Follicular lymphoma belongs to the group of low-grade non-Hodgkin's lymphomas. Usually, it does not give any symptoms for a long time. What may indicate the development of follicular lymphoma? How is it diagnosed and treated? What's the prognosis?

Follicular lymphoma(FL) is a well-differentiated neoplasm belonging to the group of non-Hodgkin lymphomas, otherwise known as Non-Hodgkin Lymphomas.

The risk factors for developing follicular lymphoma are not known so far.

It is derived from B lymphocytes, which are a component of the lymphatic system, forming centers for the reproduction of lymph nodes.

Numerous, uncontrolled division of neoplastic cells in the lymph nodes leads to the formation of tumors, the identification of which by the patient is often the first symptom of the disease and the reason for going to the primary care physician.

Lymph tissue is found throughout the body, so there is no typical site of follicular lymphoma, but it is most commonly seen in the lymph nodes of the neck, armpits and groin.

Follicular lymphoma is a low-grade neoplasm, usually characterized by slow growth and a good prognosis, spontaneous remissions of the disease are reported in the literature.

The characteristic feature of this neoplasm is its long, asymptomatic course. For this reason, in most cases, the disease is generalized at diagnosis, and bone marrow involvement occurs in approximately 60% of patients.

Follicular Lymphoma: Incidence

Follicular lymphoma is a cancer that accounts for approximately 20% of all lymphomas and approximately 70% of benign lymphomas with low development dynamics and slow progression (the so-called indolent lymphomas).

In terms of prevalence, it is the second most described lymphoma in Europe, after diffuse large B-cell lymphoma (DLBCL).

It is slightly more often diagnosed in women than in men. It almost always occurs in adults, most often it is observed in middle-aged and elderly people, the average age is 55-60 years old.

Follicular Lymphoma: Pathogenesis

Follicular lymphoma is a cancer that descended from altered B lymphocytes, which are located in the centers of reproduction of lymph nodes.

In most patients, a cytogenetic change, or more precisely the t (14,18) translocation, is responsible for the development of the disease, as a result of which a part of chromosome 18 has been transferred to chromosome 14.

As a result, an excessive amount of the anti-apoptotic protein BCL2 is produced, which results in the inhibition of programmed, physiological cell death and their pathological, uncontrolled growth.

It should be noted that the t (14,18) translocation may occur in some people physiologically and its detection alone is not a basis for the diagnosis of follicular lymphoma, nor for the introduction of specialist treatment.

Follicular Lymphoma: Symptoms

Common symptoms in lymphoma include:

  • lymphadenopathy

Enlargement of the lymph nodes in the neck and armpits is the most common symptom of cancer of the lymphatic system; enlarged nodes have a diameter of more than 2 cm and are felt by the patient as painless subcutaneous nodules or nodules, above which the skin is not reddened or inflamed, there are no fistulas.

Lymph nodes are sliding against the skin.

The situation changes when deeper lymph nodes are enlarged, which cannot be examined through the skin.

They can cause pressure on other organs and cause coughing, feeling short of breath, abdominal pain, back pain and chest pain, and even difficulty breathing.

Other organs of the lymphatic system, such as the spleen, tonsils, and more rarely extra-lymphatic organs, such as the digestive tract or skin, may also be involved in the neoplastic process.

  • dark night sweats
  • fever for no apparent reason more than 38oC, lasting at least 2 weeks
  • unintentional weight loss of more than 10% in no more than 6 months
  • fatigue
  • lack of appetite
  • anemia
  • infections, frequent colds and infections that are difficult to treat and recur
  • bleeding, ecchymosis, skin changes are caused by a reduced number of platelets; bleeding gums and nosebleeds are frequent, as well as an increased predisposition to bruising
  • splenomegaly, i.e. enlargement of the spleen

Follicular lymphoma: diagnosis and diagnosis

Symptoms reported by the patient may lead to suspected follicular lymphoma.

To diagnose the disease, it is necessary to performspecialized imaging and laboratory tests, but the final diagnosis can only be made on the basis of the histopathological and immunohistochemical examination of the lymph node.

