Lymphoma and Myeloma

What is the lymphoid tissue?

The defense cells involved in the immune response are organized into tissues and organs that are collectively recognized as the lymphatic system. The primary lymphoid organs are the bone marrow and the thymus. All defense cells are produced within them from specific progenitor lineages. The secondary lymphoid organs, on the other hand, are responsible for the cell maturation process and include the spleen, the lymph nodes, which are distributed in various areas in the body, and the lymphoid tissue associated with mucous membranes. The latter are represented by Peyer’s patches in the intestine, the appendix, the lymphoid tissue associated with the bronchi, and the amygdala with the adenoids, and are arranged in the main antigen entry pathways of the human body, making up the first line of defense. All these structures are connected by a complex network of vessels called the lymphatic network. Lymph is a clear liquid derived from plasma. It fills this system of communicating vessels, through which the body’s defense cells circulate, parallel to the bloodstream.

What is the lymphatic system function?

The primary function of the lymphatic system is to protect the body from infection or any other potential aggressors. It is distributed to the most strategic points in the body, mainly in the form of lymph nodes. Lymph nodes are the sentinels of the human body. They are small encapsulated nodular structures, containing millions of mature lymphocytes inside, ready to recognize enemy proteins and trigger the immune response. Lymphocytes play a central role in modulating the immune system and coordinate an army of highly specialized cells to fight off aggressors.

What is lymphoma?

Lymphocytes are cells that actively participate in the body’s defense and are the main cellular constituents of the lymphatic tissue. Under normal conditions, lymphoid progenitor stem cells contained in the spleen and thymus develop into B and T lymphocytes, respectively. Once formed, these structures accumulate in the secondary lymphoid organs, represented by the lymph nodes, spleen, and mucosa-associated lymphoid tissue, where they become mature cells and are assigned a specific function. B lymphocytes are responsible for humoral, antibody-mediated immunity, while T cells act in a cytotoxic manner.

Lymphoma occurs when a lymphocyte assumes malignant behavior. It loses the ability to control its replication mechanisms and begins a process of uncontrolled proliferation. Thus, a huge number of immature and dysfunctional clones circulate through the lymphoid system, with lethal potential.

Lymphomas can derive from B lymphocytes, T lymphocytes, or Natural Killers (NK) cells, the former being the most common situation. In general, they start in the lymph nodes. The pattern of dissemination, however, is highly variable, and can respect chain sequences or affect ganglia randomly. Eventually, they can appear in other areas that contain lymphatic tissue, such as the liver, spleen, and lung, for example. In advanced stages, they occasionally even infiltrate the bone marrow, assuming a behavior similar to that of leukemias.

The main clinical manifestations of lymphomas are characteristic. Most patients start with non-painful peripheral lymphadenomegaly (swelling). This is the initial manifestation in two-thirds of cases, and the main chains affected are cervical, supraclavicular, and inguinal. In addition, the so-called “B symptoms” are common. These occur in 40% of patients and are represented by fever, often in the evening, night sweats, and weight loss of more than 10% of the weight in the last 6 months. Fatigue, malaise, body itching, and weakness also make up the range of possibilities.

What is the difference between non-Hodgkin lymphoma and Hodgkin lymphoma?

Lymphomas represent a set of lymphoproliferative malignancies, with significant heterogeneity. Due to diversities in biological behavior, differences in terms of treatment and prognosis, and also due to histological alterations, lymphomas are divided into two large groups: Hodgkin lymphomas and non-Hodgkin lymphomas.

Hodgkin lymphomas, formally called Hodgkin’s disease, derive from B-cells originating from germinal centers of the lymph nodes and account for approximately 10% of lymphomas. They have a unique histological composition, containing only a small amount of neoplastic cells. These structures are known as Reed-Sternberg cells and are always interspersed with a background rich in inflammatory cells. They affect mostly young adults, around 20 years of age, or the elderly, around 65 years of age.

Most patients with classic disease present with enlarged and painless lymph nodes, typically involving the cervical region. The pattern of dissemination usually respects the sequence of lymph node chains. That is, when it starts in the cervical region, for example, it progresses to supraclavicular nodes just below. Then they move down to the armpit, to the inner chest, through the mediastinal lymph nodes, and so on down the abdomen. B-symptoms (fever, night sweats, and weight loss) are present in 20% of individuals with early disease and in 50% of those with more advanced disease. It is a disease with a relatively good prognosis. From 75 to 80% of cases are curable, and the earlier it is detected, the greater the chances of therapeutic success.

In contrast, non-Hodgkin lymphomas (NHL) encompass a much more heterogeneous spectrum of diseases, ranging from neoplasms with a good prognosis and curable to highly aggressive and lethal diseases. They can derive from T lymphocytes and, more rarely, from Natural Killers cells, however, most cases have a B lymphocyte origin.

More than 20 histological subtypes of NHL are described, which in turn are divided, according to their biological behavior, into indolent, aggressive, and highly aggressive diseases. In theory, indolent lymphomas are those with a low mitotic index, that is, they grow slowly and persistently for many years. They generally respond poorly to chemotherapy and, despite their almost benign behavior, are technically incurable. Aggressive lymphomas, on the other hand, are the most frequent and have high proliferative rates. If left untreated, these are potentially serious diseases, but they respond well to chemotherapy and radiotherapy, with considerable potential for cure, depending on their clinical stage. The highly aggressive neoplasms, as the name implies, are extremely serious, refractory to treatment, and have a high lethal potential.

