Hodgkin's lymphoma

Content

Introduction

Lymphomas, malignant tumors of the lymphatic system, are a heterogeneous group of neoplasms that originate from cells of the lymphatic systems and endothelial reticulum, which due to an uncontrolled multiplication of cells, form a mass, the tumor. They are essentially of two types: Hodgkin (about 30% of cases) and non-Hodgkin (Video). Thomas Hodgkin, in 1832 grouped together a series of symptoms that included the enlargement of the spleen and lymph nodes in a pathology that took his name from him.

The lymphatic system is a fundamental element of the immune system, and consists of a network of thin vessels distributed throughout the body, which connects the bone marrow, tonsils, thymus, spleen and lymph nodes, and which has the task of defend the body from disease and ensure proper circulation of the lymph, a clear liquid that contains lymphocytes, a type of white blood cell that has the function of fighting infections. Lymph carries excess fluids (fluids), waste materials and lymphocytes. Lymphocytes are of two types: B lymphocytes, which mature in the bone marrow or lymphatic organs, and T lymphocytes, which mature in the thymus. Hodgkin's lymphoma is type B and consists of a localized or disseminated clonal proliferation of B lymphocytes, which gives rise to cells characterized by having two distinct nuclei.

The most common disorder (symptom) caused by Hodgkin's lymphoma is swelling, usually painless, of a lymph node in the neck, armpit or groin.

Spread of Hodgkin's Lymphoma

Hodgkin's lymphoma (LH) is a relatively rare cancer (about 0.5% of confirmed cancers) and can occur at any age even if the groups most at risk are those of young people aged 15 to 35 and the elderly over 70 years old. In men, the number of new cases (incidence) is slightly higher than in women.

According to the AIRTUM Cancer Registries, in fact, the incidence of LH is increasing, with an estimate in 2013 of about 1,000 new cases among women and 1,300 among men. However, mortality is decreasing.

The precise cause of the Hodgkin's lymphoma it seems unknown there is a genetic predisposition associated with environmental factors, a thesis supported by the evidence that the probability of getting sick increases if you have first-degree relatives already affected by Hodgkin's lymphoma. Furthermore, the risk increases in the presence of diseases that weaken the body's defense system (immune system), in the case of treatments based on immunosuppressive drugs or, again, in the case of infection in the past with the Epstein-Barr virus. , responsible for infectious mononucleosis. Furthermore, the incidence is higher in people who are seropositive for the HIV virus.

The only way to ascertain the presence of the disease is to undergo a biopsy, an examination which consists of taking a small amount of tissue (sample) from a lymph node and analyzing it in the laboratory. There is a classic form of the disease, observed in 1990. % of cases and a more rare nodular form with lymphocyte predominance (10% of cases).

The Hodgkin's lymphoma it is a moderately aggressive tumor but can spread rapidly throughout the body. Despite this, it is one of the simplest types of cancer to treat.

The choice of therapies depends on the general state of health and age, because many of the possible treatments can be "heavy" for the body to bear. Furthermore, another important factor for choosing the most suitable therapy for each person is the degree of spread of the lymphoma at the time of its discovery The most commonly performed treatments are chemotherapy, followed by radiotherapy, or chemotherapy alone.

Overall, about 85% of people affected by Hodgkin's lymphoma has a survival of at least five years from the moment of ascertainment (diagnosis) of the disease and most of them recover. However, once the treatments are over, there is a risk of long-term complications, including infertility and an increase in the chances of developing other types of cancer in the future.

Symptoms

The disorder (symptom) with which Hodgkin's lymphoma most commonly occurs is an enlarged lymph nodes in the neck (cervical region) or axillary. Generally, the swelling is not painful but the pain can appear if you drink alcohol. Other symptoms arise when the disease spreads to contiguous lymph node sites. Persistent itching can be an early symptom.

The enlargement of one or more lymph nodes, however, does not necessarily mean that a lymphoma is present but, much more likely, that the body's defense system (immune system) is fighting an infection.

In the Hodgkin's lymphoma the swelling is caused by too many B lymphocytes (a particular type of lymphocytes) that multiply abnormally and accumulate in one lymph node and then invade others. Peculiar is the presence of so-called Reed-Sternberg cells, lymphocytes that are distinguished by having two nuclei and because they have lost the surface antigens normally present and characteristic of B lymphocytes.As these lymphocytes have lost the ability to fight infections, the affected person becomes more vulnerable and becomes ill more easily.

