article, here.


Have questions about this article? Reach out!
Dr. Lori Cesario
Board Certified Veterinary Oncologist 

A few other articles you might enjoy...

(1) Osteosarcoma - The #1 bone cancer in dogs
(2) Mast Cell Tumors - The Great Imitator in Canine Cancer
(3) Canine Splenic Tumors - What You Need To Know


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