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Malignant Neoplastic Diseases

Prepared for the U. S. RRB Disability Examiners February 10, 2015

Cancer is the uncontrolled growth of abnormal cells in the body.

Cancerous cells are also called malignant cells.

What is cancer?

Cells are the building blocks of living things. Cancer grows out of normal cells in the body. Normal cells multiply when the body needs them, and die when the body doesn't need them.

Cancer appears to occur when the growth of cells in the body is out of control and cells divide too quickly. It can also occur when cells “forget” how to die.

A neoplasm is a mass of cells arising from the abnormal growth of a transformed normal cell.

The transformation can be caused by viruses or radiation, but often the causes of the change from resting normal cell to growing transformed cell are unknown.

Neoplasm

The transformed cell has altered DNA, its normal tightly controlled cellular functions become disorganized, and its ability to control its growth is lost.

The degree of cellular disorganization determines whether the transformed cell (neoplasm) has behavior that is benign or malignant.

An accumulation of neoplastic cells that becomes large enough to be measurable is called a tumor.

The initial neoplastic transformation occurs in a single cell, but a single cell does not form a tumor.

Tumor

The transformed cell grows by successive doublings to create an ever increasing number of transformed cells until the number of accumulated cells is so great that a measurable mass is formed.

The original cell has now grown into a tumor.

The tumor can be either benign or malignant.

A benign tumor is so named because the transformed cells that form the tumor are capable of growth but are not capable of moving away from the location of the original transformed cell.

The transformed cells are fixed to one site and never spread through the body.

A benign tumor may grow very large and cause impairment from size alone, but rarely causes death.

Benign Tumor

A malignant tumor is so named because the transformed cells have the disastrous ability to move away from the site of the original transformed cell and spread throughout the body.

This movement away from the original site can take two different forms; either invasion or metastasis.

Malignant Tumor

A tumor is invasive when it grows into surrounding tissue. This is a major distinction between a benign tumor and a malignant tumor.

As a benign tumor grows, it will push against surrounding tissue, but will not grow into it. The distinction between where a benign tumor stops and surrounding tissue begins is very sharp.

A malignant tumor will have streams of transformed cells growing into surrounding tissue and the exact edge of the tumor is very fuzzy.

A tumor is metastatic when its cells can invade blood vessels or lymph vessels and then be carried away by the flow of the blood or lymph to other parts of the body.

If the cells are spread by the lymph flow, they will be carried first to near-by (local) lymph nodes, and ultimately to distant lymph nodes; this is termed lymphatic spread.

Spread to the near-by lymph nodes is called regional metastasis.

The lymphatic system filters fluid from around cells. It is an important part of the immune system. When people refer to swollen glands in the neck, they are usually referring to swollen lymph nodes.

Lymphatic System

Common areas where lymph nodes can be easily felt, especially if they are enlarged, are: the groin, armpits (axilla), above the clavicle (supraclavicular), in the neck (cervical), and the back of the head just above hairline (occipital).

If the cells are spread by the blood, they bypass the lymph nodes and are carried by blood flow directly to distant organs. This is called hematogenous spread.

The metastatic cells can lodge anywhere in the body and grow in their new location to form yet another tumor.

The new metastatic tumor is composed of cells that are identical to the original transformed cell and that have no relationship to any of the normal cells at the site of the metastasis.

Origin of the malignancy.

Extent of involvement

Duration, frequency, and response to antineoplastic therapy.

Effects of any post-therapeutic residuals.

Factors to Consider for severity

Need medical evidence that specifies the type, extent, and site of the primary, recurrent, or metastatic lesion.

Medical evidence

Key words to note in these group of Listings are inoperable, unresectable, persistent, Recurrent metastases beyond regional lymph node Malignant Neoplastic Diseases

Operative note.

Pathology report.

Crucial medical evidence

Gross examination of tissue and Microscopic examination of tissue reveals:

1. Primary site of tumor

2. Nature of tumor - benign or malignant, well or poorly differentiated, grade

3. Whether there is tumor at the surgical margins

Pathology reports

1. Carcinoma- organ parenchyma, skin, mucous membrane

2. Sarcoma – connective tissue or bone

3. Lymphoma – lymph node (primary)

4. Leukemia - blood Types of malignant neoplasm

There are two primary types of cancer: carcinomas and sarcomas. They differ in the kind of tissues they originate from.

