Lymphoma is one of the most common cancers in the world, and it is the most common blood cancer, It has two main types, one of them is Hodgkin lymphoma.
Cancer treatment and diagnosis methods have developed in Turkey to become a destination for many cancer patients around the world.
Cancer is the proliferation of defective, deformed cells at the expense of healthy cells, and it has serious consequences if treatment is neglected.
What is lymphoma?
The concept of lymphoma (or what is known as cancer of the lymphocytes), was derived from the cells affected by the disease, which are lymphocytes (a type of white blood cell), especially type B lymphocytes (therefore, it is classified as a blood cancer), where lymph refers to lymphocytes and oma suffix means tumor so we get the meaning of "Tumor from lymphocytes".
Lymphomas usually develop when a change or mutation occurs within lymphocytes, causing the abnormal (neoplastic) cell to multiply faster than normal lymphocytes or to live longer and not undergo programmed cell death (Apoptosis).
Cancerous lymphocytes can travel through the blood and lymph system and spread and grow in many parts of the body, including the lymph nodes, spleen, bone marrow and many other organs.
Lymphomas are divided into two main categories: Hodgkin's lymphoma(It was called Hodgkin's disease): It includes certain cell types characteristic of this disease (we will mention them later). Non-Hodgkin lymphoma: These are all tumors that do not fall under the classification of Hodgkin lymphoma.
Each type spreads, divides and responds to treatment differently, so it is necessary to know which type the patient has to choose the optimal treatment plan, whether for Hodgkin's tumors or non-Hodgkin's tumors.
Overview of the lymphatic system and lymphocytes
Before we talk about the pathological or cancerous state of the cells and the lymphatic system, we will mention an overview of the normal physiological state of the lymphatic system and lymphocytes.
The lymphatic system is an important part of the immune system in the human body and it rids the body of many toxins and eliminates many pathogens that attack the body.
The lymphatic system consists of the lymph, lymph vessels, lymph nodes, bone marrow, spleen, thymus gland, and tonsils.
B and T lymphocytes arise from the bone marrow (which is a primary lymphoid organ) and are initially precursors and then develop into mature lymphocytes in the same bone marrow for type B, while T cells develop in thymus.
The mature B cells then migrate to the lymph nodes (secondary lymphoid organs) where they gather as follicles in the lymph node cortex.
Whereas, mature T cells gather in the paracortex.
On the surface of B lymphocytes, there are protein complexes called CD (cluster of differentiation) with different numbers that act as markers that identify the body's cells and help your body distinguish different types of cells.
B cells in the normal state express CD20 and CD45.
In the event that an antigen is attached to the surface of the B cell, this cell activates, and some of it develops into plasma cells that secrete IgM, and some of them travel to the center of the lymph node and develop into a centroblast, the centroblast then divides and multiplies and forms what is known as the germ center, where A rearrangement of the immunoglobulin genes for these cells occurs and they become centrocytes, some of which secrete IgA and others IgG.
The centrocytes then differentiate into either plasma cells or memory cells, and the latter circulates in the blood, where part of it remains, or settles in the spleen or in the mucosa-associated lymphoid tissue known as MALT.
Hodgkin's disease is a type of lymphoma, named after the English physician Thomas Hodgkin who first described it.
Hodgkin's lymphoma occurs when the immunoglobulin genes in type B lymphocytes are abnormally rearranged, in which the defective cells divide uncontrollably and become nonfunctional tumor cells.
According to the National Cancer Institute (NCI) in the USA, approximately 9,000 new cases of Hodgkin lymphoma are diagnosed each year.
Although this cancer can occur in both children and adults, it is more commonly diagnosed in young adults between the ages of 15 and 35 and in older adults over 50.
Hodgkin's lymphoma is less common than non-Hodgkin lymphoma.
Although Hodgkin's lymphoma can start almost anywhere, it most often arises in the upper lymph nodes of the body.
The most common sites are in the thoracic, cervical or axillary nodes.
Hodgkin's lymphoma often spreads through the lymphatic vessels, where it travels from one node to another.