The entire lymph node is collected for examination in a hospital setting, under local or general anesthesia, and then transported to the laboratory and assessed by a specialist pathologist under a microscope.

Please note that the diagnosis should not be made on the basis of the BAC (fine needle aspiration biopsy) image of the lymph node as it cannot be used to assess the tumor's tissue structure.

It is allowed only in exceptional situations, when the lesions are in an unusual location and it is not possible to collect them in full for examination.

Additionally, cytogenetic tests, immunophenotyping tests, as well as fluorescent in situ hybridization (FISH) tests should be performed to assess whether there is a typical t (14,18) translocation.

Based on the type and number of cells that make up the lymph node, the doctor diagnoses follicular lymphoma and classifies it according to the histopathological stage: 1, 2, 3A or 3B.

For each patient diagnosed with the disease, the following should be performed:

  • myelogram and bone marrow biopsy to confirm or rule out bone marrow spread
  • peripheral blood count with smear
  • biochemical tests of liver and kidney function
  • lactate dehydrogenase (LDH) activity tests
  • beta2-microglobulin concentrations, proteinogram

and many other laboratory and imaging tests. Only after complete diagnostics and determination of the patient's he alth condition is it possible to start specialist treatment.

Follicular Lymphoma: Stage

After the histopathological examination of the lymph node and the diagnosis of follicular lymphoma, the doctor must determine the stage of the neoplastic disease (staging). It is necessary to establish the patient's further treatment plan.

The system that allows the doctor to assess the degree of spread of follicular lymphoma is the international classification according to Ann Arbor.

We assess the number of affected groups of lymph nodes and other lymphatic system organs, their ratio to the diaphragm, bone marrow involvement, and distant organ involvement.

An additional parameter taken into account when determining the severity of the disease is the presence of general symptoms of the disease, such as nocturnaldrenching sweats, a fever of more than 38oC for no apparent reason for more than 2 weeks, and a weight loss of 10% in no more than 6 months.

When the doctor determines the presence of the above symptoms, he adds the letter "B" to the Roman numerals describing the severity of the disease from I to IV, if there are no general symptoms, he adds the letter "A".

The letter "E" in the Ann Arbor classification denotes follicular lymphoma that has an extra-nodal location, i.e. it occupies an organ or tissues other than extranodal nodes.

The letter "S" is added when the spleen is involved in the cancer process.

Disease advancement stageCharacteristics
IInvolvement of only one group of lymph nodes or limited involvement of a single organ or extra-lymphatic site (I E)
IIInvolvement of two or more groups of lymph nodes on one side of the diaphragm only or localized involvement of the extra-lymphatic site with one or more lymph node areas (II E)
IIIInvolvement of the lymph nodes on both sides of the diaphragm, may be accompanied by the seizure of the extra-lymphatic site (III E)
IVDiffuse or diffuse involvement of one or more extra-lymphatic organs
AGeneral symptoms are absent
BGeneral symptoms are present
SInvolvement of the neoplastic process of the spleen

International Prognostic Index of Follicular Lymphoma

The Follicular Lymphoma-specific International Prognostic Index (FLIPI) is used to assess the prognosis of patients with follicular lymphoma.

Based on the following 5 parameters, it is possible to determine the risk of disease progression after the end of treatment and to adjust the number of follow-up visits to the attending physician.
FLIPI 1 → Overall survival forecast

  • occupying more than 4 nodal locations
  • age of the patient over 60
  • increased activity of lactate dehydrogenase (LDH)
  • clinical stage III or IV disease according to Ann Arbor
  • hemoglobin concentration less than 12 g / dL
RISKNumber of factorsSick5-year overall survival10 years of overall survival
Low0-136%91%71%
Indirect237%78%51%
High>=3 27%53%36%