The Hodgkin's lymphoma it can develop in any part of the body but the areas where it appears most frequently are, in order, the lymph nodes in the neck, then the axillary, mediastinal, inguinal and abdominal ones.

Other disorders (symptoms) may include night sweats, unexplained loss of appetite and thus weight, fever, widespread itching, persistent cough, fatigue, difficulty breathing.

In general, the disorders (symptoms) that accompany the Hodgkin's lymphoma they also depend on where the disease occurs. If, for example, it affects the lymph nodes present in the abdomen, in addition to the more general disturbances, abdominal pain and / or an unnatural sense of satiety may also occur. Often there is splenomegaly, ie enlargement of the spleen.

If swollen lymph nodes are seen for an extended period of time without any signs of infection, the family doctor should be consulted. While it is unlikely that the disorders could be caused by Hodgkin's lymphoma, it is necessary to find out the cause because they could be caused by other diseases that must, however, be ascertained and treated. If there is a tumor that compresses certain organs, other symptoms may occur, such as jaundice of obstruction of the bile duct, edema of the lower limbs, dyspnoea, lung abscesses.

Causes

Although it is certain that Hodgkin's lymphoma is caused by a change (mutation) in the DNA of B lymphocytes (a type of white blood cell), the underlying cause and exact reason for the mutation to occur are not known; it can be said that there is a genetic predisposition associated with environmental factors.

DNA provides cells with a basic set of instructions regarding their growth and reproduction.The mutation in the DNA changes these indications and, consequently, the cells continue to grow and reproduce in an uncontrolled way in one or more lymph nodes in an area of ​​the body such as, for example, the neck or groin. Later, they could move and spread to the bone marrow, spleen, liver, lungs, and skin. Recent studies have shown, in particular, that in cancer cells there is an important decrease in the function of the genes involved in the regulation of genomic stability and cytokine production.

Risk factors

Some factors have been identified that can increase the risk of getting Hodgkin's lymphoma. They include: conditions that can weaken the immune system (such as HIV, or immunosuppressive drug therapy after a transplant), situations where the immune system is not fully functioning, a previous infection with the Epstein-Barr virus (responsible for infectious mononucleosis), with Mycobacterium tuberculosis, with the Herpes 6 virus, in people with congenital immunodeficiency: ataxia-telangiectatic, Klinefelter syndrome, Chédiak-Higashi syndrome and with some autoimmune diseases, such as rheumatoid arthris , celiac disease, systemic lupus erythematosus. Or have already had non-Hodgkin's lymphoma or be obese (a major risk factor for women).

The Hodgkin's lymphoma it can occur at any age, although cases are mostly diagnosed in young adults (around 20 years of age), or in the elderly (70 years and older). The risk of getting sick also increases in the presence of first degree relatives already affected by the disease. Furthermore, men have a slightly higher risk than women.

Diagnosis

In case of suspicion of Hodgkin's lymphoma, that is in the presence of painless lymphadenopathies, it is essential to consult a doctor.If, after a thorough examination, the characteristic signs of the disease are detected, in-depth examinations will be prescribed, to make a diagnosis and, above all, to establish its stage and identify prognostic factors.

Lymph node biopsy

The assessment (diagnosis) of the disease requires the execution of a biopsy, an examination which consists in taking a fragment of a lymph node, or the entire lymph node, and then examining it under a microscope. Generally, the biopsy is done under local anesthesia, therefore it does not require hospitalization. However, if the lymph nodes to be analyzed were to be deep, it could be performed under general anesthesia. The biopsy, if the disease was present, reveals the presence of Reed-Sternberg cells (large binuclear cells) in a heterogeneous cell infiltrate, consisting of histiocytes (cells present in the connective tissue that perform a phagocytic function against different antigens), lymphocytes, monocytes, plasma cells and eosinophils. In addition, to assess the extent of the disease, it may be necessary to perform other types of tests.

Bone marrow biopsy

The doctor may ask the patient to have a bone marrow sample taken to check for the presence or absence of cancerous cells in it. The examination is carried out under local anesthesia, therefore without hospitalization, by inserting a needle into a flat bone (usually of the pelvis) and taking a sample of marrow blood and a fragment of bone marrow to be analyzed, subsequently, under a microscope.