Rarely, in advanced cases, it spreads to extranodal sites through the blood, such as the bone marrow, the lungs, or anywhere in the body.
What is the difference between Hodgkin's lymphoma and non-Hodgkin's lymphoma?
The main difference between the two types is the cell types seen on microscopic examination.
Where distinct cells of Hodgkin lymphoma are seen called Reed-Sternberg cells, which are large multinucleated cells (often arising from the union of two lymphocytes with each other) and give the appearance of owl eyes.
Reed-Sternberg cells are often surrounded by an inflammatory infiltrate of T lymphocytes. Reed-Sternberg cells activate fibroblasts and eosinophils and secrete cytokines, leading to collagen production, lymphocyte attraction, and lymph node swelling seen in most patients with Hodgkin's lymphoma.
We also see Hodgkin's cells, which are large and mononuclear cells.
There is a difference in the development and spread of the disease between the two types, as we do not see Hodgkin's lymphoma outside the lymph nodes except in rare cases, unlike non-Hodgkin's lymphoma, which is often seen outside the lymph nodes.
Causes and Risk factors
Despite the huge evolution in the studies conducted on tumor cells and studies to know the reason for their emergence in Turkey, the cause of Hodgkin lymphoma remains unclear until now, and various studies and researches are still being conducted to find out the reason for this change in the genes of lymphocytes or what triggers the uncontrolled random division.
Some scientists attribute this change in lymphocyte DNA to infection with the Epstein-Barr virus (EBV), but many patients with Hodgkin's lymphoma have not tested positive for this virus.
Some other risk factors include:
Age and Gender
The disease can appear at any age, but the incidence of infection increases in the early adulthood stages (in the twenties) and after the age of 55 years.
The incidence of infection is slightly higher in males.
A family history of a previous injury
The association of genetics and the presence of a previous family history with the high incidence of Hodgkin's lymphoma remains a subject of wide debate and controversy.
The incidence of Hodgkin lymphoma increases when there is a brother, sister, father... infected in the family. Some researchers indicate that this rise is due to the exposure of the same family to the same external stimuli (such as the Epstein-Barr virus for example), the presence of some similar genes and many other factors.
Weakened immune system
The incidence of Hodgkin's lymphoma increases in people infected with HIV.
It also rises in patients taking immunosuppressive drugs.
As the body's ability to get rid of defective cells is impaired, these causes also lead to a change in the genes of many cells and the occurrence of carcinogenic mutations.
Ironically, common infections in children can reduce the incidence of Hodgkin's lymphoma because of the immune changes that occur as a result of these infections.
Symptoms and Signs
Symptoms vary with the severity of the disease and its spread to several lymph nodes, symptoms usually include:
Painless swelling of the cervical, mediastinal, and inguinal lymph node or site of injury
Fever of unknown cause
Profuse night sweats
Unexplained weight loss
Feeling very tired most of the time
Pain in the lymph nodes after drinking alcohol
Cough and other respiratory symptoms
Symptoms (weight loss, unexplained fever, night sweats) are the so-called (B symptoms) and are essential in evaluating a patient's cancer stage and in determining the rate of recovery or relapse.
Children may have difficulty breathing, especially when lying down.
Types of Hodgkin's Lymphoma
Hodgkin's cancer is classified into two main types:
Classical Hodgkin's lymphoma
It is the most common type and accounts for approximately 93% cases of Hodgkin lymphoma.
In which the neoplastic cells express CD15 and CD30 instead of the CD20 and CD45 seen in the normal condition.
There are several sub-types of this type, namely:
Nodular Sclerosis Hodgkin's Lymphoma
It is the most common type of classical Hodgkin's lymphoma, with a rate of 80% of all cases.
In this type we see Reed-Sternberg Cells (RSCs) surrounded by normal white cells, and as a result of the activation of fibroblasts by RSCs and collagen production, fibrosis occurs within the affected lymph node, the RSCs here are called Lacunar cells.
Mixed Cellularity Hodgkin's Lymphoma
The inflammatory (non-neoplastic) infiltrate is composed of eosinophils, neutrophils, and lymphocytes.
