Chapter 1
1.1 Introduction of The Lymphatic System
The lymphatic system has three main functions. First, of the fluid that leaves the capillaries to deliver nutrients to the cells, only 90 percent returns back to the blood and the 10 percent stay to become a part of the interstitial fluid and then is called lymph. This will eventually lead to accumulation of the fluid in the tissue, which will mess up the osmotic pressure of the cell and the volume of the blood. Therefore, the lymphatic system intervenes to return excess interstitial fluid back to the bloodstream. The second function is the ability of the lymphatic system to absorb fat and fat-soluble vitamins from the digestive system. The third and the most popular function is its ability to defend the body against invading foreign particles and microbes such as viruses or bacteria. (National Cancer Institute, 2004)
1.1.2 the lymphatic system consists of:
1.1.2.a Lymph (fluid):
That is a fluid derived from blood plasma that enters the cells.
1.1.2.b Vessels to transport the lymph:
That only carries fluid away from the tissue, unlike blood vessels, which carry fluid to the tissue. The tiniest lymphatic vessels are called lymph capillaries. These capillaries are distributed all over the body except regions that lack blood vessels, such as the bone marrow, central nervous system (CNS), and tissues like the epidermis.
1.1.2.c Organs, which contain lymphoid tissues:
Are differentiated by having clusters of lymphocytes and other immune cells, such as macrophages, and branching connective lymphoid tissues. The lymphocytes originate from the bone marrow then differentiate into B-lymphocytes and T-lymphocytes. The B-lymphocytes get matured and educated in the bone marrow as well. Unlike the T-lymphocytes, that are developed and educated in the thymus, which is one of the lymphatic system organs. The lymphocytes proliferate inside the lymphatic organs and are transported in the blood to the site of the infection.
I. Lymph Nodes:
They are small bean-shaped structures that are widely distributed throughout the body where the filtration of the lymph occurs before it returns back to the blood. Lymph nodes are present in the groin and they are called inguinal nodes, in the armpit and they called the axillary nodes, and in the neck and are called the cervical nodes.
II. Tonsils:
They are clusters on lymphatic tissue beneath the mucous membrane that line the nose, mouth, and throat. They are divided into three groups according to their location. The pharyngeal tonsils, the palatine tonsils and the lingual tonsils. Lymphocytes and macrophages that are present in the tonsils grant protection against pathogens that may enter the body the opening of the mouth or nose.
III. Spleen:
It is similar to the lymph node’s morphology, however it is much larger and is located exclusively at one region, which is the body’s trunk. In fact, it is the largest lymphatic organ. The spleen consists of two tissue types, the white pulp and the red pulp. The white pulp is relatively related to the immune system as is contains mainly lymphocytes, while the red pulp is solely related to destroying any aged red blood cells.
IV. Thymus:
It is a gland situated behind the sternum and between the lungs. It is large and active only in childhood, and then after puberty, it starts to shrink and become replaced by fat tissues. The thymus gland secretes a hormone named Thymosin that stimulates the development of t-lymphocytes.
Figure 1.1: The anatomy of the lymphatic system.
1.1.3 History of Lymphoma
Lymphoma is a malignant disease in which lymphocytes that are cells of the immune system increase in number abnormally and uncontrollably into tumors accumulating in the lymph nodes, which will lead to destruction in the lymphatic system and eventually impair the immune system (Hoffbrand and Moss, 2011) (Cancer Research UK, 2014). Lymphoma can be classified into two main categories according to their morphology under the microscope, and the presence or absence of specific cells called Reed-Sternberg cells (RS cells), which are named after the two doctors who first identified them. RS cells are noticeably larger than normal lymphocytes. If RS cells were seen then it is most likely Hodgkin’s disease, however if RS cells were not seen then it is Non-Hodgkin’s disease. Additional tests may be performed to determine the specific type of lymphoma (Lymphoma Research Foundation, 2012).
Figure 1.2: Normal lymphocyte vs. Reed-Sternberg cell under the microscope
Hodgkin’s lymphoma is named after Thomas Hodgkin who was the first physician to encounter the first case of Hodgkin’s lymphoma in 1832 (Hoffbrand and Moss, 2011). There are different types of Hodgkin’s lymphoma classified by the way they appear under the microscope:
1.1.3.a Classic Hodgkin disease:
I. Nodular sclerosis Hodgkin disease.
II. Mixed cellularity Hodgkin disease.
III. Lymphocyte-rich Hodgkin disease.
IV. Lymphocyte-depleted Hodgkin disease.
1.1.3.b Nodular lymphocyte predominant Hodgkin disease.
This is crucial because each type of Hodgkin’s lymphoma may has a unique way of growth and spreading, therefore must be treated differently.
1.1.4 Types of Lymphoma
1.1.5 Pathogenesis of Lymphoma
1.1.6 Clinical Features
1.1.7 Epidemiology
1.1.8 Risk Factors
There are several factors that have shown some evidence in increasing the susceptibly of having Hodgkin lymphoma (HL) in some people more than others (Cancer Research UK, 2014):
a. Age and sex:
Statistics have proved that HL has clear bimodal (having two peaks) age distribution, with the first in incidence rates in young adults and the second one in older men and women. It is more common in males than females, as well.
b. Epstein-Barr virus (EBV):
c. Human Immunodeficiency virus (HIV):
d. Immune system-related conditions:
I. Organ transplant:
II. Autoimmune conditions:
e. Previous cancer:
f. Family history:
g. Overweight and obesity:
h. Height:
i. Tobacco:
1.1.9 Age distribution
1.1.10 Diagnostic Methods
1.1.11 Treatment
1.1.12 Introduction to EBV
EBV is the first carcogenic virus
1.1.13 History of EBV
In 1958, an Irish surgeon named Denis Burkitt was the first one to describe a type of cancer predominantly targeting children in certain areas of Africa. EBV was first
1.1.14 Molecular Biology
EBV belongs to herpesviridae family. It is a ubiquitous human gammaherpesvirus with a 184-kbp long, a single molecule of linear, double-stranded DNA genome encoding more than 85 genes, depending on the species. (Tompson and Kurzrock, 2004). EBV, like all other herpesviruses, has an icosahedral capsid surrounded by an envelope that is derived from the host’s nuclear membrane (Harvey et al, 2013).
Figure 1.3: Morphology of Herpes viruses
1.1.15 Pathogenesis of EBV
1.1.16 Clinical features of Mononucleosis Infection (Kissing Disease)
1.1.17 Epidemiology of Mononucleosis Infection
1.1.18 Burden & prevalence of EBV
1.1.19 Mode of Transmission
EBV can be transmitted easily by saliva through (National Center for Immunization and Respiratory Diseases, 2014):
a. Kissing (hence the name kissing disease).
b. Sharing drinks and food.
c. Using the same cup, eating utensils, or tooth brushes.
d. Having contact with toys that children have drooled on.
1.1.20 Diagnosis
1.1.21 Treatment
Recent Studies have shown an association between Hodgkin disease and Epstein-Barr virus (EBV). Now to understand its role in the pathogenesis, we must understand the background of the virus. EBV belongs to the herpesviridae family, gammaherpesvirinae group, class I. it is a large, icosahedral, spike-projection enveloped virus with dsDNA (Harvey et al, 2013). One thing to keep in mind is that once herpes virus has infected a patient, the infection persists for life. The primary infection may be followed by latency with subsequent reactivation.