FLIPI 2 → progression-free survival forecast

  • lymph nodes over 6 cm in size
  • bone marrow involvement
  • age of the patient over 60
  • beta2-microglobulin above upper normal limit
  • hemoglobin concentration less than 12 g / dL
RISKNumber of factorsSick5-year overall survival10 years of overall survival
Low0-120%91%80%
Indirect253%69%51%
High>=3 27%51%19%

Follicular Lymphoma: Differentiation

Follicular lymphoma should be differentiated from other neoplastic diseases of the lymphatic system, especially other non-Hodgkin's lymphomas from small B lymphocytes. Particular attention should be paid to:

  • chronic lymphocytic leukemia (CLL)
  • mantle cell lymphoma (MCL)
  • of splenic B-cell marginal zone lymphoma (SMZL)
  • lymphoplasmacytic lymphoma (LPL)

These proliferative diseases should be ruled out before making a final diagnosis, as they have similar clinical symptoms.

Follicular lymphoma should not be diagnosed without histopathological examination of the diseased tissue and immunohistochemistry.

Follicular Lymphoma: Treatment And Its Side Effects

Treatment of follicular lymphoma should be individually tailored to each patient, depending on the histopathological classification of the lymphoma, clinical stage of the disease, patient age, he alth condition and the presence of comorbidities.

It takes place most often in specialized centers, where specialist doctors select patients with appropriate treatment regimens.

The main goals of therapy are:

  • inhibition of the growth of new cancer cells
  • destruction of cancer cells
  • treatment of the symptoms of the disease
  • improving the patient's quality of life

Treatment methods for follicular lymphoma

  • OBSERVATION

A patient who has been diagnosed with a tumor of a small mass, but who is absentmoreover, symptoms such as pain, fever, weight loss or night sweats are often closely monitored without any treatment.

Patients are under the constant care of doctors, and specialist therapy is started only after the first symptoms of the disease appear or their progression. The entire process of just monitoring a patient can take up to 10 years.

There were cases (5-25% of patients) of spontaneous regression of follicular lymphoma with a low stage and low tumor burden.

The side effects of this method of treatment include the patient's increasing stress related to the lack of medication and the waiting attitude.

The conversation between the doctor and the patient is very important, during which the patient has the time and opportunity to ask any questions that bother him about the disease and therapy.

  • RADIOTHERAPY

Radiotherapy is a method of treatment that inhibits the growth and destruction of cancer cells using radiation.

In the treatment of follicular lymphoma, radical teleradiotherapy of the originally affected areas is most often used.

It is a technique in which a beam of radiation is generated by a special device placed at a distance from the tissues and directed at the area of ​​the body where the tumor is located.

Modern devices enable precise directing of the beam of rays to the affected area, which allows for the protection of he althy adjacent tissues.

Side effects of this therapy include symptoms related to the irradiation of organs affected by the proliferation or adjacent to them, which cannot be protected against radiation.

The skin can become dry, flaccid and more pigmented, and telangiectasias, or vascular spider veins, often appear on its surface.

The very rare complication of treatment is the development of a secondary tumor in the irradiated tissues. This should be borne in mind when deciding on this method of treatment.

  • CHEMOTHERAPY

Chemotherapy is a therapeutic method that consists in administering special drugs to patients, the so-called cytostatics, whose task is to destroy, inhibit the growth and block the division of neoplastic cells.

Drugs are administered intravenously, orally or intrathecally when the tumor has spread to the central nervous system and the administration of chemotherapy into the cerebrospinal fluid is required.

A specialist doctor decides on the route of administration, type and schedule of chemotherapy to be administeredpatient.

Multi-drug therapy is a treatment regimen in which several chemotherapeutic agents are used simultaneously.

Side effects of chemotherapy include anemia, malaise, headache, nausea and vomiting, fever, flu-like symptoms, mouth and throat ulcers, temporary hair loss or weakness, skin changes, diarrhea, constipation, cycle disorders as well as problems with urination, and even a change in its color.

The occurrence of side effects and their intensity depends individually on the organism of each patient, the applied therapy, treatment regimen, and combination of drugs. Side effects appear more often with multi-drug therapy than with monotherapy.