Types of malignant neoplasm

Sarcomas include cancers of the:

Bone Muscle Fat Nerves Cartilage Fibrous tissue, such as ligaments and connective tissue

Sarcomas

Blood cancers Leukemia Lymphoma Myeloma

Comprise about only 1 percent of all cancers Affect both young and old people Grow in ball-like masses Spread by satellite nodules May spread to lungs

Carcinomas, on the other hand, originate in the epithelial tissue, such as the lining of the breast, lung, colon or prostate.

Carcinoma

This include cancers of the:

Breast Lung Kidney Thyroid Colon Prostate Stomach Many others

Carcinomas

Most common cancers in the world Comprise more than 90 percent of all cancers Primarily affect people age 50 or older Spread throughout body through blood and lymph May spread to lymph nodes, lungs and bones

Carcinoma

How well the malignant cell represents the cell of origin:

A. WELL DIFFERENTIATED – Retains enough of the characteristics of the cells of origin to be able to identify the site of origin.

B. MODERATLY DIFFERENTIATED – Retains some of the characteristics of the cells of origin.

C POORLY DIFFERENTIATED – Retains even fewer of the characteristics of the cells of origin.

D. UNDIFFERENTIATED (ANAPLASTIC) – Has lost most of the characteristics of the cells of origin.

CLASSIFICATION OF MALIGNANT NEOPLASMS- DIFFERENTIATION

Aggressiveness of the tumor:

A. GRADE I – Least aggressive

B. GRADE II – More aggressive

C. GRADE III – More aggressive than grade II, or most aggressive, depending on the grading system

D. GRADE IV – Most aggressive

CLASSIFICATION OF MALIGNANT NEOPLASMS - GRADE

Size and extent of spread STAGE 0 – In situ

STAGE I – Localized tumor

STAGE II – Beginning regional

STAGE III – Late regional

STAGE IV – Usually distant metastases

CLASSIFICATION OF MALIGNANT NEOPLASMS - STAGING

The TNM system is one of the most commonly used staging systems. This system has been accepted by the International Union Against Cancer (UICC) and the American Joint Committee on Cancer (AJCC).

Most medical facilities use the TNM system as their main method for cancer reporting. PDQ®, the NCI’s comprehensive cancer database, also uses the TNM system.

CLASSIFICATION OF MALIGNANT NEOPLASMS – The TNM System

The TNM system is based on the extent of the tumor (T), the extent of spread to the lymph nodes (N), and the presence of metastasis (M).

A number is added to each letter to indicate the size or extent of the tumor and the extent of spread.

CLASSIFICATION OF MALIGNANT NEOPLASMS – The TNM System

TX Primary tumor cannot be evaluated

T0 No evidence of primary tumor

Tis Carcinoma in situ (early cancer that has not spread to neighboring tissue)

T1, T2, T3, T4 Size and/or extent of the primary tumor Primary Tumor -T

NX Regional lymph nodes cannot be evaluated

N0 No regional lymph node involvement (no cancer found in the lymph nodes)

N1, N2, N3 Involvement of regional lymph nodes (number and/or extent of spread) Regional Lymph Nodes (N)

MX Distant metastasis cannot be evaluated

M0 No distant metastasis (cancer has not spread to other parts of the body)

M1 Distant metastasis (cancer has spread to distant parts of the body)

Distant Metastasis (M)

For many cancers, TNM combinations correspond to one of five stages.

Criteria for stages differ for different types of cancer.

For example, bladder cancer T3 N0 M0 is stage III; however, colon cancer T3 N0 M0 is stage II.

Stage 0 Carcinoma in situ (early cancer that is present only in the layer of cells in which it began).

Stage I, Stage II, and Stage III Higher numbers indicate more extensive disease: greater tumor size, and/or spread of the cancer to nearby lymph nodes and/or organs adjacent to the primary tumor.

Stage IV The cancer has spread to another organ.

Stage Definition

For tumors with distant metastases that are expected to respond to antineoplastic therapy:

Longitudinal record of 3 months after therapy starts to determine whether the intended effect of therapy has been achieved and is likely to persist.