The signs and symptoms manifested in non-Hodgkin lymphoma can be different, depending on the degree of aggressiveness and location of the tumor. The most common manifestation is the swelling of lymph nodes in various regions of the body. The pattern of dissemination is random and does not respect any sequence, that is, at the same time that cervical lymph nodes are affected, others in the groin region may also be affected. Voluminous masses on the face, chest, or abdomen are also not uncommon and are signs of more aggressive disease. B symptoms confer a worse prognosis on the patient and are present in approximately 40 to 50% of cases.

Comparatively, non-Hodgkin’s lymphomas, in general, are more aggressive than Hodgkin’s. However, with the therapeutic advances seen more recently, the prognosis of a good number of patients has changed radically. It can be said that, today, the therapeutic success rates are practically equivalent.

What causes non-Hodgin's lymphoma?

The causes of non-Hodgkin lymphomas are still unknown. It is known that, by the general principles of carcinogenesis, its origin is based on the superposition of genetic alterations, such as mutations, deletions or translocations, for example. Nowadays, the absence of more precise information about the main aberrant pathways involved in this process is deleterious. Understanding them would be the first step towards the development of target-specific drugs, capable of aiding in the treatment.

What are the risk factors for non-Hodgkin's lymphoma (NHL)?

Researchers have identified a number of risk factors that may be involved in the development of non-Hodgkin’s lymphoma.

Age: The aging process favors the onset of NHL. Most cases affect people over 60, although certain histological subtypes have a preference for younger people.

Gender: overall, the risk of developing NHL is higher in men than in women.

Race/ethnicity: In the United States, white individuals are more likely to develop NHL than those of African/American descent. Worldwide, this is a disease more common in developed countries.

Diet and weight: Some studies suggest that overweight and obesity may increase the risk of NHL. Similarly, diets high in fat and meat also have this effect.

Exposure to ionizing radiation: Studies of survivors of nuclear accidents have shown higher incidence rates of NHL in survivors. In addition, people who have undergone radiotherapy treatment for other neoplasms also have an increased risk of developing the disease during their lives. The chance is even greater in those who received chemotherapy with alkylating agents at the same time.

Chemical exposure: scientific data reveal that benzene, herbicides, and insecticides may be related to increased risk of developing NHL. Similarly, the use of chemotherapeutic agents for the treatment of other neoplasms, at a different stage of life, also demonstrates this relationship.

Immune deficiencies: people with immune deficiencies, such as organ transplant recipients who use immunosuppressants, or people with HIV, for example, are clearly at greater risk of lymphoma. Autoimmune diseases: some diseases such as rheumatoid arthritis, systemic lupus erythematosus, Sjogren’s syndrome, or celiac disease are linked to higher rates of developing NHL.

Infections: Viruses that can directly affect the DNA of lymphocytes, such as HTLV-1, herpes virus 8, and Epstein-Barr virus, for example, are linked to the development of some specific types of NHL. Infection with H. pylori bacteria is also markedly linked to the emergence of MALT lymphomas.

Breast prostheses: Although rare, some women develop anaplastic large cell lymphomas in the surgical scar of silicone prostheses.

Can non-Hodgkin's lymphoma (NHL) be prevented?

Most patients with non-Hodgkin’s lymphoma have no risk factors that can be changed, and it is usually impossible to protect oneself from developing it. There is no way to change a person’s age, gender, race or background. Nor can you go back in time and avoid exposure to radiation or chemotherapeutic agents. However, it is possible to invest in the prevention of certain factors in order to minimize the chances of the disease developing.

For example, we have seen that immunodeficiencies can increase the risk of NHL, as can infection with viruses that alter the DNA of lymphocytes. Both the HIV virus and HTLV-1 and herpes viruses are transmissible through sexual contact. Adopting a more responsible sexual behavior and adopting simple measures such as the use of condoms, besides preventing against STDs, also reduces the chances of developing NHL in the future.

Another infection linked to a specific subtype of lymphoma, MALT, is due to Helicobacter pylori. This bacterium affects the stomach and promotes chronic inflammation, which stimulates neoplastic development after years of occurrence. Treating it is a simple and highly effective measure in reducing the chances of lymphoma.

There are data suggesting a positive relationship between obesity and a high-fat, high-meat diet and the development of various subtypes of NHL. It is not clear whether these are real risk factors, but in any case eating better and losing weight are appropriate measures for all people, regardless of any other relationship.

Is non-Hodgkin's lymphoma curable?

Several treatment modalities can be used against non-Hodgkin’s lymphomas. The choices will depend, basically, on their histological type, their degree of aggressiveness, and the stage of dissemination of the disease. They include chemotherapy, immunotherapy, target-specific therapy, radiotherapy, and bone marrow transplantation.

More modern imaging methods and greater population access to health care professionals and the therapeutic arsenal have positively altered patient survival prospects. Earlier diagnosis, better radiotherapy techniques, and the development of new drugs that are highly effective against malignant lymphocytic cells have been important milestones in recent years. Together, these measures have been responsible for a huge leap in the quality of treatment of these patients and have provided several of them with real possibilities of cure.

Is myeloma leukemia?

No. Myeloma is a tumor that originates from the plasmocyte, a type of cell present in the bone marrow. Leukemia, on the other hand, is the name given to a group of diseases that affect leukocytes (white blood cells), also originating in the bone marrow.