Diagnostic rachycentesis

It is used to take a sample of cerebrospinal fluid, through a lumbar puncture, to check for the presence of a possible inflammatory and / or infectious process affecting the brain.

Blood tests

They are performed right from the assessment of the disease, for example, the value of the ESR at diagnosis is of particular importance and, subsequently, for the entire duration of treatment to evaluate the general state of health, the values ​​of white and red blood cells, platelets and the functioning of organs such as the liver and kidneys.

Diagnostic for images

An x-ray is done to check if the cancer has spread to the chest and lungs. Other tests such as computerized axial tomography (CT), positron emission tomography (PET) which is based on the knowledge that tumors consume more glucose than healthy cells, so during this investigation a radioactive sugar-containing compound is administered intravenously which immediately spreads throughout the body. After about 2 hours, the parts that absorb the most glucose can be visualized. Magnetic resonance imaging (MRI) and scans may be ordered by the doctor to assess how far the disease has spread throughout the body.

Staging

Once the disease has been ascertained (diagnosed) it is possible to verify its spread in the organism by means of the so-called staging (Video). It is a fundamental and necessary classification system from a diagnostic and prognostic point of view to start the most suitable treatments. At the moment the Hodgkin's lymphoma is classified with the Ann-Arbor system or an updated version thereof, the Cotswold classification.

Both distinguish four stages of the disease (I, II, III, IV):

  • THE: apparent involvement of a single lymphodonal gland, or of a single extralymphonodal organ
  • II: involvement of two or more lymphoglandular stations close to each other (for example: all in the neck and chest, or all in the abdomen)
  • III: involvement of multiple lymphoglandular stations both at an overdiaphragmatic level (neck / chest) than subdiaphragmatic (abdominal or groin)
  • IV: extensive involvement of multiple lymph node stations and other extra-lymph node organs, such as the lungs, liver or bones

Furthermore, to indicate the stage more precisely, the numbers are also associated with the letters A (no symptoms), B (presence of specific symptoms), E (disease involving other organs adjacent to the lymph node structure involved), S (disease involving the spleen) and X (large tumor mass with a maximum diameter> 10cm or involving more than 1/3 of the thoracic diameter).

As already mentioned above, there are different types of Hodgkin's lymphoma but according to the classification of the World Health Organization (WHO) it is considered a classic Hodgkin's lymphoma and a nodular lymphocyte predominance.

In classical Hodgkin's lymphoma, which accounts for 85% of lymphomas, cells usually have a defective B-cell differentiation program and abnormal immunoglobulin expression.

Four different subtypes were identified based on histological characteristics:

  • 1: with nodular lymphocyte sclerosis
  • 2: with mixed cellularity
  • 3: with low amount of lymphocytes
  • 4: with many lymphocytes

Having this information is essential for the clinic, although it is often difficult to identify the subtype because the amount of biopsy material is not sufficient.

The first type mainly affects young people aged 15 to 34, with a female predominance and is less common in the elderly. It appears more common among the wealthiest social strata, possibly due to late exposure to common infections and is often associated with Epstein-Barr virus infection. Most patients show lymphadenopathy, mainly the cervical, mediastinal, supraclavicular and axillary lymph nodes.It is characterized by a scarcity of neoplastic cells and a rich inflammatory context; the lymph nodes present nodular clusters surrounded by bands of collagen, containing a variable number of tumor cells, all immersed in an inflammatory environment. These cells form aggregates which, depending on the quantity, guide the therapy to be carried out.

The second type is always positive for the Epstein-Barr virus and shows association with other viruses that create immunodeficiency in humans. It is characterized by the classic Reed-Steinberg tumor cells immersed in an inflammatory environment.

The third type is characterized by the presence of small B lymphocytes that form nodules, often with regressed germinal centers in the periphery. Other inflammatory-type cells are rare.

The fourth type is the rarest and is characterized by an "abundance of Reed-Sternberg cells and an almost absence of small reactive B lymphocytes.