Longitudinal evidence

When there are no distant metastases, many of the listings require that we consider response to initial antineoplastic therapy; that is, the initial planned treatment regimen.

This initial therapy may consist of a single modality or a combination of modalities (multimodal) given in close proximity as a unified whole, and is usually planned before any treatment(s) is initiated.

In many cases, malignancies meet listing criteria only if the therapy does not achieve the intended effect: the malignancy persists, progresses, or recurs despite treatment.

In many malignancies, the diagnosis alone may meet the Listing in and of itself because of the severity and the poor prognosis of the cancer Cancers that meet the Listings

Acute leukemia (including T-cell lymphoblastic lymphoma)

Chronic myelogenous leukemia in Accelerated or blast phase.

Anaplastic (undifferentiated) carcinoma of the thyroid gland.

Examples

Locally advanced carcinoma (inflammatory carcinoma) of the breast

Highly malignant tumors, such as Grades III and IV astrocytomas, glioblastoma multiforme, ependymoblastoma, medulloblastoma (Brain)

Small-cell (oat cell) carcinoma. (lungs)

Malignant mesothelioma of pleura.

Carcinoma or sarcoma of the esophagus.

Liver or Gallbladder- tumors of the liver, gallbladder, or bile ducts.

Carcinoma of the pancreas

Surgical Destruction

• Surgery

• Cryotherapy

• Radio-frequency ablation

Treatment for malignancies

The mechanism of destruction in cryotherapy (cryosurgery) is necrosis (“killing the tissue), which results from the freezing and thawing of cells.

Cryotherapy

In radiofrequency ablation (RFA), heat is generated locally by a high frequency, alternating current that flows from the electrodes. A probe is inserted into the center of the tumor and the non-insulated electrodes, which are shaped like prongs, are projected into the tumor.

Radiofrequency Ablation

Irradiation

• External beam radiation

• Brachytherapy

• Radio-iodine therapy

External beam radiation therapy uses high-energy rays (or particles) to destroy cancer cells or slow their rate of growth. A carefully focused beam of radiation is delivered from a machine outside the body.

Brachytherapy is a minimally invasive procedure where the doctor implants tiny permanent radioactive seeds (about the size of a grain of rice) into the prostate where they irradiate the cancer from inside the gland.

The seeds remain in the prostate, where the radioactive material gives off localized radiation for a number of months to destroy the prostate cancer.

Systemic Drug Therapy

• Chemotherapy

• Hormonal therapy

• Immunotherapy

Bone Marrow or Stem Cell Transplantation

• Autologous

• Syngeneic

• Allogeneic

When a person receives stem cells that have come from their own blood, it is referred to as an autologous transplant.

An allogeneic transplant is when the stem cells come from someone other than the person who requires them.

Stem cell Transplant

Stem cell are cells with the ability to divide for indefinite periods in culture and to give rise to specialized cells.

They have the remarkable potential to develop into many different cell types in the body during early life and growth.

Stem cells

In addition, in many tissues they serve as a sort of internal repair system, dividing essentially without limit to replenish other cells as long as the person or animal is still alive.

When a stem cell divides, each new cell has the potential either to remain a stem cell or become another type of cell with a more specialized function, such as a muscle cell, a red blood cell, or a brain cell.

Stem cells

Bone Marrow Transplant

A benefit of an autologous transplant is that the body is able to recognize the stem cells and therefore does not attack them or reject them (graft-versus-host disease or GVHD).

Transplant

For some diseases, like leukemia, an allogeneic transplant is the preferred method.

However, a person who receives an allogeneic transplant will require heavy medication in order to avoid GVHD.

Allogeneic transplantation. Consider under a disability until at least 12 months from the date of transplantation. Thereafter, evaluate any residual impairment(s) under the criteria for the affected body system.

Autologous transplantation. Consider under a disability until at least 12 months from the date of the first treatment under the treatment plan that includes transplantation.

Thereafter, evaluate any residual impairment(s) under the criteria for the affected body system.

In using autologous bone marrow or stem cell transplantation to support intense chemotherapy, it is general practice to treat the individual with one or two cycles of "standard" chemotherapy to demonstrate some tumor responsiveness to treatment.