Lymphocytes-Rich Hodgkin's Lymphoma
It has the best prognosis of these types.
As the name indicates, lymphocytes are dominant in the inflammatory arena.
Lymphocytes-Depleted Hodgkin's Lymphoma
It is the rarest and has the worst prognosis.
Where lymphocytes are absent or scarce, with a large number of tumor cells, whether RSCs or Hodgkin's cells.
Nodular lymphocyte predominant lymphoma
It is very rare and often does not present specific symptoms.
In which the neoplastic cells express CD20 and CD45 in contrast to the classic type.
In it, the nucleus of the RS cell appears as a cauliflower or a popcorn, so it is called in this type the Popcorn Cell.
Diagnosing Hodgkin's lymphoma in Turkey
Early detection of the disease did not show any improvement in the cure rate for patients with Hodgkin's lymphoma.
Pathological history and clinical examination: The symptoms seen in Hodgkin's lymphoma are looked for, and the most common are swollen lymph nodes.
Complete Blood Count (CBC) and white cell formula.
Several blood tests: LDH, ESR, HIV antibody titer, HCV and HBV antibody titer.
Medical Imaging: CT scan, simple chest x-ray, positron emission tomography (PET) scan, magnetic resonance imaging (MRI).
Lymph node biopsy: It is used to confirm the diagnosis as the lymph node can swell for several reasons (such as infections), and a biopsy can also determine the type of Hodgkin's lymphoma present in the patient.
Bone marrow biopsy: It is not used in diagnosing the disease, but in post-diagnosis tests to find out whether the disease has spread to the bone marrow or not and how bad the condition is.
Hodgkin's Lymphoma Staging
Determining the stage of lymphoma helps in choosing the appropriate treatment plan, the patient's recovery rate, and the expectation of recurrence after treatment or full recovery.
The classification of any cancer is a complex process that mainly depends on the experience of the doctor and his ability to choose the appropriate treatment for each patient, so we will not go into detail about the staged classification too much, but we will mention the main points.
The Lugano Staging classification is used here. Based on this classification, Hodgkin's Lymphoma is divided into four stages:
The disease is present in a single node or group of nodes of one location or in a single lymphoid organ.
Or the cancer is only present in one part of one organ outside the lymphatic system.
Cancer is in two groups of lymph nodes either above or below the diaphragm, or has spread to a nearby organ of the affected node.
Cancer affects two groups of lymph nodes above and below the diaphragm, or it affects a nodular group above the diaphragm and spleen.
The cancer has spread extensively to other organs that are not close to or near the affected lymph nodes.
It most commonly spreads to the liver, bone marrow, and lungs.
Hodgkin lymphoma treatment in Turkey
Hodgkin's lymphoma has a very high rate of recovery and improvement compared to other leukemias or even its sister non-Hodgkin lymphoma.
New treatments in Turkey have achieved rates that exceed expectations in terms of recovery and increased survival, and diagnostic and investigation methods have been developed, and awareness campaigns have spread about this disease.
After successful and effective treatment, patients with Hodgkin's lymphoma can live a long, healthy life with little to no problems.
Hematomas, especially Hodgkin's lymphoma, offer great diversity in the cellular arena and extent of spread, so there are many treatment options and protocols.
Treatment is based mainly on the non-surgical treatment, where the removal of lymph nodes in this disease does not give good results and does not help in curing the disease.
Surgery may be used for investigational reasons, such as taking a biopsy.
Splenectomy can be useful in some cases, but this option remains dependent on the doctor's opinion and consideration and whether the patient's general health allows it or not.
It is the preferred and most common treatment for lymphoma, and for Hodgkin's lymphoma in particular.
Usually Chemotherapy is given either orally or intravenously, as it kills cancer cells or prevents their division, but the drugs given affect any rapidly dividing cell (such as hair cells), which gives many side effects of chemotherapy.
Medicines are given in cycles to relax the body in the period between cycles, where each cycle lasts a week or several weeks.