Despite the variability in the histological appearance of the 4 subtypes, tumor cells in Hodgkin's lymphoma show a common phenotype and immunohistochemistry is a useful tool for diagnosis. CD30 protein is expressed in all cases, while CD15 in 75-85% of cases; these evidences have allowed the development of specific therapies for this neoplasm. It has also been seen that components of the tumor microenvironment have an impact on the prognosis of the disease, for example the number of tumor macrophages is closely associated with refractory to therapy, early relapse and reduced survival in adult patients.

Therapy

In most cases of Hodgkin's lymphoma it is possible to heal with chemotherapy, alone or in combination with radiotherapy, a disease-free survival 5 years after the end of therapy is considered a cure.

Chemotherapy

Given that some available chemotherapies subject the patient to severe physical stress, the choice of treatments is strictly dependent on the age and general state of health of the patient. In any case, these are therapies that allow healing or the stage where the lymphoma does not cause disturbances (remission) for many years, especially if the disease was discovered before it reached other organs outside the lymphatic system.

The choice of the therapeutic approach, therefore, is rather complex and is based on the exact staging of the disease. Before starting it, the patient is asked to conserve the seminal fluid or the oocytes, to preserve fertility. Thereafter, therapy is carried out. In the early stages of the disease (IA-IIA, IB and IIB) a short duration chemotherapy consisting of doxorubicin, vinblastine, bleomycin and dacarbazine (ABVD) is given, followed by radiotherapy or chemotherapy alone for a longer time. "80% of the sick. Stages IIIA and IIIB are treated with ABVD only and healing was observed in 70-80% of cases. The IVA and IVB stages are always treated with ABVD, but in cases where there is a positive PET (positron emission tomography) which allows a metabolic characterization of the disease, an increased administration of bleomycin is carried out, with the addition of etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisolone. For a better prognosis all patients must have, at the end of the chemotherapy cycles, a negative PET. In the cases refractory to chemotherapy, biological therapies based on monoclonal antibodies such as Nivolumab and Pembrolizumab have been introduced in recent years. The drugs used for chemotherapy are administered into a vein or by mouth (oral route).The treatment generally lasts a few months and is carried out without hospitalization, unless there are unwanted effects (side effects) that make it necessary.

Among these, the most critical is damage to the bone marrow which can cause fatigue, shortness of breath, increased susceptibility to infections, easy bruising and bleeding. In the presence of these effects, treatment is likely to be temporarily suspended until the number of healthy blood cells has returned to adequate values. Other side effects that may occur include nausea, vomiting, diarrhea, fatigue, loss of appetite, mouth ulcers, hair loss and infertility. Some chemotherapy drugs can adversely affect cardiac activity, others can increase the risk of developing a second cancer in the future. Many of these effects stop at the end of treatment.

In the event that chemotherapy does not give the expected results and the patients are not negative for PET, it is essential to resort to autologous transplantation using the patient's hematopoietic stem cells (the cells from which all blood cells derive). They can be taken directly from the blood or bone marrow, the reinfusion of stem cells allows to accelerate the recovery of blood cells by reducing the toxic effects of high-dose chemotherapy. In cases with multiple relapses it is possible to activate a donor transplant (allogeneic transplant) which is able to heal a good percentage of patients.

Radiotherapy

Radiotherapy consists of the "use of high-energy radiation in order to destroy cancer cells, safeguarding healthy ones. It is mainly used in the initial stage of the disease, when it has not yet spread to other parts of the body.It is usually performed on large sections of the body (neck / chest, abdomen or pelvis), so as to include in the irradiated field both the lymph node affected by the neoplastic process, and the surrounding lymph nodes, apparently normal, in which small aggregates of malignant cells can be migrated through the lymphatic vessels. Generally, it is carried out with short daily sessions for several weeks and does not require hospitalization. This type of treatment in itself is not painful nor makes it radioactive, so you can be in contact with others, even with children without any danger but it can have some significant side effects, albeit temporary, both in the part of the body treated and of a general nature such as fatigue, nausea, vomiting, dry (parched) mouth, loss of appetite, hair loss. Other effects, such as infertility or darker skin in the treated area, could be permanent.

Steroid drugs

Chemotherapy combined with the administration of steroid drugs is useful for people who discover the disease when it is already in an advanced stage or for individuals who have not benefited from initial therapy. In turn, steroid drugs can cause increased appetite, a sense of indigestion, sleep disturbances and agitation. These are effects that disappear when the therapy is stopped.