A cancer that is totally unresponsive to standard chemotherapy is unlikely to respond successfully to therapy using autologous bone marrow or stem cell support.

If the therapy plan consists of several cycles of standard chemotherapy to be followed by bone marrow or stem cell transplantation, the date of "first treatment" is the date of the first standard chemotherapy.

If there is no standard chemotherapy planned prior to the bone marrow or stem cell transplantation, the date of "first treatment" is the date of the transplant.

Chemotherapy (or other treatment) given prior to planning for the bone marrow or stem cell transplantation is not considered when we determine the date of "first treatment."

Surgery Disfigurement

Loss of function

Lymphedema

Side Effects of Treatment

Irradiation Edema

Extreme skin dryness and burns

Radiation cystitis or enteritis

Pulmonary fibrosis

Stunted growth

Chemotherapy Nausea, vomiting, alopecia (hair loss)

Decreased blood counts--anemia, thrombocytopenia, neutropenia

Cardiotoxic effects

Severe infection

Neurotoxic effects

Immunotherapy

Hormonal Therapy Blood clots

Osteoporosis

Uterine cancer

Vaginal bleeding

Breast tenderness

Increase in breast size

Bone Marrow/Stem Cell Transplant

Graft versus host (GVH) disease

Liver disease

Because the severity of the adverse effects of antineoplastic therapy may change during treatment, enough time must pass to allow us to evaluate the therapy's effect.

The residual effects of treatment are temporary in most instances.

Consider an impairment(s) that meets or medically equals a listing in this body system to be disabling until at least 3 years after onset of complete remission.

Diary

When the impairment(s) has been in complete remission for at least 3 years, that is, the original tumor and any metastases have not been evident for at least 3 years, the impairment(s) will no longer meet or medically equal the criteria of a listing in this body system.

Diary

To establish the existence of a disabling impairment prior to the date of the evidence that shows the malignancy satisfies the criteria of a listing the following factors have to be considered:

1. The type of malignancy and its location.

2. The extent of involvement when the malignancy was first demonstrated.

3. the symptoms.

Onset

Inoperable:

Surgery is thought to be of no therapeutic value or the surgery cannot be performed; for example, when one cannot tolerate anesthesia or surgery because of another impairment(s), or the tumor is too large or has invaded crucial structures.

Terminology

This term does not include situations in which the tumor could have been surgically removed but another method of treatment was chosen; for example, an attempt at organ preservation.

The physician may determine whether a tumor is inoperable before or after neoadjuvant therapy.

Neoadjuvant therapy is antineoplastic therapy, such as chemotherapy or radiation, given before surgery in order to reduce the size of the tumor.

Metastases: The spread of tumor cells by blood, lymph, or other body fluid.

This term does not include the spread of tumor cells by direct extension of the tumor to other tissues or organs.

Multimodal therapy: A combination of at least two types of treatment modalities given in close proximity as a unified whole and usually planned before any treatment has begun.

There are three types of treatment modalities: Surgery, radiation, and systemic drug therapy (chemotherapy, hormonal therapy, and immunotherapy).

Examples of multimodal therapy include:

a. Surgery followed by chemotherapy or radiation.

b. Chemotherapy followed by surgery.

c. Chemotherapy and concurrent radiation

Unresectable: Surgery was performed, but the malignant tumor was not removed. This term includes situations in which the tumor is incompletely resected or the surgical margins are positive.

It does not include situations in which a tumor is completely resected but adjuvant therapy is being done.

Adjuvant therapy is antineoplastic therapy, such as chemotherapy or radiation, given after surgery in order to eliminate any remaining cancer cells and lessen the chance of recurrence.

Brain tumors. We use the criteria in 13.13 to evaluate malignant brain tumors.

We consider a brain tumor to be malignant if it is classified as grade II or higher under the World Health Organization (WHO) classification of tumors of the central nervous system (WHO Classification of Tumours of the Central Nervous System, 2007 WHO classification of tumors

The 2007 WHO classification is based on the consensus of an international Working Group of 25 pathologists and geneticists, as well as contributions from more than 70 international experts overall, and is presented as the standard for the definition of brain tumors to the clinical oncology and cancer research communities world-wide.

WHO

Please refer to the handout on the WHO classification.

WHO

THE END

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