Usually, a number of medicines are shared to give better results. We mention the most common combination, which is an abbreviation for the first letter of the name of each medicine:
Of course, there are many other combinations, but this combination is widely used and the most effective one.
It should be noted that if the patient is pregnant, we will not be able to protect the fetus from the effects of chemical drugs, and many deformities may occur in the fetus.
As a result, many clinical trials have been conducted to find out which drugs have the least effect on the fetus.
Studies have shown that Vinblastine didn't cause any malformations if given in the last two trimesters of pregnancy.
The aim of Immunotherapy in Turkey is to stimulate or help the body's defenses (particularly killer T lymphocytes) to kill and eliminate tumor cells.
An example of Immunotherapy is:
Inhibitory therapy for PD1 and PD-L1
PD1 is a surface protein found on the surface of killer T cells and PD-L1 (found on the surface of some tumor cells) binds with PD1 preventing the tumor cell from being destroyed.
Therefore, this treatment works to inhibit or prevent this association, which helps the immune system to get rid of tumor cells.
Radiation therapy uses high-energy X-rays to kill and destroy tumor cells.
Radiation therapy is usually combined with other treatments as it is given after or before chemotherapy as required by the patient's condition.
Targeted therapy is one of the most successful, accurate, and has the least side effects of all treatments. It is similar to chemotherapy, except that it is more precise as it targets only tumor cells, making it the preferred option in many cases.
of its types:
Antibody-Drug Conjugate (ADC
It is a synthetic antibodies combined with a chemotherapy drug. The antibodies recognize and bind to surface proteins on the surface of tumor cells such as CD30 (mentioned earlier) and then release the chemical drug to kill the tumor cell.
The most famous of these drugs is Brentuximab Vedotin,It is a compound used in many joints with other chemotherapy drugs to increase the rate of cure and decrease the rate of relapse of the disease.
These are lab-made antibodies that are similar to those of the human immune system and work the same way as ADCs.
The most famous of these drugs is Rituximab.
This treatment uses monoclonal antibodies loaded with doses of radiation to kill tumor cells.
Stem cell transplant (bone marrow transplant)
This method allows the doctor to give high doses of chemotherapy as it increases the rate of eliminating tumor cells but destroys the normal cells that produce blood cells, but in this case, after giving a dose of chemotherapy for a certain period, the doctor Injects stem cells into the bone marrow To replace the destroyed normal cells, thus relieving symptoms and shortage of blood cells.
Generally speaking, Stem Cells are immature cells that are usually taken from the same patient in an earlier period of his life, and in the absence of them, they can be taken from a person with similar genes (such as a sister, father, or…).
As we have seen, the treatment methods are many and complex, and each patient has his own treatment protocol.
Hodgkin's Lymphoma Awareness Month
In the ninth month of each year, an awareness campaign is conducted to educate patients about Hodgkin's lymphoma, and on the 15th day of this month.
The symptoms of Hodgkin lymphoma and what patients usually suffer from is described and doctors encourage regular check-ups for all patients, especially those with some of the symptoms mentioned earlier and high-risk patients.
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The main difference is the type of cells and the spread of cancer outside the lymphatic system. In Hodgkin's lymphoma, we see Reed-Sternberg cells and Hodgkin's tumor cells, and the disease is often limited to the lymphatic system.
Unlike non-Hodgkin's lymphoma, which is often diagnosed outside the lymphatic system and does not contain precancerous cells.
It is a monoclonal antibody loaded with a chemical drug (Antibody-Drug Conjugate ADC) and is a quantum leap in the treatment of lymphoma, especially Hodgkin's lymphoma, as it targets surface proteins on the surface of tumor cells and releases the chemical drug to kill them.
Any cancer poses a threat to the patient's life if treatment is neglected. But Hodgkin lymphoma has a high cure rate, especially in Turkey, after the development of diagnostic and treatment methods significantly in its hospitals.
The five-year survival rate is often between 80-90 percent of cases where lymphoma has not spread to distant organs.
In the event of metastases, this percentage decreases according to the case, the number of metastases, and their location.