Rituximab

If Hodgkin's lymphoma is a nodular lymphocyte predominance, a rare type of lymphoma, it is possible that chemotherapy is supplemented with rituximab, a biologic drug that works by killing B lymphocytes, both diseased and not, and thus allowing the development of a new healthy cell population. It is given by infusion and can cause side effects such as fever, headache, body aches, tiredness, nausea, diarrhea. As therapy progresses these symptoms tend to ease.

At the end of the treatment, it will be necessary to undergo regular check-ups to check and prevent any relapses of the disease. In patients relapsing after therapy or refractory to it, a cure called "CAR-T Cell Terapy" has been tried on an experimental basis, which consists of genetically modifying a patient's T lymphocytes so that they specifically recognize B cells. neoplastic, through a membrane antigen called CD30, and induce its death once reintroduced into the patient. It has been seen that this treatment has a high rate of lasting response over time, with an excellent safety profile. This highlights the feasibility of this therapy in all B cell neoplasms.

Complications

One of the most common complications of Hodgkin's lymphoma is immunodeficiency, a weakening of the body's defense system (immune system) which causes a reduction in the ability to fight infections and can worsen once treatment is started. For this reason, people with Hodgkin's lymphoma are also prescribed antibiotics to be taken regularly and it is recommended to follow medical prescriptions carefully, to maintain good dental and personal hygiene, to avoid contact with sick people, even if these are infectious diseases already contracted before, such as measles or chicken pox.

In addition, it is important to report any symptoms (symptoms), such as high fever, headache, muscle aches, diarrhea and fatigue, to the treating doctor if they persist over time.

While it is essential to continue to go out regularly, both for physical exercise and for your psychological well-being, it is essential to avoid crowded places and public transport during rush hours. In addition, it is advisable to ensure that all vaccinations are up to date, even if it will not be possible to carry them out during treatment.

Chemo and radiation therapy can cause infertility, sometimes temporary, most often permanent. Therefore, the sick person will be offered to keep their sperm or eggs to protect them from treatment and use them for possible future procreation.

People affected by Hodgkin's lymphoma they are more prone to later have “secondary” tumors such as lymphoma, leukemia or others. Chemo and radiation therapy increase this risk. It is also possible that tumors such as breast or lung cancers appear even more than ten years after the end of treatment for the Hodgkin's lymphoma; leukemia or other types of lymphoma may, however, occur earlier.

The chances of having cardiovascular or lung problems are also greater for people who have had the Hodgkin's lymphoma. To reduce the risks, it is essential, once the treatment is finished, to follow a correct lifestyle, avoiding smoking, maintaining a balanced weight and a balanced diet and exercising regularly.

Psychological aspects of Hodgkin's lymphoma

Find out you are sick of Hodgkin's lymphoma it can be very painful and even more difficult to accept when the signs and complaints (symptoms) caused by the disease are not yet fully evident. Having to wait to learn about the evolution of the disease and its effects can cause stress, anxiety and depression.

Talking to a counselor or psychologist can help combat these feelings, and better cope with the situation by increasing the likelihood of recovery.

Living with

Knowing that you have Hodgkin's lymphoma can cause different reactions from person to person: anger, confusion, stress, anxiety, depression, fear, uncertainty are the emotions that appear first. Talking about it with the specialist and with friends and family can be of great help.

Some medications used to treat LH can cause physical changes that are difficult to cope with and that can affect self-perception and relationships with others. However, many of the most common side effects are temporary or, in any case, reducible with the help of complementary therapies.

In addition to managing emotions and treatments, it is also necessary to follow the practical aspects of life, from economic issues to family ones, up to strictly personal ones. It is not essential to face and resolve everything on your own and all at once, an interview with the doctor or the specialized nurse can help.

Further links

NHS. Hodgkin lymphoma (English)

Italian Association for Cancer Research (AIRC). Hodgkin's lymphoma

Italian Association of Cancer Patients, Relatives and Friends (AIMaC). Hodgkin's lymphoma

MedlinePlus. Hodgkin disease (English)

National Cancer Institute (NCI). Adult Hodgkin lymphoma treatment (English)

Longley J, Johnson PWM. Current treatment paradigms for advanced stage Hodgkin lymphoma. British Journal of Hematology. 2019; 184:60-71

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