  • MAIN SCHEMES OF THE TREATMENT OF LAMINARY Lymphoma

Treatment regimens with the use of several chemotherapeutic agents are determined depending on the clinical advancement of the tumor according to the Ann Arbor classification and the prognostic index FLIPI.

The therapy usually consists of 2-4 or 6-8 cycles of chemotherapy given every 3-4 weeks.

  • CVP (cyclophosphamide, vincristine, prednisone)
  • R-CVP (rituximab, cyclophosphamide, vincristine, prednisone)
  • CHVP (cyclophosphamide, doxorubicin, vincristine, prednisone)
  • R-CVP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone)
  • IMMUNOTHERAPY

Radioimmunotherapy, i.e. treatment with a monoclonal antibody to which a radioactive substance is attached.

It is a specialist drug which, after recognizing antigens on cancer cells, releases a radioactive substance and thus destroys cancerous cells.

Antibodies used in the treatment of follicular lymphoma are rituximab, as well as radiolabelled antibodies such as 90Y- ibritumomab tiuxetan and sodium iodide-131 tositumomab.

  • SURGICAL TREATMENT

Tumors of the lymphatic system rarely cover one area of ​​the body, so surgical treatment happens in exceptional situations, it is not a typical method of treating lymphomas, but solid tumors.

  • STEM CELL TRANSPLANT

Stem cell transplantation is a treatment method with many side effects and therefore is not used routinely. It consists in collecting the patient's own stem cells (autograft, autograft) or from a specially selected donor (allograft, transplantallogeneic) and implanted back after high-dose chemotherapy, which is designed to destroy cancer cells. Stem cells are introduced into the patient's body through intravenous infusion.

  • FOLLOWING TREATMENT

A patient who has undergone follicular lymphoma treatment should stay in constant contact with the attending hematologist and report to the scheduled follow-up visits.

The patient's medical history and physical examination as well as laboratory tests should be performed every 3-6 months after completing the therapy, and then every 1 year, or more frequently when the patient's doctor deems it necessary.

Imaging tests, such as computed tomography, should not be performed at every medical visit due to the high doses of harmful X-rays.

It is enough if they are commissioned every 6 months for the first 2 years, and then once a year.

Frequent medical checkups and thorough diagnosis of patients allow for the early detection of disease recurrence and re-initiation of treatment.

Follicular Lymphoma: Recurrence

Relapsing disease means the reappearance of cancer cells in the patient's body.

To determine if follicular lymphoma has developed into an aggressive form, re-harvest the lymph node for histopathological examination.

The treatment regimen of a patient with recurrent neoplastic disease depends largely on his he alth condition and the effectiveness of previously used treatment methods.

In the treatment of relapsed disease, immunochemotherapy, rituximab monotherapy and high-dose chemotherapy with transplantation of the patient's own stem cells are most often used.

Remember to perform imaging examinations during treatment and assess the response to treatment using computed tomography (CT), magnetic resonance (MRI) or positron emission tomography (PET).

PET examination is a specialized imaging technique that uses radiation produced in the patient's tissues with diseased diseases, after prior administration of a radiopharmaceutical intravenously.

The most common is 18F fluorodeoxyglucose (FDG), which contains the radioactive isotope of fluorine.

Since the metabolism of labeled glucose in neoplastic tissues is identical to that of normal glucose and much more intense than in he althy tissues, it is possible to locate the areas in the patient's body where neoplastic processes are taking place.

Follicular Lymphoma: prognosis

Follicular lymphoma is a slow progressive, low-grade, and usually good prognosis neoplasm of the lymphatic system.

Its characteristic feature is many years of course, a patient can live for about 10 years without treatment, when the lymphoma does not cause any symptoms and is diagnosed at an early stage of clinical advancement.

In 15% of patients, disease progression occurs very quickly, only about 2 years pass from the diagnosis of cancer to death.

The international prognostic index of follicular lymphoma FLIPI1 and FLIPI2 is used to assess the prognosis of patients with follicular lymphoma, both of which are discussed in more detail above.

Category:

Oncology